Trial Outcomes & Findings for Study to Determine the Intra-subject Variability of Pharmacokinetics of Lomitapide in Healthy Subjects (NCT NCT01915771)
NCT ID: NCT01915771
Last Updated: 2020-03-11
Results Overview
Maximum observed concentration of lomitapide and its metabolites, M1 \& M3.
COMPLETED
PHASE1
15 participants
Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.
2020-03-11
Participant Flow
Participant milestones
| Measure |
Lomitapide
It will comprise of 2 single oral doses with at least a 14-day washout between doses.
lomitapide: 20 mg dose
|
|---|---|
|
Day 1
STARTED
|
15
|
|
Day 1
COMPLETED
|
14
|
|
Day 1
NOT COMPLETED
|
1
|
|
Day 15
STARTED
|
14
|
|
Day 15
COMPLETED
|
13
|
|
Day 15
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Lomitapide
It will comprise of 2 single oral doses with at least a 14-day washout between doses.
lomitapide: 20 mg dose
|
|---|---|
|
Day 1
Withdrawal by Subject
|
1
|
|
Day 15
Withdrawal by Subject
|
1
|
Baseline Characteristics
Study to Determine the Intra-subject Variability of Pharmacokinetics of Lomitapide in Healthy Subjects
Baseline characteristics by cohort
| Measure |
Lomitapide
n=15 Participants
It will comprise of 2 single oral doses with at least a 14-day washout between doses.
lomitapide: 20 mg dose
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
15 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
26.2 years
STANDARD_DEVIATION 4.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
15 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.Population: Only 13 subjects who had evaluable PK data in both study periods were included in the PK analysis of lomitapide. One subject was excluded from PK analysis of M1 and M3 during Period 1 due to early termination. Another subject was excluded from PK analysis of M1 and M3 during Period 2 because the subject did not complete both Periods 1 and 2.
Maximum observed concentration of lomitapide and its metabolites, M1 \& M3.
Outcome measures
| Measure |
PK of Lomitapide
n=13 Participants
PK of Lomitapide Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
|
PK of M1
n=14 Participants
PK of M1 Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
|
PK of M3
n=14 Participants
PK of M3 Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
|
|---|---|---|---|
|
Cmax
Period 1
|
0.961 ng/mL
Standard Deviation 0.556
|
2.34 ng/mL
Standard Deviation 0.593
|
23.6 ng/mL
Standard Deviation 7.08
|
|
Cmax
Period 2
|
1.02 ng/mL
Standard Deviation 0.843
|
2.20 ng/mL
Standard Deviation 0.664
|
22.8 ng/mL
Standard Deviation 9.33
|
PRIMARY outcome
Timeframe: Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.Population: Only 13 subjects who had evaluable PK data in both study periods were included in the PK analysis of lomitapide. One subject was excluded from PK analysis of M1 and M3 during Period 1 due to early termination. Another subject was excluded from PK analysis of M1 and M3 during Period 2 because the subject did not complete both Periods 1 and 2.
Time to reach maximum plasma concentration
Outcome measures
| Measure |
PK of Lomitapide
n=13 Participants
PK of Lomitapide Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
|
PK of M1
n=14 Participants
PK of M1 Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
|
PK of M3
n=14 Participants
PK of M3 Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
|
|---|---|---|---|
|
Tmax
Period 1
|
4.0 hr
Interval 1.0 to 18.0
|
5.00 hr
Interval 3.0 to 10.0
|
3.00 hr
Interval 1.0 to 4.03
|
|
Tmax
Period 2
|
5.00 hr
Interval 3.0 to 18.0
|
5.00 hr
Interval 2.0 to 6.0
|
3.00 hr
Interval 1.0 to 4.0
|
PRIMARY outcome
Timeframe: Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.Population: Only 13 subjects who had evaluable PK data in both study periods were included in the PK analysis of lomitapide. One subject was excluded from PK analysis of M1 and M3 during Period 1 due to early termination. Another subject was excluded from PK analysis of M1 and M3 during Period 2 because the subject did not complete both Periods 1 and 2.
Area under the concentration-time curve from hour 0 to the last measurable concentration of lomitapide and its metabolites, M1 \& M3.
Outcome measures
| Measure |
PK of Lomitapide
n=13 Participants
PK of Lomitapide Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
|
PK of M1
n=14 Participants
PK of M1 Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
|
PK of M3
n=14 Participants
PK of M3 Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
|
|---|---|---|---|
|
AUC0-t
Period 2
|
44.0 ng*hr/mL
Standard Deviation 21.7
|
62.8 ng*hr/mL
Standard Deviation 23.3
|
319 ng*hr/mL
Standard Deviation 176
|
|
AUC0-t
Period 1
|
40.2 ng*hr/mL
Standard Deviation 18.1
|
65.8 ng*hr/mL
Standard Deviation 22.7
|
319 ng*hr/mL
Standard Deviation 153
|
PRIMARY outcome
Timeframe: Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.Population: Only 13 subjects who had evaluable PK data in both study periods were included in the PK analysis of lomitapide. One subject was excluded from PK analysis of M1 and M3 during Period 1 due to early termination. Another subject was excluded from PK analysis of M1 and M3 during Period 2 because the subject did not complete both Periods 1 and 2.
