Evaluate the Effect of Ethinyl Estradiol/Norgestimate on the Pharmacokinetics of Lomitapide in Healthy Female Subjects

NCT02080468 | Completed Phase 1 Results

• 1 other identifier: AEGR-733-029
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to assess the effect of ethinyl estradiol (EE)/norgestimate, a weak cytochrome P450 (CYP) 3A4 inhibitor, on the pharmacokinetics (PK) of lomitapide and 2 primary metabolites, M1 and M3.

Conditions

Healthy

Keywords

Effect; Ethinyl Estradiol/Norgestimate; Pharmacokinetics; Lomitapide.

Outcome Measures

Primary Outcomes (5)

• Cmax for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together)

  Maximum observed plasma concentration of lomitapide and its 2 primary metabolites, M1 \& M3

  1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing

• Tmax for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together)

  Time to reach maximum observed plasma concentration of lomitapide and its 2 primary metabolites, M1 \& M3.

  1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing

• AUC0-t for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together)

  Area under the concentration-time curve from zero to last quantifiable concentration of lomitapide and its 2 primary metabolites, M1 \& M3.

  1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing

• AUC0-∞ for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together)

  Area under the concentration-time curve from zero to infinity of lomitapide and its 2 primary metabolites, M1 \& M3.

  1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing

• t1/2 for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together)

  Apparent terminal elimination half-life of lomitapide and its 2 primary metabolites, M1 \& M3.

  1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing

Secondary Outcomes (5)

• Cmax for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart)

  1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing

• Tmax for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart)

  1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing

• AUC0-t for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart)

  1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing

• AUC0-∞ for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart)

  1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing

• t1/2 for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart)

  1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing

Study Arms (2)

Arm 1: Lomitapide & EE/Norgestimate - Taken Together

EXPERIMENTAL

Lomitapide \& EE/Norgestimate - Taken Together 2 single oral doses of lomitapide (20 mg) (Day 1 \& Day 22) 21 single oral doses of EE/Norgestimate(Day 8 through day 28)

Drug: lomitapide; Drug: EE/norgestimate

Arm 2: Lomitapide & EE/Norgestimate - Taken 12 Hours Apart

EXPERIMENTAL

Lomitapide \& EE/Norgestimate - Taken 12 hours apart 2 single oral doses of lomitapide (20 mg) (Day 1 \& Day 22) 21 single oral doses of EE/Norgestimate(Day 9 through day 29)

Drug: lomitapide; Drug: EE/norgestimate

Interventions

lomitapide DRUG

20 mg

Also known as: Juxtapid

Arm 1: Lomitapide & EE/Norgestimate - Taken Together; Arm 2: Lomitapide & EE/Norgestimate - Taken 12 Hours Apart

EE/norgestimate DRUG

1x0.035-mg EE/0.25-mg norgestimate tablet

Also known as: Ortho Cylclen

Arm 1: Lomitapide & EE/Norgestimate - Taken Together; Arm 2: Lomitapide & EE/Norgestimate - Taken 12 Hours Apart

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy females, between 18 and 40 years of age inclusive
• BMI between 18.5 and 30.0 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 physical exam
• no known history of hypersensitivity or previous intolerance to lomitapide or EE/norgestimate
• 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
• are of childbearing potential(ie, not postmenopausal or surgically sterile). All subjects must have a negative serum beta pregnancy test.
• able to comprehend and willing to sign an Informed Consent Form

You may not qualify if:

• significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, GI, neurological, or psychiatric disorder
• history of unexplained breast abnormalities or abnormal uterine bleeding
• 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
• use of oral (except scheduled administration of EE/norgestimate), implantable, injectable, or transdermal contraceptives
• use of hormone replacement therapy

Sponsors & Collaborators

• Aegerion Pharmaceuticals, Inc.: lead

Study Sites (1)

Covance Clinical Research Unit, Inc

Dallas, Texas, 75247, United States

Location

MeSH Terms

Interventions

BMS201038

Results Point of Contact

• Title: Alison Long, MD - VP Clinical
• Organization: Aegerion Pharmaceuticals, Inc.

alison.long@aegerion.com

617-500-5142

Study Officials

• Mark Sumeray, MD

  Cheif Medical Officer

  STUDY CHAIR

• T. Alex King, MD, CPI

  Covance

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2014
• First Posted: March 6, 2014
• Study Start: February 19, 2014
• Primary Completion: April 24, 2014
• Study Completion: April 24, 2014
• Last Updated: March 11, 2019
• Results First Posted: March 11, 2019

Record last verified: 2018-11

Locations

US (1)