A Comparative Bioavailability Study of Lomitapide 20 mg Intact vs Sprinkled
Study Details
Study Description
Brief Summary
To compare the relative bioavailability of lomitapide when administered by sprinkling the contents of a 20 mg capsule of lomitapide in applesauce or in mashed banana to a single oral intact capsule dose of 20 mg lomitapide in healthy subjects.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: lomitapide sprinkled in applesauce Contents of single 20 mg capsule of lomitapide sprinkled in applesauce |
Drug: lomitapide
Other Names:
|
| Experimental: lomitapide sprinkled in mashed banana Contents of single 20 mg capsule of lomitapide sprinkled in mashed banana |
Drug: lomitapide
Other Names:
|
| Experimental: lomitapide (intact) Intact capsule of 20 mg lomitapide |
Drug: lomitapide
Other Names:
|
Outcome Measures
Primary Outcome Measures
- AUC0-t [predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post-dose]
Area under the concentration-time curve from hour 0 to the last measurable concentration of lomitapide and its metabolites (M1& M3).
- Cmax [predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post-dose]
Maximum observed concentration of lomitapide and its metabolites (M1& M3).
- Tmax [predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post-dose]
Time to reach maximum plasma concentration of lomitapide and its metabolites (M1& M3).
- t1/2 [predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post-dose]
Terminal elimination half-life of lomitapide and its metabolites (M1& M3).
- AUC0-∞ [predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post-dose]
Area under the plasma concentration vs time curve from zero to infinity of lomitapide and its metabolites (M1& M3).
- λz [predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post-dose]
Elimination rate constant estimated from individual linear regression of the terminal part of the log concentration vs time curve of lomitapide and its metabolites (M1& M3).
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Subject is a non-smoking healthy male or female, aged between 18 and 40 years of age.
-
Subject has a BMI of 18.5 - 25 kg/m2.
-
Subject has total body weight between > 50 kg to ≤ 100 kg.
-
Subjects must agree to use acceptable methods of contraception.
-
All females, regardless of childbearing potential, must have a negative serum beta human chorionic gonadotropin pregnancy test at Screening and on admission.
-
In good health, determined by no clinically significant or relevant abnormalities identified by a detailed medical history & full physical examination.
-
No known history of hypersensitivity or previous intolerance to lomitapide, applesauce, and/or banana.
-
Subjects must be capable of understanding and complying with the requirements of the protocol and must have signed the informed consent form prior to undergoing any study-related procedures.
Exclusion Criteria:
-
Subject has a clinically significant disease or any condition or disease that might affect drug absorption, distribution or excretion.
-
History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs.
-
Any clinically significant abnormal laboratory, vital signs or other safety findings as determined by medical history, physical examination or other evaluations.
-
History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator;
-
Electrocardiogram (ECG) abnormalities in the standard 12-lead ECG (at screening) such as a QTcF interval of >450 msec, a history of a prolonged QTc interval or Brugada syndrome.
-
History or current evidence of any clinically relevant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, haematological, endocrinological, allergic, dermatological, metabolic, neurological, psychiatric or other disease.
-
History or laboratory evidence of Gilbert's syndrome.
-
Positive results in any of the serology tests for Hepatitis B Surface Antigen (HbsAg), anti-Hepatitis core antibody (anti-HBc Ig G [and anti-HBc IgM if IgG is positive], Hepatitis C antibodies (anti-HCV), and HIV 1 and 2 antibodies, (anti-HIV 1/2).
-
Use of any drugs of abuse within 6 months prior to admission.
-
Confirmed positive results from urine drug screen (amphetamines, benzodiazepines, cocaine, cannabinoids, opiates, barbiturates and methadone) or from the alcohol breath test at screening and on admission (Day -1).
-
History or clinical evidence of alcohol or drug abuse within one year prior to admission.
-
Mentally handicapped.
-
Participation in a drug trial within 90 days prior to first drug administration.
-
Use of any prescription medication within 2 weeks prior to admission (Day -1), with the exception of the oral contraceptive pill.
-
Use of any substance inducing or inhibiting CYP3A4 enzymes within 30 days prior to admission (Day -1).
-
Use of any over-the-counter (OTC) medication (including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations) within 7 days prior to admission (Day -1), unless deemed acceptable by the Investigator and Sponsor.
-
Use of alcohol-, grapefruit-, starfruit-, or caffeine-containing foods or beverages within 72 hours prior to admission and through Study Completion.
-
Donation of more than 500 mL of blood within 90 days prior to drug administration.
-
Receipt of blood products within 2 months prior to admission.
-
Poor peripheral venous access.
