Headache, Migraine
Conditions
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.
Interventions
DRUGErenumab
A single dose of erenumab administered in the abdomen.
DRUGEthynil 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.
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 3 centers in the United States of America. Participants were enrolled from 12 February 2016 to 15 April 2016.
Participants by arm
| Arm | Count |
|---|---|
| Erenumab 140 mg + Estrogen/Progestin Contraceptive Participants received a combination oral contraceptive for three 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. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Decision by Sponsor | 7 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Withdrawal by Subject | 10 |
Baseline characteristics
| Characteristic | Erenumab 140 mg + Estrogen/Progestin Contraceptive |
|---|---|
| Age, Continuous | 33.4 years STANDARD_DEVIATION 6.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Asian | 10 Participants |
| Race/Ethnicity, Customized Black (or African American) | 6 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized White | 7 Participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 13 / 24 |
| serious Total, serious adverse events | 0 / 24 |
Outcome results
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.
Time frame: 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.
Population: The pharmacokinetic (PK) analysis set included all participants for whom at least 1 EE, NGMN, and NG PK parameter or endpoint could be adequately estimated. Data are reported for participants with observations at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours Postdose (AUCtau) for Ethinyl Estradiol | Cycle 2 (EE/norgestimate alone) | 1010 pg/mL*hr | Standard Deviation 367 |
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours Postdose (AUCtau) for Ethinyl Estradiol | Cycle 3 (EE/norgestimate with erenumab) | 1060 pg/mL*hr | Standard Deviation 508 |
Comparison: The log-transformed AUCtau was analyzed using a linear mixed effects model with treatment as a fixed effect and subject as a random effect.90% CI: [0.91, 1.14]
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.
Time frame: 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.
Population: The pharmacokinetic (PK) analysis set included all participants for whom at least 1 EE, NGMN, and NG PK parameter or endpoint could be adequately estimated. Data are reported for participants with observations at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours Postdose (AUCtau) for Norelgestromin | Cycle 2 (EE/norgestimate alone) | 16800 pg/mL*hr | Standard Deviation 5120 |
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours Postdose (AUCtau) for Norelgestromin | Cycle 3 (EE/norgestimate with erenumab) | 16900 pg/mL*hr | Standard Deviation 4200 |
Comparison: The log-transformed AUCtau was analyzed using a linear mixed effects model with treatment as a fixed effect and subject as a random effect.90% CI: [0.94, 1.12]
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.
Time frame: 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.
Population: The pharmacokinetic (PK) analysis set included all participants for whom at least 1 EE, NGMN, and NG PK parameter or endpoint could be adequately estimated. Data are reported for participants with observations at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours Postdose (AUCtau) for Norgestrel | Cycle 2 (EE/norgestimate alone) | 50700 pg/mL*hr | Standard Deviation 17400 |
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours Postdose (AUCtau) for Norgestrel | Cycle 3 (EE/norgestimate with erenumab) | 52400 pg/mL*hr | Standard Deviation 17400 |
Comparison: The log-transformed AUCtau was analyzed using a linear mixed effects model with treatment as a fixed effect and subject as a random effect.90% CI: [0.96, 1.1]
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.
Time frame: 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.
Population: The pharmacokinetic (PK) analysis set included all participants for whom at least 1 EE, NGMN, and NG PK parameter or endpoint could be adequately estimated. Data are reported for participants with observations at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol | Cycle 2 (EE/norgestimate alone) | 132 pg/mL | Standard Deviation 46.3 |
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol | Cycle 3 (EE/norgestimate with erenumab) | 143 pg/mL | Standard Deviation 64.5 |
Comparison: The log-transformed Cmax was analyzed using a linear mixed effects model with treatment as a fixed effect and subject as a random effect.90% CI: [0.88, 1.22]
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.
Time frame: 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.
