Pharmacodynamics and Pharmacokinetics Study of Existing DMPA Contraceptive Methods

Study Overview
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Brief Summary
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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
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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

Official Title
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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®

Conditions
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Contraception

Intervention / Treatment
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* Drug: DMPA 150
* Drug: DMPA 300
* Drug: DMPA 104


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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depot medroxyprogesterone acetate (DMPA), confidence interval (CI), Subcutaneous (sub-Q), Intrauterine device (IUD), Levonorgestrel (LNG), intrauterine system (IUS)