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Study to Determine the Intra-subject Variability of Pharmacokinetics of Lomitapide in Healthy Subjects

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ClinicalTrials.gov Identifier: NCT01915771
Recruitment Status : Completed
First Posted : August 5, 2013
Results First Posted : March 11, 2020
Last Update Posted : March 11, 2020
Sponsor:
Information provided by (Responsible Party):
Aegerion Pharmaceuticals, Inc.

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Condition Intra-subject Variability of Pharmacokinetics
Intervention Drug: lomitapide
Enrollment 15
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Lomitapide
Hide Arm/Group Description

It will comprise of 2 single oral doses with at least a 14-day washout between doses.

lomitapide: 20 mg dose

Period Title: Day 1
Started 15
Completed 14
Not Completed 1
Reason Not Completed
Withdrawal by Subject             1
Period Title: Day 15
Started 14
Completed 13
Not Completed 1
Reason Not Completed
Withdrawal by Subject             1
Arm/Group Title Lomitapide
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It will comprise of 2 single oral doses with at least a 14-day washout between doses.

lomitapide: 20 mg dose

Overall Number of Baseline Participants 15
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
<=18 years
0
   0.0%
Between 18 and 65 years
15
 100.0%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants
26.2  (4.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
Female
6
  40.0%
Male
9
  60.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United Kingdom Number Analyzed 15 participants
15
1.Primary Outcome
Title Cmax
Hide Description Maximum observed concentration of lomitapide and its metabolites, M1 & M3.
Time Frame Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PK of Lomitapide PK of M1 PK of M3
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PK of Lomitapide Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
PK of M1 Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
PK of M3 Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
Overall Number of Participants Analyzed 13 14 14
Mean (Standard Deviation)
Unit of Measure: ng/mL
Period 1 Number Analyzed 13 participants 14 participants 14 participants
0.961  (0.556) 2.34  (0.593) 23.6  (7.08)
Period 2 Number Analyzed 13 participants 13 participants 13 participants
1.02  (0.843) 2.20  (0.664) 22.8  (9.33)
2.Primary Outcome
Title Tmax
Hide Description Time to reach maximum plasma concentration
Time Frame Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PK of Lomitapide PK of M1 PK of M3
Hide Arm/Group Description:
PK of Lomitapide Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
PK of M1 Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
PK of M3 Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
Overall Number of Participants Analyzed 13 14 14
Median (Full Range)
Unit of Measure: hr
Period 1 Number Analyzed 13 participants 14 participants 14 participants
4.0
(1.00 to 18.0)
5.00
(3.00 to 10.0)
3.00
(1.00 to 4.03)
Period 2 Number Analyzed 13 participants 13 participants 13 participants
5.00
(3.00 to 18.0)
5.00
(2.00 to 6.00)
3.00
(1.00 to 4.00)
3.Primary Outcome
Title AUC0-t
Hide Description Area under the concentration-time curve from hour 0 to the last measurable concentration of lomitapide and its metabolites, M1 & M3.
Time Frame Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PK of Lomitapide PK of M1 PK of M3
Hide Arm/Group Description:
PK of Lomitapide Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
PK of M1 Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
PK of M3 Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
Overall Number of Participants Analyzed 13 14 14
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
Period 1 Number Analyzed 13 participants 14 participants 14 participants
40.2  (18.1) 65.8  (22.7) 319  (153)
Period 2 Number Analyzed 13 participants 13 participants 13 participants
44.0  (21.7) 62.8  (23.3) 319  (176)
4.Primary Outcome
Title AUC0-∞
Hide Description Area under the concentration-time curve extrapolated to infinity for lomitapide and its metabolites, M1 & M3.