Area under the concentration-time curve extrapolated to infinity for lomitapide and its metabolites, M1 \& M3.
Outcome measures
| Measure |
PK of Lomitapide
n=13 Participants
PK of Lomitapide Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
|
PK of M1
n=14 Participants
PK of M1 Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
|
PK of M3
n=14 Participants
PK of M3 Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
|
|---|---|---|---|
|
AUC0-∞
Period 1
|
44.4 ng*hr/mL
Standard Deviation 19.9
|
68.3 ng*hr/mL
Standard Deviation 23.6
|
330 ng*hr/mL
Standard Deviation 158
|
|
AUC0-∞
Period 2
|
48.3 ng*hr/mL
Standard Deviation 23.4
|
65.3 ng*hr/mL
Standard Deviation 24.1
|
330 ng*hr/mL
Standard Deviation 181
|
PRIMARY outcome
Timeframe: Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.Population: Only 13 subjects who had evaluable PK data in both study periods were included in the PK analysis of lomitapide. One subject was excluded from PK analysis of M1 and M3 during Period 1 due to early termination. Another subject was excluded from PK analysis of M1 and M3 during Period 2 because the subject did not complete both Periods 1 and 2.
Elimination rate constant estimated from individual linear regression of the terminal part of the log concentration vs time curve
Outcome measures
| Measure |
PK of Lomitapide
n=13 Participants
PK of Lomitapide Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
|
PK of M1
n=14 Participants
PK of M1 Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
|
PK of M3
n=14 Participants
PK of M3 Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
|
|---|---|---|---|
|
λz
Period 2
|
0.0146 1/hr
Standard Deviation 0.00139
|
0.0189 1/hr
Standard Deviation 0.00410
|
0.0172 1/hr
Standard Deviation 0.00272
|
|
λz
Period 1
|
0.0141 1/hr
Standard Deviation 0.00196
|
0.0200 1/hr
Standard Deviation 0.00754
|
0.0155 1/hr
Standard Deviation 0.00370
|
PRIMARY outcome
Timeframe: Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.Population: Only 13 subjects who had evaluable PK data in both study periods were included in the PK analysis of lomitapide. One subject was excluded from PK analysis of M1 and M3 during Period 1 due to early termination. Another subject was excluded from PK analysis of M1 and M3 during Period 2 because the subject did not complete both Periods 1 and 2.
Apparent terminal elimination half-life
Outcome measures
| Measure |
PK of Lomitapide
n=13 Participants
PK of Lomitapide Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
|
PK of M1
n=14 Participants
PK of M1 Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
|
PK of M3
n=14 Participants
PK of M3 Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
|
|---|---|---|---|
|
t1/2
Period 1
|
50.3 hr
Standard Deviation 7.56
|
38.3 hr
Standard Deviation 10.6
|
46.9 hr
Standard Deviation 10.4
|
|
t1/2
Period 2
|
47.8 hr
Standard Deviation 4.35
|
38.0 hr
Standard Deviation 6.61
|
41.2 hr
Standard Deviation 6.90
|
Adverse Events
Period 1
Period 2
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Period 1
n=15 participants at risk
All 15 subjects who were enrolled in the study received at least one 20 mg dose of lomitapide and had assessments for the analysis of safety during Period 1.
|
Period 2
n=13 participants at risk
Only 13 subjects who were enrolled in the study received 2 single daily doses of 20 mg lomitapide as planned (one dose in each of the two study periods). 2 subjects who only received one dose in Period 1 due to early withdrawal were not included in analysis of safety during Period 2.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
6.7%
1/15
|
0.00%
0/13
|
|
Gastrointestinal disorders
Diarrhoea
|
20.0%
3/15
|
0.00%
0/13
|
|
Gastrointestinal disorders
Flatulence
|
6.7%
1/15
|
0.00%
0/13
|
|
Gastrointestinal disorders
Nausea
|
13.3%
2/15
|
0.00%
0/13
|
|
Gastrointestinal disorders
Abdominal Discomfort
|
13.3%
2/15
|
7.7%
1/13
|
|
Nervous system disorders
Headache
|
0.00%
0/15
|
7.7%
1/13
|
|
Blood and lymphatic system disorders
Lymphdenopathy
|
6.7%
1/15
|
0.00%
0/13
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
6.7%
1/15
|
0.00%
0/13
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
6.7%
1/15
|
0.00%
0/13
|
|
Psychiatric disorders
Anxiety
|
6.7%
1/15
|
0.00%
0/13
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.7%
1/15
|
0.00%
0/13
|
|
Nervous system disorders
Dizziness
|
6.7%
1/15
|
0.00%
0/13
|
Additional Information
Alison Long, MD - VP Clinical
Aegerion Pharmaceuticals, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee Described in contract
- Publication restrictions are in place
Restriction type: OTHER