Clinical trial NCT02456584: Pharmacodynamics and Pharmacokinetics Study of Existing DMPA Contraceptive Methods
Official title: Pharmacodynamics (Suppression of Ovulation) and Pharmacokinetics Following a Single Subcutaneous Administration of Depo Provera® CI 150 mg/mL, Depo Provera® CI 300 mg/2 mL, or During Two Cycles of Depo-subQ Provera 104®
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Contraception
Keywords: depot medroxyprogesterone acetate (DMPA)
confidence interval (CI)
Subcutaneous (sub-Q)
Intrauterine device (IUD)
Levonorgestrel (LNG)
intrauterine system (IUS)
Lead sponsor: FHI 360
Sponsor class: OTHER
Collaborators: name: Oregon Health and Science University
name: Asociación Dominicana Pro Bienestar de la Familia, Inc.
First posted: 2015-05-28
Enrollment: 42
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a randomized, multi-center, parallel-group Phase I study to evaluate the pharmacodynamics (PD) of Medroxyprogesterone Acetate (MPA) after a single subcutaneous (SC) injection of 150 mg/mL or 300 mg/2 mL Depo-Provera CI in the abdomen of women of reproductive age with a confirmed ovulatory baseline cycle.

Detailed description: This is a randomized, multi-center, parallel-group Phase I study with a primary objective to evaluate the pharmacodynamics (PD) of Medroxyprogesterone Acetate (MPA) after a single subcutaneous (SC) injection of 150mg/mL or 300mg/2mL Depo-Provera CI in the abdomen of women of reproductive age with a confirmed ovulatory baseline cycle.

Secondary study objectives are:

* To evaluate and compare the pharmacokinetics (PK) of MPA after a single SC injection of 150mg/mL or 300mg/2mL of Depo-Provera CI to two injections of Depo-subQ 104 administered 3 months apart
* To evaluate the relationship between serum MPA concentration and suppression of ovulation
* To evaluate and compare the safety, tolerability and acceptability of a SC injection of DMPA of different frequencies, doses and volumes

Eligibility criteria: inclusion

Women may be included in the study if they meet all of the following criteria:

* in good general health
* age 18 to 40 years, inclusive
* willing to provide informed consent and follow all study requirements
* not pregnant
* does not desire to become pregnant in the next 24 months
* regular menstrual cycle (24 to 35 days)
* confirmed ovulation by serum P ≥ 4.7 ng/mL in two consecutive samples during the pre-treatment phase of the study
* at low risk of pregnancy (e.g., sterilized, in exclusively same sex partnership, in monogamous relationship with vasectomized partner, abstinent, using non-hormonal IUD or condoms)
* has a body mass index of 18.0 to 35.0
* has hemoglobin ≥10.5 g/L

exclusion

Women will be excluded from participating in this study if they meet any of the following criteria:

* medical contraindications to DMPA use
* use of any of the following medications within 1 month prior to enrollment:

  * any investigational drug
  * prohibited drugs (per protocol)
  * oral contraceptives
  * LNG IUS or implant
* use of DMPA in the past 12 months
* use of a combined injectable contraceptive in the past 6 months
* recent pregnancy (within 3 months)
* current lactation
* ongoing or anticipated use of prohibited drugs (per protocol)
* known sensitivity to MPA
* plan to move to another location in the next 18 months
* any condition (social or medical) which in the opinion of the site investigator would make study participation unsafe, would interfere with adherence to study requirements or complicate data interpretation.

Primary outcomes:
measure: Measure of time to ovulation
timeFrame: up to 18 months
Secondary outcomes:
measure: Cmax
timeFrame: up to 18 months
measure: Aggregate of individual Cmax measurements and parameters
timeFrame: up to 18 months
measure: Type and frequency of adverse events
timeFrame: up to 18 months
measure: Blood pressure at follow up
timeFrame: up to 18 months
measure: Pulse at follow up
timeFrame: up to 18 months
measure: Weight at follow up
timeFrame: up to 18 months
measure: Measure of delayed return to ovulation
timeFrame: up to 18 months
measure: Serum concentrations of cortisol
timeFrame: 7.5 months
measure: Number of participants with Injection site reactions
timeFrame: up to 18 months
measure: Product acceptability
timeFrame: up to 18 months
measure: Tmax
timeFrame: up to 18 months
measure: Aggregate of individual Tmax measurements and parameters
timeFrame: Up to 18 months
measure: MPA concentration at Day 91 (C91)
timeFrame: 91 days after injection
measure: Aggregate of individual C91 measurements and parameters
timeFrame: 18 months after injection
measure: MPA concentration at Day 182 (C182)
timeFrame: 182 days after injection
measure: Aggregate of individual C182 measurements and parameters
timeFrame: 18 months after injection
measure: MPA concentration at Day 210 (C210)
timeFrame: 210 days after injection
measure: Aggregate of individual C210 measurements and parameters
timeFrame: 18 months after injection
measure: Area under the curve (AUC 0-182)
timeFrame: 182 days after injection
measure: Terminal elimination half-life (t1/2)
timeFrame: up to 18 months
Other outcomes:
Locations:
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Santo Domingo
country: Dominican Republic
facility: Asociación Dominicana Pro Bienestar de la Familia, Inc. (PROFAMILIA)
Study officials:
affiliation: FHI 360
name: Vera Halpern, MD
role: STUDY_DIRECTOR
References:
citation: Halpern V, Brache V, Taylor D, Lendvay A, Cochon L, Jensen JT, Dorflinger LJ. Clinical trial to evaluate pharmacokinetics and pharmacodynamics of medroxyprogesterone acetate after subcutaneous administration of Depo-Provera. Fertil Steril. 2021 Apr;115(4):1035-1043. doi: 10.1016/j.fertnstert.2020.11.002. Epub 2021 Jan 21.