Trial Outcomes & Findings for Dose-Escalation, Safety, Pharmacokinetics Study of Cabazitaxel With Gemcitabine In Patients With Solid Tumor (NCT NCT01001221)
NCT ID: NCT01001221
Last Updated: 2013-09-11
Results Overview
Dose Limiting Toxicities (DLTs) were defined as clinical adverse events (AE) or laboratory abnormalities considered drug-related as assessed by the Investigator or Sponsor, and achieving a Common Terminology Criteria for Adverse Events v3.0 (CTCAE) severity rating of severe (3) or life-threatening (4).
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
19 participants
Primary outcome timeframe
Day 1 to Day 21 of the first treatment cycle
Results posted on
2013-09-11
Participant Flow
Participants were enrolled in 4 sites in the United States. Since it was not possible to determine the maximum Tolerated Dose (MTD) in study part 1, no participant was enrolled in study part 2 and the study was stopped.
At each dose level, there was a 1-week gap between the treatment of the first participant and the next 2 participants to evaluate toxicity. Before escalating to the next dose level, at least 3 participants were to be evaluable for the criteria defining dose limiting toxicity (DLT).
Participant milestones
| Measure |
Part 1: Cabazitaxel + Gemcitabine Dose Level 0
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Part 1: Cabazitaxel + Gemcitabine Dose Level -1
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Part 1: Cabazitaxel + Gemcitabine Dose Level -2
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Part 1: Gemcitabine + Cabazitaxel Dose Level 0
gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Part 2: Cabazitaxel + Gemcitabine MTD
Cabazitaxel IV and gemcitabine IV on Day 1 then, gemcitabine IV on Day 8 at the Maximum Tolerated Dose (MTD) as determined in study part 1
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
5
|
5
|
3
|
6
|
0
|
|
Overall Study
Treated
|
5
|
5
|
2
|
6
|
0
|
|
Overall Study
Completed 1st Treatment Cycle
|
5
|
5
|
2
|
6
|
0
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
5
|
5
|
3
|
6
|
0
|
Reasons for withdrawal
| Measure |
Part 1: Cabazitaxel + Gemcitabine Dose Level 0
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Part 1: Cabazitaxel + Gemcitabine Dose Level -1
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Part 1: Cabazitaxel + Gemcitabine Dose Level -2
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Part 1: Gemcitabine + Cabazitaxel Dose Level 0
gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Part 2: Cabazitaxel + Gemcitabine MTD
Cabazitaxel IV and gemcitabine IV on Day 1 then, gemcitabine IV on Day 8 at the Maximum Tolerated Dose (MTD) as determined in study part 1
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
2
|
0
|
2
|
0
|
|
Overall Study
Disease progression
|
3
|
2
|
2
|
4
|
0
|
|
Overall Study
Other
|
1
|
1
|
0
|
0
|
0
|
|
Overall Study
Not treated; protocol exclusion
|
0
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Dose-Escalation, Safety, Pharmacokinetics Study of Cabazitaxel With Gemcitabine In Patients With Solid Tumor
Baseline characteristics by cohort
| Measure |
Part 1: Cabazitaxel + Gemcitabine Dose Level 0
n=5 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Part 1: Cabazitaxel + Gemcitabine Dose Level -1
n=5 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Part 1: Cabazitaxel + Gemcitabine Dose Level -2
n=3 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Part 1: Gemcitabine + Cabazitaxel Dose Level 0
n=6 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Total
n=19 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age Continuous
|
60.8 years
STANDARD_DEVIATION 6.6 • n=99 Participants
|
59.2 years
STANDARD_DEVIATION 9.2 • n=107 Participants
|
53.0 years
STANDARD_DEVIATION 14.8 • n=206 Participants
|
56.3 years
STANDARD_DEVIATION 16.1 • n=7 Participants
|
57.7 years
STANDARD_DEVIATION 11.5 • n=31 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
3 Participants
n=7 Participants
|
11 Participants
n=31 Participants
|
|
Race/Ethnicity, Customized
Asian/Oriental
|
0 participants
n=99 Participants
|
0 participants
n=107 Participants
|
1 participants
n=206 Participants
|
0 participants
n=7 Participants
|
1 participants
n=31 Participants
|
|
Race/Ethnicity, Customized
Black
|
0 participants
n=99 Participants
|
1 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
1 participants
n=31 Participants
|
|
Race/Ethnicity, Customized
Caucasian/White
|
4 participants
n=99 Participants
|
4 participants
n=107 Participants
|
2 participants
n=206 Participants
|
6 participants
n=7 Participants
|
16 participants
n=31 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
1 participants
n=31 Participants
|
|
Body Surface Area
|
1.87 m^2
STANDARD_DEVIATION 0.32 • n=99 Participants
|
1.82 m^2
