Trial Outcomes & Findings for BRIM-P: A Study of Vemurafenib in Pediatric Patients With Stage IIIC or Stage IV Melanoma Harboring BRAFV600 Mutations (NCT NCT01519323)
NCT ID: NCT01519323
Last Updated: 2016-10-10
Results Overview
The MTD was defined as the dose level at which six evaluable participants had been treated and at most one participant experienced a dose limiting toxicity (DLT) and the next highest dose level was too toxic. Dose escalation occurred if 0 out of 3 or at most 1 out of 6 participant experienced DLT while being treated at a dose level; otherwise the dose was declared unsafe and thus above the MTD.
Recruitment status
TERMINATED
Study phase
PHASE1
Target enrollment
6 participants
Primary outcome timeframe
Up to 28 days of treatment
Results posted on
2016-10-10
Participant Flow
First investigational site was activated on 22 December 2011.
Participants were enrolled in two separate cohorts with different starting doses based on greater than or equal to (\>=)45 kilogram (kg) and other weighing less than (\<)45 kg. Participants \>=45 kg were then enrolled in a dose escalation period. No participants were enrolled in the \<45 kg cohort.
Participant milestones
| Measure |
Vemurafenib Dose Escalation Cohort Level 1
Participants received 720 milligram (mg) of vemurafenib by mouth twice daily (BID).
|
Vemurafenib Dose Escalation Cohort Level 2
Participants received 960 mg of vemurafenib by mouth BID.
|
|---|---|---|
|
Overall Study
STARTED
|
3
|
3
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
3
|
3
|
Reasons for withdrawal
| Measure |
Vemurafenib Dose Escalation Cohort Level 1
Participants received 720 milligram (mg) of vemurafenib by mouth twice daily (BID).
|
Vemurafenib Dose Escalation Cohort Level 2
Participants received 960 mg of vemurafenib by mouth BID.
|
|---|---|---|
|
Overall Study
Death
|
3
|
2
|
|
Overall Study
Study terminated by sponsor
|
0
|
1
|
Baseline Characteristics
BRIM-P: A Study of Vemurafenib in Pediatric Patients With Stage IIIC or Stage IV Melanoma Harboring BRAFV600 Mutations
Baseline characteristics by cohort
| Measure |
Vemurafenib
n=6 Participants
Participants received vemurafenib into two separate cohorts with different starting doses based on greater than or equal to (\>=)45 kilogram (kg) and other weighing less than (\<)45 kg. The starting dose for participants (\>=45 kg) was 720 milligram (mg) of vemurafenib by mouth twice daily (BID) and the next dose level for participants in this cohort was 960 mg by mouth BID. The starting dose level for participants weighing \<45 kg was to be 480 mg of vemurafenib by mouth BID, but no participants were enrolled into this cohort.
|
|---|---|
|
Age, Continuous
|
15.8 years
STANDARD_DEVIATION 0.8 • n=99 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Up to 28 days of treatmentPopulation: A MTD could not be determined in this study because of the low number of participants enrolled.
The MTD was defined as the dose level at which six evaluable participants had been treated and at most one participant experienced a dose limiting toxicity (DLT) and the next highest dose level was too toxic. Dose escalation occurred if 0 out of 3 or at most 1 out of 6 participant experienced DLT while being treated at a dose level; otherwise the dose was declared unsafe and thus above the MTD.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Pre-dose, 2, 4, 8, 12 hours post dose on Cycle 1 Day 1 and Cycle 1 Day 22 (each cycle is of 28 days)Population: Pharmacokinetic (PK) population included all enrolled participants who received at least one dose or a partial dose of study treatment and provided at least one post-dose blood sample for PK analysis.