Time Frame Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PK of Lomitapide PK of M1 PK of M3
Hide Arm/Group Description:
PK of Lomitapide Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
PK of M1 Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
PK of M3 Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
Overall Number of Participants Analyzed 13 14 14
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
Period 1 Number Analyzed 13 participants 14 participants 14 participants
44.4  (19.9) 68.3  (23.6) 330  (158)
Period 2 Number Analyzed 13 participants 13 participants 13 participants
48.3  (23.4) 65.3  (24.1) 330  (181)
5.Primary Outcome
Title λz
Hide Description Elimination rate constant estimated from individual linear regression of the terminal part of the log concentration vs time curve
Time Frame Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PK of Lomitapide PK of M1 PK of M3
Hide Arm/Group Description:
PK of lomitapide Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
PK of M1 Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
PK of M3 Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
Overall Number of Participants Analyzed 13 14 14
Mean (Standard Deviation)
Unit of Measure: 1/hr
Period 1 Number Analyzed 13 participants 14 participants 14 participants
0.0141  (0.00196) 0.0200  (0.00754) 0.0155  (0.00370)
Period 2 Number Analyzed 13 participants 13 participants 13 participants
0.0146  (0.00139) 0.0189  (0.00410) 0.0172  (0.00272)
6.Primary Outcome
Title t1/2
Hide Description Apparent terminal elimination half-life
Time Frame Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PK of Lomitapide PK of M1 PK of M3
Hide Arm/Group Description:
PK of Lomitapide Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
PK of M1 Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
PK of M3 Following a Single Oral Capsule Dose of 20 mg Lomitapide During Periods 1 and 2 (PK Set)
Overall Number of Participants Analyzed 13 14 14
Mean (Standard Deviation)
Unit of Measure: hr
Period 1 Number Analyzed 13 participants 14 participants 14 participants
50.3  (7.56) 38.3  (10.6) 46.9  (10.4)
Period 2 Number Analyzed 13 participants 13 participants 13 participants
47.8  (4.35) 38.0  (6.61) 41.2  (6.90)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Period 1 Period 2
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Period 1 Period 2
Affected / at Risk (%) Affected / at Risk (%)
Total   0/15 (0.00%)   0/13 (0.00%) 
Hide Serious Adverse Events
Period 1 Period 2
Affected / at Risk (%) Affected / at Risk (%)
Total   0/15 (0.00%)   0/13 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Period 1 Period 2
Affected / at Risk (%) Affected / at Risk (%)
Total   4/15 (26.67%)   1/13 (7.69%) 
Blood and lymphatic system disorders     
Lymphdenopathy  1  1/15 (6.67%)  0/13 (0.00%) 
Gastrointestinal disorders     
Abdominal Pain  1  1/15 (6.67%)  0/13 (0.00%) 
Diarrhoea  1  3/15 (20.00%)  0/13 (0.00%) 
Flatulence  1  1/15 (6.67%)  0/13 (0.00%) 
Nausea  1  2/15 (13.33%)  0/13 (0.00%) 
Abdominal Discomfort  1  2/15 (13.33%)  1/13 (7.69%) 
Infections and infestations     
Upper Respiratory Tract Infection  1  1/15 (6.67%)  0/13 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back Pain  1  1/15 (6.67%)  0/13 (0.00%) 
Nervous system disorders     
Headache  1  0/15 (0.00%)  1/13 (7.69%) 
Dizziness  1  1/15 (6.67%)  0/13 (0.00%) 
Psychiatric disorders     
Anxiety  1  1/15 (6.67%)  0/13 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash  1  1/15 (6.67%)  0/13 (0.00%) 
1
Term from vocabulary, MedDRA 16.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Described in contract
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Alison Long, MD - VP Clinical
Organization: Aegerion Pharmaceuticals, Inc.
Phone: 617-500-5142
EMail: alison.long@aegerion.com
Layout table for additonal information
Responsible Party: Aegerion Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01915771    
Other Study ID Numbers: AEGR-733-026
2013-002692-17 ( EudraCT Number )
First Submitted: August 1, 2013
First Posted: August 5, 2013
Results First Submitted: June 23, 2015
Results First Posted: March 11, 2020
Last Update Posted: March 11, 2020