Trial Outcomes & Findings for A Study to Evaluate Injection Pain and Local Tolerability Following Subcutaneous (SC) Administration of TV-46046 (NCT NCT03700658)

Last Updated: 2022-01-26

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

27 participants

Primary outcome timeframe

Day 0 (immediately after and 1 hour after the injection) up to Month 18

Results posted on

2022-01-26

Participant Flow

Participant milestones

Participant milestones
Measure	Overall Study Participants received TV-46046 undiluted (120 milligrams \[mg\]/0.3 milliliters \[mL\] of 400 mg/mL) and TV-46046 saline-diluted (60 mg/0.3 mL of 200 mg/mL) subcutaneous (SC) injection as a test formulation, Depo-subQ 104 (medroxyprogesterone acetate injectable suspension; 104 mg/0.65 mL) SC injection as a reference formulation, and TV-46046 placebo SC injection in a crossover design. The 4 study drug injections were administered approximately 1 hour apart.
Overall Study STARTED	27
Overall Study Received at Least 1 Dose of Study Drug	27
Overall Study COMPLETED	27
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Overall Study n=27 Participants Participants received TV-46046 undiluted (120 mg/0.3 mL of 400 mg/mL) and TV-46046 saline-diluted (60 mg/0.3 mL of 200 mg/mL) SC injection as a test formulation, Depo-subQ 104 (medroxyprogesterone acetate injectable suspension; 104 mg/0.65 mL) SC injection as a reference formulation, and TV-46046 placebo SC injection in a crossover design. The 4 study drug injections were administered approximately 1 hour apart.
Age, Continuous	35.7 years STANDARD_DEVIATION 6.20 • n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · Biracial	26 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 0 (immediately after and 1 hour after the injection) up to Month 18

Population: The treated analysis set included all participants who received at least 1 of the 4 study drug injections excluding 3 participants who had partial injections.

Outcome measures

Outcome measures
Measure	TV-46046 Undiluted n=25 Participants Participants received TV-46046 undiluted (120 mg/0.3 mL of 400 mg/mL) subcutaneous (SC) injection as a test formulation.	TV-46046 Diluted n=27 Participants Participants received TV-46046 saline-diluted (60 mg/0.3 mL of 200 mg/mL) SC injection as a test formulation.	TV-46046 Placebo n=27 Participants Participants received TV-46046 placebo (0.3 mL) SC injection.	Depo-subQ 104 n=26 Participants Participants received Depo-subQ 104 (medroxyprogesterone acetate injectable suspension; 104 mg/0.65 mL) SC injection as a reference formulation.
Number of Participants With Injection Site Reactions (ISRs) (Excluding Injection Site Pain)	12 Participants	6 Participants	0 Participants	8 Participants

SECONDARY outcome

Timeframe: Day 0 (Immediately after and 1 hour after injection)

Population: The treated analysis set included all participants who received at least 1 of the 4 study drug injections excluding 5 participants with needle blockage/manipulation.

Participants assessed their injection site pain using an 11-point NRS (0 = no pain at all; 10 = worst pain). Higher scores denote worse outcome.

Outcome measures

Outcome measures
Measure	TV-46046 Undiluted n=22 Participants Participants received TV-46046 undiluted (120 mg/0.3 mL of 400 mg/mL) subcutaneous (SC) injection as a test formulation.	TV-46046 Diluted n=22 Participants Participants received TV-46046 saline-diluted (60 mg/0.3 mL of 200 mg/mL) SC injection as a test formulation.	TV-46046 Placebo n=22 Participants Participants received TV-46046 placebo (0.3 mL) SC injection.	Depo-subQ 104 n=22 Participants Participants received Depo-subQ 104 (medroxyprogesterone acetate injectable suspension; 104 mg/0.65 mL) SC injection as a reference formulation.
Injection Site Pain Score, as Assessed by Numerical Rating Scale (NRS) Immediately after injection	2.1 units on a scale Standard Deviation 1.72	1.9 units on a scale Standard Deviation 1.46	3.3 units on a scale Standard Deviation 2.15	1.2 units on a scale Standard Deviation 1.40
Injection Site Pain Score, as Assessed by Numerical Rating Scale (NRS) 1 hour after injection	0.2 units on a scale Standard Deviation 0.50	0.2 units on a scale Standard Deviation 0.50	0.6 units on a scale Standard Deviation 1.00	0.1 units on a scale Standard Deviation 0.29

SECONDARY outcome

Timeframe: Day 0 (1 hour after injection)

Population: The treated analysis set included all participants who received at least 1 of the 4 study drug injections excluding 5 participants with needle blockage/manipulation.

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).

