Trial Outcomes & Findings for Erenumab (AMG 334) Plus Combined Oral Contraceptive Drug Interaction Study in Healthy Females (NCT NCT02792517)
NCT ID: NCT02792517
Last Updated: 2018-12-20
Results Overview
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.
COMPLETED
PHASE1
41 participants
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.
2018-12-20
Participant Flow
This study was conducted at 3 centers in the United States of America. Participants were enrolled from 12 February 2016 to 15 April 2016.
Participant milestones
| Measure |
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.
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|---|---|
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Overall Study
STARTED
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41
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Overall Study
Received Erenumab
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24
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Overall Study
COMPLETED
|
21
|
|
Overall Study
NOT COMPLETED
|
20
|
Reasons for withdrawal
| Measure |
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.
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|---|---|
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Overall Study
Withdrawal by Subject
|
10
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Overall Study
Decision by Sponsor
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7
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Overall Study
Lost to Follow-up
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3
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Baseline Characteristics
Erenumab (AMG 334) Plus Combined Oral Contraceptive Drug Interaction Study in Healthy Females
Baseline characteristics by cohort
| Measure |
Erenumab 140 mg + Estrogen/Progestin Contraceptive
n=24 Participants
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.
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|---|---|
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Age, Continuous
|
33.4 years
STANDARD_DEVIATION 6.9 • n=5 Participants
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Sex: Female, Male
Female
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24 Participants
n=5 Participants
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Sex: Female, Male
Male
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0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
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2 Participants
n=5 Participants
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|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
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22 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
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Race/Ethnicity, Customized
Asian
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10 Participants
n=5 Participants
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Race/Ethnicity, Customized
Black (or African American)
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6 Participants
n=5 Participants
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Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
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1 Participants
n=5 Participants
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Race/Ethnicity, Customized
White
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7 Participants
n=5 Participants
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PRIMARY outcome
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.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.
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.
Outcome measures
| Measure |
Erenumab 140 mg + Estrogen/Progestin Contraceptive
n=25 Participants
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.
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|---|---|
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Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol
Cycle 2 (EE/norgestimate alone)
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132 pg/mL
Standard Deviation 46.3
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Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol
Cycle 3 (EE/norgestimate with erenumab)
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143 pg/mL
Standard Deviation 64.5
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PRIMARY outcome
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.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.
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.
Outcome measures
| Measure |
Erenumab 140 mg + Estrogen/Progestin Contraceptive
n=25 Participants
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.
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|---|---|
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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
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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
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PRIMARY outcome
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.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.
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.
Outcome measures
| Measure |
Erenumab 140 mg + Estrogen/Progestin Contraceptive
n=25 Participants
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.
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|---|---|
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Maximum Observed Plasma Concentration (Cmax) of Norgestrel
Cycle 2 (EE/norgestimate alone)
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2690 pg/mL
Standard Deviation 887
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Maximum Observed Plasma Concentration (Cmax) of Norgestrel
Cycle 3 (EE/norgestimate with erenumab)
|
2860 pg/mL
Standard Deviation 927
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PRIMARY outcome
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.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.
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.
Outcome measures
| Measure |
Erenumab 140 mg + Estrogen/Progestin Contraceptive
n=25 Participants
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.
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|---|---|
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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
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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
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PRIMARY outcome
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.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.
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.
Outcome measures
| Measure |
Erenumab 140 mg + Estrogen/Progestin Contraceptive
n=25 Participants
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.
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|---|---|
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Maximum Observed Plasma Concentration (Cmax) of Norelgestromin
Cycle 2 (EE/norgestimate alone)
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1800 pg/mL
Standard Deviation 641
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Maximum Observed Plasma Concentration (Cmax) of Norelgestromin
Cycle 3 (EE/norgestimate with erenumab)
|
1870 pg/mL
Standard Deviation 553
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PRIMARY outcome
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.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.
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.
Outcome measures
| Measure |
Erenumab 140 mg + Estrogen/Progestin Contraceptive
n=25 Participants
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.
|
|---|---|
|
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
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|
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
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SECONDARY outcome
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.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.
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.
Outcome measures
| Measure |
Erenumab 140 mg + Estrogen/Progestin Contraceptive
n=25 Participants
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.
