Effect of Atorvastatin on the Pharmacokinetics of LomitapidePhase 1NCT02080455

Evaluate the Effect of Atorvastatin on the Pharmacokinetics of Lomitapide in Healthy Subjects.

A Phase 1 study testing lomitapide and Atorvastatin in people with Effect of Atorvastatin on the Pharmacokinetics of Lomitapide, run by Aegerion Pharmaceuticals, Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Effect of Atorvastatin on the Pharmacokinetics of Lomitapide
What is being tested?: lomitapide and Atorvastatin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 32 participants
Where: 1 siteUnited States
Study dates: 27 Jan 2014to 7 Mar 2014
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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

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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

Who cannot join

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;

Show all 17Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Covance Clinical Research Unit, Inc
Dallas, Texas, 75247

Other trials in United States

About this study

Official title: 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

Read the 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.

Conditions: Effect of Atorvastatin on the Pharmacokinetics of Lomitapide
Being tested: lomitapide, Atorvastatin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

lomitapideDrug
Also called Juxtapid
20 mg dose
AtorvastatinDrug
Also called Lipitor
80 mg

Study groups in NCT02080455
Study group	Role	What they receive
Lomitapide & Atorvastatin - Taken Together	Experimental	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) Receives: Drug: lomitapide; Drug: Atorvastatin
Lomitapide & Atorvastatin - Approx. 12 hours between	Experimental	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) Receives: Drug: lomitapide; Drug: Atorvastatin

What is being measured

The primary outcome is the main question the study is designed to answer.

Cmax
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)
Measured: 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 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)
Measured: 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
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)
Measured: 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-∞
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)
Measured: 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
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)
Measured: 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 outcomes (5)

Cmax
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)
Measured: 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 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)
Measured: 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
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)
Measured: 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-∞
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)
Measured: 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
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)
Measured: Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 Jan 20147 Mar 2014

First posted6 Mar 2014 (estimated)
Study start27 Jan 2014
Primary completion7 Mar 2014
Study completion7 Mar 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Effect of Atorvastatin on the Pharmacokinetics of LomitapideStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 32 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02080455
Sponsor's protocol ID: AEGR-733-024
Status last verified: Feb 2020
First submitted: 5 Mar 2014
Last updated: 10 Mar 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Study at a glance

From the registry record, last updated by the sponsor on 10 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT02080455
Acronym / sponsor ID: AEGR-733-024
Conditions: Effect of Atorvastatin on the Pharmacokinetics of Lomitapide
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 32 participants (actual)
Lead sponsor: Aegerion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
Study start: 27 Jan 2014 (actual)
Primary completion: 7 Mar 2014 (actual)
Study completion: 7 Mar 2014 (actual)
First posted: 6 Mar 2014 (estimated)
Results: Posted 10 Mar 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Lomitapide & Atorvastatin - Taken Together	Experimental	Drug: lomitapide, Drug: Atorvastatin2 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)
Lomitapide & Atorvastatin - Approx. 12 hours between	Experimental	Drug: lomitapide, Drug: Atorvastatin2 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)

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (10 listed)

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

Key exclusion criteria (17 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
lomitapideAlso: Juxtapid20 mg dose	Drug	Lomitapide & Atorvastatin - Approx. 12 hours between, Lomitapide & Atorvastatin - Taken Together
AtorvastatinAlso: Lipitor80 mg	Drug	Lomitapide & Atorvastatin - Approx. 12 hours between, Lomitapide & Atorvastatin - Taken Together

Primary outcome

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)
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)
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)
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)
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)

5 secondary outcomes

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
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
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
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
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

Results and safety

Results posted to the registry on 10 Mar 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Lomitapide & Atorvastatin - Taken Together	16	16
Lomitapide & Atorvastatin - Approx. 12 Hours Between	16	16

Primary outcome: 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. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	PK of Lomitapide (Lomitapide Alone) n = 16	PK of Lomitapide (Coadministered Simultaneously) n = 16	PK of M1 (Lomitapide Alone) n = 16	PK of M1 (Coadministered Simultaneously) n = 16	PK of M3 (Lomitapide Alone) n = 16	PK of M3 (Coadministered Simultaneously) n = 16
Value	0.940 (34.5)	2.00 (52.9)	2.24 (22.8)	2.11 (31.9)	32.3 (40.6)	27.2 (62.0)

Population analysed: The PK Population consisted of all subjects who received at least one dose of study drug and have evaluable PK data.

Primary outcome: 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. Median (Full Range). Unit: hr

Measure	PK of Lomitapide (Lomitapide Alone) n = 16	PK of Lomitapide (Coadministered Simultaneously) n = 16	PK of M1 (Lomitapide Alone) n = 16	PK of M1 (Coadministered Simultaneously) n = 16	PK of M3 (Lomitapide Alone) n = 16	PK of M3 (Coadministered Simultaneously) n = 16
Value	6.00 (3.00 to 10.0)	10.0 (3.00 to 23.8)	6.02 (4.00 to 10.0)	10.0 (4.00 to 23.8)	4.00 (3.00 to 12.0)	6.00 (3.00 to 23.8)

Population analysed: The PK Population consisted of all subjects who received at least one dose of study drug and had evaluable PK data.

Primary outcome: 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. Geometric mean (Geometric Coefficient of Variation). Unit: ng*hr/mL

Measure	PK of Lomitapide (Lomitapide Alone) n = 16	PK of Lomitapide (Coadministered Simultaneously) n = 16	PK of M1 (Lomitapide Alone) n = 16	PK of M1 (Coadministered Simultaneously) n = 16	PK of M3 (Lomitapide Alone) n = 16	PK of M3 (Coadministered Simultaneously) n = 16
Value	36.4 (38.4)	71.5 (45.3)	76.8 (34.4)	76.3 (36.0)	434 (65.5)	475 (55.0)

Population analysed: The PK Population consisted of all subjects who received at least one dose of study drug and had evaluable PK data.

Primary outcome: 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. Geometric mean (Geometric Coefficient of Variation). Unit: ng*hr/mL

Measure	PK of Lomitapide (Lomitapide Alone) n = 16	PK of Lomitapide (Coadministered Simultaneously) n = 16	PK of M1 (Lomitapide Alone) n = 16	PK of M1 (Coadministered Simultaneously) n = 16	PK of M3 (Lomitapide Alone) n = 14	PK of M3 (Coadministered Simultaneously) n = 16
Value	40.4 (40.8)	76.7 (45.1)	79.1 (34.7)	78.7 (36.3)	469 (68.6)	487 (544)

Population analysed: The PK Population consisted of all subjects who received at least one dose of study drug and had evaluable PK data. 2 subjects were removed from formal statistical analysis of "PK of M3 (Lomitapide alone)" due to missing value of AUC0-∞ for Analyte M3.

5 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Lomitapide & Atorvastatin - Taken Together	0 of 16 (0%)	12 of 16 (75%)	0 of 16
Lomitapide & Atorvastatin - Approx. 12 Hours Between	0 of 16 (0%)	5 of 16 (31.3%)	0 of 16

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Mark Sumeray, MD study chair

Cheif Medical Officer

T. Alex King, MD, CPI principal investigator

Covance

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing lomitapide and Atorvastatin in people with Effect of Atorvastatin on the Pharmacokinetics of Lomitapide, run by Aegerion Pharmaceuticals, Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02080455.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2020.