Intra-subject Variability of PharmacokineticsPhase 1NCT01915771

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

A Phase 1 study testing lomitapide in people with Intra-subject Variability of Pharmacokinetics, run by Aegerion Pharmaceuticals, Inc. at 1 site in United Kingdom.

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

Objectives: To evaluate the intra-subject variability of the pharmacokinetics (PK) of single oral capsule doses of 20 mg lomitapide. Read more about this study

Who is it for?: Ages 18 to 40 yearsHealthy volunteers can take part
Conditions the study is for: Intra-subject Variability of Pharmacokinetics
What is being tested?: lomitapide
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 15 participants
Where: 1 siteUnited Kingdom
Study dates: 29 Jul 2013to 23 Aug 2013
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 40 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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.
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.

Who cannot join

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.

Show all 25Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Richmond Pharmacology
Croydon, Surrey, CR7 7YE

Other trials in United Kingdom

About this study

Official title: A Phase 1, Open-label, Crossover Study to Determine the Intra-subject Variability of the Pharmacokinetics of Single Oral CapsuleDose of 20 mg Lomitapide in Healthy Subjects

Objectives:

To evaluate the intra-subject variability of the pharmacokinetics (PK) of single oral capsule doses of 20 mg lomitapide.

Read the detailed description

This study will be a single centre, open-label study. It will comprise of 2 single oral doses with at least a 14-day washout between doses. Following the first dose subjects will be discharged from the unit for the remainder of the washout period. Subjects will be re-admitted to the unit on Day -1 (Period 2) and following an overnight fast they will be administered the second dose on Day 1 (Period 2). Subjects will be discharged from the unit following the 168 h PK blood draw.

Conditions: Intra-subject Variability of Pharmacokinetics
Being tested: lomitapide

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

Study groups in NCT01915771
Study group	Role	What they receive
lomitapide	Experimental	It will comprise of 2 single oral doses with at least a 14-day washout between doses. Receives: Drug: lomitapide

What is being measured

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

Cmax
Maximum observed concentration of lomitapide and its metabolites, M1 \& M3.
Measured: Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.
Tmax
Time to reach maximum plasma concentration
Measured: Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.
AUC0-t
Area under the concentration-time curve from hour 0 to the last measurable concentration of lomitapide and its metabolites, M1 \& M3.
Measured: Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.
AUC0-∞
Area under the concentration-time curve extrapolated to infinity for lomitapide and its metabolites, M1 \& M3.
Measured: Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.
λz
Elimination rate constant estimated from individual linear regression of the terminal part of the log concentration vs time curve
Measured: Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.
t1/2
Apparent terminal elimination half-life
Measured: Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.

Timeline

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

29 Jul 201323 Aug 2013

First posted5 Aug 2013 (estimated)
Study start29 Jul 2013
Primary completion23 Aug 2013
Study completion23 Aug 2013

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 Intra-subject Variability of PharmacokineticsStudies 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 15 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01915771
Sponsor's protocol ID: AEGR-733-026
Other IDs: 2013-002692-17
Status last verified: Feb 2020
First submitted: 1 Aug 2013
Last updated: 11 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 11 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, Open-label, Crossover Study to Determine the Intra-subject Variability of the Pharmacokinetics of Single Oral CapsuleDose of 20 mg Lomitapide in Healthy Subjects
ClinicalTrials.gov ID: NCT01915771
Acronym / sponsor ID: AEGR-733-026
Conditions: Intra-subject Variability of Pharmacokinetics
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 15 participants (actual)
Lead sponsor: Aegerion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
Study start: 29 Jul 2013 (actual)
Primary completion: 23 Aug 2013 (actual)
Study completion: 23 Aug 2013 (actual)
First posted: 5 Aug 2013 (estimated)
Results: Posted 11 Mar 2020

Clinical summary

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

Objectives:

To evaluate the intra-subject variability of the pharmacokinetics (PK) of single oral capsule doses of 20 mg lomitapide.

Detailed description

Study design

Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
lomitapide	Experimental	Drug: lomitapideIt will comprise of 2 single oral doses with at least a 14-day washout between doses.

Who may qualify

Ages: 18 to 40 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (8 listed)

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.

Key exclusion criteria (25 listed)

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.

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

Primary outcome

Cmax
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.
Maximum observed concentration of lomitapide and its metabolites, M1 \& M3.
Tmax
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.
Time to reach maximum plasma concentration
AUC0-t
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.
Area under the concentration-time curve from hour 0 to the last measurable concentration of lomitapide and its metabolites, M1 \& M3.
AUC0-∞
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.
Area under the concentration-time curve extrapolated to infinity for lomitapide and its metabolites, M1 \& M3.
λz
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.
Elimination rate constant estimated from individual linear regression of the terminal part of the log concentration vs time curve
t1/2
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.
Apparent terminal elimination half-life

Results and safety

Results posted to the registry on 11 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	15	14

Primary outcome: Cmax

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.. Mean (Standard Deviation). Unit: ng/mL

Measure	PK of Lomitapide n = 13	PK of M1 n = 14	PK of M3 n = 14
Period 1	0.961 (0.556)	2.34 (0.593)	23.6 (7.08)
Period 2	1.02 (0.843)	2.20 (0.664)	22.8 (9.33)

Population analysed: 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.

Primary outcome: Tmax

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.. Median (Full Range). Unit: hr

Measure	PK of Lomitapide n = 13	PK of M1 n = 14	PK of M3 n = 14
Period 1	4.0 (1.00 to 18.0)	5.00 (3.00 to 10.0)	3.00 (1.00 to 4.03)
Period 2	5.00 (3.00 to 18.0)	5.00 (2.00 to 6.00)	3.00 (1.00 to 4.00)

Primary outcome: AUC0-t

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.. Mean (Standard Deviation). Unit: ng*hr/mL

Measure	PK of Lomitapide n = 13	PK of M1 n = 14	PK of M3 n = 14
Period 1	40.2 (18.1)	65.8 (22.7)	319 (153)
Period 2	44.0 (21.7)	62.8 (23.3)	319 (176)

Primary outcome: AUC0-∞

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.. Mean (Standard Deviation). Unit: ng*hr/mL

Measure	PK of Lomitapide n = 13	PK of M1 n = 14	PK of M3 n = 14
Period 1	44.4 (19.9)	68.3 (23.6)	330 (158)
Period 2	48.3 (23.4)	65.3 (24.1)	330 (181)

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Period 1	0 of 15 (0%)	4 of 15 (26.7%)	0 of 15
Period 2	0 of 13 (0%)	1 of 13 (7.7%)	0 of 13

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 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

Aegerion Pharmaceuticals, Inc.

Ulrike Lorch, MD principal investigator

Richmond Pharmacology Limited

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 in people with Intra-subject Variability of Pharmacokinetics, run by Aegerion Pharmaceuticals, Inc. at 1 site in United Kingdom.

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 8 inclusion and 25 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 11 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 Kingdom. 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 11 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: Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.). The study lists 6 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 NCT01915771.

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 11 Mar 2020.