STANDARD_DEVIATION 0.21 • n=107 Participants
|
1.98 m^2
STANDARD_DEVIATION 0.42 • n=206 Participants
|
1.84 m^2
STANDARD_DEVIATION 0.12 • n=7 Participants
|
1.87 m^2
STANDARD_DEVIATION 0.24 • n=31 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
0
|
0 participants
n=99 Participants
|
2 participants
n=107 Participants
|
1 participants
n=206 Participants
|
1 participants
n=7 Participants
|
4 participants
n=31 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
1
|
5 participants
n=99 Participants
|
3 participants
n=107 Participants
|
2 participants
n=206 Participants
|
5 participants
n=7 Participants
|
15 participants
n=31 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
2
|
0 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
0 participants
n=31 Participants
|
|
Primary Tumor Site
Bladder
|
0 participants
n=99 Participants
|
0 participants
n=107 Participants
|
1 participants
n=206 Participants
|
1 participants
n=7 Participants
|
2 participants
n=31 Participants
|
|
Primary Tumor Site
Colon
|
0 participants
n=99 Participants
|
1 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
1 participants
n=31 Participants
|
|
Primary Tumor Site
Head/neck
|
0 participants
n=99 Participants
|
1 participants
n=107 Participants
|
1 participants
n=206 Participants
|
0 participants
n=7 Participants
|
2 participants
n=31 Participants
|
|
Primary Tumor Site
Lung
|
2 participants
n=99 Participants
|
1 participants
n=107 Participants
|
1 participants
n=206 Participants
|
0 participants
n=7 Participants
|
4 participants
n=31 Participants
|
|
Primary Tumor Site
Muscle/soft tissue
|
0 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
1 participants
n=7 Participants
|
1 participants
n=31 Participants
|
|
Primary Tumor Site
Other
|
0 participants
n=99 Participants
|
1 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
1 participants
n=31 Participants
|
|
Primary Tumor Site
Ovaries
|
0 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
1 participants
n=7 Participants
|
1 participants
n=31 Participants
|
|
Primary Tumor Site
Pancreas
|
1 participants
n=99 Participants
|
1 participants
n=107 Participants
|
0 participants
n=206 Participants
|
1 participants
n=7 Participants
|
3 participants
n=31 Participants
|
|
Primary Tumor Site
Pelvis
|
0 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
1 participants
n=7 Participants
|
1 participants
n=31 Participants
|
|
Primary Tumor Site
Prostate
|
2 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
2 participants
n=31 Participants
|
|
Primary Tumor Site
Skin
|
0 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
1 participants
n=7 Participants
|
1 participants
n=31 Participants
|
|
Histological Type
Adenocarcinoma
|
2 participants
n=99 Participants
|
4 participants
n=107 Participants
|
0 participants
n=206 Participants
|
2 participants
n=7 Participants
|
8 participants
n=31 Participants
|
|
Histological Type
Squamous cell carcinoma
|
0 participants
n=99 Participants
|
1 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
1 participants
n=31 Participants
|
|
Histological Type
Other
|
3 participants
n=99 Participants
|
0 participants
n=107 Participants
|
3 participants
n=206 Participants
|
4 participants
n=7 Participants
|
10 participants
n=31 Participants
|
|
Stage at Diagnosis
Stage I
|
0 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
0 participants
n=31 Participants
|
|
Stage at Diagnosis
Stage II
|
0 participants
n=99 Participants
|
1 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
1 participants
n=31 Participants
|
|
Stage at Diagnosis
Stage III
|
0 participants
n=99 Participants
|
3 participants
n=107 Participants
|
0 participants
n=206 Participants
|
1 participants
n=7 Participants
|
4 participants
n=31 Participants
|
|
Stage at Diagnosis
Stage IV
|
5 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
2 participants
n=7 Participants
|
7 participants
n=31 Participants
|
|
Stage at Diagnosis
Unknown
|
0 participants
n=99 Participants
|
1 participants
n=107 Participants
|
3 participants
n=206 Participants
|
3 participants
n=7 Participants
|
7 participants
n=31 Participants
|
|
Number of Organs Involved
|
4.0 organs
STANDARD_DEVIATION 1.6 • n=99 Participants
|
2.6 organs
STANDARD_DEVIATION 0.5 • n=107 Participants
|
3.3 organs
STANDARD_DEVIATION 0.6 • n=206 Participants
|
2.0 organs
STANDARD_DEVIATION 0.6 • n=7 Participants
|
2.9 organs
STANDARD_DEVIATION 1.2 • n=31 Participants
|
PRIMARY outcome
Timeframe: Day 1 to Day 21 of the first treatment cyclePopulation: DLT population: All participants who completed assessments for DLT evaluation for Cycle 1 and either: * received study treatment during Cycle 1 and had DLT or * did not have DLT and received a full dose of study treatment (no delay/reduction) during Cycle 1 and did not receive hematopoietic growth factors.
