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

Teva Branded Pharmaceutical Products R&D, Inc.60 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

DOUBLE

Enrollment

Conditions

Contraception

Interventions

TV-46046

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (3)

Teva Investigational Site 14002

Cypress, California, United States

Teva Investigational Site 14003

San Antonio, Texas, United States

Teva Investigational Site 18001

Santo Domingo, Dominican Republic

Outcomes

Primary Outcomes

Maximum Observed Serum Concentration (Cmax) of Medroxyprogesterone Acetate (MPA)

Time frame: Day 0 to Day 365

Time to Reach Cmax (Tmax) of MPA

Time frame: Day 0 to Day 365

Serum MPA Concentration at Day 91 (C91)

Time frame: Day 91

Serum MPA Concentration at Day 182 (C182)

Time frame: Day 182

Serum MPA Concentration at Day 210 (C210)

Time frame: Day 210

Area Under the Serum Drug Concentration-Time Curve From Time 0 to Day 182 (AUC0-182) of MPA

Time frame: Day 0 to Day 182

Area Under the Serum Drug Concentration-Time Curve From Time 0 to Day 210 (AUC0-210) of MPA

Time frame: Day 0 to Day 210

Area Under the Serum Drug Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of MPA

Time frame: Day 0 to Day 365

Apparent Terminal Half-life (t½) of MPA

Time frame: Day 0 to Day 365

Secondary Outcomes

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

Time frame: Day 0 up to Week 78

Number of Participants With at Least 1 Concomitant Medication Use During Treatment

Concomitant medications included acetic acid derivatives and substances, aminoalkyl ethers, anilides, calcium compounds, other viral vaccines, and propionic acid derivatives etc.

Time frame: Day 0 up to Week 78

Number of Participants With Clinically Significant Changes in Vital Signs

Vital signs examination included blood pressure, respiration rate, pulse, and body temperature.

Time frame: Day 0 to Day 365

Change From Baseline in Body Weight at Day 7 and Weeks 13, 26, and 52

Time frame: Day 7 and Weeks 13, 26, and 52

Number of Participants With Overall Opinion of Vaginal Bleeding Pattern

Number of participants with overall opinion of vaginal bleeding pattern as acceptable or not acceptable has been reported.

Time frame: Weeks 13, 26, and 52

Number of Participants With Patient Health Questionnaire (PHQ-9) Mood Scores

The PHQ-9 is a participant-rated depressive symptom severity scale to monitor severity over time for newly diagnosed participants or participants in current treatment for depression. Scoring was based on participants' responses to each of the 9 questions, as follows: 0=not at all; 1=several days; 2=more than half the days; and 3=nearly every day. The PHQ-9 total score was calculated as the sum of the 9 individual item scores. The PHQ-9 total score was categorized as follows: 0 = no depression, 1 to 4=minimal depression, 5 to 9=mild depression, 10 to 14=moderate depression, 15 to 19=moderately severe depression; and 20 to 27=severe depression. Higher scores indicate more severe depression.

Time frame: Baseline, Weeks 4, 13, 26, and 52

Number of Participants With Clinically Significant Changes in Liver Function Tests

Time frame: Day 0 to Day 365

Estradiol Concentrations

Time frame: Baseline, Weeks 4, 13, 26, 30, and 52

Number of Participants With No Ovulation in 12 Months

Ovulation was defined as one or more progesterone measurements ≥ 4.7 ng/mL in Weeks 48, 49, 50, 51 or 52.

Time frame: 12 months

Number of Participants With 1 or More Injection Site Reactions (ISRs)

The ISRs included erythema, swelling, pruritus, bleeding, tenderness, bruising, hypopigmentation, atrophy, and injection site pain.

Time frame: 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.

Time frame: Weeks 26 and 52

Number of Participants With Responses to the Acceptability Question (What do You Not Like About the Method?)

Acceptability questions include likes and dislikes of the method and willingness to use the product in the future.

Time frame: Weeks 26 and 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?)

Acceptability questions include likes and dislikes of the method and willingness to use the product in the future.

Time frame: Weeks 26 and 52

Number of Participants With Responses to the Acceptability Question (If You Had a Choice, Which Injectable Contraceptive Method Would You Prefer?)

Acceptability questions include likes and dislikes of the method and willingness to use the product in the future.

Time frame: Weeks 26 and 52

Progesterone Concentration

Time frame: Weeks 48, 49, 50, 51, and 52