-
Use of any tobacco- or nicotine-containing products within 6 months prior to admission (Day -1).
-
Any acute or chronic condition, scheduled hospitalisation (inclusive of elective surgery during study), or scheduled travel prior to completion of all study procedures.
-
Any circumstances or conditions, which, in the opinion of the PI, may affect full participation in the trial or compliance with the protocol.
-
Legal incapacity or limited legal capacity at screening.
-
Subjects who are vegetarians, vegans or have any dietary restrictions conflicting with the study standardised menus.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Richmond Pharmacology Ltd | Croydon | Surrey | United Kingdom | CR7 7YE |
Sponsors and Collaborators
- Aegerion Pharmaceuticals, Inc.
Investigators
- Study Chair: Mark Sumeray, MD, Aegerion Pharmaceuticals, Inc.
- Principal Investigator: Ulrike Lorch, MD, Richmond Phamacology, LTD
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AEGR-733-032
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Applesauce, Mashed Banana, Intact Capsule (ABC) | Mashed Banana, Intact Capsule, Applesauce (BCA) | Intact Capsule, Applesauce, Mashed Banana (CAB) |
|---|---|---|---|
| Arm/Group Description | First Intervention: Contents of single 20 mg capsule of lomitapide sprinkled in applesauce Second Intervention: Contents of single 20 mg capsule of lomitapide sprinkled in mashed banana Third Intervention: Intact capsule of 20 mg lomitapide | First Intervention: Contents of single 20 mg capsule of lomitapide sprinkled in mashed banana Second Intervention: Intact capsule of 20 mg lomitapide Third Intervention: Contents of single 20 mg capsule of lomitapide sprinkled in applesauce | First Intervention: Contents of single 20 mg capsule of lomitapide sprinkled in applesauce Second Intervention: Contents of single 20 mg capsule of lomitapide sprinkled in mashed banana Third Intervention: Intact capsule of 20 mg lomitapide |
| Period Title: First Intervention | |||
| STARTED | 11 | 10 | 11 |
| COMPLETED | 11 | 9 | 10 |
| NOT COMPLETED | 0 | 1 | 1 |
| Period Title: First Intervention | |||
| STARTED | 11 | 9 | 10 |
| COMPLETED | 11 | 9 | 10 |
| NOT COMPLETED | 0 | 0 | 0 |
| Period Title: First Intervention | |||
| STARTED | 11 | 9 | 10 |
| COMPLETED | 11 | 9 | 10 |
| NOT COMPLETED | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Applesauce, Mashed Banana, Intact Capsule (ABC) | Mashed Banana, Intact Capsule, Applesauce (BCA) | Intact Capsule, Applesauce, Mashed Banana (CAB) | Total |
|---|---|---|---|---|
| Arm/Group Description | Contents of single 20 mg capsule of lomitapide sprinkled in applesauce, mashed banana Capsule taken intact lomitapide | Contents of single 20 mg capsule of lomitapide sprinkled in applesauce& mashed banana Capsule taken intact lomitapide | Contents of single 20 mg capsule of lomitapide sprinkled in applesauce& mashed banana Capsule taken intact lomitapide | Total of all reporting groups |
| Overall Participants | 11 | 10 | 11 | 32 |
| Age (Count of Participants) | ||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
11
100%
|
10
100%
|
11
100%
|
32
100%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
28.45
(5.837)
|
25.90
(5.131)
|
27.91
(3.27)
|
27.42
(4.746)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
3
27.3%
|
6
60%
|
6
54.5%
|
15
46.9%
|
| Male |
8
72.7%
|
4
40%
|
5
45.5%
|
17
53.1%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
0
0%
|
0
0%
|
1
9.1%
|
1
3.1%
|
| Not Hispanic or Latino |
11
100%
|
10
100%
|
10
90.9%
|
31
96.9%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
1
9.1%
|
1
10%
|
1
9.1%
|
3
9.4%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
3
27.3%
|
2
20%
|
4
36.4%
|
9
28.1%
|
| White |
7
63.6%
|
6
60%
|
5
45.5%
|
18
56.3%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
1
10%
|
1
9.1%
|
2
6.3%
|
| Region of Enrollment (participants) [Number] | ||||
| United Kingdom |
11
100%
|
10
100%
|
11
100%
|
32
100%
|
Outcome Measures
| Title | AUC0-t |
|---|---|
| Description | Area under the concentration-time curve from hour 0 to the last measurable concentration of lomitapide and its metabolites (M1& M3). |