Dose Limiting Toxicities (DLTs) were defined as clinical adverse events (AE) or laboratory abnormalities considered drug-related as assessed by the Investigator or Sponsor, and achieving a Common Terminology Criteria for Adverse Events v3.0 (CTCAE) severity rating of severe (3) or life-threatening (4).
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=2 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=5 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=2 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=5 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Participants With Dose Limiting Toxicities During Dose Escalation
|
2 participants
|
2 participants
|
2 participants
|
2 participants
|
PRIMARY outcome
Timeframe: Fron Day 1 up to a maximum of 12 monthsObjective response was defined as a confirmed complete response (CR) or a confirmed partial response (PR) during the treatment period, based on RECIST 1.1, as assessed by the Investigator. CR: Disappearance of all target lesions, all non-target lesions, and no new lesion. Any pathological lymph nodes must have had reduction in the short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesion. The objective response rate (ORR) was to be calculated as the proportion of participants with confirmed objective response relative to the total number of participants in the analysis population. Due to the inability to determine MTD during the study part 1, the analysis was not performed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Fron Day 1 up to a maximum of 12 monthsTime to progression (TTP) was defined as the time from first treatment administration to first documentation of RECIST-defined objective tumor progression (\>=20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of \>=1 new lesion and/or unequivocal progression of existing non-target lesions). Median TTP was to be estimated using the Kaplan-Meier method. Due to the inability to determine MTD during the study part 1, the analysis was not performed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Fron Day 1 up to a maximum of 12 monthsDuration of Response (DR) was defined as the time from the first documentation of RECIST-defined objective tumor response to the first documentation of RECIST-defined objective tumor progression or death. Median DR was to be estimated using the Kaplan-Meier method. Due to the inability to determine MTD during the study part 1, the analysis was not performed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)Population: all treated (AT) population: All enrolled participants who received at least 1 part of a dose of study treatment
Summary of participants with adverse events (AEs) according to severity and relationship to study drug as assessed by the investigator. The National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE), version 3.0 was used to grade the severity of AE. Treatment-emergent adverse events (TEAEs) are AEs that occurred or worsened from start of treatment up to 30 days after treatment ceased. NCI CTCAE v.3.0 grade 3 =severe and grade 4= life-threatening or disabling.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=5 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=5 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=2 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=6 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Participants With Adverse Events
AE leading to dose delay
|
4 participants
|
2 participants
|
1 participants
|
4 participants
|
|
Participants With Adverse Events
Any AE
|
5 participants
|
5 participants
|
2 participants
|
6 participants
|
|
Participants With Adverse Events
Any TEAE
|
5 participants
|
5 participants
|
2 participants
|
6 participants
|
|
Participants With Adverse Events
- Drug-related TEAE
|
5 participants
|
5 participants
|
2 participants
|
6 participants
|
|
Participants With Adverse Events
Grade 3-4 TEAE
|
5 participants
|
5 participants
|
2 participants
|
6 participants
|
|
Participants With Adverse Events
- Grade 3-4 drug-related TEAE
|
4 participants
|
5 participants
|
2 participants
|
6 participants
|
|
Participants With Adverse Events
Serious TEAE
|
5 participants
|
2 participants
|
2 participants
|
4 participants
|
|
Participants With Adverse Events
- Drug-related serious TEAE
|
3 participants
|
2 participants
|
2 participants
|
3 participants
|
|
Participants With Adverse Events
AE leading to drug withdrawn
|
2 participants
|
2 participants
|
0 participants
|
2 participants
|
|
Participants With Adverse Events
- Drug-related AE leading to drug withdrawn
|
0 participants
|
2 participants
|
0 participants
|
1 participants
|
|
Participants With Adverse Events
AE leading to death
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Participants With Adverse Events
AE leading to dose reduction
|
3 participants
|
4 participants
|
2 participants
|
4 participants
|
SECONDARY outcome
Timeframe: before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusionPopulation: PK population: All enrolled participants who received at least 1 part of a dose of study treatment and had at least 1 post treatment analyzable PK sample, and with no prohibited concomitant medications
Blood samples for cabazitaxel assay were collected during cycle 1 and cabazitaxel plasma concentrations were determined using a validated liquid chromatography with tandem mass spectometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1 ng/mL. Pharmacokinetic (PK) parameters were calculated from plasma concentrations using non-compartmental analysis.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=5 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=4 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=2 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=6 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Cabazitaxel on Cycle 1: Maximum Plasma Concentration Observed (Cmax)
