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

NCT02817464 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: TV46046-WH-10075
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Pregnancy; Contraception

Outcome Measures

Primary Outcomes (14)

• Part 1: Serum Medroxyprogesterone Acetate (MPA) Concentration at Day 1

  'Overall number of participants analyzed' = participants evaluable for this outcome measure.

  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 Outcomes (10)

• Part 1: Time to Ovulation

  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

Study Arms (2)

TV-46046 - 1

EXPERIMENTAL

Drug: TV-46046 - 400 mg/mL

TV-46046 - 2

EXPERIMENTAL

Drug: TV-46046 - 200 mg/mL

Interventions

TV-46046 - 400 mg/mL DRUG

A single subcutaneous injection in the abdomen of undiluted TV-46046 - 400 mg/mL

TV-46046 - 1

TV-46046 - 200 mg/mL DRUG

A single subcutaneous injection in the abdomen of saline-diluted TV-46046 - 200 mg/mL

TV-46046 - 2

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.: lead
• FHI 360: collaborator

Study Sites (2)

Teva Investigational Site 001

Philadelphia, Pennsylvania, 19104, United States

Location

Teva Investigational Site 002

Norfolk, Virginia, 23507, United States

Location

Related Publications (1)

• Halpern V, Wheeless A, Brache V, Lendvay A, Cochon L, Taylor D, Dorflinger LJ. A randomized crossover study to evaluate local tolerability following subcutaneous administration of a new depot medroxyprogesterone acetate contraceptive formulation. Contracept X. 2023 Sep 12;5:100100. doi: 10.1016/j.conx.2023.100100. eCollection 2023.

  PMID: 37823034 DERIVED

Limitations and Caveats

This study was planned to be conducted in 2 parts (Part 1: Exploratory PK, and Part 2: Dose-range Finding). Due to suboptimal long-term stability and re-suspendability, the decision was made not to initiate Part 2 of this clinical study.

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products, R&D Inc.

USMedInfo@tevapharm.com

888-483-8279

Study Officials

• Teva Medical Expert, MD

  Teva Branded Pharmaceutical Products R&D, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2016
• First Posted: June 29, 2016
• Study Start: October 26, 2016
• Primary Completion: December 3, 2018
• Study Completion: December 3, 2018
• Last Updated: February 12, 2024
• Results First Posted: February 12, 2024

Record last verified: 2023-06

Locations

US (2)