Outcome measures
| Measure |
Vemurafenib
n=3 Participants
Participants received vemurafenib into two separate cohorts with different starting doses based on greater than or equal to (\>=)45 kilogram (kg) and other weighing less than (\<)45 kg. The starting dose for participants (\>=45 kg) was 720 milligram (mg) of vemurafenib by mouth twice daily (BID) and the next dose level for participants in this cohort was 960 mg by mouth BID. The starting dose level for participants weighing \<45 kg was to be 480 mg of vemurafenib by mouth BID, but no participants were enrolled into this cohort.
|
Vemurafenib 960 mg
n=3 Participants
Participants enrolled in the second cohort received vemurafenib 960 mg by mouth BID.
|
|---|---|---|
|
Area Under the Concentration-Time Curve for Vemurafenib
Cycle 1 Day 1
|
16300 hour*nanogram per millitre (h*ng/mL)
Geometric Coefficient of Variation 80.5
|
57000 hour*nanogram per millitre (h*ng/mL)
Geometric Coefficient of Variation 95.5
|
|
Area Under the Concentration-Time Curve for Vemurafenib
Cycle 1 Day 22
|
486000 hour*nanogram per millitre (h*ng/mL)
Geometric Coefficient of Variation 26.7
|
963000 hour*nanogram per millitre (h*ng/mL)
Geometric Coefficient of Variation 23.4
|
SECONDARY outcome
Timeframe: Up to approximately 2 years 11 monthsPopulation: Safety population included all participants who received at least one dose or a partial dose of study treatment.
An AE was defined as any untoward medical occurrence in a patient administered a pharmaceutical product and which did not necessarily have to have a causal relationship with study treatment.
Outcome measures
| Measure |
Vemurafenib
n=6 Participants
Participants received vemurafenib into two separate cohorts with different starting doses based on greater than or equal to (\>=)45 kilogram (kg) and other weighing less than (\<)45 kg. The starting dose for participants (\>=45 kg) was 720 milligram (mg) of vemurafenib by mouth twice daily (BID) and the next dose level for participants in this cohort was 960 mg by mouth BID. The starting dose level for participants weighing \<45 kg was to be 480 mg of vemurafenib by mouth BID, but no participants were enrolled into this cohort.
|
Vemurafenib 960 mg
Participants enrolled in the second cohort received vemurafenib 960 mg by mouth BID.
|
|---|---|---|
|
Number of Participants With an Adverse Event (AE)
|
6 participants
|
—
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: Intent to treat population included all participants enrolled.
BORR was assessed by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. BORR was defined as the number of participants who achieved a complete response (CR) or partial response (PR). CR was defined as complete disappearance of all target lesions and non-target disease. PR was defined as a \>=30% decrease under baseline of the sum of diameters of all target lesions. BORR was summarized along with the associated exact 95% confidence interval (CI) using the method of Clopper-Pearson.
Outcome measures
| Measure |
Vemurafenib
n=6 Participants
Participants received vemurafenib into two separate cohorts with different starting doses based on greater than or equal to (\>=)45 kilogram (kg) and other weighing less than (\<)45 kg. The starting dose for participants (\>=45 kg) was 720 milligram (mg) of vemurafenib by mouth twice daily (BID) and the next dose level for participants in this cohort was 960 mg by mouth BID. The starting dose level for participants weighing \<45 kg was to be 480 mg of vemurafenib by mouth BID, but no participants were enrolled into this cohort.
|
Vemurafenib 960 mg
Participants enrolled in the second cohort received vemurafenib 960 mg by mouth BID.
|
|---|---|---|
|
Best Overall Response Rate (BORR)
|
0 percentage of participants
Interval 0.0 to 45.93
|
—
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: Intent to treat population included all participants enrolled.
CBR was defined as the number of participants that achieved a CR, PR or stable disease (SD) (SD for at least 6 weeks) as assessed by investigators according to the RECIST v1.1. CR was defined as complete disappearance of all target lesions and non-target disease. PR was defined as at \>=30% decrease under baseline of the sum of diameters of all target lesions. SD was defined as steady state of disease with neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD).