|
123 ng/ml
Standard Deviation 43.7
|
150 ng/ml
Standard Deviation 80.9
|
273 ng/ml
Standard Deviation 21.9
|
118 ng/ml
Standard Deviation 43.9
|
SECONDARY outcome
Timeframe: before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusionPopulation: PK population as previously defined
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=5 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=4 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=2 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=6 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Cabazitaxel on Cycle 1: Time to Maximum Concentration (Tmax)
|
1.00 hours (hr)
Interval 0.92 to 1.05
|
0.94 hours (hr)
Interval 0.87 to 0.95
|
0.94 hours (hr)
Interval 0.88 to 1.0
|
0.93 hours (hr)
Interval 0.92 to 1.03
|
SECONDARY outcome
Timeframe: before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusionPopulation: PK population as previously defined
Area under the plasma concentration versus time curve calculated using the trapezoidal method from time 0 to the last measurable concentration at time t.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=5 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=4 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=2 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=6 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Cabazitaxel on Cycle 1: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast)
|
556 ng*hr/ml
Standard Deviation 500
|
352 ng*hr/ml
Standard Deviation 101
|
344 ng*hr/ml
Standard Deviation 114
|
315 ng*hr/ml
Standard Deviation 208
|
SECONDARY outcome
Timeframe: before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusionPopulation: PK population as previously defined. Six participants' assays could not be used for AUC.
Area under the plasma concentration versus time curve extrapolated to infinity
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=3 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=3 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=2 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=3 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Cabazitaxel on Cycle 1: Area Under the Time Concentration Curve (AUC)
|
876 ng*hr/ml
Standard Deviation 730
|
420 ng*hr/ml
Standard Deviation 77.3
|
462 ng*hr/ml
Standard Deviation 156
|
306 ng*hr/ml
Standard Deviation 50.1
|
SECONDARY outcome
Timeframe: before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusionPopulation: PK population as previously defined
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=5 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=4 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=2 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=6 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Cabazitaxel on Cycle 1: Terminal Half-life (t1/2z)
|
92.1 hours (hr)
Standard Deviation 40.3
|
88.3 hours (hr)
Standard Deviation 35.1
|
75.6 hours (hr)
Standard Deviation 27.8
|
70.3 hours (hr)
Standard Deviation 43.1
|
SECONDARY outcome
Timeframe: before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusionPopulation: PK population as previously defined. Six participants' assays could not be used for CL.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=3 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=3 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=2 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=3 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Cabazitaxel on Cycle 1: Total Plasma Clearance (CL)
|
61.0 L/hr
Standard Deviation 38.4
|
64.3 L/hr
Standard Deviation 16.2
|
59.5 L/hr
Standard Deviation 6.38
|
90.8 L/hr
Standard Deviation 7.15
|
SECONDARY outcome
Timeframe: before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusionPopulation: PK population as previously defined. One participant's assay could not be used for Vss.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=5 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=4 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=2 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=5 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Cabazitaxel on Cycle 1: Volume of Distribution at Steady State (Vss)
|
6780 L
Standard Deviation 3250
|
4980 L
Standard Deviation 818
|
3930 L
Standard Deviation 1170
|
5570 L
Standard Deviation 2100
|
SECONDARY outcome
Timeframe: before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusionPopulation: PK population as previously defined. Six participants' assays could not be used for CL/BSA.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=3 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=3 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=2 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=3 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Cabazitaxel on Cycle 1: Total Plasma Clearance Normalized to Body Surface Area (CL/BSA)
|
32.4 L/hr/m^2
Standard Deviation 18.3
|
36.1 L/hr/m^2
Standard Deviation 6.58
|
31.9 L/hr/m^2
Standard Deviation 12.6
|
49.6 L/hr/m^2
Standard Deviation 8.56
|
SECONDARY outcome
Timeframe: before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusionPopulation: PK population as previously defined. One participant's assays could not be used for Vss/BSA.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=5 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=4 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=2 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=5 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Cabazitaxel on Cycle 1: Volume of Distribution at Steady State Normalized to Body Surface Area (Vss/BSA)
|
3530 L/m^2
Standard Deviation 1650
|
2690 L/m^2
Standard Deviation 434
|
1980 L/m^2
Standard Deviation 8.83
|
3020 L/m^2
Standard Deviation 1130
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined.
