Trial Outcomes & Findings for High-Dose PEG-Intron Pharmacokinetic Study in Patients With Melanoma (Study P04831 AM2) (NCT NCT00457418)
NCT ID: NCT00457418
Last Updated: 2017-06-07
Results Overview
AUC was defined as the actual body exposure to drug after administration of a dose of the drug.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
32 participants
Primary outcome timeframe
Predose, and 24, 48, 72, 96, and 168 hours postdose at 12 weeks
Results posted on
2017-06-07
Participant Flow
Participant milestones
| Measure |
PEG-Intron
6 ug/kg/week, SC (first 8 weeks)
3 ug/kg/week, SC (252 weeks \[weeks 9-260\], maintenance)
|
|---|---|
|
Pharmacokinetic (PK) Sampling Phase
STARTED
|
32
|
|
Pharmacokinetic (PK) Sampling Phase
COMPLETED
|
27
|
|
Pharmacokinetic (PK) Sampling Phase
NOT COMPLETED
|
5
|
|
Post PK Maintenance
STARTED
|
31
|
|
Post PK Maintenance
COMPLETED
|
3
|
|
Post PK Maintenance
NOT COMPLETED
|
28
|
Reasons for withdrawal
| Measure |
PEG-Intron
6 ug/kg/week, SC (first 8 weeks)
3 ug/kg/week, SC (252 weeks \[weeks 9-260\], maintenance)
|
|---|---|
|
Pharmacokinetic (PK) Sampling Phase
Adverse Event
|
2
|
|
Pharmacokinetic (PK) Sampling Phase
Progression of Disease
|
1
|
|
Pharmacokinetic (PK) Sampling Phase
Non-compliance with protocol
|
2
|
|
Post PK Maintenance
Adverse Event
|
10
|
|
Post PK Maintenance
Progression of Disease
|
6
|
|
Post PK Maintenance
Withdrawal by Subject
|
11
|
|
Post PK Maintenance
Lost to Follow-up
|
1
|
Baseline Characteristics
High-Dose PEG-Intron Pharmacokinetic Study in Patients With Melanoma (Study P04831 AM2)
Baseline characteristics by cohort
| Measure |
PEG-Intron
n=32 Participants
6 ug/kg/week, SC (first 8 weeks)
3 ug/kg/week, SC (252 weeks \[weeks 9-260\], maintenance)
|
|---|---|
|
Age, Continuous
|
49.1 years
STANDARD_DEVIATION 12.8 • n=39 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=39 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=39 Participants
|
PRIMARY outcome
Timeframe: Predose, and 24, 48, 72, 96, and 168 hours postdose at 12 weeksPopulation: Participants who completed the full 12 weeks of treatment without any significant dose modification (dose reduction or missing dose)
AUC was defined as the actual body exposure to drug after administration of a dose of the drug.
Outcome measures
| Measure |
PEG-Intron
n=20 Participants
6 ug/kg/week, SC (first 8 weeks)
3 ug/kg/week, SC (252 weeks \[weeks 9-260\], maintenance)
|
|---|---|
|
Area Under the Curve (AUC) of PEG-Intron at 12 Weeks
|
235000 pg*hr/mL
Standard Deviation 56400 • Interval 207592.0 to 251430.0
|
PRIMARY outcome
Timeframe: Predose, and 24, 48, 72, 96, and 168 hours postdose at 12 weeksPopulation: Participants who completed the full 12 weeks of treatment without any significant dose modification (dose reduction or missing dose)
Cmax was defined as observed maximum plasma concentration.
Outcome measures
| Measure |
PEG-Intron
n=20 Participants
6 ug/kg/week, SC (first 8 weeks)
3 ug/kg/week, SC (252 weeks \[weeks 9-260\], maintenance)
|
|---|---|
|
Maximum Serum Concentration (Cmax) of PEG-Intron at 12 Weeks
|
2620 pg/mL
Standard Deviation 865 • Interval 2173.0 to 2829.0
|
PRIMARY outcome
Timeframe: Predose, and 24, 48, 72, 96, and 168 hours postdose at 12 weeksPopulation: Participants who completed the full 12 weeks of treatment without any significant dose modification (dose reduction or missing dose)
Cavg was defined as average plasma concentration.
