- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02080455
Evaluate the Effect of Atorvastatin on the Pharmacokinetics of Lomitapide in Healthy Subjects.
February 25, 2020 updated by: Aegerion Pharmaceuticals, Inc.
A Phase 1, Open-Label, Randomized, 2-Arm Study to Evaluate the Effect of Atorvastatin, a Weak CYP3A4 Inhibitor, on the Pharmacokinetics of Lomitapide in Healthy Subjects
The primary objective of this study is to assess the effect of atorvastatin, a weak cytochrome P450 (CYP) 3A4 inhibitor, on the pharmacokinetics (PK) of lomitapide and its 2 primary metabolites, M1 and M3.
Study Overview
Status
Completed
Intervention / Treatment
Detailed Description
This study will be a single center, randomized, open-label, 2-arm study to evaluate the effects of atorvastatin, a weak CYP3A4 inhibitor, on the PK of lomitapide in healthy male and female subjects when atorvastatin is administered simultaneously with lomitapide and when it is administered 12 hours after lomitapide.
Study Type
Interventional
Enrollment (Actual)
32
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Texas
-
Dallas, Texas, United States, 75247
- Covance Clinical Research Unit, Inc
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 55 years (ADULT)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Healthy males and females, between 18 and 55 years of age inclusive
- BMI between 18.5 and 32.0 kg/m2, inclusive; total body weight of >110 lbs (50 kg);
- in good health, determined by no clinically significant or relevant abnormalities identified by a detailed medical history and medical exam
- creatine phosphokinase, AST, and ALT levels must be below 1.5 times the upper limit of normal
- clinical laboratory evaluations within the reference range for the test laboratory
- negative test for selected drugs of abuse
- negative hepatitis panel and negative HIV antibody screens
- males will either be sterile or agree to use approved methods of contraception
- all females must have a negative serum beta human chorionic gonadotropin pregnancy test and will be required to use a medically acceptable method of contraception.
- able to comprehend and willing to sign an Informed Consent Form
Exclusion Criteria:
- significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, GI, neurological, or psychiatric disorder
- history of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance
- history of stomach or intestinal surgery or resection
- history of Gilbert's Syndrome or suspicion of Gilbert's Syndrome
- subjects who have an abnormality in the 12-lead ECG
- use of any drugs of abuse for 6 months prior to Check-in;
- subjects who consume more than 14 units of alcohol per week or who have a significant history of alcoholism or drug/chemical abuse within 1 year prior to Check-in
- use of any tobacco- or nicotine-containing products within 6 months prior to Check-in;
- participation in any other investigational study drug trial within 30 days prior to Check-in;
- use of any prescription medications/products within 14 days prior to Check-in unless deemed acceptable by the Investigator and Sponsor
- use of any over-the-counter, nonprescription preparations within 7 days prior to Check-in, unless deemed acceptable by the Investigator and Sponsor
- use of alcohol-, grapefruit- (including star fruit), or caffeine-containing foods or beverages within 72 hours prior to Check-in and through Study Completion
- poor peripheral venous access;
- donation of blood (500 mL) from 30 days prior to Screening through Study Completion
- receipt of blood products within 2 months prior to Check-in;
- any acute or chronic condition, scheduled hospitalization (inclusive of elective surgery during study) or scheduled travel prior to completion of all study procedures which, in the opinion of the Investigator, would limit the subject's ability to complete and/or participate in this clinical study;
- subjects who, in the opinion of the Investigator, should not participate in this study.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: OTHER
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Lomitapide & Atorvastatin - Taken Together
2 single oral doses of lomitapide (20 mg) with a 14-day washout between (Day 1 & Day 15) 11 single oral doses of atorvastatin (80 mg) (Day 11 through day 21) |
20 mg dose
Other Names:
80 mg
Other Names:
|
EXPERIMENTAL: Lomitapide & Atorvastatin - Approx. 12 hours between
2 single oral doses of lomitapide (20 mg) with a 14-day washout between (Day 1 & Day 15) 11 single oral doses of atorvastatin (80 mg) (Day 12 through day 22) |
20 mg dose
Other Names:
80 mg
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cmax
Time Frame: Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing
|
Maximum observed plasma concentration of lomitapide and its 2 primary metabolites (M1 & M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1)
|
Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing
|
Tmax
Time Frame: Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing
|
Time to reach maximum observed plasma concentration of lomitapide and its 2 primary metabolites (M1 & M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1)
|
Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing
|
AUC0-t
Time Frame: Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing
|
Area under the concentration-time curve from zero to the last quantifiable concentration of lomitapide and its 2 primary metabolites (M1 & M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1)
|
Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing
|
AUC0-∞
Time Frame: Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing
|
Area under the concentration-time curve from zero to infinity of lomitapide and its 2 primary metabolites (M1 & M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1)
|
Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing
|
t1/2
Time Frame: Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing
|
Apparent terminal elimination half-life of lomitapide and its 2 primary metabolites (M1 & M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1)
|
Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cmax
Time Frame: Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing
|
Maximum observed plasma concentration of lomitapide and its 2 primary metabolites (M1 & M3) following administration of lomitapide alone and coadministered with atorvastatin 12 hours apart (Arm 2)
|
Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing
|
Tmax
Time Frame: Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing
|
Time to reach maximum observed plasma concentration of lomitapide and its 2 primary metabolites (M1 & M3) following administration of lomitapide alone and coadministered with atorvastatin 12 hours apart (Arm 2)
|
Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing
|
AUC0-t
Time Frame: Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing
|
Area under the concentration-time curve from zero to the last quantifiable concentration of lomitapide and its 2 primary metabolites (M1 & M3) following administration of lomitapide alone and coadministered with atorvastatin 12 hours apart (Arm 2)
|
Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing
|
AUC0-∞
Time Frame: Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing
|
Area under the concentration-time curve from zero to infinity of lomitapide and its 2 primary metabolites (M1 & M3) following administration of lomitapide alone and coadministered with atorvastatin 12 hours apart (Arm 2)
|
Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing
|
t1/2
Time Frame: Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing
|
Apparent terminal elimination half-life of lomitapide and its 2 primary metabolites (M1 & M3) following administration of lomitapide alone and coadministered with atorvastatin 12 hours apart (Arm 2)
|
Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
January 27, 2014
Primary Completion (ACTUAL)
March 7, 2014
Study Completion (ACTUAL)
March 7, 2014
Study Registration Dates
First Submitted
March 5, 2014
First Submitted That Met QC Criteria
March 5, 2014
First Posted (ESTIMATE)
March 6, 2014
Study Record Updates
Last Update Posted (ACTUAL)
March 10, 2020
Last Update Submitted That Met QC Criteria
February 25, 2020
Last Verified
February 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- AEGR-733-024
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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