Study to Evaluate Suppression of Ovulation and Pharmacokinetics of Medroxyprogesterone Acetate Following Administration of TV-46046 in Women With Ovulatory Cycle

Study Overview
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Brief Summary
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The purpose of this pharmacodynamic and pharmacokinetic study is to identify a dose of TV-46046 (within the range 80 to 300 mg) that is both safe and consistent with contraceptive effect when injected every 6 months.

Official Title
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A Two-part, Phase 1, Exploratory and Dose-range Finding Study to Evaluate Suppression of Ovulation and Pharmacokinetics of Medroxyprogesterone Acetate Following a Single Subcutaneous Administration of TV-46046 in Women With Ovulatory Cycle

Conditions
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Pregnancy, Contraception

Intervention / Treatment
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* Drug: TV-46046 - 400 mg/mL
* Drug: TV-46046 - 200 mg/mL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: has regular menstrual cycle (24 to 35 days) is at low risk of pregnancy (ie, sterilized, in exclusively same-sex partnership, in monogamous relationship with vasectomized partner, or using non-hormonal IUD) is in good general health as determined by a medical history and physical examination is not pregnant and does not have desire to become pregnant in the subsequent 36 months has had a normal mammogram within the last year (for Part 1 only) additional criteria apply, please contact the investigator for more information Exclusion Criteria: has hypertension: systolic blood pressure (BP) ≥160 mm Hg or diastolic BP ≥100 mm Hg vascular disease has current or history of ischemic heart disease has history of stroke has history of thromboembolic event has systemic lupus erythematosus positive (or unknown) antiphospholipid antibodies severe thrombocytopenia has rheumatoid arthritis on immunosuppressive therapy has migraine with aura has unexplained vaginal bleeding has diabetes has strong family history of breast cancer (defined as one or more first degree relatives, breast cancer occurring before menopause in three or more family members, regardless of degree of relationship, and any male family member with breast cancer), or current or history of breast cancer, or undiagnosed mass detected by breast exam has current or history of cervical cancer has severe cirrhosis (decompensated) or liver tumors has known significant renal disease used Depo-Provera Contraceptive Injection or Depo-subcutaneous Provera 104 (DMPA) products in the past 12 months used any of the following medications within 1 month prior to enrollment: any investigational drug prohibited drugs per protocol oral contraceptives, contraceptive ring or patch levonorgestrel intrauterine system (LNG IUS) or contraceptive implant used a combined injectable contraceptive in the past 6 months less than 3 months since the end of last pregnancy currently lactating is using or plans to use prohibited drugs per protocol in the next 18 months has known sensitivity to MPA or inactive ingredients has a plan to move to another location in the next 24 months in the opinion of the investigator, potentially at elevated risk of HIV infection (eg, HIV -positive partner, IV drug use by self or by partner) additional criteria apply, please contact the investigator for more information

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: Other
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TV-46046 - 1<br> | Drug: TV-46046 - 400 mg/mL<br>* A single subcutaneous injection in the abdomen of undiluted TV-46046 - 400 mg/mL<br>|
| Experimental: TV-46046 - 2<br> | Drug: TV-46046 - 200 mg/mL<br>* A single subcutaneous injection in the abdomen of saline-diluted TV-46046 - 200 mg/mL<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Serum Medroxyprogesterone acetate (MPA) Concentration at Day 1 |  | Day 1 | 
| Part 1: Serum MPA Concentration at Day 7 |  | Day 7 | 
| Part 1: Serum MPA Concentration at Day 28 |  | Day 28 | 
| Part 1: Serum MPA Concentration at Day 91 |  | Day 91 | 
| Part 1: Serum MPA Concentration at Day 182 |  | Day 182 | 
| Part 1: Serum MPA Concentration at Day 210 |  | Day 210 | 
| Part 1: Maximum Observed Serum Concentration (Cmax) of MPA |  | Day 0 up to Week 52 | 
| Part 1: Observed Serum Drug Concentration at Day 182 (C182) of MPA |  | Day 182 | 
| Part 1: Time to Reach Cmax (Tmax) of MPA |  | Day 0 up to Week 52 | 
| Part 1: Area Under the Serum Drug Concentration by Time Curve From Time 0 to Day 182 (AUC0-182) of MPA |  | Day 0 up to Day 182 | 
| Part 1: Area Under the Serum Drug Concentration by Time Curve From Time 0 to Day 210 (AUC0-210) of MPA |  | Day 0 up to Day 210 | 
| Part 1: Area Under the Serum Drug Concentration by Time Curve From Time 0 to Infinity (AUC0-∞) of MPA |  | Day 0 up to Week 52 | 
| Part 1: Apparent Terminal Half-life (t1/2) of MPA |  | Day 0 up to Week 52 | 
| Part 2: Time to Ovulation | Ovulation was defined as a single elevated serum progesterone ≥4.7 ng/mL | Day 0 up to Week 78 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Time to Ovulation | Ovulation was defined as a single elevated serum progesterone ≥4.7 ng/mL. Time to ovulation was computed as the difference in days between detection of the first post-randomization elevated progesterone and the date of treatment initiation. Median time to ovulation was derived using Kaplan-Meier estimate. | Day 0 up to Week 78 | 
| Part 2: Cmax of MPA |  | Day 0 up to Week 52 | 
| Part 2: Tmax of MPA |  | Day 0 up to Week 52 | 
| Part 2: Observed Serum Drug Concentration at Day 210 (C210) of MPA |  | Day 0 up to Day 210 | 
| Part 2: C182 of MPA |  | Day 0 up to Day 182 | 
| Part 2: AUC0-182 of MPA |  | Day 0 up to Day 182 | 
| Part 2: AUC0-210 of MPA |  | Day 0 up to Day 210 | 
| Part 2: AUC0-∞ of MPA |  | Day 0 up to Week 52 | 
| Part 2: Apparent Terminal Half Life (t1/2) of MPA |  | Day 0 up to Week 52 | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse events (SAEs) were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. AEs were considered TEAEs if onset occurred on or after the first dose date. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section | Day 0 up to Week 78 |