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

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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02080468

Enrollment

Registered

2014-03-06

Start date

2014-02-19

Completion date

2014-04-24

Last updated

2019-03-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Keywords

Effect, Ethinyl Estradiol/Norgestimate, Pharmacokinetics, Lomitapide.

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.

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.

Interventions

DRUGlomitapide

20 mg

DRUGEE/norgestimate

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

OTHER

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to 40 Years

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.

Design outcomes

Primary

Measure	Time frame	Description
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.
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
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.
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.
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.

Secondary

Measure	Time frame	Description
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.
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.
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.
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.
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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
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) lomitapide: 20 mg EE/norgestimate: 1x0.035-mg EE/0.25-mg norgestimate tablet	16
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) lomitapide: 20 mg EE/norgestimate: 1x0.035-mg EE/0.25-mg norgestimate tablet	16
Total	32

Baseline characteristics

Characteristic	Lomitapide & EE/Norgestimate - Taken Together	Lomitapide & EE/Norgestimate - Taken 12 Hours Apart	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	16 Participants	16 Participants	32 Participants
Age, Continuous	30 years STANDARD_DEVIATION 6.4	29 years STANDARD_DEVIATION 5.7	29 years STANDARD_DEVIATION 6
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants	3 Participants	9 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants	13 Participants	23 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	9 Participants	10 Participants	19 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) White	7 Participants	5 Participants	12 Participants
Region of Enrollment United States	16 participants	16 participants	32 participants
Sex: Female, Male Female	16 Participants	16 Participants	32 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 16	0 / 16
other Total, other adverse events	8 / 16	7 / 16
serious Total, serious adverse events	0 / 16	0 / 16

Outcome results

Primary

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.