Clincosm LogoSign in Get a demo

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

Sponsor
Aegerion Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02080468
Collaborator
(none)
32
Enrollment
1
Location
2
Arms
2.1
Actual Duration (Months)
15.2
Patients Per Site Per Month

Study Details

Study Description

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
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.

Study Design

Study Type:
Interventional
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 :
Feb 19, 2014
Actual Primary Completion Date :
Apr 24, 2014
Actual Study Completion Date :
Apr 24, 2014

Arms and Interventions

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 Names:
  • Juxtapid

    • Drug: EE/norgestimate
    1x0.035-mg EE/0.25-mg norgestimate tablet
    Other Names:
  • 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 Names:
  • Juxtapid

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

    		•

    Outcome Measures

    Primary Outcome Measures

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 40 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    Yes
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Covance Clinical Research Unit, Inc Dallas Texas United States 75247

    Sponsors and Collaborators

    • Aegerion Pharmaceuticals, Inc.

    Investigators

    • Study Chair: Mark Sumeray, MD, Cheif Medical Officer
    • Principal Investigator: T. Alex King, MD, CPI, Covance

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Aegerion Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT02080468
    Other Study ID Numbers:
    • AEGR-733-029
    First Posted:
    Mar 6, 2014
    Last Update Posted:
    Mar 11, 2019
    Last Verified:
    Nov 1, 2018
    Keywords provided by Aegerion Pharmaceuticals, Inc.
    Effect
    Ethinyl Estradiol/Norgestimate
    Pharmacokinetics
    Lomitapide.
    Additional relevant MeSH terms:
    Norgestimate

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Lomitapide & EE/Norgestimate - Taken Together Lomitapide & EE/Norgestimate - Taken 12 Hours Apart
    Arm/Group Description 2 single oral doses of lomitapide (20 mg) (Day 1 & Day 22) 21 single oral doses of EE/Norgestimate(Day 8 through day 28) lomitapide: 20 mg EE/norgestimate: 1x0.035-mg EE/0.25-mg norgestimate tablet 2 single oral doses of lomitapide (20 mg) (Day 1 & Day 22) 21 single oral doses of EE/Norgestimate(Day 9 through day 29) lomitapide: 20 mg EE/norgestimate: 1x0.035-mg EE/0.25-mg norgestimate tablet
    Period Title: Overall Study
    STARTED 16 16
    COMPLETED 14 14
    NOT COMPLETED 2 2

    Baseline Characteristics

    Arm/Group Title Lomitapide & EE/Norgestimate - Taken Together Lomitapide & EE/Norgestimate - Taken 12 Hours Apart Total
    Arm/Group Description 2 single oral doses of lomitapide (20 mg) (Day 1 & Day 22) 21 single oral doses of EE/Norgestimate(Day 8 through day 28) lomitapide: 20 mg EE/norgestimate: 1x0.035-mg EE/0.25-mg norgestimate tablet 2 single oral doses of lomitapide (20 mg) (Day 1 & Day 22) 21 single oral doses of EE/Norgestimate(Day 9 through day 29) lomitapide: 20 mg EE/norgestimate: 1x0.035-mg EE/0.25-mg norgestimate tablet Total of all reporting groups
    Overall Participants 16 16 32
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    16
    100%
    16
    100%
    32
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    30
    (6.4)
    29
    (5.7)
    29
    (6.0)
    Sex: Female, Male (Count of Participants)
    Female
    16
    100%
    16
    100%
    32
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    6
    37.5%
    3
    18.8%
    9
    28.1%
    Not Hispanic or Latino
    10
    62.5%
    13
    81.3%
    23
    71.9%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    9
    56.3%
    10
    62.5%
    19
    59.4%
    White
    7
    43.8%
    5
    31.3%
    12
    37.5%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    1
    6.3%
    1
    3.1%
    Region of Enrollment (participants) [Number]
    United States
    16
    100%
    16
    100%
    32
    100%

    Outcome Measures

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

    Outcome Measure Data

    Analysis Population Description
    The Pharmacokinetic Analysis population included all subjects. Only subjects who completed both periods were included in the ANOVA analyses.
    Arm/Group Title PK of Lomitapide (Lomitapide Alone) PK of Lomitapide (Coadministered Simultaneously) PK of M1 (Lomitapide Alone) PK of M1 (Coadministered Simultaneously) PK of M3 (Lomitapide Alone) PK of M3 (Coadministered Simultaneously)
    Arm/Group Description PK of lomitapide following administration of lomitapide alone PK of lomitapide following administration of lomitapide coadministered with EE/Norgestimate simultaneously PK of M1 following administration of lomitapide alone PK of M1 following administration of lomitapide coadministered with EE/Norgestimate simultaneously PK of M3 following administration of lomitapide alone PK of M3 following administration of lomitapide coadministered with EE/Norgestimate simultaneously
    Measure Participants 16 14 16 14 16 14
    Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
    1.03
    (39.1)
    1.39
    (58.4)
    2.96
    (27.0)
    2.95
    (19.4)
    36.3
    (32.1)
    34.0
    (27.9)
    2. Primary Outcome
    Title Tmax for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together)
    Description Time to reach maximum observed plasma concentration of lomitapide and its 2 primary metabolites, M1 & M3.
    Time Frame 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing

    Outcome Measure Data

    Analysis Population Description
    The Pharmacokinetic Analysis population included all subjects. Only subjects who completed both periods were included in the ANOVA analyses.
    Arm/Group Title PK of Lomitapide (Lomitapide Alone) PK of Lomitapide (Coadministered Simultaneously) PK of M1 (Lomitapide Alone) PK of M1 (Coadministered Simultaneously) PK of M3 (Lomitapide Alone) PK of M3 (Coadministered Simultaneously)
    Arm/Group Description PK of lomitapide following administration of lomitapide alone PK of lomitapide following administration of lomitapide coadministered with EE/Norgestimate simultaneously PK of M1 following administration of lomitapide alone PK of M1 following administration of lomitapide coadministered with EE/Norgestimate simultaneously PK of M3 following administration of lomitapide alone PK of M3 following administration of lomitapide coadministered with EE/Norgestimate simultaneously
    Measure Participants 16 14 16 14 16 14
    Median (Full Range) [hr]
    6.00
    5.00
    8.28
    6.00
    5.02
    3.97
    3. Primary Outcome
    Title AUC0-t for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together)
    Description Area under the concentration-time curve from zero to last quantifiable concentration of lomitapide and its 2 primary metabolites, M1 & M3.
    Time Frame 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing

    Outcome Measure Data

    Analysis Population Description
    The Pharmacokinetic Analysis population included all subjects. Only subjects who completed both periods were included in the ANOVA analyses.
    Arm/Group Title PK of Lomitapide (Lomitapide Alone) PK of Lomitapide (Coadministered Simultaneously) PK of M1 (Lomitapide Alone) PK of M1 (Coadministered Simultaneously) PK of M3 (Lomitapide Alone) PK of M3 (Coadministered Simultaneously)
    Arm/Group Description PK of lomitapide following administration of lomitapide alone PK of lomitapide following administration of lomitapide coadministered with EE/Norgestimate simultaneously PK of M1 following administration of lomitapide alone PK of M1 following administration of lomitapide coadministered with EE/Norgestimate simultaneously PK of M3 following administration of lomitapide alone PK of M3 following administration of lomitapide coadministered with EE/Norgestimate simultaneously
    Measure Participants 16 14 16 14 16 14
    Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]
    33.5
    (35.0)
    42.7
    (49.5)
    89.3
    (35.6)
    96.8
    (32.1)
    456
    (41.2)
    371
    (36.1)
    4. Primary Outcome
    Title AUC0-∞ for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together)
    Description Area under the concentration-time curve from zero to infinity of lomitapide and its 2 primary metabolites, M1 & M3.
    Time Frame 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing

    Outcome Measure Data

    Analysis Population Description
    The Pharmacokinetic Analysis population included all subjects. Only subjects who completed both periods were included in the ANOVA analyses.
    Arm/Group Title PK of Lomitapide (Lomitapide Alone) PK of Lomitapide (Coadministered Simultaneously) PK of M1 (Lomitapide Alone) PK of M1 (Coadministered Simultaneously) PK of M3 (Lomitapide Alone) PK of M3 (Coadministered Simultaneously)
    Arm/Group Description PK of lomitapide following administration of lomitapide alone PK of lomitapide following administration of lomitapide coadministered with EE/Norgestimate simultaneously PK of M1 following administration of lomitapide alone PK of M1 following administration of lomitapide coadministered with EE/Norgestimate simultaneously PK of M3 following administration of lomitapide alone PK of M3 following administration of lomitapide coadministered with EE/Norgestimate simultaneously
    Measure Participants 16 14 16 14 16 14
    Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]
    36.5
    (34.8)
    46.5
    (49.1)
    91.4
    (35.8)
    99.4
    (32.4)
    463
    (40.9)
    377
    (36.0)
    5. Primary Outcome
    Title t1/2 for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together)
    Description Apparent terminal elimination half-life of lomitapide and its 2 primary metabolites, M1 & M3.
    Time Frame 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing

    Outcome Measure Data

    Analysis Population Description
    The Pharmacokinetic Analysis population included all subjects. Only subjects who completed both periods were included in the ANOVA analyses.
    Arm/Group Title PK of Lomitapide (Lomitapide Alone) PK of Lomitapide (Coadministered Simultaneously) PK of M1 (Lomitapide Alone) PK of M1 (Coadministered Simultaneously) PK of M3 (Lomitapide Alone) PK of M3 (Coadministered Simultaneously)
    Arm/Group Description PK of lomitapide following administration of lomitapide alone PK of lomitapide following administration of lomitapide coadministered with EE/Norgestimate simultaneously PK of M1 following administration of lomitapide alone PK of M1 following administration of lomitapide coadministered with EE/Norgestimate simultaneously PK of M3 following administration of lomitapide alone PK of M3 following administration of lomitapide coadministered with EE/Norgestimate simultaneously
    Measure Participants 16 14 16 14 16 14
    Geometric Mean (Geometric Coefficient of Variation) [hr]
    51.0
    (16.1)
    53.6
    (19.0)
    32.5
    (20.3)
    36.8
    (30.3)
    38.3
    (32.7)
    39.8
    (26.2)
    6. Secondary Outcome
    Title Cmax for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart)
    Description Maximum observed plasma concentration of lomitapide and its metabolites, M1 & M3.
    Time Frame 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing

    Outcome Measure Data

    Analysis Population Description
    The Pharmacokinetic Analysis population included all subjects. Only subjects who completed both periods were included in the ANOVA analyses.
    Arm/Group Title PK of Lomitapide (Lomitapide Alone) PK of Lomitapide (Codministered 12 Hours Apart) PK of M1 (Lomitapide Alone) PK of M1 (Coadministered 12 Hours Apart) PK of M3 (Lomitapide Alone) PK of M3 (Coadministered 12 Hours Apart)
    Arm/Group Description PK of lomitapide following administration of lomitapide alone PK of lomitapide following administration of lomitapide coadministered with EE/Norgestimate 12 hours apart PK of M1 following administration of lomitapide alone PK of M1 following administration of lomitapide coadministered with EE/Norgestimate 12 hours apart PK of M3 following administration of lomitapide alone PK of M3 following administration of lomitapide coadministered with EE/Norgestimate 12 hours apart
    Measure Participants 16 14 16 14 16 14
    Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
    1.05
    (50.7)
    1.39
    (56.5)
    2.87
    (20.6)
    3.04
    (22.8)
    37.8
    (26.2)
    33.0
    (28.0)
    7. Secondary Outcome
    Title Tmax for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart)
    Description Time to reach maximum observed plasma concentration of lomitapide and its metabolites, M1 & M3.
    Time Frame 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing

    Outcome Measure Data

    Analysis Population Description
    The Pharmacokinetic Analysis population included all subjects. Only subjects who completed both periods were included in the ANOVA analyses.
    Arm/Group Title PK of Lomitapide (Lomitapide Alone) PK of Lomitapide (Codministered 12 Hours Apart) PK of M1 (Lomitapide Alone) PK of M1 (Coadministered 12 Hours Apart) PK of M3 (Lomitapide Alone) PK of M3 (Coadministered 12 Hours Apart)
    Arm/Group Description PK of lomitapide following administration of lomitapide alone PK of lomitapide following administration of lomitapide coadministered with EE/Norgestimate 12 hours apart PK of M1 following administration of lomitapide alone PK of M1 following administration of lomitapide coadministered with EE/Norgestimate 12 hours apart PK of M3 following administration of lomitapide alone PK of M3 following administration of lomitapide coadministered with EE/Norgestimate 12 hours apart
    Measure Participants 16 14 16 14 16 14
    Mean (Full Range) [hr]
    8.00
    8.00
    9.07
    8.00
    6.00
    5.50
    8. Secondary Outcome
    Title AUC0-t for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart)
    Description Area under the concentration-time curve from zero to last quantifiable concentration of lomitapide and its metabolites, M1 & M3.
    Time Frame 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing

    Outcome Measure Data

    Analysis Population Description
    The Pharmacokinetic Analysis population included all subjects. Only subjects who completed both periods were included in the ANOVA analyses.
    Arm/Group Title PK of Lomitapide (Lomitapide Alone) PK of Lomitapide (Codministered 12 Hours Apart) PK of M1 (Lomitapide Alone) PK of M1 (Coadministered 12 Hours Apart) PK of M3 (Lomitapide Alone) PK of M3 (Coadministered 12 Hours Apart)
    Arm/Group Description PK of lomitapide following administration of lomitapide alone PK of lomitapide following administration of lomitapide coadministered with EE/Norgestimate 12 hours apart PK of M1 following administration of lomitapide alone PK of M1 following administration of lomitapide coadministered with EE/Norgestimate 12 hours apart PK of M3 following administration of lomitapide alone PK of M3 following administration of lomitapide coadministered with EE/Norgestimate 12 hours apart
    Measure Participants 16 14 16 14 16 14
    Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]
    37.6
    (49.9)
    46.5
    (55.1)
    92.3
    (31.1)
    93.7
    (34.2)
    520
    (30.1)
    377
    (31.9)
    9. Secondary Outcome
    Title AUC0-∞ for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart)
    Description Area under the concentration-time curve from zero to infinity of lomitapide and its metabolites, M1 & M3.
    Time Frame 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing

    Outcome Measure Data

    Analysis Population Description
    The Pharmacokinetic Analysis population included all subjects. Only subjects who completed both periods were included in the ANOVA analyses.
    Arm/Group Title PK of Lomitapide (Lomitapide Alone) PK of Lomitapide (Codministered 12 Hours Apart) PK of M1 (Lomitapide Alone) PK of M1 (Coadministered 12 Hours Apart) PK of M3 (Lomitapide Alone) PK of M3 (Coadministered 12 Hours Apart)
    Arm/Group Description PK of lomitapide following administration of lomitapide alone PK of lomitapide following administration of lomitapide coadministered with EE/Norgestimate 12 hours apart PK of M1 following administration of lomitapide alone PK of M1 following administration of lomitapide coadministered with EE/Norgestimate 12 hours apart PK of M3 following administration of lomitapide alone PK of M3 following administration of lomitapide coadministered with EE/Norgestimate 12 hours apart
    Measure Participants 16 14 16 14 16 14
    Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]
    41.1
    (50.9)
    51.2
    (55.3)
    94.5
    (31.3)
    96.4
    (34.6)
    528
    (30.0)
    383
    (31.7)
    10. Secondary Outcome
    Title t1/2 for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart)
    Description Apparent terminal elimination half-life of lomitapide and its metabolites, M1 & M3.
    Time Frame 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing

    Outcome Measure Data

    Analysis Population Description
    The Pharmacokinetic Analysis population included all subjects. Only subjects who completed both periods were included in the ANOVA analyses.
    Arm/Group Title PK of Lomitapide (Lomitapide Alone) PK of Lomitapide (Codministered 12 Hours Apart) PK of M1 (Lomitapide Alone) PK of M1 (Coadministered 12 Hours Apart) PK of M3 (Lomitapide Alone) PK of M3 (Coadministered 12 Hours Apart)
    Arm/Group Description PK of lomitapide following administration of lomitapide alone PK of lomitapide following administration of lomitapide coadministered with EE/Norgestimate 12 hours apart PK of M1 following administration of lomitapide alone PK of M1 following administration of lomitapide coadministered with EE/Norgestimate 12 hours apart PK of M3 following administration of lomitapide alone PK of M3 following administration of lomitapide coadministered with EE/Norgestimate 12 hours apart
    Measure Participants 16 14 16 14 16 14
    Geometric Mean (Geometric Coefficient of Variation) [hr]
    51.0
    (22.2)
    52.0
    (16.1)
    36.2
    (21.0)
    37.2
    (19.1)
    38.0
    (28.0)
    33.6
    (23.2)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Lomitapide & EE/Norgestimate - Taken Together Lomitapide & EE/Norgestimate - Taken 12 Hours Apart
    Arm/Group Description 2 single oral doses of lomitapide (20 mg) (Day 1 & Day 22) 21 single oral doses of EE/Norgestimate(Day 8 through day 28) lomitapide: 20 mg EE/norgestimate: 1x0.035-mg EE/0.25-mg norgestimate tablet 2 single oral doses of lomitapide (20 mg) (Day 1 & Day 22) 21 single oral doses of EE/Norgestimate(Day 9 through day 29) lomitapide: 20 mg EE/norgestimate: 1x0.035-mg EE/0.25-mg norgestimate tablet
    All Cause Mortality
    Lomitapide & EE/Norgestimate - Taken Together Lomitapide & EE/Norgestimate - Taken 12 Hours Apart
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/16 (0%) 0/16 (0%)
    Serious Adverse Events
    Lomitapide & EE/Norgestimate - Taken Together Lomitapide & EE/Norgestimate - Taken 12 Hours Apart
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/16 (0%) 0/16 (0%)
    Other (Not Including Serious) Adverse Events
    Lomitapide & EE/Norgestimate - Taken Together Lomitapide & EE/Norgestimate - Taken 12 Hours Apart
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 8/16 (50%) 7/16 (43.8%)
    Gastrointestinal disorders
    Nausea 4/16 (25%) 5 1/16 (6.3%) 1
    Vomitting 4/16 (25%) 4 1/16 (6.3%) 1
    Abdominal pain 1/16 (6.3%) 1 0/16 (0%) 0
    Abdominal pain upper 1/16 (6.3%) 1 0/16 (0%) 0
    Diarrhoea 1/16 (6.3%) 1 0/16 (0%) 0
    General disorders
    Vessel Punction Site Pain 2/16 (12.5%) 2 0/16 (0%) 0
    Infections and infestations
    Fungal infection 1/16 (6.3%) 1 0/16 (0%) 0
    Injury, poisoning and procedural complications
    Procedural dizziness 1/16 (6.3%) 1 2/16 (12.5%) 2
    Procedural Nausea 0/16 (0%) 0 2/16 (12.5%) 2
    Laceration 1/16 (6.3%) 1 0/16 (0%) 0
    Investigations
    Body temperature increased 0/16 (0%) 0 1/16 (6.3%) 1
    Musculoskeletal and connective tissue disorders
    Back pain 1/16 (6.3%) 1 0/16 (0%) 0
    Nervous system disorders
    Headache 2/16 (12.5%) 2 3/16 (18.8%) 3
    Presyncope 1/16 (6.3%) 1 0/16 (0%) 0
    Sensory disturbance 0/16 (0%) 0 1/16 (6.3%) 1
    Psychiatric disorders
    Insomnia 0/16 (0%) 0 1/16 (6.3%) 1
    Renal and urinary disorders
    Dysuria 1/16 (6.3%) 1 0/16 (0%) 0
    Reproductive system and breast disorders
    Dysmenorrhoea 2/16 (12.5%) 3 0/16 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain 0/16 (0%) 0 2/16 (12.5%) 2
    Nasal congestion 0/16 (0%) 0 1/16 (6.3%) 2
    Pulmonary congestion 0/16 (0%) 0 1/16 (6.3%) 1
    Rhinorrhea 0/16 (0%) 0 1/16 (6.3%) 1
    Sneezing 0/16 (0%) 0 1/16 (6.3%) 1
    Skin and subcutaneous tissue disorders
    Rash 0/16 (0%) 0 1/16 (6.3%) 2
    hyperhidrosis 0/16 (0%) 0 1/16 (6.3%) 1
    Vascular disorders
    Hot flush 1/16 (6.3%) 1 0/16 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Described in site contract

    Results Point of Contact

    Name/Title Alison Long, MD - VP Clinical
    Organization Aegerion Pharmaceuticals, Inc.
    Phone 617-500-5142
    Email alison.long@aegerion.com
    Responsible Party:
    Aegerion Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT02080468
    Other Study ID Numbers:
    • AEGR-733-029
    First Posted:
    Mar 6, 2014
    Last Update Posted:
    Mar 11, 2019
    Last Verified:
    Nov 1, 2018