Clinical trial NCT02792517: Erenumab (AMG 334) Plus Combined Oral Contraceptive Drug Interaction Study in Healthy Females
Official title: A Multi-Center, Open-label, Pharmacokinetic Drug Interaction Study of AMG 334 and a Combined Oral Contraceptive in Healthy Female Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Headache, Migraine
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2016-06-07
Enrollment: 41
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: A pharmacokinetic drug interaction study of erenumab and an oral contraceptive containing progestin and estrogen.

Detailed description: A pharmacokinetic (PK) drug interaction study of erenumab and an oral contraceptive containing progestin and estrogen. All participants will receive an oral contraceptive containing progestin and estrogen throughout the duration of the study. Participants will also receive a single dose of erenumab, administered by a healthcare provider in cycle 3. Serial PK samples will be collected at specified time points to characterize the PK of the oral contraceptive progestin and estrogen components with and without the presence of erenumab.

The study consists of three 28-day cycles and a follow-up period. The first 28 day cycle is an acclimation period when participants initiate oral contraception (Cycle 1). During Cycle 2 and 3 the PK of ethinyl estradiol (EE) and active metabolites of norgestimate (ie, norelgestromin \[NGMN\] and norgestrel \[NG\]) will be characterized following the last active dose of oral contraceptive in each cycle (cycle day 21). Erenumab will be given in cycle 3 (cycle day 10); 24-hour PK characterization of norgestimate and EE metabolites will occur 11 days after administration of erenumab, which will maximize the potential for detecting a drug-drug interaction.

Eligibility criteria: Inclusion Criteria:

* Healthy female ≥18 to ≤45 years old at the time of enrollment
* Regular monthly menstrual cycle during the last 12 months
* Good general health based on a medical history evaluation and physical examination
* No clinically significant abnormalities in laboratory tests at screening
* Subject has provided informed consent/assent prior to initiation of any study specific activities/procedures

Exclusion Criteria:

* Intolerance to any recent oral contraceptive in the last three (3) years,
* Female subjects with a positive serum pregnancy test at screening
* Female subjects not willing to inform her sexual partner of her participation in the clinical study
* Use of any over the counter or prescription medications within the 14 days or 5 half lives (whichever is longer)
* Nicotine use eg cigarettes or equivalent during 12 months prior to day 1 and through the duration of the study

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol
timeFrame: Cycle 2, day 21 and cycle 3, day 21 at predose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, and 24 hours post oral contraceptive dose.
measure: Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours Postdose (AUCtau) for Ethinyl Estradiol
timeFrame: Cycle 2, day 21 and cycle 3, day 21 at predose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, and 24 hours post oral contraceptive dose.
measure: Maximum Observed Plasma Concentration (Cmax) of Norgestrel
timeFrame: Cycle 2, day 21 and cycle 3, day 21 at predose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, and 24 hours post oral contraceptive dose.
measure: Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours Postdose (AUCtau) for Norgestrel
timeFrame: Cycle 2, day 21 and cycle 3, day 21 at predose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, and 24 hours post oral contraceptive dose.
measure: Maximum Observed Plasma Concentration (Cmax) of Norelgestromin
timeFrame: Cycle 2, day 21 and cycle 3, day 21 at predose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, and 24 hours post oral contraceptive dose.
measure: Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours Postdose (AUCtau) for Norelgestromin
timeFrame: Cycle 2, day 21 and cycle 3, day 21 at predose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, and 24 hours post oral contraceptive dose.
Secondary outcomes:
measure: Time to Reach the Maximum Concentration (Tmax) of Ethinyl Estradiol
timeFrame: Cycle 2, day 21 and cycle 3, day 21 at predose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, and 24 hours post oral contraceptive dose.
measure: Time to Reach the Maximum Concentration (Tmax) of Norgestrel
timeFrame: Cycle 2, day 21 and cycle 3, day 21 at predose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, and 24 hours post oral contraceptive dose.
measure: Time to Reach the Maximum Concentration (Tmax) of Norelgestromin
timeFrame: Cycle 2, day 21 and cycle 3, day 21 at predose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, and 24 hours post oral contraceptive dose.
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: From administration of erenumab on study day 66 through the end of the follow-up period on study day 150 (up to 84 days).
measure: Number of Participants Who Developed Anti-erenumab Binding Antibodies
timeFrame: Baseline and day 150
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Research Site
state: California
city: Cypress
country: United States
facility: Research Site
state: California
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Madison
country: United States
facility: Research Site
state: Wisconsin
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Xu Y, Gabriel K, Wang Y, Zhou Y, Eisele O, Vutikullird A, Mikol DD, Lee E. A Multi-Center, Open-Label, Pharmacokinetic Drug Interaction Study of Erenumab and a Combined Oral Contraceptive in Healthy Females. CNS Drugs. 2019 May;33(5):513-522. doi: 10.1007/s40263-019-00626-2.