Contraception, Migraine, Migraine;Menstrual
Conditions
Brief summary
A prospective, non-inferiority study to evaluate the pharmacokinetic effect of topiramate on serum Etonogestrel (ENG) levels in contraceptive implant users.
Interventions
DRUGTopiramate
Topiramate - Participants will undergo a 6 week titrated regimen of oral topiramate to reach a maximum dose of 400mg per day: Week 1 - topiramate PO 25mg daily Week 2 - topiramate PO 25mg twice daily Week 3 - topiramate PO 50mg twice daily Week 4 - topiramate PO 100mg twice daily Week 5 - topiramate PO 150mg twice daily Week 6 - topiramate PO 200mg twice daily
Sponsors
Merck Sharp & Dohme LLC
University of Colorado, Denver
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective, non-inferiority study to evaluate the pharmacokinetic effect of topiramate on serum ENG levels in contraceptive implant users
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy women, who have had an ENG implant for 12-36 months at the time of enrollment; * Will maintain their implant during the study without modifications.
Exclusion criteria
* Women who are taking any medications or supplements known to be 1. Cytochrome P-450 enzyme inducers, inhibitors, or substrates, and 2. are not willing to abstain from any of these medications or supplements during the entire course of the study. * Women with liver disease (i.e. hepatitis, fatty liver disease), and * Women with abnormal liver or renal function, or * Women with abnormal electrolytes on their screening blood work.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Etonogestrel Concentrations | Enrollment (Baseline), 4 weeks (Visit 2), 5 weeks (Visit 3), 6 weeks (Visit 4) | The investigators will collect serum from participants at enrollment and at each of the three study follow-up visits. All samples will be batched for analysis. Analysis will be performed using a liquid-chromatography mass-spectrometry validated assay for measurement of serum etonogestrel concentration. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ENG Implant Users Healthy women using an ENG implant for at least 12 months and no greater than 36 months will be administered a 6 week titration schedule of topiramate to a max dose of 200mg bid by the final week.
Topiramate: Topiramate - Participants will undergo a 6 week titrated regimen of oral topiramate to reach a maximum dose of 400mg per day:
Week 1 - topiramate PO 25mg daily Week 2 - topiramate PO 25mg twice daily Week 3 - topiramate PO 50mg twice daily Week 4 - topiramate PO 100mg twice daily Week 5 - topiramate PO 150mg twice daily Week 6 - topiramate PO 200mg twice daily | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Not eligible due to laboratory criteria | 3 |
| Overall Study | Withdrawal by Subject | 18 |
Baseline characteristics
| Characteristic | ENG Implant Users |
|---|---|
| Age, Continuous | 25.3 years |
| Body-mass index | 25.5 kg/m^2 |
| Duration of implant use | 24 months |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Region of Enrollment United States | 32 participants |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 32 |
| other Total, other adverse events | 0 / 32 |
| serious Total, serious adverse events | 0 / 32 |
Outcome results
Primary
Serum Etonogestrel Concentrations
The investigators will collect serum from participants at enrollment and at each of the three study follow-up visits. All samples will be batched for analysis. Analysis will be performed using a liquid-chromatography mass-spectrometry validated assay for measurement of serum etonogestrel concentration.
Time frame: Enrollment (Baseline), 4 weeks (Visit 2), 5 weeks (Visit 3), 6 weeks (Visit 4)
Population: Due to early discontinuation from the study, data are available for only 31 participants for Visit 3 and 27 participants for Visit 4.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| ENG Implant Users | Serum Etonogestrel Concentrations | Visit 2 | 126.0 pg/mL |
| ENG Implant Users | Serum Etonogestrel Concentrations | Visit 3 | 119.0 pg/mL |
| ENG Implant Users | Serum Etonogestrel Concentrations | Baseline | 142.0 pg/mL |
| ENG Implant Users | Serum Etonogestrel Concentrations | Visit 4 | 105.0 pg/mL |