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

A Two-part, Phase 1, Exploratory and Dose-range Finding Study to Evaluate Suppression of Ovulation and Pharmacokinetics of Medroxyprogesterone Acetate Following a Single Subcutaneous Administration of TV-46046 in Women With Ovulatory Cycle

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.

Study Overview

• Status: Completed
• Conditions: Pregnancy; Contraception
• Intervention / Treatment: Drug: TV-46046 - 400 mg/mL; Drug: TV-46046 - 200 mg/mL

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Teva Investigational Site 001
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Teva Investigational Site 002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• has severe cirrhosis (decompensated) or liver tumors
• has known significant renal disease
• used Depo-Provera Contraceptive Injection or Depo-subcutaneous Provera 104 (DMPA) products in the past 12 months

• used any of the following medications within 1 month prior to enrollment:

  • any investigational drug
  • prohibited drugs per protocol
  • oral contraceptives, contraceptive ring or patch
  • levonorgestrel intrauterine system (LNG IUS) or contraceptive implant
• used a combined injectable contraceptive in the past 6 months
• less than 3 months since the end of last pregnancy
• currently lactating
• is using or plans to use prohibited drugs per protocol in the next 18 months
• has known sensitivity to MPA or inactive ingredients
• has a plan to move to another location in the next 24 months

• in the opinion of the investigator, potentially at elevated risk of HIV infection (eg, HIV -positive partner, IV drug use by self or by partner)

  • additional criteria apply, please contact the investigator for more information

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TV-46046 - 1	Drug: TV-46046 - 400 mg/mL; A single subcutaneous injection in the abdomen of undiluted TV-46046 - 400 mg/mL
Experimental: TV-46046 - 2	Drug: TV-46046 - 200 mg/mL; A single subcutaneous injection in the abdomen of saline-diluted TV-46046 - 200 mg/mL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 1: Serum Medroxyprogesterone Acetate (MPA) Concentration at Day 1	'Overall number of participants analyzed' = participants evaluable for this outcome measure.	Day 1
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Time to Ovulation	Ovulation was defined as a single elevated serum progesterone ≥4.7 ng/mL. Time to ovulation was computed as the difference in days between detection of the first post-randomization elevated progesterone and the date of treatment initiation. Median time to ovulation was derived using Kaplan-Meier estimate.	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
Part 2: AUC0-182 of MPA		Day 0 up to Day 182
Part 2: AUC0-210 of MPA		Day 0 up to Day 210
Part 2: AUC0-∞ of MPA		Day 0 up to Week 52
Part 2: Apparent Terminal Half Life (t1/2) of MPA		Day 0 up to Week 52
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse events (SAEs) were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. AEs were considered TEAEs if onset occurred on or after the first dose date. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.	Day 0 up to Week 78

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
• Collaborators: FHI 360
• Investigators: Study Director: Teva Medical Expert, MD, Teva Branded Pharmaceutical Products R&D, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2016
• Primary Completion (Actual): December 3, 2018
• Study Completion (Actual): December 3, 2018

Study Registration Dates

• First Submitted: June 27, 2016
• First Submitted That Met QC Criteria: June 27, 2016
• First Posted (Estimated): June 29, 2016

Study Record Updates

• Last Update Posted (Actual): February 12, 2024
• Last Update Submitted That Met QC Criteria: June 2, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: TV46046-WH-10075

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No