Lower Dose Depo Provera® Contraceptive Injection

A Study to Evaluate Suppression of Ovulation Following a Single Subcutaneous Administration of Various Doses of Depo-Provera CI

This is a randomized, partially-blinded, multi-center, parallel-group study to evaluate and compare the PD and PK of MPA after a single SC injection of either 45 mg/0.3 mL, 75 mg/0.5 mL or 105 mg/0.7 mL of Depo-Provera CI, and one cycle of Depo-subQ 104 use when injected in the abdomen, in women of reproductive age with confirmed ovulatory baseline cycle

Study Overview

• Status: Completed
• Conditions: Contraception
• Intervention / Treatment: Drug: Depo-Provera CI; Drug: Depo-subQ 104

Detailed Description

This is a randomized, partially-blinded, multi-center, parallel-group study to evaluate and compare the PD and PK of MPA after a single SC injection of either 45 mg/0.3 mL, 75 mg/0.5 mL or 105 mg/0.7 mL of Depo-Provera CI, and one cycle of Depo-subQ 104 use when injected in the abdomen, in women of reproductive age with confirmed ovulatory baseline cycle. Baseline ovulation will be confirmed in all women by measuring serum progesterone (P) approximately twice a week during the 2-3 weeks preceding expected menses. Between 48 and 60 participants (12-15 per group) with confirmed ovulation who meet other eligibility criteria will be enrolled and randomized to receive a single SC injection in the abdomen of 1 of 3 doses of Depo-Provera CI: 45 mg/0.3 mL, 75 mg/0.5 mL or 105 mg/0.7 mL or a single dose of Depo-subQ Provera (104 mg/0.65mL). Participants will be followed for 32 weeks (7.5 months) after the injection During the study participants will provide blood samples for MPA, P and estradiol (E2) prior to injection and then frequently at predefined time points through 7.5 months. In addition, for more accurate ascertainment of the PD response we will perform transvaginal ultrasound (TVS) and assess cervical mucus at predefined time points through 7.5 months. Information on adverse events and concomitant medications will be collected throughout the study. Information on acceptability will be collected at predefined time points through 7.5 months.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• Brazil
  • CAmpinas, Brazil
    • Universidade Estadual de Campinas (UNICAMP)
• Chile
  • Santiago, Chile
    • Instituto Chileno de Medicina Reproductiva (ICMER)
• Dominican Republic
  • Santo Domingo, Dominican Republic
    • Asociación Dominicana Pro Bienestar de la Familia, Inc. (PROFAMILIA)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• has typical menstrual cycle of 24 to 35 days
• has confirmed ovulatory cycle during the pretreatment phase (serum progesterone ≥ 4.7 ng/mL in 2 consecutive samples)
• is sterilized or using non hormonal intrauterine device (IUD)
• is in good general health as determined by a medical history and physical examination
• 18 to 40 years of age (inclusive)
• willing to provide informed consent and follow all study requirements
• has negative urine pregnancy test and has no desire to become pregnant in the subsequent 12 months
• has a body mass index (BMI) of 18.0 to 35.0 kg/m2, inclusive
• has hemoglobin ≥10.5 g/dL

Exclusion Criteria:

• has medical contraindications to depot medroxyprogesterone acetate (DMPA) [16]
• has undiagnosed mass in breast
• used DMPA in the past 12 months
• used a combined injectable contraceptive in the past 6 months

• used any of the following medications within 1 month prior to enrollment:

  • any investigational drug
  • prohibited drugs per protocol
  • oral contraceptives
  • Nuva-ring
  • contraceptive patch
  • levonorgestrel intrauterine system (LNG IUS) or contraceptive implant
• has been pregnant within last 3 months
• Is currently lactating
• in the opinion of the investigator, is potentially at elevated risk of HIV infection (HIV-positive partner, IV drug use by self or by partner)
• has more than one male sexual partner
• is using or plans to use prohibited drugs per protocol in the next 9 months
• has known sensitivity to MPA
• plans to move to another location in the next 9 months
• has any condition (social or medical), which in the opinion of the investigator would make study participation unsafe, would interfere with adherence to the clinical study requirements or complicate data interpretation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Depo-Provera CI 45 mg; a single subcutaneous (SC) injection of 45 mg/0.3 mL	Drug: Depo-Provera CI; The active ingredient in Depo-Provera is Medroxyprogesterone acetate (MPA); Other Names: Depo Provera® Contraceptive Injection
Experimental: Depo-Provera CI 75 mg; a single subcutaneous (SC) injection of 75 mg/0.5 mL	Drug: Depo-Provera CI; The active ingredient in Depo-Provera is Medroxyprogesterone acetate (MPA); Other Names: Depo Provera® Contraceptive Injection
Experimental: Depo-Provera CI 105 mg; a single subcutaneous (SC) injection of 105 mg/0.7 mL	Drug: Depo-Provera CI; The active ingredient in Depo-Provera is Medroxyprogesterone acetate (MPA); Other Names: Depo Provera® Contraceptive Injection
Active Comparator: Depo-subQ 104; a single subcutaneous (SC) injection of 104 mg/0.65 mL	Drug: Depo-subQ 104; The active ingredient in Depo-Provera is Medroxyprogesterone acetate (MPA). Depo-subQ provera 104® (medroxyprogesterone acetate injectable suspension, 104 mg/0.65mL) for subcutaneous injection; Other Names: depo-subQ provera 104®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to ovulation	Time to ovulation indicated by time to reach rupture of the lead follicle based on transvaginal ultrasound (TVS) findings followed by serum progesterone level of >=4.7 ng/mL. The primary objective will be assessed by estimating the cumulative probability of return to ovulation through Month 7.5 from start of therapy in each test group based on the Kaplan-Meier product-limit method, with 95% confidence intervals derived using the complementary log-log transformation.	32 weeks after receiving drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of serum MPA concentrations	Measure of Peak Concentrations (Cmax)	32 weeks after receiving drug
Time to maximum serum concentration of MPA	Time to reach peak concentration of MPA(Tmax)	32 weeks after receiving drug
Occurrence of adverse events		32 weeks after receiving drug

Collaborators and Investigators

• Sponsor: FHI 360
• Investigators: Principal Investigator: Vera Halpern, MD, FHI 360

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2016
• Primary Completion (Actual): May 15, 2018
• Study Completion (Actual): May 15, 2018

Study Registration Dates

• First Submitted: March 30, 2016
• First Submitted That Met QC Criteria: April 4, 2016
• First Posted (Estimate): April 8, 2016

Study Record Updates

• Last Update Posted (Actual): June 14, 2018
• Last Update Submitted That Met QC Criteria: June 12, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: CI-contraceptive injection; DMPA-Depot medroxyprogesterone acetate; MPA-Medroxyprogesterone Acetate; subQ-subcutaneous
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Contraceptive Agents, Male; Contraceptive Agents; Medroxyprogesterone Acetate; Medroxyprogesterone
• Other Study ID Numbers: 834119

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There is no plan to share individual participant data

Drug and device information, study documents

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