Outcome measures
| Measure |
PEG-Intron
n=20 Participants
6 ug/kg/week, SC (first 8 weeks)
3 ug/kg/week, SC (252 weeks \[weeks 9-260\], maintenance)
|
|---|---|
|
Average Concentration Within the Dosing Interval (Cavg) of PEG-Intron at 12 Weeks
|
1400 pg/mL
Standard Deviation 336 • Interval 1236.0 to 1497.0
|
PRIMARY outcome
Timeframe: Predose, and 24, 48, 72, 96, and 168 hours postdose at 12 weeksPopulation: There were 19 evaluable participants (20 participants completed the full 12 weeks of treatment without any significant dose modification and there was no concentration data for 1 participant at Week 12).
Cmin was defined as observed minimum plasma concentration.
Outcome measures
| Measure |
PEG-Intron
n=19 Participants
6 ug/kg/week, SC (first 8 weeks)
3 ug/kg/week, SC (252 weeks \[weeks 9-260\], maintenance)
|
|---|---|
|
Minimum Serum Concentration (Cmin) of PEG-Intron at 12 Weeks
|
626 pg/mL
Standard Deviation 269 • Interval 498.0 to 678.0
|
PRIMARY outcome
Timeframe: Predose, and 24, 48, 72, 96, and 168 hours postdose at 12 weeksPopulation: Participants who completed the full 12 weeks of treatment without any significant dose modification (dose reduction or missing dose).
Tmax was defined as time of maximum plasma concentration.
Outcome measures
| Measure |
PEG-Intron
n=20 Participants
6 ug/kg/week, SC (first 8 weeks)
3 ug/kg/week, SC (252 weeks \[weeks 9-260\], maintenance)
|
|---|---|
|
Observed Time to Achieve Cmax (Tmax) of PEG-Intron at 12 Weeks
|
24.00 hours
Interval 24.0 to 48.0
|
PRIMARY outcome
Timeframe: Predose, and 24, 48, 72, 96, and 168 hours postdose at 12 weeksPopulation: There were 15 evaluable participants (20 participants completed the full 12 weeks of treatment without any significant dose modification but for 5 participants CL/F could not be reported because t1/2 could not be accurately determined).
CL/F was defined apparent clearance - the volume of plasma in the vascular compartment cleared of drug per unit of time and per kilogram of body weight by the processes of metabolism and excretion.
Outcome measures
| Measure |
PEG-Intron
n=15 Participants
6 ug/kg/week, SC (first 8 weeks)
3 ug/kg/week, SC (252 weeks \[weeks 9-260\], maintenance)
|
|---|---|
|
Apparent Clearance(CL/F) of PEG-Intron at 12 Weeks
|
0.0129 L/hr/kg
Standard Deviation 0.00284
|
SECONDARY outcome
Timeframe: Entire study duration (up to 5 years)An adverse event (AE) was defined as any untoward medical occurrence or unfavorable and unintended sign in a subject administered a pharmaceutical product, biologic (at any dose), or medical device, whether or not considered related to the use of that product.