| Time Frame | predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Analysis Set included all subjects who received at least one single dose of lomitapide and who had evaluable PK data |
| Arm/Group Title | Lomitapide Sprinkled in Applesauce (Treatment A) | Lomitapide Sprinkled in Mashed Banana (Treatment B) | Intact Capsule of 20 mg Lomitapide (Treatment C) |
|---|---|---|---|
| Arm/Group Description | Contents of single 20 mg capsule of lomitapide sprinkled in applesauce | Contents of single 20 mg capsule of lomitapide sprinkled in mashed banana | Intact capsule of 20 mg lomitapide |
| Measure Participants | 30 | 30 | 30 |
| Lomitapide |
38.3
(15.2)
|
40.2
(13.4)
|
43.6
(17.7)
|
| M1 |
70.4
(20.2)
|
72.9
(23.1)
|
75.2
(22.8)
|
| M3 |
443
(308)
|
450
(292)
|
460
(325)
|
| Title | Cmax |
|---|---|
| Description | Maximum observed concentration of lomitapide and its metabolites (M1& M3). |
| Time Frame | predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Analysis Set included all subjects who received at least one single dose of lomitapide and who had evaluable PK data |
| Arm/Group Title | Lomitapide Sprinkled in Applesauce (Treatment A) | Lomitapide Sprinkled in Mashed Banana (Treatment B) | Intact Capsule of 20 mg Lomitapide (Treatment C) |
|---|---|---|---|
| Arm/Group Description | Contents of single 20 mg capsule of lomitapide sprinkled in applesauce | Contents of single 20 mg capsule of lomitapide sprinkled in mashed banana | Intact capsule of 20 mg lomitapide |
| Measure Participants | 30 | 30 | 30 |
| Lomitapide |
0.986
(0.536)
|
1.03
(0.463)
|
1.13
(0.591)
|
| M1 |
2.52
(0.748)
|
2.65
(0.813)
|
2.74
(0.796)
|
| M3 |
30.2
(15.6)
|
31.0
(13.3)
|
28.6
(13.7)
|
| Title | Tmax |
|---|---|
| Description | Time to reach maximum plasma concentration of lomitapide and its metabolites (M1& M3). |
| Time Frame | predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Analysis Set included all subjects who received at least one single dose of lomitapide and who had evaluable PK data |
| Arm/Group Title | Lomitapide Sprinkled in Applesauce (Treatment A) | Lomitapide Sprinkled in Mashed Banana (Treatment B) | Intact Capsule of 20 mg Lomitapide (Treatment C) |
|---|---|---|---|
| Arm/Group Description | Contents of single 20 mg capsule of lomitapide sprinkled in applesauce | Contents of single 20 mg capsule of lomitapide sprinkled in mashed banana | Intact capsule of 20 mg lomitapide |
| Measure Participants | 30 | 30 | 30 |
| Lomitapide |
4.00
|
5.00
|
5.00
|
| M1 |
5.00
|
5.00
|
5.00
|
| M3 |
2.03
|
3.00
|
3.00
|
| Title | t1/2 |
|---|---|
| Description | Terminal elimination half-life of lomitapide and its metabolites (M1& M3). |
| Time Frame | predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Analysis Set included all subjects who received at least one single dose of lomitapide and who had evaluable PK data |
| Arm/Group Title | Lomitapide Sprinkled in Applesauce (Treatment A) | Lomitapide Sprinkled in Mashed Banana (Treatment B) | Intact Capsule of 20 mg Lomitapide (Treatment C) |
|---|---|---|---|
| Arm/Group Description | Contents of single 20 mg capsule of lomitapide sprinkled in applesauce | Contents of single 20 mg capsule of lomitapide sprinkled in mashed banana | Intact capsule of 20 mg lomitapide |
| Measure Participants | 30 | 30 | 30 |
| Lomitapide |
52.4
(13.3)
|
47.7
(12.2)
|
48.8
(10.7)
|
| M1 |
38.7
(7.56)
|
37.0
(6.78)
|
39.1
(6.32)
|
| M3 |
46.0
(13.1)
|
45.7
(11.5)
|
44.0
(11.6)
|
| Title | AUC0-∞ |
|---|---|
| Description | Area under the plasma concentration vs time curve from zero to infinity of lomitapide and its metabolites (M1& M3). |
| Time Frame | predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Analysis Set included all subjects who received at least one single dose of lomitapide and who had evaluable PK data |
| Arm/Group Title | Lomitapide Sprinkled in Applesauce (Treatment A) | Lomitapide Sprinkled in Mashed Banana (Treatment B) | Intact Capsule of 20 mg Lomitapide (Treatment C) |
|---|---|---|---|
| Arm/Group Description | Contents of single 20 mg capsule of lomitapide sprinkled in applesauce | Contents of single 20 mg capsule of lomitapide sprinkled in mashed banana | Intact capsule of 20 mg lomitapide |
