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

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

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 Overview

• Status: Completed
• Conditions: Contraception
• Intervention / Treatment: Drug: TV-46046; Drug: Depo-subQ Provera

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• Dominican Republic
  • Santo Domingo, Dominican Republic, 99999
    • Teva Investigational Site 18001
• United States
  • California
    • Cypress, California, United States, 90630
      • Teva Investigational Site 14002
  • Texas
    • San Antonio, Texas, United States, 78209
      • Teva Investigational Site 14003

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 - 120 mg/0.4 mL	Drug: TV-46046; SC injection of 300 mg/mL (120 mg/0.4mL; 180 mg/0.6mL; 240 mg/0.8mL)
Experimental: Group 2 - 180 mg/0.6 mL	Drug: TV-46046; SC injection of 300 mg/mL (120 mg/0.4mL; 180 mg/0.6mL; 240 mg/0.8mL)
Experimental: Group 3 - 240 mg/0.8 mL	Drug: TV-46046; SC injection of 300 mg/mL (120 mg/0.4mL; 180 mg/0.6mL; 240 mg/0.8mL)
Active Comparator: Group 4 - 104 mg/0.65 mL	Drug: Depo-subQ Provera; SC injection of 104 mg/0.65 mL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Day 182 (AUC0-182) of MPA	Day 0 to Day 182
Area Under the Serum Drug Concentration-Time Curve From Time 0 to Day 210 (AUC0-210) of MPA	Day 0 to Day 210
Area Under the Serum Drug Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of MPA	Day 0 to Day 365
Maximum Observed Serum Concentration (Cmax) of Medroxyprogesterone Acetate (MPA)	Day 0 to Day 365
Time to Reach Cmax (Tmax) of MPA	Day 0 to Day 365
Apparent Terminal Half-life (t½) of MPA	Day 0 to Day 365

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)		Day 0 up to Week 78
Change From Baseline in Body Weight at Day 7 and Weeks 13, 26, and 52		Day 7 and Weeks 13, 26, and 52
Estradiol Concentrations		Baseline, Weeks 4, 13, 26, 30, and 52
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.	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.	Day 0 to Day 365
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.	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.	Baseline, Weeks 4, 13, 26, and 52
Number of Participants With Clinically Significant Changes in Liver Function Tests		Day 0 to Day 365
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.	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.	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.	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.	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.	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.	Weeks 26 and 52
Progesterone Concentration		Weeks 48, 49, 50, 51, and 52

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): December 14, 2020
• Primary Completion (Actual): July 11, 2022
• Study Completion (Actual): January 12, 2023

Study Registration Dates

• First Submitted: December 4, 2020
• First Submitted That Met QC Criteria: December 20, 2020
• First Posted (Actual): December 23, 2020

Study Record Updates

• Last Update Posted (Actual): February 26, 2024
• Last Update Submitted That Met QC Criteria: July 11, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Pharmacokinetics
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Contraceptive Agents, Male; Medroxyprogesterone Acetate; Medroxyprogesterone
• Other Study ID Numbers: TV46046-WH-10159

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Upon primary clinical trial manuscript publication, researchers may request access to underlying study data. Each accepted article must be accompanied by a Data Availability Statement that describes where any primary data, associated metadata, original software, and any additional relevant materials necessary to understand, assess, and replicate the reported study findings in totality can be found. Underlying study data will be de-identified and study documents will be redacted to protect the privacy of trial participants and to protect commercially confidential information. Requests will be reviewed for scientific merit, product approval status, and conflicts of interest. Please email manuscript primary author to make your request.

Drug and device information, study documents

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