Outcome measures
| Measure |
Vemurafenib
n=6 Participants
Participants received vemurafenib into two separate cohorts with different starting doses based on greater than or equal to (\>=)45 kilogram (kg) and other weighing less than (\<)45 kg. The starting dose for participants (\>=45 kg) was 720 milligram (mg) of vemurafenib by mouth twice daily (BID) and the next dose level for participants in this cohort was 960 mg by mouth BID. The starting dose level for participants weighing \<45 kg was to be 480 mg of vemurafenib by mouth BID, but no participants were enrolled into this cohort.
|
Vemurafenib 960 mg
Participants enrolled in the second cohort received vemurafenib 960 mg by mouth BID.
|
|---|---|---|
|
Clinical Benefit Rate (CBR)
|
66.7 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Randomization date of first subject until disease progression or death or which ever occur first (2 years)Population: Intent to treat population included all participants enrolled.
PFS was defined as the time between the day of first treatment and the first documentation of progressive disease or death. Progression was defined as a 20% increase in the sum of the longest diameter of target lesions, the appearance of new lesions and increase of at least 5 mm in the sum of diameters of target lesions. Participants who were withdrawn from the study without documented progression were to be censored at the date of the last known tumor assessment when the participant was known to be progression free. Median PFS was estimated using Kaplan-Meier method and 95% CI for median was computed using the Brookmeyer and Crowley method.
Outcome measures
| Measure |
Vemurafenib
n=6 Participants
Participants received vemurafenib into two separate cohorts with different starting doses based on greater than or equal to (\>=)45 kilogram (kg) and other weighing less than (\<)45 kg. The starting dose for participants (\>=45 kg) was 720 milligram (mg) of vemurafenib by mouth twice daily (BID) and the next dose level for participants in this cohort was 960 mg by mouth BID. The starting dose level for participants weighing \<45 kg was to be 480 mg of vemurafenib by mouth BID, but no participants were enrolled into this cohort.
|
Vemurafenib 960 mg
Participants enrolled in the second cohort received vemurafenib 960 mg by mouth BID.
|
|---|---|---|
|
Progression-free Survival (PFS)
|
134.5 days
Interval 83.0 to 157.0
|
—
|
SECONDARY outcome
Timeframe: Randomization date of first subject until death (2 years)Population: Intent to treat population included all participants enrolled.
Overall survival was defined as the time between the date of first treatment to the date of death, regardless of the cause of death. Participants who were alive at the time of the analysis were censored at the date of their last being known alive. Median overall survival was estimated using Kaplan-Meier method and 95% CI for median was computed using the Brookmeyer and Crowley method.
Outcome measures
| Measure |
Vemurafenib
n=6 Participants
Participants received vemurafenib into two separate cohorts with different starting doses based on greater than or equal to (\>=)45 kilogram (kg) and other weighing less than (\<)45 kg. The starting dose for participants (\>=45 kg) was 720 milligram (mg) of vemurafenib by mouth twice daily (BID) and the next dose level for participants in this cohort was 960 mg by mouth BID. The starting dose level for participants weighing \<45 kg was to be 480 mg of vemurafenib by mouth BID, but no participants were enrolled into this cohort.
|
Vemurafenib 960 mg
Participants enrolled in the second cohort received vemurafenib 960 mg by mouth BID.
|
|---|---|---|
|
Overall Survival (OS)
|
246.5 days
Interval 156.0 to 364.0
|
—
|
Adverse Events
Vemurafenib
Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Vemurafenib
n=6 participants at risk
Participants received vemurafenib into two separate cohorts with different starting doses based on greater than or equal to (\>=)45 kilogram (kg) and other weighing less than (\<)45 kg. The starting dose for participants (\>=45 kg) was 720 milligram (mg) of vemurafenib by mouth twice daily (BID) and the next dose level for participants in this cohort was 960 mg by mouth BID. The starting dose level for participants weighing \<45 kg was to be 480 mg of vemurafenib by mouth BID, but no participants were enrolled into this cohort.