Blood samples for gemcitabine assay were collected on Day 1 of cycle 1 at the following timepoints: * Cabazitaxel + Gemcitabine: prior the start of cabazitaxel infusion, immediately before the end of gemcitabine infusion, 15, 30 minutes, 1.5, 3.5 and 22.5 hours after the end of gemcitabine infusion; * Gemcitabine + cabazitaxel: prior the start of gemcitabine infusion, immediately before the end of gemcitabine infusion, 15, 30 minutes, 1, 1.5, 2.5, 9 and 23.5 hours after the end of cabazitaxel infusion; Gemcitabine plasma concentrations were determined using validated LC-MS/MS methods with a LLOQ of 50 ng/mL. PK parameters were calculated from plasma concentrations using non-compartmental analysis.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=4 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=5 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=2 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=5 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Maximum Plasma Concentration Observed (Cmax)
|
14600 ng/ml
Standard Deviation 6050
|
35600 ng/ml
Standard Deviation 27200
|
11400 ng/ml
Standard Deviation 3270
|
19000 ng/ml
Standard Deviation 9130
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=4 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=5 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=2 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=5 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Time to Maximum Concentration (Tmax)
|
0.49 hours (hr)
Interval 0.47 to 0.5
|
0.38 hours (hr)
Interval 0.37 to 0.55
|
0.60 hours (hr)
Interval 0.53 to 0.67
|
0.42 hours (hr)
Interval 0.37 to 0.5
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=4 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=5 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=2 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=5 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast)
|
7320 ng*hr/ml
Standard Deviation 1650
|
16000 ng*hr/ml
Standard Deviation 11100
|
6120 ng*hr/ml
Standard Deviation 3350
|
9920 ng*hr/ml
Standard Deviation 5290
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined. Five participants' assays could not be used in the analysis.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=2 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=3 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=1 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=5 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Area Under the Time Concentration Curve (AUC)
|
6290 ng*hr/ml
Standard Deviation 1440
|
21900 ng*hr/ml
Standard Deviation 10800
|
8530 ng*hr/ml
Standard Deviation NA
Single participant in analysis
|
9970 ng*hr/ml
Standard Deviation 5310
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined. Five participants' assays could not be used in the analysis.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=2 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=3 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=1 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=5 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Terminal Half-life (t1/2z)
|
0.295 hours
Standard Deviation 0.118
|
0.254 hours
Standard Deviation 0.0570
|
0.202 hours
Standard Deviation NA
Single participant in analysis
|
0.256 hours
Standard Deviation 0.0933
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined. Five participants' assays could not be used in the analysis.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=2 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=3 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=1 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=5 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Total Plasma Clearance (CL)
|
313 L/hr
Standard Deviation 120
|
85.1 L/hr
Standard Deviation 40.6
|
123 L/hr
Standard Deviation NA
Single participant in analysis
|
174 L/hr
Standard Deviation 106
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined. Five participants' assays could not be used in the analysis.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=2 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=3 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=1 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=5 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Volume of Distribution at Steady State (Vss)
|
135 L
Standard Deviation 86.2
|
28.9 L
Standard Deviation 30.4
|
47.0 L
Standard Deviation NA
Single participant in analysis
|
51.6 L
Standard Deviation 28.8
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined. Five participants' assays could not be used in the analysis.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=2 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=3 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=1 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=5 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Total Plasma Clearance Normalized to Body Surface Area (CL/BSA)
|
159 L/hr/m^2
Standard Deviation 31.3
|
49.8 L/hr/m^2
Standard Deviation 27.0
|
78.4 L/hr/m^2
Standard Deviation NA
Single participant in analysis
|
96.4 L/hr/m^2
Standard Deviation 62.8
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined. Five participants' assays could not be used in the analysis.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=2 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=3 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=1 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=5 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Volume of Distribution at Steady State Normalized to Body Surface Area (Vss/BSA)
|
66.5 L/m^2
Standard Deviation 31.7
|
17.3 L/m^2
Standard Deviation 18.9
|
29.9 L/m^2
Standard Deviation NA
Single participant in analysis
|
28.7 L/m^2
Standard Deviation 17.4
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined
Blood samples for gemcitabine assay were collected on Day 8 of cycle 1 at the following timepoints: * Cabazitaxel + Gemcitabine: prior the start of infusion, immediately before the end of infusion, 15, 30 minutes, 1.5, 3.5 and 22.5 hours after the end of infusion; * Gemcitabine + cabazitaxel: prior the start of infusion, immediately before the end of infusion, 15, 30 minutes, 1, 1.5, 2.5, 9 and 23.5 hours after the end of infusion; Gemcitabine plasma concentrations were determined using validated LC-MS/MS methods with a LLOQ of 50 ng/mL. PK parameters were calculated from plasma concentrations using non-compartmental analysis.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=2 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=4 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=3 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Maximum Plasma Concentration Observed (Cmax)
|
10200 ng/ml
Standard Deviation 283
|
34500 ng/ml
Standard Deviation 30800
|
—
|
14100 ng/ml
Standard Deviation 12200
