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A pharmacokinetic drug interaction study of erenumab and an oral contraceptive containing progestin and estrogen.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Erenumab + Estrogen/Progestin Contraceptive | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Erenumab | Drug | A single dose of erenumab administered in the abdomen. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Anaheim | California | 92801 | United States | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30963506 | Derived | 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. |
| Label | URL |
|---|---|
| AmgenTrials clinical trials website | View source |
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This study was conducted at 3 centers in the United States of America. Participants were enrolled from 12 February 2016 to 15 April 2016.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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All participants who received at least one dose of study drug (erenumab).
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Mean | Standard Deviation | pg/mL | 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. |
|
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Amgen Inc. | 866-572-6436 |
Not provided
| ID | Term |
|---|---|
| D008881 | Migraine Disorders |
| ID | Term |
|---|---|
| D051270 | Headache Disorders, Primary |
| D020773 | Headache Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| C000605816 | erenumab |
| D000077266 | Moxifloxacin |
| ID | Term |
|---|---|
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
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| Ethynil Estradiol/Norgestimate Oral Contraceptive | Drug | 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. |
|
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| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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 |
| Cypress |
| California |
| 90630 |
| United States |
| Research Site | Dallas | Texas | 75247 | United States |
| Research Site | Madison | Wisconsin | 53704 | United States |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
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| 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. | 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. | Posted | Mean | Standard Deviation | pg/mL*hr | 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. |
|
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|
| 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. | 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. | Posted | Mean | Standard Deviation | pg/mL | 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. |
|
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| 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. | 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. | Posted | Mean | Standard Deviation | pg/mL*hr | 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. |
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| 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. | 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. | Posted | Mean | Standard Deviation | pg/mL | 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. |
|
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| 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. | 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. | Posted | Mean | Standard Deviation | pg/mL*hr | 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. |
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| 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. | 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. | Posted | Median | Full Range | hours | 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. | 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. | Posted | Median | Full Range | hours | 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. | 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. | Posted | Median | Full Range | hours | 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. |
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| 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. | The safety analysis set consisted of all participants who received at least one dose of study drug (erenumab). | Posted | Count of Participants | Participants | From administration of erenumab on study day 66 through the end of the follow-up period on study day 150 (up to 84 days). |
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| 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. | The safety analysis set consisted of all participants who received at least one dose of study drug (erenumab). | Posted | Count of Participants | Participants | Baseline and day 150 |
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|
| 0 |
| 24 |
| 13 |
| 24 |
| Fatigue | General disorders | MedDRA 19.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Migraine | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Breast pain | Reproductive system and breast disorders | MedDRA 19.0 | Systematic Assessment |
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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.
| D009422 | Nervous System Diseases |
| D006574 |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Title | Measurements |
|---|---|
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| Treatment-related adverse events |
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| Treatment-related serious adverse events |
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| Device-related adverse events |
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| Device-related serious adverse events |
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