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

Phase 1

Completed

• Conditions: Contraception
• Interventions: Drug: TV-46046; Drug: TV-46046 Placebo; Drug: Depo-subQ 104

• Registration Number: NCT03700658
• Lead Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Brief Summary

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.

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 Timeline

• Study First Submitted: 2018-10-03
• Study First Submitted QC: 2018-10-05
• Study First Posted: 2018-10-09
• Study Start: 2019-01-15
• Primary Completion: 2020-10-02
• Study Completion: 2020-10-02
• Results First Submitted: 2021-09-29
• Status Verified: 2021-11
• Results First Submitted QC: 2021-11-18
• Last Update Submitted: 2021-11-18
• Results First Posted: 2022-01-26
• Last Update Posted: 2022-01-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 27

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
TV-46046 Undiluted	TV-46046	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.
TV-46046 Diluted	TV-46046	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.
TV-46046 Placebo	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.
Depo-subQ 104	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Injection Site Reactions (ISRs) (Excluding Injection Site Pain)	Day 0 (immediately after and 1 hour after the injection) up to Month 18	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).

Secondary Outcome Measures

Name	Time	Method
Injection Site Pain Score, as Assessed by Numerical Rating Scale (NRS)	Day 0 (Immediately after and 1 hour after injection)	Participants assessed their injection site pain using an 11-point NRS (0 = no pain at all; 10 = worst pain). Higher scores denote worse outcome.
Participant's Perception of Pain, as Assessed by an Overall Ranking of the 4 Study Injections From Least to Most Painful	Day 0 (1 hour after injection)	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).
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Day 0 up to Month 18	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.

Trial Locations

Locations (1)

Teva Investigational Site 1; 🇩🇴 Santo Domingo, Dominican Republic