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=2 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=4 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=3 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Time to Maximum Concentration (Tmax)
|
0.52 hours (hr)
Interval 0.52 to 0.52
|
0.45 hours (hr)
Interval 0.42 to 0.55
|
—
|
0.47 hours (hr)
Interval 0.4 to 0.48
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=2 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=4 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=3 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast)
|
5530 ng*hr/ml
Standard Deviation 1150
|
15300 ng*hr/ml
Standard Deviation 11900
|
—
|
7710 ng*hr/ml
Standard Deviation 6840
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined. Two participants' assays could not be used in the analysis.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=1 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=3 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=3 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Terminal Half-life (t1/2z)
|
0.222 hours (hr)
Standard Deviation NA
Single participant in analysis
|
0.282 hours (hr)
Standard Deviation 0.0218
|
—
|
0.317 hours (hr)
Standard Deviation 0.113
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined. Two participants' assays could not be used in the analysis.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=1 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=3 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=3 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Area Under the Time Concentration Curve (AUC)
|
6360 ng*hr/ml
Standard Deviation NA
Single participant in analysis
|
18500 ng*hr/ml
Standard Deviation 12300
|
—
|
7780 ng*hr/ml
Standard Deviation 6880
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined. Two participants' assays could not be used in the analysis.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=1 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=3 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=3 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Total Plasma Clearance (CL)
|
262 L/hr
Standard Deviation NA
Single participant in analysis
|
110 L/hr
Standard Deviation 55.8
|
—
|
252 L/hr
Standard Deviation 158
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined. Two participants' assays could not be used in the analysis.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=1 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=3 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=3 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Volume of Distribution at Steady State (Vss)
|
104 L
Standard Deviation NA
Single participant in analysis
|
36.2 L
Standard Deviation 19.4
|
—
|
93.3 L
Standard Deviation 51.7
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined. Two participants' assays could not be used in the analysis.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=1 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=3 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=3 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Total Plasma Clearance Normalized to Body Surface Area (CL/BSA)
|
157 L/hr/m^2
Standard Deviation NA
Single participant in analysis
|
62.8 L/hr/m^2
Standard Deviation 32.7
|
—
|
143 L/hr/m^2
Standard Deviation 93.3
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined. Two participants' assays could not be used in the analysis.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=1 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=3 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=3 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Volume of Distribution at Steady State Normalized to Body Surface Area (Vss/BSA)
|
62.2 L/m^2
Standard Deviation NA
Single participant in analysis
|
20.6 L/m^2
Standard Deviation 11.6
|
—
|
52.3 L/m^2
Standard Deviation 28.6
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined
Blood samples collected for gemcitabine assay were used to assay gemcitabine metabolite, 2',2' difluorodeoxyuridine(dFdU). 2',2' difluorodeoxyuridine plasma concentrations were determined using validated LC-MS/MS methods with a LLOQ of 50 ng/mL. PK parameters were calculated from plasma concentrations using non-compartmental analysis.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=5 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=5 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=2 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=5 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Maximum Plasma Concentration Observed (Cmax)
|
32200 ng/ml
Standard Deviation 10000
|
32500 ng/ml
Standard Deviation 10800
|
25500 ng/ml
Standard Deviation 8770
|
21100 ng/ml
Standard Deviation 5980
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=5 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=5 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=2 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=5 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Time to Maximum Concentration (Tmax)
|
0.73 hours
Interval 0.5 to 0.77
|
0.77 hours
Interval 0.47 to 0.83
|
0.65 hours
Interval 0.53 to 0.77
|
0.77 hours
Interval 0.5 to 1.47
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=5 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=5 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=2 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=5 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast)
|
227000 ng*hr/ml
Standard Deviation 27500
|
235000 ng*hr/ml
Standard Deviation 47400
|
167000 ng*hr/ml
Standard Deviation 47500
|
168000 ng*hr/ml
Standard Deviation 57000
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=5 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=5 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=2 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=5 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Terminal Half-life (t1/2z)
|
9.07 hours
Standard Deviation 2.22
|
9.41 hours
Standard Deviation 0.837
|
7.96 hours
Standard Deviation 1.87
|
12.1 hours
Standard Deviation 5.17
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined. Two participants' assays could not be used in the analysis.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=5 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=5 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=2 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=3 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Area Under the Time Concentration Curve (AUC)
|
273000 ng*hr/ml
Standard Deviation 58100
|
285000 ng*hr/ml
Standard Deviation 61200
|
191000 ng*hr/ml
Standard Deviation 66900
|
151000 ng*hr/ml
Standard Deviation 37700
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: All enrolled participants who received at least 1 part of a dose of study treatment and had at least 1 post treatment analyzable PK sample and with no prohibited concomitant medications.
