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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Contraception

Intervention / Treatment
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* Drug: TV-46046
* Drug: Depo-subQ 104
* Drug: TV-46046 Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TV-46046 Undiluted<br>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<br>* TV-46046 will be administered per dose and schedule specified in the arm.<br>|
| Experimental: TV-46046 Diluted<br>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<br>* TV-46046 will be administered per dose and schedule specified in the arm.<br>|
| Placebo Comparator: TV-46046 Placebo<br>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<br>* TV-46046 Placebo will be administered per schedule specified in the arm.<br>|
| Active Comparator: Depo-subQ 104<br>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<br>* Depo-subQ 104 will be administered per dose and schedule specified in the arm.<br>* Other names: Depo-subQ Provera 104®;|

What is the study measuring?
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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 |