|
|---|---|
|
Endocrine disorders
Adrenal insufficiency
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Musculoskeletal and connective tissue disorders
Spinal pain
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Intracranial tumour haemorrage
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Renal and urinary disorders
Nephrolithiasis
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
Other adverse events
| Measure |
Vemurafenib
n=6 participants at risk
Participants received vemurafenib into two separate cohorts with different starting doses based on greater than or equal to (\>=)45 kilogram (kg) and other weighing less than (\<)45 kg. The starting dose for participants (\>=45 kg) was 720 milligram (mg) of vemurafenib by mouth twice daily (BID) and the next dose level for participants in this cohort was 960 mg by mouth BID. The starting dose level for participants weighing \<45 kg was to be 480 mg of vemurafenib by mouth BID, but no participants were enrolled into this cohort.
|
|---|---|
|
Skin and subcutaneous tissue disorders
Photosensitivity reaction
|
50.0%
3/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Skin and subcutaneous tissue disorders
Rash
|
50.0%
3/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
33.3%
2/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
33.3%
2/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Skin and subcutaneous tissue disorders
Pain of skin
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Skin and subcutaneous tissue disorders
Palmar-Plantar erythrodysesthesia syndrome
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Skin and subcutaneous tissue disorders
Skin mass
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Gastrointestinal disorders
Diarrhoea
|
66.7%
4/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Gastrointestinal disorders
Nausea
|
50.0%
3/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
2/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Gastrointestinal disorders
Abdominal pain
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Gastrointestinal disorders
Aphthous ulcer
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Gastrointestinal disorders
Constipation
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Gastrointestinal disorders
Stomatitis
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Gastrointestinal disorders
Toothache
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
33.3%
2/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
33.3%
2/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Musculoskeletal and connective tissue disorders
Osteoporosis
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
General disorders
Fatigue
|
50.0%
3/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
General disorders
Chest pain
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
General disorders
Influenza like illness
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
General disorders
Pain
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Infections and infestations
Hand-foot-and-mouth disease
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Infections and infestations
Nasopharyngitis
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Infections and infestations
Oral candidiasis
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Infections and infestations
Oral herpes
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Infections and infestations
Scrotal abscess
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Infections and infestations
Skin infection
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Infections and infestations
Upper respiratory tract infection
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Infections and infestations
Viral pharyngitis
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Investigations
Alanine aminotransferase increased
|
33.3%
2/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Investigations
Platelet count decreased
|
33.3%
2/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Investigations
White blood cell count decreased
|
33.3%
2/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Investigations
Aspartate aminotransferase increased
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Investigations
Blood alkaline phosphatase increased
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Investigations
Blood cholesterol increased
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Investigations
Blood creatinine increased
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Investigations
Blood phosphorus increased
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Investigations
Carbon dioxide decreased
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Investigations
Electrocardiogram QT prolonged
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Investigations
Lymphocyte count decreased
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Investigations
Neutrophil count decreased
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Nervous system disorders
Headache
|
66.7%
4/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Nervous system disorders
Dizziness
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Nervous system disorders
Paraesthesia
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Nervous system disorders
Seizure
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Nervous system disorders
Tremor
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
33.3%
2/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Renal and urinary disorders
Haematuria
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Renal and urinary disorders
Haemoglobinuria
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Renal and urinary disorders
Nephrolithiasis
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Renal and urinary disorders
Proteinuria
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Renal and urinary disorders
Renal colic
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
33.3%
2/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal inflammation
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Vascular disorders
Flushing
|
33.3%
2/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Vascular disorders
Hypertension
|
33.3%
2/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Vascular disorders
Hot flush
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Blood and lymphatic system disorders
Anaemia
|
33.3%
2/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Blood and lymphatic system disorders
Lymphopenia
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Cardiac disorders
Palpitations
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Cardiac disorders
Sinus bradycardia
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Injury, poisoning and procedural complications
Contusion
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Injury, poisoning and procedural complications
Overdose
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Endocrine disorders
Hypothyroidism
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
|
Reproductive system and breast disorders
Vaginal discharge
|
16.7%
1/6 • All AEs were reported for approximately 2 years 11 months. Related serious adverse events were required to be reported regardless of the time elapsed from the last study drug administration, even if the study had been closed.
An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER