Pharmacodynamics and Pharmacokinetics Study of Existing DMPA Contraceptive Methods

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®

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.

Study Overview

• Status: Completed
• Conditions: Contraception
• Intervention / Treatment: Drug: DMPA 150; Drug: DMPA 300; Drug: DMPA 104

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

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• Dominican Republic
  • Santo Domingo, Dominican Republic
    • Asociación Dominicana Pro Bienestar de la Familia, Inc. (PROFAMILIA)
• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: DMPA 150; single subcutaneous injection of 150mg/mL of DMPA in the abdomen	Drug: DMPA 150; injectable contraceptive; Other Names: Depo-Provera® CI (150mg/mL, intramuscular)
EXPERIMENTAL: DMPA 300; single subcutaneous injection of 300mg/2mL of DMPA in the abdomen	Drug: DMPA 300; injectable contraceptive; Other Names: Depo-Provera® CI (300mg/2mL, intramuscular)
ACTIVE_COMPARATOR: DMPA 104; two injections, given at three months intervals, of 104mg/0.65mL of DMPA in the abdomen	Drug: DMPA 104; injectable contraceptive; Other Names: depo-subQ provera 104® (104mg/0.65mL, sub-cutaneous)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Measure of time to ovulation	up to 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Up to ovulation or 18 months following injection, whichever comes first	up to 18 months
Aggregate of individual Cmax measurements and parameters		up to 18 months
Type and frequency of adverse events		up to 18 months
Blood pressure at follow up		up to 18 months
Pulse at follow up		up to 18 months
Weight at follow up		up to 18 months
Measure of delayed return to ovulation		up to 18 months
Serum concentrations of cortisol		7.5 months
Number of participants with Injection site reactions		up to 18 months
Product acceptability		up to 18 months
Tmax	Up to ovulation or 18 months following injection, whichever comes first	up to 18 months
Aggregate of individual Tmax measurements and parameters		Up to 18 months
MPA concentration at Day 91 (C91)		91 days after injection
Aggregate of individual C91 measurements and parameters		18 months after injection
MPA concentration at Day 182 (C182)		182 days after injection
Aggregate of individual C182 measurements and parameters		18 months after injection
MPA concentration at Day 210 (C210)		210 days after injection
Aggregate of individual C210 measurements and parameters		18 months after injection
Area under the curve (AUC 0-182)		182 days after injection
Terminal elimination half-life (t1/2)	Up to ovulation or 18 months following injection, whichever comes first	up to 18 months

Collaborators and Investigators

• Sponsor: FHI 360
• Collaborators: Oregon Health and Science University; Asociación Dominicana Pro Bienestar de la Familia, Inc.
• Investigators: Study Director: Vera Halpern, MD, FHI 360

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (ACTUAL): August 30, 2018
• Study Completion (ACTUAL): August 30, 2018

Study Registration Dates

• First Submitted: May 11, 2015
• First Submitted That Met QC Criteria: May 27, 2015
• First Posted (ESTIMATE): May 28, 2015

Study Record Updates

• Last Update Posted (ACTUAL): October 18, 2018
• Last Update Submitted That Met QC Criteria: October 16, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Intrauterine device (IUD); Levonorgestrel (LNG); depot medroxyprogesterone acetate (DMPA); confidence interval (CI); Subcutaneous (sub-Q); intrauterine system (IUS)
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Contraceptive Agents, Male; Medroxyprogesterone Acetate; Medroxyprogesterone
• Other Study ID Numbers: 702179

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No