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

Phase 1
Completed
Conditions
Contraception
Interventions
Registration Number
NCT04682353
Lead Sponsor
Teva Branded Pharmaceutical Products R&D, Inc.
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
60
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group 1 - 120 mg/0.4 mLTV-46046-
Group 2 - 180 mg/0.6 mLTV-46046-
Group 4 - 104 mg/0.65 mLDepo-subQ Provera-
Group 3 - 240 mg/0.8 mLTV-46046-
Primary Outcome Measures
NameTimeMethod
Maximum Observed Serum Concentration (Cmax) of Medroxyprogesterone Acetate (MPA)Day 0 to Day 365
Time to Reach Cmax (Tmax) of MPADay 0 to Day 365
Apparent Terminal Half-life (t½) of MPADay 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 Infinity (AUC0-inf) of MPADay 0 to Day 365
Area Under the Serum Drug Concentration-Time Curve From Time 0 to Day 182 (AUC0-182) of MPADay 0 to Day 182
Area Under the Serum Drug Concentration-Time Curve From Time 0 to Day 210 (AUC0-210) of MPADay 0 to Day 210
Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Body Weight at Day 7 and Weeks 13, 26, and 52Day 7 and Weeks 13, 26, and 52
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 TreatmentDay 0 up to Week 78

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

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?)Weeks 26 and 52

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

Estradiol ConcentrationsBaseline, Weeks 4, 13, 26, 30, and 52
Number of Participants With Responses to the Acceptability Question (What do You Not Like About the Method?)Weeks 26 and 52

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

Number of Participants With Patient Health Questionnaire (PHQ-9) Mood ScoresBaseline, Weeks 4, 13, 26, and 52

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.

Number of Participants With Clinically Significant Changes in Liver Function TestsDay 0 to Day 365
Number of Participants With 1 or More Injection Site Reactions (ISRs)Day 0 to Day 365

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

Number of Participants With Responses to the Acceptability Question (What do You Like About the Method?)Weeks 26 and 52

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

Number of Participants With Responses to the Acceptability Question (If You Had a Choice, Which Injectable Contraceptive Method Would You Prefer?)Weeks 26 and 52

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

Number of Participants With Clinically Significant Changes in Vital SignsDay 0 to Day 365

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

Number of Participants With Overall Opinion of Vaginal Bleeding PatternWeeks 13, 26, and 52

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

Number of Participants With No Ovulation in 12 Months12 months

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

Progesterone ConcentrationWeeks 48, 49, 50, 51, and 52

Trial Locations

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

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