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

Headache, Migraine Clinical Trial

Official title:

A Multi-Center, Open-label, Pharmacokinetic Drug Interaction Study of AMG 334 and a Combined Oral Contraceptive in Healthy Female Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02792517
• Other study ID #: 20150334
• Status: Completed
• Phase: Phase 1
• Start date: February 12, 2016
• Est. completion date: September 9, 2016

Study information

• Verified date: May 2018
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: September 9, 2016
• Est. primary completion date: September 9, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Headache
• Headache, Migraine
• Migraine Disorders

Intervention

Drug:
• Erenumab
A single dose of erenumab administered in the abdomen.
• Ethynil Estradiol/Norgestimate Oral Contraceptive
Ethynil estradiol (EE)/norgestimate combination oral contraceptive is a 28-tablet cycle in which 1 oral tablet is taken daily; each containing 0.250 mg norgestimate and 0.035 mg EE for 21 days, after which a tablet only containing inert ingredients is taken for last 7 days of the 28 day cycle.

Locations

Country	Name	City	State
United States	Research Site	Anaheim	California
United States	Research Site	Cypress	California
United States	Research Site	Dallas	Texas
United States	Research Site	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol	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.	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.
Primary	Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours Postdose (AUCtau) for Ethinyl Estradiol	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.	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.
Primary	Maximum Observed Plasma Concentration (Cmax) of Norgestrel	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.	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.
Primary	Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours Postdose (AUCtau) for Norgestrel	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.	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.
Primary	Maximum Observed Plasma Concentration (Cmax) of Norelgestromin	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.	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.
Primary	Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours Postdose (AUCtau) for Norelgestromin	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.	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	Time to Reach the Maximum Concentration (Tmax) of Ethinyl Estradiol	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.	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	Time to Reach the Maximum Concentration (Tmax) of Norgestrel	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.	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	Time to Reach the Maximum Concentration (Tmax) of Norelgestromin	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.	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	Number of Participants With Treatment-emergent Adverse Events	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.	From administration of erenumab on study day 66 through the end of the follow-up period on study day 150 (up to 84 days).
Secondary	Number of Participants Who Developed Anti-erenumab Binding Antibodies	Blood samples were assessed for anti-erenumab binding antibodies. Samples testing positive for binding antibodies were also tested for neutralizing antibodies.	Baseline and day 150

External Links

•   AmgenTrials clinical trials website