A Study to Evaluate the Pharmacokinetics (PK) of Medroxyprogesterone Acetate Following an Injection of TV-46046 in Healthy Women of Reproductive Age

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate and compare the pharmacokinetic profile of Medroxyprogesterone acetate following subcutaneous administration of 3 different doses of TV-46046 and a dose of Depo-subQ Provera in healthy female participants. The secondary objectives of the study are to evaluate and compare the safety, local tolerability, and acceptability of a subcutaneous injection of 3 different doses of TV-46046 and a dose of Depo-subQ Provera in healthy female participants. The total duration of the study for each participant is expected to be up to 19.5 months.

Official Title
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A Randomized, Dose-range Finding Study to Evaluate Pharmacokinetics of Medroxyprogesterone Acetate Following a Single Subcutaneous Administration of TV-46046 in Healthy Women of Reproductive Age

Conditions
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Contraception

Intervention / Treatment
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* Drug: TV-46046
* Drug: Depo-subQ Provera


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: has regular menstrual cycle (21 to 35 days) has a low risk of pregnancy (ie, sterilized, in exclusively same-sex partnership, abstinent, in monogamous relationship with vasectomized partner, using nonhormonal intrauterine device (IUD), or consistently using barrier methods of contraception) had a normal mammogram within the last year, if 40 years of age or older NOTE- Additional criteria apply, please contact the investigator for more information. Exclusion Criteria: has multiple risk factors for cardiovascular disease (eg, smoking, obesity, hypertension, known low HDL, high LDL, or high triglyceride levels) has current or history of ischemic heart disease has active thrombophlebitis, current or past history of thromboembolic disorders, cerebral vascular disease or stroke has systemic lupus erythematosus has rheumatoid arthritis on immunosuppressive therapy has unexplained vaginal bleeding has diabetes has strong family history of breast cancer (defined as one or more first degree relatives with breast cancer, breast cancer occurring before menopause in three or more family members, regardless of degree of relationship, and any male family member with breast cancer) has current or history of breast cancer, or undiagnosed mass detected by breast exam has current or history of cervical cancer has cirrhosis or liver tumors has known osteoporosis or osteopenia has history of diagnosed clinical depression or bipolar disorder, with or without suicidal ideation, and/or history of suicide attempt, except short-lived situational depression that did not require medication and has not recurred in last five years used MPA-containing injectable products 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 oral contraceptives, contraceptive ring or patch levonorgestrel intrauterine system (LNG IUS) or contraceptive implant is participating in another clinical trial is pregnant desires to become pregnant in subsequent 24 months has been pregnant in last 3 months is currently lactating NOTE- Additional criteria apply, please contact the investigator for more information.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 - 120 mg/0.4 mL<br> | Drug: TV-46046<br>* SC injection of 300 mg/mL (120 mg/0.4mL; 180 mg/0.6mL; 240 mg/0.8mL)<br>|
| Experimental: Group 2 - 180 mg/0.6 mL<br> | Drug: TV-46046<br>* SC injection of 300 mg/mL (120 mg/0.4mL; 180 mg/0.6mL; 240 mg/0.8mL)<br>|
| Experimental: Group 3 - 240 mg/0.8 mL<br> | Drug: TV-46046<br>* SC injection of 300 mg/mL (120 mg/0.4mL; 180 mg/0.6mL; 240 mg/0.8mL)<br>|
| Active Comparator: Group 4 - 104 mg/0.65 mL<br> | Drug: Depo-subQ Provera<br>* SC injection of 104 mg/0.65 mL<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Serum Concentration (Cmax) of Medroxyprogesterone Acetate (MPA) |  | Day 0 to day 365 | 
| Time to Reach Cmax (Tmax) of MPA |  | Day 0 to day 365 | 
| Serum MPA Concentration at Day 91 (C91) |  | Day 91 | 
| Serum MPA Concentration at Day 182 (C182) |  | Day 182 | 
| Serum MPA Concentration at Day 210 (C210) |  | Day 210 | 
| Area Under the Serum Drug Concentration-Time Curve From Time 0 to Day 182 (AUC0-182) of MPA |  | Day 0 to Day 182 | 
| Area Under the Serum Drug Concentration-Time Curve From Time 0 to Day 210 (AUC0-210) of MPA |  | Day 0 to Day 210 | 
| Area Under the Serum Drug Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of MPA |  | Day 0 to Day 365 | 
| Apparent Terminal Half-life (t½) of MPA |  | Day 0 to day 365 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) |  | Day 0 up to Week 78 | 
| Number of Participants with at least 1 Concomitant Medication Use During Treatment |  | Day 0 up to Week 78 | 
| Number of Participants with Clinically Significant Changes in Vital Signs |  | Day 0 to day 365 | 
| Change From Baseline in Body Weight at Day 7 and Weeks 13, 26, and 52 |  | Day 7 and Weeks 13, 26, and 52 | 
| Number of Participants With Overall Opinion of Vaginal Bleeding Pattern |  | Weeks 13, 26, and 52 | 
| Number of Participants With Patient Health Questionnaire (PHQ-9) Mood Scores | The Patient Health Questionnaire (PHQ-9) will be used to ascertain the frequency of a variety of somatic and emotional indicators of well-being and produce an overall score for the severity of depression. The minimum overall score is 0 and the maximum overall score for the PHQ-9 is 27. Higher values represent more severe depression status. | Baseline, Weeks 4, 13, 26, and 52 | 
| Number of Participants with Clinically Significant Changes in Liver Function Tests |  | Day 0 to day 365 | 
| Estradiol Concentrations |  | Baseline, Weeks 4, 13, 26, 30, and 52 | 
| Number of Participants With No Ovulation in 12 Months |  | 12 months | 
| Number of Participants With 1 or More Injection Site Reactions (ISRs) |  | Day 0 to day 365 | 
| Number of Participants With Responses to the Acceptability Question (What do you like about the method?) | acceptability questions include likes and dislikes of the method and willingness to use the product in the future will be tabulated in frequency tables and compared between the test and the reference groups using descriptive Chi-squared tests. | Week 26, Week 52 | 
| Number of Participants With Responses to the Acceptability Question (What do you not like about the method?) |  | Week 26, Week 52 | 
| Number of Participants With Responses to the Acceptability Question (If you were at risk for pregnancy, would you use this method of contraception outside of this study?) |  | Week 26, Week 52 | 
| Number of Participants With Responses to the Acceptability Question (If you had a choice, which injectable contraceptive method would you prefer?) |  | Week 26, Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics