Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02080468
Recruitment Status : Completed
First Posted : March 6, 2014
Results First Posted : March 11, 2019
Last Update Posted : March 11, 2019
Sponsor:
Information provided by (Responsible Party):
Aegerion Pharmaceuticals, Inc.

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.

Condition or disease Intervention/treatment Phase
Healthy Drug: lomitapide Drug: EE/norgestimate Phase 1

Detailed Description:
This study will be a single center, randomized, open-label, 2 arm study to evaluate the effects of EE/norgestimate, a weak CYP3A4 inhibitor, on the PK of lomitapide in healthy female subjects when EE/norgestimate is administered simultaneously with lomitapide and when administration is separated by 12 hours.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Phase 1, Open-Label, Randomized, 2-Arm Study to Evaluate the Effect of Ethinyl Estradiol/Norgestimate (Ortho Cyclen®), a Weak CYP3A4 Inhibitor, on the Pharmacokinetics of Lomitapide in Healthy Female Subjects
Actual Study Start Date : February 19, 2014
Actual Primary Completion Date : April 24, 2014
Actual Study Completion Date : April 24, 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm 1: Lomitapide & EE/Norgestimate - Taken Together
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
20 mg
Other Name: Juxtapid

Drug: EE/norgestimate
1x0.035-mg EE/0.25-mg norgestimate tablet
Other Name: Ortho Cylclen

Experimental: Arm 2: Lomitapide & EE/Norgestimate - Taken 12 Hours Apart
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
20 mg
Other Name: Juxtapid

Drug: EE/norgestimate
1x0.035-mg EE/0.25-mg norgestimate tablet
Other Name: Ortho Cylclen




Primary Outcome Measures :
  1. Cmax for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together) [ Time Frame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing ]
    Maximum observed plasma concentration of lomitapide and its 2 primary metabolites, M1 & M3

  2. Tmax for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together) [ Time Frame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing ]
    Time to reach maximum observed plasma concentration of lomitapide and its 2 primary metabolites, M1 & M3.

  3. AUC0-t for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together) [ Time Frame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing ]
    Area under the concentration-time curve from zero to last quantifiable concentration of lomitapide and its 2 primary metabolites, M1 & M3.

  4. AUC0-∞ for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together) [ Time Frame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing ]
    Area under the concentration-time curve from zero to infinity of lomitapide and its 2 primary metabolites, M1 & M3.

  5. t1/2 for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together) [ Time Frame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing ]
    Apparent terminal elimination half-life of lomitapide and its 2 primary metabolites, M1 & M3.


Secondary Outcome Measures :
  1. Cmax for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart) [ Time Frame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing ]
    Maximum observed plasma concentration of lomitapide and its metabolites, M1 & M3.

  2. Tmax for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart) [ Time Frame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing ]
    Time to reach maximum observed plasma concentration of lomitapide and its metabolites, M1 & M3.

  3. AUC0-t for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart) [ Time Frame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing ]
    Area under the concentration-time curve from zero to last quantifiable concentration of lomitapide and its metabolites, M1 & M3.

  4. AUC0-∞ for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart) [ Time Frame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing ]
    Area under the concentration-time curve from zero to infinity of lomitapide and its metabolites, M1 & M3.

  5. t1/2 for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart) [ Time Frame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing ]
    Apparent terminal elimination half-life of lomitapide and its metabolites, M1 & M3.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Healthy females, between 18 and 40 years of age inclusive
  2. BMI between 18.5 and 30.0 kg/m2, inclusive; total body weight of >110 lbs (50 kg);
  3. in good health, determined by no clinically significant or relevant abnormalities identified by a detailed medical history and physical exam
  4. no known history of hypersensitivity or previous intolerance to lomitapide or EE/norgestimate
  5. creatine phosphokinase, AST, and ALT levels must be below 1.5 times the upper limit of normal
  6. clinical laboratory evaluations within the reference range for the test laboratory
  7. negative test for selected drugs of abuse
  8. negative hepatitis panel and negative HIV antibody screens
  9. are of childbearing potential(ie, not postmenopausal or surgically sterile). All subjects must have a negative serum beta pregnancy test.
  10. able to comprehend and willing to sign an Informed Consent Form

Exclusion Criteria:

  1. significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, GI, neurological, or psychiatric disorder
  2. history of unexplained breast abnormalities or abnormal uterine bleeding
  3. history of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance
  4. history of stomach or intestinal surgery or resection
  5. history of Gilbert's Syndrome or suspicion of Gilbert's Syndrome
  6. subjects who have an abnormality in the 12-lead ECG
  7. use of any drugs of abuse for 6 months prior to Check-in;
  8. 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
  9. use of any tobacco- or nicotine-containing products within 6 months prior to Check-in;
  10. participation in any other investigational study drug trial within 30 days prior to Check-in;
  11. use of any prescription medications/products within 14 days prior to Check-in unless deemed acceptable by the Investigator and Sponsor
  12. use of any over-the-counter, nonprescription preparations within 7 days prior to Check-in, unless deemed acceptable by the Investigator and Sponsor
  13. use of alcohol-, grapefruit- (including star fruit), or caffeine-containing foods or beverages within 72 hours prior to Check-in and through Study Completion
  14. use of oral (except scheduled administration of EE/norgestimate), implantable, injectable, or transdermal contraceptives
  15. use of hormone replacement therapy
  16. poor peripheral venous access;
  17. donation of blood (500 mL) from 30 days prior to Screening through Study Completion
  18. receipt of blood products within 2 months prior to Check-in;
  19. 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;
  20. subjects who, in the opinion of the Investigator, should not participate in this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02080468


Locations
Layout table for location information
United States, Texas
Covance Clinical Research Unit, Inc
Dallas, Texas, United States, 75247
Sponsors and Collaborators
Aegerion Pharmaceuticals, Inc.
Investigators
Layout table for investigator information
Study Chair: Mark Sumeray, MD Cheif Medical Officer
Principal Investigator: T. Alex King, MD, CPI Covance

Layout table for additonal information
Responsible Party: Aegerion Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02080468    
Other Study ID Numbers: AEGR-733-029
First Posted: March 6, 2014    Key Record Dates
Results First Posted: March 11, 2019
Last Update Posted: March 11, 2019
Last Verified: November 2018
Keywords provided by Aegerion Pharmaceuticals, Inc.:
Effect
Ethinyl Estradiol/Norgestimate
Pharmacokinetics
Lomitapide.
Additional relevant MeSH terms:
Layout table for MeSH terms
Moxifloxacin
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Norgestimate
Norgestrel
Norgestimate, ethinyl estradiol drug combination
Estradiol
Polyestradiol phosphate
Ethinyl Estradiol
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Contraceptives, Oral, Combined