Population: The pharmacokinetic (PK) analysis set included all participants for whom at least 1 EE, NGMN, and NG PK parameter or endpoint could be adequately estimated. Data are reported for participants with observations at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Maximum Observed Plasma Concentration (Cmax) of Norelgestromin | Cycle 2 (EE/norgestimate alone) | 1800 pg/mL | Standard Deviation 641 |
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Maximum Observed Plasma Concentration (Cmax) of Norelgestromin | Cycle 3 (EE/norgestimate with erenumab) | 1870 pg/mL | Standard Deviation 553 |
Comparison: The log-transformed Cmax was analyzed using a linear mixed effects model with treatment as a fixed effect and subject as a random effect.90% CI: [0.9, 1.23]
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.
Time frame: 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.
Population: The pharmacokinetic (PK) analysis set included all participants for whom at least 1 EE, NGMN, and NG PK parameter or endpoint could be adequately estimated. Data are reported for participants with observations at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Maximum Observed Plasma Concentration (Cmax) of Norgestrel | Cycle 2 (EE/norgestimate alone) | 2690 pg/mL | Standard Deviation 887 |
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Maximum Observed Plasma Concentration (Cmax) of Norgestrel | Cycle 3 (EE/norgestimate with erenumab) | 2860 pg/mL | Standard Deviation 927 |
Comparison: The log-transformed Cmax was analyzed using a linear mixed effects model with treatment as a fixed effect and subject as a random effect.90% CI: [0.97, 1.16]
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.
Time frame: Baseline and day 150
Population: The safety analysis set consisted of all participants who received at least one dose of study drug (erenumab).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Number of Participants Who Developed Anti-erenumab Binding Antibodies | Binding antibody positive | 2 Participants |
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Number of Participants Who Developed Anti-erenumab Binding Antibodies | Neutralizing antibody positive | 1 Participants |
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.
Time frame: From administration of erenumab on study day 66 through the end of the follow-up period on study day 150 (up to 84 days).
Population: The safety analysis set consisted of all participants who received at least one dose of study drug (erenumab).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Number of Participants With Treatment-emergent Adverse Events | All treatment-emergent adverse events | 17 Participants |
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events | 0 Participants |
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Number of Participants With Treatment-emergent Adverse Events | Fatal adverse events | 0 Participants |
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Number of Participants With Treatment-emergent Adverse Events | Treatment-related adverse events | 2 Participants |
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Number of Participants With Treatment-emergent Adverse Events | Treatment-related serious adverse events | 0 Participants |
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Number of Participants With Treatment-emergent Adverse Events | Device-related adverse events | 1 Participants |
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Number of Participants With Treatment-emergent Adverse Events | Device-related serious adverse events | 0 Participants |
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.
Time frame: 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.
Population: The pharmacokinetic (PK) analysis set included all participants for whom at least 1 EE, NGMN, and NG PK parameter or endpoint could be adequately estimated. Data are reported for participants with observations at each time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Time to Reach the Maximum Concentration (Tmax) of Ethinyl Estradiol | Cycle 2 (EE/norgestimate alone) | 1.0 hours |
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Time to Reach the Maximum Concentration (Tmax) of Ethinyl Estradiol | Cycle 3 (EE/norgestimate with erenumab) | 1.0 hours |
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.
Time frame: 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.
Population: The pharmacokinetic (PK) analysis set included all participants for whom at least 1 EE, NGMN, and NG PK parameter or endpoint could be adequately estimated. Data are reported for participants with observations at each time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Time to Reach the Maximum Concentration (Tmax) of Norelgestromin | Cycle 2 (EE/norgestimate alone) | 1.0 hours |
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Time to Reach the Maximum Concentration (Tmax) of Norelgestromin | Cycle 3 (EE/norgestimate with erenumab) | 1.0 hours |
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.
Time frame: 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.
Population: The pharmacokinetic (PK) analysis set included all participants for whom at least 1 EE, NGMN, and NG PK parameter or endpoint could be adequately estimated. Data are reported for participants with observations at each time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Time to Reach the Maximum Concentration (Tmax) of Norgestrel | Cycle 2 (EE/norgestimate alone) | 1.5 hours |
| Erenumab 140 mg + Estrogen/Progestin Contraceptive | Time to Reach the Maximum Concentration (Tmax) of Norgestrel | Cycle 3 (EE/norgestimate with erenumab) | 1.5 hours |