Clinical trial NCT04682353: A Study to Evaluate the Pharmacokinetics (PK) of Medroxyprogesterone Acetate Following an Injection of TV-46046 in Healthy Women of Reproductive Age
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Contraception
Keywords: Pharmacokinetics
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
Collaborators: name: FHI 360
First posted: 2020-12-23
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) of Medroxyprogesterone Acetate (MPA)
timeFrame: Day 0 to Day 365
measure: Time to Reach Cmax (Tmax) of MPA
timeFrame: Day 0 to Day 365
measure: Serum MPA Concentration at Day 91 (C91)
timeFrame: Day 91
measure: Serum MPA Concentration at Day 182 (C182)
timeFrame: Day 182
measure: Serum MPA Concentration at Day 210 (C210)
timeFrame: Day 210
measure: Area Under the Serum Drug Concentration-Time Curve From Time 0 to Day 182 (AUC0-182) of MPA
timeFrame: Day 0 to Day 182
measure: Area Under the Serum Drug Concentration-Time Curve From Time 0 to Day 210 (AUC0-210) of MPA
timeFrame: Day 0 to Day 210
measure: Area Under the Serum Drug Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of MPA
timeFrame: Day 0 to Day 365
measure: Apparent Terminal Half-life (t½) of MPA
timeFrame: Day 0 to Day 365
Secondary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Day 0 up to Week 78
measure: Number of Participants With at Least 1 Concomitant Medication Use During Treatment
timeFrame: Day 0 up to Week 78
measure: Number of Participants With Clinically Significant Changes in Vital Signs
timeFrame: Day 0 to Day 365
measure: Change From Baseline in Body Weight at Day 7 and Weeks 13, 26, and 52
timeFrame: Day 7 and Weeks 13, 26, and 52
measure: Number of Participants With Overall Opinion of Vaginal Bleeding Pattern
timeFrame: Weeks 13, 26, and 52
measure: Number of Participants With Patient Health Questionnaire (PHQ-9) Mood Scores
timeFrame: Baseline, Weeks 4, 13, 26, and 52
measure: Number of Participants With Clinically Significant Changes in Liver Function Tests
timeFrame: Day 0 to Day 365
measure: Estradiol Concentrations
timeFrame: Baseline, Weeks 4, 13, 26, 30, and 52
measure: Number of Participants With No Ovulation in 12 Months
timeFrame: 12 months
measure: Number of Participants With 1 or More Injection Site Reactions (ISRs)
timeFrame: Day 0 to Day 365
measure: Number of Participants With Responses to the Acceptability Question (What do You Like About the Method?)
timeFrame: Weeks 26 and 52
measure: Number of Participants With Responses to the Acceptability Question (What do You Not Like About the Method?)
timeFrame: Weeks 26 and 52
measure: 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?)
timeFrame: Weeks 26 and 52
measure: Number of Participants With Responses to the Acceptability Question (If You Had a Choice, Which Injectable Contraceptive Method Would You Prefer?)
timeFrame: Weeks 26 and 52
measure: Progesterone Concentration
timeFrame: Weeks 48, 49, 50, 51, and 52
Other outcomes:
Locations:
city: Cypress
country: United States
facility: Teva Investigational Site 14002
state: California
city: San Antonio
country: United States
facility: Teva Investigational Site 14003
state: Texas
city: Santo Domingo
country: Dominican Republic
facility: Teva Investigational Site 18001
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Teva Medical Expert, MD
role: STUDY_DIRECTOR
References: