Contraception, Obesity
Conditions
Keywords
obesity, body weight, BMI, emergency contraception, levonorgestrel, ulipristal acetate
Brief summary
Obese women are significantly more likely than their normal BMI counterparts to experience failure of orally-dosed emergency contraceptives. Our preliminary data provides evidence for testing a dose escalation strategy in an effort to provide improved efficacy from orally-dosed emergency contraceptives in obese women. More data is needed regarding emergency contraception containing ulipristal acetate. The overall project will be focused on both levonorgestrel (LNG) - and ulipristal acetate (UPA)-containing emergency contraception but this protocol registration is for the UPA aspect of the study procedures.
Detailed description
Emergency contraception (EC) provides a woman with an additional line of defense against unintended pregnancy following an act of unprotected intercourse. Orally-dosed EC works by delaying ovulation and reduces the risk of pregnancy for a single act of unprotected intercourse by 50-70%. Unfortunately, obese women are significantly more likely than their normal BMI counterparts to experience failure of orally-dosed EC and in some instances EC is equivalent to placebo. Our preliminary data provides evidence for testing a dose escalation strategy in an effort to provide improved efficacy from orally-dosed EC in obese women. We hypothesize that increasing the dose of orally-dosed EC agents will normalize the pharmacokinetics resulting in the expected treatment effect (delay in follicle rupture) in obese women. In the overall proposal, we plan to perform detailed pharmacokinetic and pharmacodynamic studies of UPA-based EC in obese women and expand upon our preliminary findings of LNG-based EC. This protocol registration is for the UPA aspect of the study procedures focused on the pharmacokinetics and pharmacodynamics of UPA and will include a dose escalation intervention.
Interventions
DRUGUPA-ECx1
Evaluating the pharmacodynamic and pharmacokinetic outcomes in obese women using 30mg of UPA-based EC
DRUGUPA-ECx2
Evaluating the pharmacodynamic and pharmacokinetic outcomes in obese women using 60mg of UPA-based EC
Sponsors
National Institutes of Health (NIH)
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Generally healthy women * Aged 18-35 years old * Regular menses (every 21-35 days) experiencing an ovulatory screening cycle with a progesterone level of 3 ng/mL or greater * Subjects must have a BMI of \>30kg/m2 and weight at least 80kg or more OR a BMI \<25kg/m2 and a weight of less than 80kg.
Exclusion criteria
* Metabolic disorders including uncontrolled thyroid dysfunction and Polycystic Ovarian Syndrome * Impaired liver or renal function * Actively seeking or involved in a weight loss program (must be weight stable) pregnancy, breastfeeding, or seeking pregnancy * Recent (within last 8 weeks) use of hormonal contraception * Current use of drugs that interfere with metabolism of sex steroids * Smokers.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Delay in Follicular Rupture Beyond 5 Days | 1 menstrual cycle, assessed up to 38 days | Follicular rupture (yes/no) beyond 5 days from EC dosing by ultrasound in participants with a BMI \>/=30 kg/m2. The comparison is between menstrual cycles where 30 versus 60 mg of UPA was taken. Follicular rupture is defined as the disappearance of or \>50% reduction in size of the leading follicle. The day of EC dosing is defined as day zero. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Serum Concentration of Ulipristal Acetate | 24 hours | Maximum serum concentration (Cmax) of UPA in participants with BMI \>/=30 kg/m2 with 30 mg UPA, with BMI \>/= 30 kg/m2 with 60 mg UPA, and normal BMI participants with 30mg UPA |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| UPA-ECx1 Followed by ECx2 Ulipristal acetate 30mg orally x 1 dose, washout cycle and then in the next menstrual cycle, 60mg x 1 dose. Timing of dosage depends on follicle measurements.
UPA-ECx1: Evaluating the pharmacodynamic and pharmacokinetic outcomes in obese women using 30mg of UPA-based EC
UPA-ECx2: Evaluating the pharmacodynamic and pharmacokinetic outcomes in obese women using 60mg of UPA-based EC | 25 |
| UPA-ECx2 Followed by ECx1 Ulipristal acetate 60mg orally x 1 dose, washout cycle, and then in next menstrual cycle 30mg orally x 1 dose. Timing of dosage depends on follicle measurements.
UPA-ECx1: Evaluating the pharmacodynamic and pharmacokinetic outcomes in obese women using 30mg of UPA-based EC
UPA-ECx2: Evaluating the pharmacodynamic and pharmacokinetic outcomes in obese women using 60mg of UPA-based EC | 27 |
| UPA-ECx1 Normal BMI/Weight Ulipristal acetate 30mg orally x 1 dose. timing of dosage depends on follicle measurements. This is to obtain a normal BMI control group.
UPA-ECx1: Evaluating the pharmacodynamic and pharmacokinetic outcomes in obese women using 30mg of UPA-based EC | 12 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Study drug not dosed (no dominant follicle) | 2 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 0 |
Baseline characteristics
| Characteristic | UPA-ECx1 Followed by ECx2 | UPA-ECx2 Followed by ECx1 | UPA-ECx1 Normal BMI/Weight | Total |
|---|---|---|---|---|
| Age, Continuous | 30 years STANDARD_DEVIATION 3.4 | 28.7 years STANDARD_DEVIATION 3.7 | 30 years STANDARD_DEVIATION 3.5 | 29.6 years STANDARD_DEVIATION 3.6 |
| BMI | 37.9 kg/m2 STANDARD_DEVIATION 6.7 | 39.3 kg/m2 STANDARD_DEVIATION 5.4 | 22.6 kg/m2 STANDARD_DEVIATION 1.4 | 35.2 kg/m2 STANDARD_DEVIATION 8.1 |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Black | 3 Participants | 3 Participants | 1 Participants | 7 Participants |
| Race/Ethnicity, Customized Declined to specify | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 2 Participants | 5 Participants | 0 Participants | 7 Participants |
| Race/Ethnicity, Customized Not Hispanic/Latino | 23 Participants | 22 Participants | 12 Participants | 57 Participants |
| Race/Ethnicity, Customized White | 20 Participants | 24 Participants | 9 Participants | 53 Participants |
| Region of Enrollment United States | 25 participants | 27 participants | 12 participants | 64 participants |
| Sex: Female, Male Female | 25 Participants | 27 Participants | 12 Participants | 64 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 46 | 0 / 12 |
| other Total, other adverse events | 0 / 49 | 0 / 46 | 0 / 12 |
| serious Total, serious adverse events | 0 / 49 | 0 / 46 | 0 / 12 |
Outcome results
Primary
Number of Participants With Delay in Follicular Rupture Beyond 5 Days
Follicular rupture (yes/no) beyond 5 days from EC dosing by ultrasound in participants with a BMI \>/=30 kg/m2. The comparison is between menstrual cycles where 30 versus 60 mg of UPA was taken. Follicular rupture is defined as the disappearance of or \>50% reduction in size of the leading follicle. The day of EC dosing is defined as day zero.
Time frame: 1 menstrual cycle, assessed up to 38 days
Population: The total analyzed number is the menstrual cycle of the participant with a BMI \>/=30kg/m2 when dosed with ECx1 or ECx2 who experienced a delay in follicular rupture beyond 5 days after dosing EC.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ECx1 BMI>/=30kg/m2 | Number of Participants With Delay in Follicular Rupture Beyond 5 Days | 46 Participants |
| ECx2 BMI >/=30 | Number of Participants With Delay in Follicular Rupture Beyond 5 Days | 43 Participants |
| ECx1 BMI <25kg/m2 | Number of Participants With Delay in Follicular Rupture Beyond 5 Days | 12 Participants |
Secondary
Maximum Serum Concentration of Ulipristal Acetate
Maximum serum concentration (Cmax) of UPA in participants with BMI \>/=30 kg/m2 with 30 mg UPA, with BMI \>/= 30 kg/m2 with 60 mg UPA, and normal BMI participants with 30mg UPA
Time frame: 24 hours
Population: This was a voluntary aspect of the protocol so data were only collected on a subset of the sample.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ECx1 BMI>/=30kg/m2 | Maximum Serum Concentration of Ulipristal Acetate | 197.1 ng/mL | Standard Deviation 118.5 |
| ECx2 BMI >/=30 | Maximum Serum Concentration of Ulipristal Acetate | 312.4 ng/mL | Standard Deviation 215.3 |
| ECx1 BMI <25kg/m2 | Maximum Serum Concentration of Ulipristal Acetate | 98.4 ng/mL | Standard Deviation 40.7 |