A Study to Evaluate Injection Pain and Local Tolerability Following Subcutaneous (SC) Administration of TV-46046

A Randomized Cross-Over Study to Evaluate Local Tolerability Following Subcutaneous Administration of TV-46046

The purpose of this study is to evaluate the local tolerability associated with the SC administration of TV-46046, and inform next steps of the TV-46046 development program.

Study Overview

• Status: Completed
• Conditions: Contraception
• Intervention / Treatment: Drug: TV-46046; Drug: TV-46046 Placebo; Drug: Depo-subQ 104

Detailed Description

Eligible participants will be enrolled and receive 1 of each of the 4 SC study injections in each abdominal quadrant approximately 1 hour apart: 120 milligrams (mg)/0.3 milliliter (mL) of TV-46046, 60 mg/0.3 mL of 1:1 saline diluted TV-46046, 0.3 mL of TV-46046 Placebo and 104 mg/0.65 mL Depo-subQ 104 per the assigned sequence.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• Dominican Republic
  • Santo Domingo, Dominican Republic
    • Teva Investigational Site 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Participant has a low risk of pregnancy (that is, sterilized, in exclusively same-sex partnership, in menopause and/or post-menopausal, abstinent, in a monogamous relationship with vasectomized partner, using nonhormonal intrauterine device [IUD], or consistent use of condoms)
• Participant is not pregnant and does not have desire to become pregnant in the subsequent 18 months
• Participant had a normal mammogram within the last year, if 40 years or older

• Participant has no skin disorders or skin allergies

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

Exclusion Criteria:

• Participant has hypertension
• Participant has ischemic heart disease or a history of ischemic heart disease
• Participant has a history of stroke
• Participant has a history of thromboembolic event(s)
• Participant has systemic lupus erythematosus
• Participant has rheumatoid arthritis and is undergoing immunosuppressive therapy
• Participant has migraine with aura
• Participant has unexplained vaginal bleeding
• Participant has diabetes
• Participant has a strong family history of breast cancer
• Participant has cervical cancer or a history of cervical cancer
• Participant has severe cirrhosis (decompensated) or liver tumors
• Participant has known significant renal disease
• Participant has a history of diagnosed clinical depression or bipolar disorder, with or without suicidal ideation, and/or history of suicide attempt
• Participant is currently using hormonal contraception
• Participant had an injection of DMPA (Depo-Provera CI or Depo-subQ 104) in the past 12 months; or combined injectable in the last 3 months
• Participant is chronically using pain medication

• Participant has a plan to move to another location in the next 18 months

  • 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: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TV-46046 Undiluted; Participants will receive TV-46046 undiluted (120 mg/0.3 mL of 400 mg/mL) SC injection as a test formulation in a crossover design with the other 3 SC study drug injections. The 4 study drug injections will be administered approximately 1 hour apart.	Drug: TV-46046; TV-46046 will be administered per dose and schedule specified in the arm.
Experimental: TV-46046 Diluted; Participants will receive TV-46046 saline-diluted (60 mg/0.3 mL of 200 mg/mL) SC injection as a test formulation in a crossover design with the other 3 SC study drug injections. The 4 study drug injections will be administered approximately 1 hour apart.	Drug: TV-46046; TV-46046 will be administered per dose and schedule specified in the arm.
Placebo Comparator: TV-46046 Placebo; Participants will receive TV-46046 placebo (0.3 mL) SC injection in a crossover design with the other 3 SC study drug injections. The 4 study drug injections will be administered approximately 1 hour apart.	Drug: TV-46046 Placebo; TV-46046 Placebo will be administered per schedule specified in the arm.
Active Comparator: Depo-subQ 104; Participants will receive Depo-subQ 104 (medroxyprogesterone acetate injectable suspension; 104 mg/0.65 mL) SC injection as a reference formulation in a crossover design with the other 3 SC study drug injections. The 4 study drug injections will be administered approximately 1 hour apart.	Drug: Depo-subQ 104; Depo-subQ 104 will be administered per dose and schedule specified in the arm.; Other Names: Medroxyprogesterone acetate injectable suspension; Depo-subQ Provera 104®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Injection Site Reactions (ISRs) (Excluding Injection Site Pain)	ISRs were assessed by self-reports and direct observation for each injection at least twice on the day of injection. ISRs included erythema (redness), swelling, pruritus (itching), bleeding, bruising, injection site discoloration (for example, hypopigmentation), or atrophy (that is, dimple).	Day 0 (immediately after and 1 hour after the injection) up to Month 18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Injection Site Pain Score, as Assessed by Numerical Rating Scale (NRS)	Participants assessed their injection site pain using an 11-point NRS (0 = no pain at all; 10 = worst pain). Higher scores denote worse outcome.	Day 0 (Immediately after and 1 hour after injection)
Participant's Perception of Pain, as Assessed by an Overall Ranking of the 4 Study Injections From Least to Most Painful	Each participant was asked to rank the injections according to overall pain from least (score = 1) to most (score = 4) painful. If a participant could not rank all of her injections from least to most painful or could not uniquely identify which injection was the most painful, then her responses were appropriately weighted across groups (for example, if a participant ranked all 4 treatments as equally most painful, then that participant contributed a score of 0.25 to each group when assessing the distribution of the most painful injection and in the event of a tie between 2 rankings, 0.5 was assigned to each tied ranking).	Day 0 (1 hour after injection)
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. AEs were considered treatment emergent if (a) the onset occurred on or after the time of first injection or (b) an event had an onset prior to the first injection but increased in severity after administration of the injection. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.	Day 0 up to Month 18

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
• Collaborators: FHI 360

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2019
• Primary Completion (Actual): October 2, 2020
• Study Completion (Actual): October 2, 2020

Study Registration Dates

• First Submitted: October 3, 2018
• First Submitted That Met QC Criteria: October 5, 2018
• First Posted (Actual): October 9, 2018

Study Record Updates

• Last Update Posted (Actual): January 26, 2022
• Last Update Submitted That Met QC Criteria: November 18, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• 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-10147

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the study protocol and the statistical analysis plan. Requests will be reviewed for scientific merit, product approval status, and conflicts of interest. Patient level data will be de-identified and study documents will be redacted to protect the privacy of trial participants and to protect commercially confidential information. Please email USMedInfo@tevapharm.com 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