Outcome measures
| Measure |
PEG-Intron
n=32 Participants
6 ug/kg/week, SC (first 8 weeks)
3 ug/kg/week, SC (252 weeks \[weeks 9-260\], maintenance)
|
|---|---|
|
Number of Participants Who Experienced an Adverse Event (AE)
|
32 participants
|
Adverse Events
PEG-Intron
Serious events: 9 serious events
Other events: 32 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
PEG-Intron
n=32 participants at risk
6 ug/kg/week, SC (first 8 weeks)
3 ug/kg/week, SC (252 weeks \[weeks 9-260\], maintenance)
|
|---|---|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
6.2%
2/32 • Number of events 2
|
|
Cardiac disorders
CARDIAC ARREST
|
3.1%
1/32 • Number of events 1
|
|
Eye disorders
GLAUCOMA
|
3.1%
1/32 • Number of events 1
|
|
Hepatobiliary disorders
CHOLECYSTITIS
|
3.1%
1/32 • Number of events 1
|
|
Immune system disorders
DRUG HYPERSENSITIVITY
|
3.1%
1/32 • Number of events 1
|
|
Infections and infestations
APPENDICITIS PERFORATED
|
3.1%
1/32 • Number of events 1
|
|
Infections and infestations
BRONCHITIS
|
3.1%
1/32 • Number of events 1
|
|
Infections and infestations
SEPSIS
|
3.1%
1/32 • Number of events 1
|
|
Injury, poisoning and procedural complications
LOWER LIMB FRACTURE
|
3.1%
1/32 • Number of events 1
|
|
Injury, poisoning and procedural complications
WRIST FRACTURE
|
3.1%
1/32 • Number of events 1
|
|
Renal and urinary disorders
RENAL FAILURE
|
3.1%
1/32 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
URTICARIA
|
3.1%
1/32 • Number of events 1
|
Other adverse events
| Measure |
PEG-Intron
n=32 participants at risk
6 ug/kg/week, SC (first 8 weeks)
3 ug/kg/week, SC (252 weeks \[weeks 9-260\], maintenance)
|
|---|---|
|
Blood and lymphatic system disorders
ANAEMIA
|
6.2%
2/32 • Number of events 3
|
|
Blood and lymphatic system disorders
LEUKOPENIA
|
9.4%
3/32 • Number of events 14
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
21.9%
7/32 • Number of events 31
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
6.2%
2/32 • Number of events 2
|
|
Ear and labyrinth disorders
EAR PAIN
|
6.2%
2/32 • Number of events 3
|
|
Endocrine disorders
HYPOTHYROIDISM
|
9.4%
3/32 • Number of events 3
|
|
Eye disorders
DRY EYE
|
9.4%
3/32 • Number of events 3
|
|
Eye disorders
VISION BLURRED
|
6.2%
2/32 • Number of events 2
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
12.5%
4/32 • Number of events 7
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
6.2%
2/32 • Number of events 3
|
|
Gastrointestinal disorders
CONSTIPATION
|
12.5%
4/32 • Number of events 5
|
|
Gastrointestinal disorders
DIARRHOEA
|
62.5%
20/32 • Number of events 33
|
|
Gastrointestinal disorders
DRY MOUTH
|
9.4%
3/32 • Number of events 3
|
|
Gastrointestinal disorders
FLATULENCE
|
6.2%
2/32 • Number of events 2
|
|
Gastrointestinal disorders
GASTROOESOPHAGEAL REFLUX DISEASE
|
6.2%
2/32 • Number of events 2
|
|
Gastrointestinal disorders
NAUSEA
|
71.9%
23/32 • Number of events 41
|
|
Gastrointestinal disorders
VOMITING
|
25.0%
8/32 • Number of events 13
|
|
General disorders
CHEST PAIN
|
6.2%
2/32 • Number of events 2
|
|
General disorders
CHILLS
|
81.2%
26/32 • Number of events 39
|
|
General disorders
FATIGUE
|
90.6%
29/32 • Number of events 52
|
|
General disorders
INFLUENZA LIKE ILLNESS
|
18.8%
6/32 • Number of events 8
|
|
General disorders
INJECTION SITE RASH
|
6.2%
2/32 • Number of events 2
|
|
General disorders
INJECTION SITE REACTION
|
40.6%
13/32 • Number of events 15
|
|
General disorders
MUCOSAL INFLAMMATION
|
6.2%
2/32 • Number of events 3
|
|
General disorders
OEDEMA
|
12.5%
4/32 • Number of events 4
|
|
General disorders
PAIN
|
6.2%
2/32 • Number of events 2
|
|
General disorders
PYREXIA
|
84.4%
27/32 • Number of events 44
|
|
Infections and infestations
BRONCHITIS
|
6.2%
2/32 • Number of events 2
