Erenumab (AMG 334) Plus Combined Oral Contraceptive Drug Interaction Study in Healthy Females

Phase 1

Completed

• Conditions: Headache, Migraine
• Interventions: Drug: Erenumab; Drug: Ethynil Estradiol/Norgestimate Oral Contraceptive

• Registration Number: NCT02792517
• Lead Sponsor: Amgen

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.

Study Timeline

• Study Start: 2016-02-12
• Study First Submitted: 2016-02-23
• Study First Submitted QC: 2016-06-02
• Study First Posted: 2016-06-07
• Primary Completion: 2016-09-09
• Study Completion: 2016-09-09
• Status Verified: 2018-05
• Results First Submitted: 2018-06-06
• Results First Submitted QC: 2018-06-06
• Last Update Submitted: 2018-06-06
• Results First Posted: 2018-12-20
• Last Update Posted: 2018-12-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 41

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Erenumab + Estrogen/Progestin Contraceptive	Ethynil Estradiol/Norgestimate Oral Contraceptive	Participants received a combination oral contraceptive for 3 28-day cycles during the study. A single 140 mg dose of erenumab was administered subcutaneously to the abdomen on day 10 of cycle 3 by a healthcare provider.
Erenumab + Estrogen/Progestin Contraceptive	Erenumab	Participants received a combination oral contraceptive for 3 28-day cycles during the study. A single 140 mg dose of erenumab was administered subcutaneously to the abdomen on day 10 of cycle 3 by a healthcare provider.

Primary Outcome Measures

Name	Time	Method
Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours Postdose (AUCtau) for Norelgestromin	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.	The pharmacokinetics of norelgestromin (NGMN), an active metabolite of norgestimate, were characterized during cycle 2 following the last active dose of oral contraceptive in the cycle (cycle day 21) without erenumab, and during cycle 3 following the last active dose of oral contraceptive in the cycle (cycle day 21), 11 days after a single dose of erenumab.
Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol	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.	The pharmacokinetics of ethinyl estradiol (EE) were characterized during cycle 2 following the last active dose of oral contraceptive in the cycle (cycle day 21) without erenumab, and during cycle 3 following the last active dose of oral contraceptive in the cycle (cycle day 21), 11 days after a single dose of erenumab.
Maximum Observed Plasma Concentration (Cmax) of Norgestrel	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.	The pharmacokinetics of norgestrel (NG), an active metabolite of norgestimate, were characterized during cycle 2 following the last active dose of oral contraceptive in the cycle (cycle day 21) without erenumab, and during cycle 3 following the last active dose of oral contraceptive in the cycle (cycle day 21), 11 days after a single dose of erenumab.
Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours Postdose (AUCtau) for Ethinyl Estradiol	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.	The pharmacokinetics of ethinyl estradiol (EE) were characterized during cycle 2 following the last active dose of oral contraceptive in the cycle (cycle day 21) without erenumab, and during cycle 3 following the last active dose of oral contraceptive in the cycle (cycle day 21), 11 days after a single dose of erenumab.
Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours Postdose (AUCtau) for Norgestrel	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.	The pharmacokinetics of norgestrel (NG), an active metabolite of norgestimate, were characterized during cycle 2 following the last active dose of oral contraceptive in the cycle (cycle day 21) without erenumab, and during cycle 3 following the last active dose of oral contraceptive in the cycle (cycle day 21), 11 days after a single dose of erenumab.
Maximum Observed Plasma Concentration (Cmax) of Norelgestromin	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.	The pharmacokinetics of norelgestromin (NGMN), an active metabolite of norgestimate, were characterized during cycle 2 following the last active dose of oral contraceptive in the cycle (cycle day 21) without erenumab, and during cycle 3 following the last active dose of oral contraceptive in the cycle (cycle day 21), 11 days after a single dose of erenumab.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-emergent Adverse Events	From administration of erenumab on study day 66 through the end of the follow-up period on study day 150 (up to 84 days).	A treatment-related adverse event (AE) is any treatment-emergent AE that per investigator review has a reasonable possibility of being caused by the study drug.; A device-related AE is any treatment-emergent AE that per investigator review has a reasonable possibility of being caused by the device (prefilled syringe) used to administer study drug.
Time to Reach the Maximum Concentration (Tmax) of Ethinyl Estradiol	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.	The pharmacokinetics of ethinyl estradiol (EE) were characterized during cycle 2 following the last active dose of oral contraceptive in the cycle (cycle day 21) without erenumab, and during cycle 3 following the last active dose of oral contraceptive in the cycle (cycle day 21), 11 days after a single dose of erenumab.
Time to Reach the Maximum Concentration (Tmax) of Norgestrel	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.	The pharmacokinetics of norgestrel (NG), an active metabolite of norgestimate, were characterized during cycle 2 following the last active dose of oral contraceptive in the cycle (cycle day 21) without erenumab, and during cycle 3 following the last active dose of oral contraceptive in the cycle (cycle day 21), 11 days after a single dose of erenumab.
Time to Reach the Maximum Concentration (Tmax) of Norelgestromin	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.	The pharmacokinetics of norelgestromin (NGMN), an active metabolite of norgestimate, were characterized during cycle 2 following the last active dose of oral contraceptive in the cycle (cycle day 21) without erenumab, and during cycle 3 following the last active dose of oral contraceptive in the cycle (cycle day 21), 11 days after a single dose of erenumab.
Number of Participants Who Developed Anti-erenumab Binding Antibodies	Baseline and day 150	Blood samples were assessed for anti-erenumab binding antibodies. Samples testing positive for binding antibodies were also tested for neutralizing antibodies.

Trial Locations

Locations (1)

Research Site; 🇺🇸 Madison, Wisconsin, United States