Blood samples collected for gemcitabine assay were used to assay gemcitabine metabolite, 2',2' difluorodeoxyuridine(dFdU). 2',2' difluorodeoxyuridine plasma concentrations were determined using validated LC-MS/MS methods with a LLOQ of 50 ng/mL. PK parameters were calculated from plasma concentrations using non-compartmental analysis.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=2 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=5 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=3 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Maximum Plasma Concentration Observed (Cmax)
|
27400 ng/ml
Standard Deviation 3180
|
34800 ng/ml
Standard Deviation 8630
|
—
|
18700 ng/ml
Standard Deviation 4740
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=2 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=5 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=3 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Time to Maximum Concentration (Tmax)
|
0.69 hours
Interval 0.52 to 0.85
|
0.68 hours
Interval 0.55 to 1.02
|
—
|
0.72 hours
Interval 0.7 to 1.0
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=2 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=5 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=3 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast)
|
216000 ng*hr/ml
Standard Deviation 3700
|
287000 ng*hr/ml
Standard Deviation 77500
|
—
|
141000 ng*hr/ml
Standard Deviation 26400
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=2 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=5 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=3 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Terminal Half-life (t1/2z)
|
7.29 hours
Standard Deviation 1.11
|
8.55 hours
Standard Deviation 0.820
|
—
|
9.10 hours
Standard Deviation 0.484
|
SECONDARY outcome
Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1Population: PK population as previously defined
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=2 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=5 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=3 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Area Under the Time Concentration Curve (AUC)
|
240000 ng*hr/ml
Standard Deviation 11300
|
340000 ng*hr/ml
Standard Deviation 100000
|
—
|
168000 ng*hr/ml
Standard Deviation 27600
|
SECONDARY outcome
Timeframe: Day 1 (7 to 9 timepoints from start of infusion up to 24h hours after the end of infusion) and Day 8 (7 to 9 timepoints from start of infusion up to 24h hours after the end of infusion)Population: Enrolled participants who received at least 1 part of a dose of study treatment and had valid Day 1 and Day 8 PK samples. Valid PK samples included at least 1 post treatment analyzable PK sample and no prohibited concomitant medications.
Ratio Day 1/Day 8 for AUClast and AUC were calculated to assess the effect of cabazitaxel on gemcitabine exposure.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=1 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=3 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=3 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Pharmacokinetic of Gemcitabine on Cycle 1: Ratio Day 1/Day 8 for AUClast and AUC
AUClast
|
1.15 ratio
Single participant in analysis
|
1.17 ratio
Interval 0.661 to 2.49
|
—
|
1.11 ratio
Interval 0.994 to 1.25
|
|
Pharmacokinetic of Gemcitabine on Cycle 1: Ratio Day 1/Day 8 for AUClast and AUC
AUC
|
1.15 ratio
Single participant in analysis
|
1.24 ratio
Interval 0.66 to 2.47
|
—
|
1.11 ratio
Interval 0.994 to 1.25
|
POST_HOC outcome
Timeframe: Up to a maximum of 22 cycles (median 4 cycles)Population: all treated (AT) population: All enrolled participants who received at least 1 part of a dose of study treatment.
Participant Best response was assessed by investigator using the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1: * Complete response (CR): Disappearance of all target lesions, all non-target lesions, and no new lesion. Any pathological lymph nodes must have had reduction in the short axis to \<10 mm: * Partial response (PR): At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesion; * Progressive disease (PD): \>=20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of \>=1 new lesion and/or unequivocal progression of existing non-target lesions; * Stable disease (SD): not a CR, PR or PD.