|
|
Infections and infestations
LOCALISED INFECTION
|
6.2%
2/32 • Number of events 2
|
|
Infections and infestations
SINUSITIS
|
9.4%
3/32 • Number of events 6
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
25.0%
8/32 • Number of events 11
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
15.6%
5/32 • Number of events 5
|
|
Investigations
BLOOD TRIGLYCERIDES INCREASED
|
6.2%
2/32 • Number of events 5
|
|
Investigations
NEUTROPHIL COUNT DECREASED
|
34.4%
11/32 • Number of events 25
|
|
Investigations
PLATELET COUNT DECREASED
|
9.4%
3/32 • Number of events 5
|
|
Investigations
WEIGHT DECREASED
|
9.4%
3/32 • Number of events 3
|
|
Investigations
WHITE BLOOD CELL COUNT DECREASED
|
25.0%
8/32 • Number of events 26
|
|
Metabolism and nutrition disorders
DECREASED APPETITE
|
84.4%
27/32 • Number of events 33
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
12.5%
4/32 • Number of events 4
|
|
Metabolism and nutrition disorders
HYPERTRIGLYCERIDAEMIA
|
40.6%
13/32 • Number of events 43
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
15.6%
5/32 • Number of events 8
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
21.9%
7/32 • Number of events 9
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
|
9.4%
3/32 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
56.2%
18/32 • Number of events 24
|
|
Nervous system disorders
DIZZINESS
|
15.6%
5/32 • Number of events 5
|
|
Nervous system disorders
DYSGEUSIA
|
9.4%
3/32 • Number of events 3
|
|
Nervous system disorders
HEADACHE
|
71.9%
23/32 • Number of events 48
|
|
Nervous system disorders
SOMNOLENCE
|
15.6%
5/32 • Number of events 6
|
|
Psychiatric disorders
AGITATION
|
6.2%
2/32 • Number of events 3
|
|
Psychiatric disorders
ANXIETY
|
21.9%
7/32 • Number of events 7
|
|
Psychiatric disorders
DEPRESSION
|
37.5%
12/32 • Number of events 12
|
|
Psychiatric disorders
INSOMNIA
|
28.1%
9/32 • Number of events 11
|
|
Psychiatric disorders
MENTAL STATUS CHANGES
|
6.2%
2/32 • Number of events 2
|
|
Psychiatric disorders
MOOD ALTERED
|
12.5%
4/32 • Number of events 5
|
|
Renal and urinary disorders
DYSURIA
|
6.2%
2/32 • Number of events 2
|
|
Reproductive system and breast disorders
ERECTILE DYSFUNCTION
|
15.6%
5/32 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
37.5%
12/32 • Number of events 15
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
18.8%
6/32 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
NASAL CONGESTION
|
6.2%
2/32 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN
|
6.2%
2/32 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
SINUS CONGESTION
|
6.2%
2/32 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
6.2%
2/32 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
HYPERHIDROSIS
|
6.2%
2/32 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
NIGHT SWEATS
|
12.5%
4/32 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
21.9%
7/32 • Number of events 7
|
|
Skin and subcutaneous tissue disorders
RASH
|
31.2%
10/32 • Number of events 20
|
|
Vascular disorders
HYPERTENSION
|
6.2%
2/32 • Number of events 2
|
Additional Information
Senior Vice President,Global CLinical Development
Merck Sharp & Dohme Corp.
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The principal investigator (PI) agrees not to publish/present any interim results of the study without Sponsor's prior written consent. The PI further agrees to provide to the sponsor 30 days prior to submission, review copies. The sponsor shall have editorial rights and the right to review and comment. If the parties disagree, PI agrees to meet with the sponsor's representatives for the purpose of making good faith efforts to discuss and resolve any such issues or disagreement.
- Publication restrictions are in place
Restriction type: OTHER