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|---|---|
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Time to Reach the Maximum Concentration (Tmax) of Ethinyl Estradiol
Cycle 2 (EE/norgestimate alone)
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1.0 hours
Interval 1.0 to 2.0
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Time to Reach the Maximum Concentration (Tmax) of Ethinyl Estradiol
Cycle 3 (EE/norgestimate with erenumab)
|
1.0 hours
Interval 1.0 to 1.8
|
SECONDARY outcome
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.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.
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.
Outcome measures
| Measure |
Erenumab 140 mg + Estrogen/Progestin Contraceptive
n=25 Participants
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.
|
|---|---|
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Time to Reach the Maximum Concentration (Tmax) of Norgestrel
Cycle 2 (EE/norgestimate alone)
|
1.5 hours
Interval 0.5 to 6.0
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Time to Reach the Maximum Concentration (Tmax) of Norgestrel
Cycle 3 (EE/norgestimate with erenumab)
|
1.5 hours
Interval 1.0 to 6.0
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SECONDARY outcome
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.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.
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.
Outcome measures
| Measure |
Erenumab 140 mg + Estrogen/Progestin Contraceptive
n=25 Participants
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.
|
|---|---|
|
Time to Reach the Maximum Concentration (Tmax) of Norelgestromin
Cycle 2 (EE/norgestimate alone)
|
1.0 hours
Interval 0.5 to 4.0
|
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Time to Reach the Maximum Concentration (Tmax) of Norelgestromin
Cycle 3 (EE/norgestimate with erenumab)
|
1.0 hours
Interval 0.5 to 4.0
|
SECONDARY outcome
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).Population: The safety analysis set consisted of all participants who received at least one dose of study drug (erenumab).
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.
Outcome measures
| Measure |
Erenumab 140 mg + Estrogen/Progestin Contraceptive
n=24 Participants
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.
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|---|---|
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Number of Participants With Treatment-emergent Adverse Events
All treatment-emergent adverse events
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17 Participants
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Number of Participants With Treatment-emergent Adverse Events
Serious adverse events
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0 Participants
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Number of Participants With Treatment-emergent Adverse Events
Fatal adverse events
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0 Participants
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Number of Participants With Treatment-emergent Adverse Events
Treatment-related adverse events
|
2 Participants
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Number of Participants With Treatment-emergent Adverse Events
Treatment-related serious adverse events
|
0 Participants
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Number of Participants With Treatment-emergent Adverse Events
Device-related adverse events
|
1 Participants
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Number of Participants With Treatment-emergent Adverse Events
Device-related serious adverse events
|
0 Participants
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SECONDARY outcome
Timeframe: Baseline and day 150Population: The safety analysis set consisted of all participants who received at least one dose of study drug (erenumab).
Blood samples were assessed for anti-erenumab binding antibodies. Samples testing positive for binding antibodies were also tested for neutralizing antibodies.
Outcome measures
| Measure |
Erenumab 140 mg + Estrogen/Progestin Contraceptive
n=24 Participants
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.
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|---|---|
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Number of Participants Who Developed Anti-erenumab Binding Antibodies
Binding antibody positive
|
2 Participants
|
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Number of Participants Who Developed Anti-erenumab Binding Antibodies
Neutralizing antibody positive
|
1 Participants
|
Adverse Events
Erenumab 140 mg + Estrogen/Progestin Contraceptive
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Erenumab 140 mg + Estrogen/Progestin Contraceptive
n=24 participants at risk
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.
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|---|---|
|
Gastrointestinal disorders
Nausea
|
20.8%
5/24 • From administration of erenumab on study day 66 through the end of the follow-up period on study day 150 (up to 84 days).
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
General disorders
Fatigue
|
12.5%
3/24 • From administration of erenumab on study day 66 through the end of the follow-up period on study day 150 (up to 84 days).
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Infections and infestations
Upper respiratory tract infection
|
16.7%
4/24 • From administration of erenumab on study day 66 through the end of the follow-up period on study day 150 (up to 84 days).
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Nervous system disorders
Headache
|
33.3%
8/24 • From administration of erenumab on study day 66 through the end of the follow-up period on study day 150 (up to 84 days).
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Nervous system disorders
Migraine
|
8.3%
2/24 • From administration of erenumab on study day 66 through the end of the follow-up period on study day 150 (up to 84 days).
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Reproductive system and breast disorders
Breast pain
|
8.3%
2/24 • From administration of erenumab on study day 66 through the end of the follow-up period on study day 150 (up to 84 days).
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
Additional Information
Study Director
Amgen Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
- Publication restrictions are in place
Restriction type: OTHER