Outcome measures
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=5 Participants
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=5 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=2 Participants
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=6 Participants
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Participant Best Response as Per the Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1
Complete response
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Participant Best Response as Per the Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1
Partial response
|
1 participants
|
1 participants
|
0 participants
|
1 participants
|
|
Participant Best Response as Per the Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1
Stable disease
|
2 participants
|
3 participants
|
0 participants
|
3 participants
|
|
Participant Best Response as Per the Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1
Progressive disease
|
1 participants
|
1 participants
|
2 participants
|
2 participants
|
|
Participant Best Response as Per the Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1
Not evaluable
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
Adverse Events
Cabazitaxel + Gemcitabine Dose Level 0
Serious events: 5 serious events
Other events: 5 other events
Deaths: 0 deaths
Cabazitaxel + Gemcitabine Dose Level -1
Serious events: 2 serious events
Other events: 5 other events
Deaths: 0 deaths
Cabazitaxel + Gemcitabine Dose Level -2
Serious events: 2 serious events
Other events: 2 other events
Deaths: 0 deaths
Gemcitabine + Cabazitaxel Dose Level 0
Serious events: 4 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=5 participants at risk
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=5 participants at risk
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=2 participants at risk
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=6 participants at risk
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Infections and infestations
Bronchiolitis
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Infections and infestations
Pneumonia
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Infections and infestations
Sepsis
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
100.0%
2/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Blood and lymphatic system disorders
Neutropenia
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Blood and lymphatic system disorders
Pancytopenia
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Nervous system disorders
Headache
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Cardiac disorders
Supraventricular tachycardia
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Gastrointestinal disorders
Intestinal dilatation
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Gastrointestinal disorders
Intestinal obstruction
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
General disorders
Disease progression
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
General disorders
Chest pain
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
General disorders
Pyrexia
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Investigations
Blood electrolytes abnormal
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
Other adverse events
| Measure |
Cabazitaxel + Gemcitabine Dose Level 0
n=5 participants at risk
Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -1
n=5 participants at risk
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Cabazitaxel + Gemcitabine Dose Level -2
n=2 participants at risk
Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
Gemcitabine + Cabazitaxel Dose Level 0
n=6 participants at risk
Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8
21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
|
|---|---|---|---|---|
|
Infections and infestations
Upper respiratory tract infection
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Infections and infestations
Eye infection
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Infections and infestations
Oral herpes
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Infections and infestations
Viral infection
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Seborrhoeic keratosis
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Blood and lymphatic system disorders
Neutropenia
|
80.0%
4/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
60.0%
3/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
3/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Blood and lymphatic system disorders
Lymphopenia
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
40.0%
2/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
3/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
66.7%
4/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Blood and lymphatic system disorders
Normochromic normocytic anaemia
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Immune system disorders
Drug hypersensitivity
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
40.0%
2/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
60.0%
3/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
66.7%
4/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Metabolism and nutrition disorders
Dehydration
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Metabolism and nutrition disorders
Gout
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Psychiatric disorders
Abnormal dreams
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Psychiatric disorders
Depression
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
33.3%
2/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Nervous system disorders
Neuropathy peripheral
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Nervous system disorders
Paraesthesia
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Nervous system disorders
Balance disorder
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Nervous system disorders
Dizziness
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
40.0%
2/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
33.3%
2/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Nervous system disorders
Headache
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Nervous system disorders
Memory impairment
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Nervous system disorders
Somnolence
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Eye disorders
Vision blurred
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Eye disorders
Vitreous floaters
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
40.0%
2/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Vascular disorders
Hypotension
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
33.3%
2/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
100.0%
2/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal inflammation
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Upper-airway cough syndrome
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Gastrointestinal disorders
Diarrhoea
|
40.0%
2/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
80.0%
4/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
33.3%
2/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Gastrointestinal disorders
Abdominal pain
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Gastrointestinal disorders
Constipation
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Gastrointestinal disorders
Nausea
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
80.0%
4/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
33.3%
2/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
40.0%
2/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Skin and subcutaneous tissue disorders
Rash
|
40.0%
2/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Skin and subcutaneous tissue disorders
Hyperkeratosis
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Musculoskeletal and connective tissue disorders
Arthalgia
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
33.3%
2/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Reproductive system and breast disorders
Vaginal discharge
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
General disorders
Asthenia
|
40.0%
2/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
40.0%
2/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
General disorders
Fatigue
|
40.0%
2/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
80.0%
4/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
83.3%
5/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
General disorders
Chest discomfort
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
General disorders
Chills
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
General disorders
Pain
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
General disorders
Catheter site haematoma
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
General disorders
Catheter site pain
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
General disorders
Early satiety
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
General disorders
Generalized oedema
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
General disorders
Injection site reaction
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
General disorders
Musosal inflammation
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
General disorders
Oedema peripheral
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
3/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
General disorders
Pyrexia
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
33.3%
2/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Investigations
Weight decreased
|
60.0%
3/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
50.0%
1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Investigations
Alanine aminotransferase increased
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Investigations
Aspartate aminotransferase increased
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Investigations
Blood alkalne phosphatase increased
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
16.7%
1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Injury, poisoning and procedural complications
Excoriation
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
|
Injury, poisoning and procedural complications
Anastomotic ulcer
|
0.00%
0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
20.0%
1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
0.00%
0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee At least 45 days in advance of proposed submission, the Investigator should forward a copy of the manuscript or abstract for review by the sponsor, and, if necessary, delay publication or communication for a limited time in order to protect the confidentiality or proprietary nature of any information contained therein.
- Publication restrictions are in place
Restriction type: OTHER