| Measure Participants | 30 | 30 | 30 |
| Lomitapide |
42.5
(17.7)
|
43.8
(15.3)
|
47.7
(20.6)
|
| M1 |
72.8
(20.8)
|
75.2
(23.7)
|
77.8
(23.9)
|
| M3 |
457
(317)
|
464
(300)
|
474
(333)
|
| Title | λz |
|---|---|
| Description | Elimination rate constant estimated from individual linear regression of the terminal part of the log concentration vs time curve of lomitapide and its metabolites (M1& M3). |
| Time Frame | predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Analysis Set included all subjects who received at least one single dose of lomitapide and who had evaluable PK data |
| Arm/Group Title | Lomitapide Sprinkled in Applesauce (Treatment A) | Lomitapide Sprinkled in Mashed Banana (Treatment B) | Intact Capsule of 20 mg Lomitapide (Treatment C) |
|---|---|---|---|
| Arm/Group Description | Contents of single 20 mg capsule of lomitapide sprinkled in applesauce | Contents of single 20 mg capsule of lomitapide sprinkled in mashed banana | Intact capsule of 20 mg lomitapide |
| Measure Participants | 30 | 30 | 30 |
| Lomitapide |
0.0140
(0.00341)
|
0.0153
(0.00343)
|
0.0149
(0.00320)
|
| M1 |
0.0185
(0.00344)
|
0.0195
(0.00457)
|
0.0182
(0.00309)
|
| M3 |
0.0161
(0.00408)
|
0.0162
(0.00428)
|
0.0167
(0.00405)
|
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Lomitapide Sprinkled in Applesauce (Treatment A) | Lomitapide Sprinkled in Mashed Banana (Treatment B) | Intact Capsule of 20 mg Lomitapide (Treatment C) | |||
| Arm/Group Description | Contents of single 20 mg capsule of lomitapide sprinkled in applesauce | Contents of single 20 mg capsule of lomitapide sprinkled in mashed banana | Intact capsule of 20 mg lomitapide | |||
All Cause Mortality |
||||||
| Lomitapide Sprinkled in Applesauce (Treatment A) | Lomitapide Sprinkled in Mashed Banana (Treatment B) | Intact Capsule of 20 mg Lomitapide (Treatment C) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/30 (0%) | 0/31 (0%) | 0/31 (0%) | |||
Serious Adverse Events |
||||||
| Lomitapide Sprinkled in Applesauce (Treatment A) | Lomitapide Sprinkled in Mashed Banana (Treatment B) | Intact Capsule of 20 mg Lomitapide (Treatment C) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/30 (0%) | 0/31 (0%) | 0/31 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Lomitapide Sprinkled in Applesauce (Treatment A) | Lomitapide Sprinkled in Mashed Banana (Treatment B) | Intact Capsule of 20 mg Lomitapide (Treatment C) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/30 (16.7%) | 6/31 (19.4%) | 6/31 (19.4%) | |||
| Eye disorders | ||||||
| Conjunctival haemorrhage | 0/30 (0%) | 0 | 1/31 (3.2%) | 1 | 0/31 (0%) | 0 |
| Eye swelling | 0/30 (0%) | 0 | 1/31 (3.2%) | 1 | 0/31 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal Pain | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 |
| Constipation | 0/30 (0%) | 0 | 1/31 (3.2%) | 1 | 0/31 (0%) | 0 |
| Vomiting | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 |
| Dry mouth | 0/30 (0%) | 0 | 1/31 (3.2%) | 1 | 0/31 (0%) | 0 |
| Glossodynia | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 |
| Oral pain | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 |
| General disorders | ||||||
| Catheter site pain | 0/30 (0%) | 0 | 1/31 (3.2%) | 1 | 0/31 (0%) | 0 |
| Infections and infestations | ||||||
| Herpes simplex | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 |
| Nervous system disorders | ||||||
| Headache | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
| Renal and urinary disorders | ||||||
| Polyuria | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Nasopharyngitis | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||
| Rash | 0/30 (0%) | 0 | 1/31 (3.2%) | 1 | 1/31 (3.2%) | 1 |
| Vascular disorders | ||||||
| Presyncope | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
| Epistaxis | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Described in contract.
Results Point of Contact
| Name/Title | Alison Long, MD - VP Clinical |
|---|---|
| Organization | Aegerion Pharmaceuticals, Inc. |
| Phone | 857-242-5142 |
| alison.long@aegerion.com |
- AEGR-733-032