Outcome measures

Outcome measures
Measure	TV-46046 Undiluted n=22 Participants Participants received TV-46046 undiluted (120 mg/0.3 mL of 400 mg/mL) subcutaneous (SC) injection as a test formulation.	TV-46046 Diluted n=22 Participants Participants received TV-46046 saline-diluted (60 mg/0.3 mL of 200 mg/mL) SC injection as a test formulation.	TV-46046 Placebo n=22 Participants Participants received TV-46046 placebo (0.3 mL) SC injection.	Depo-subQ 104 n=22 Participants Participants received Depo-subQ 104 (medroxyprogesterone acetate injectable suspension; 104 mg/0.65 mL) SC injection as a reference formulation.
Participant's Perception of Pain, as Assessed by an Overall Ranking of the 4 Study Injections From Least to Most Painful Pain Rank 1	4 frequency (number of times) of ranking	5 frequency (number of times) of ranking	4 frequency (number of times) of ranking	9 frequency (number of times) of ranking
Participant's Perception of Pain, as Assessed by an Overall Ranking of the 4 Study Injections From Least to Most Painful Pain Rank 2	8.5 frequency (number of times) of ranking	8.5 frequency (number of times) of ranking	0 frequency (number of times) of ranking	5 frequency (number of times) of ranking
Participant's Perception of Pain, as Assessed by an Overall Ranking of the 4 Study Injections From Least to Most Painful Pain Rank 3	4.5 frequency (number of times) of ranking	4.5 frequency (number of times) of ranking	6 frequency (number of times) of ranking	7 frequency (number of times) of ranking
Participant's Perception of Pain, as Assessed by an Overall Ranking of the 4 Study Injections From Least to Most Painful Pain Rank 4	5 frequency (number of times) of ranking	4 frequency (number of times) of ranking	12 frequency (number of times) of ranking	1 frequency (number of times) of ranking

SECONDARY outcome

Timeframe: Day 0 up to Month 18

Population: The treated analysis set included all participants who received at least 1 of the 4 study drug injections.

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.

Outcome measures

Outcome measures
Measure	TV-46046 Undiluted n=27 Participants Participants received TV-46046 undiluted (120 mg/0.3 mL of 400 mg/mL) subcutaneous (SC) injection as a test formulation.	TV-46046 Diluted Participants received TV-46046 saline-diluted (60 mg/0.3 mL of 200 mg/mL) SC injection as a test formulation.	TV-46046 Placebo Participants received TV-46046 placebo (0.3 mL) SC injection.	Depo-subQ 104 Participants received Depo-subQ 104 (medroxyprogesterone acetate injectable suspension; 104 mg/0.65 mL) SC injection as a reference formulation.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	23 Participants	—	—	—

Adverse Events

Follow-up After Treatment

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

TV-46046 Undiluted

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

TV-46046 Diluted

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

TV-46046 Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Depo-subQ 104

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Follow-up After Treatment n=27 participants at risk All Participants were followed for at least 6 months after receiving their injections. Participants with unresolved injection site reactions (ISRs) were followed monthly through the resolution of ISRs or Month 18, whichever came first.	TV-46046 Undiluted n=27 participants at risk Participants received TV-46046 undiluted (120mg/0.3 mL of 400 mg/mL) SC injection as a test formulation.	TV-46046 Diluted n=27 participants at risk Participants received TV-46046 saline-diluted (60 mg/0.3 mL of 200 mg/mL) SC injection as a test formulation.	TV-46046 Placebo n=27 participants at risk Participants received TV-46046 placebo SC injection.	Depo-subQ 104 n=27 participants at risk Participants received Depo-subQ 104 (medroxyprogesterone acetate injectable suspension; 104 mg/0.65 mL) SC injection as a reference formulation.
Hepatobiliary disorders Cholelithiasis	3.7% 1/27 • Number of events 1 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".

Other adverse events

Other adverse events
Measure	Follow-up After Treatment n=27 participants at risk All Participants were followed for at least 6 months after receiving their injections. Participants with unresolved injection site reactions (ISRs) were followed monthly through the resolution of ISRs or Month 18, whichever came first.	TV-46046 Undiluted n=27 participants at risk Participants received TV-46046 undiluted (120mg/0.3 mL of 400 mg/mL) SC injection as a test formulation.	TV-46046 Diluted n=27 participants at risk Participants received TV-46046 saline-diluted (60 mg/0.3 mL of 200 mg/mL) SC injection as a test formulation.	TV-46046 Placebo n=27 participants at risk Participants received TV-46046 placebo SC injection.	Depo-subQ 104 n=27 participants at risk Participants received Depo-subQ 104 (medroxyprogesterone acetate injectable suspension; 104 mg/0.65 mL) SC injection as a reference formulation.
Gastrointestinal disorders Abdominal pain lower	7.4% 2/27 • Number of events 2 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".
General disorders Injection site pain	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	3.7% 1/27 • Number of events 1 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	7.4% 2/27 • Number of events 2 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".
Infections and infestations Acarodermatitis	11.1% 3/27 • Number of events 3 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".
Infections and infestations Influenza	11.1% 3/27 • Number of events 3 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".
Infections and infestations Urinary tract infection	11.1% 3/27 • Number of events 3 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".
Infections and infestations Vulvitis	7.4% 2/27 • Number of events 2 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".
Nervous system disorders Dizziness	11.1% 3/27 • Number of events 3 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".
Nervous system disorders Headache	29.6% 8/27 • Number of events 13 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".
Reproductive system and breast disorders Breast pain	11.1% 3/27 • Number of events 3 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".
Reproductive system and breast disorders Dysmenorrhoea	7.4% 2/27 • Number of events 2 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".	0.00% 0/27 • Day 0 up to Month 18 The treated analysis set included all participants who received at least 1 of the 4 study injections. The adverse events which occurred during the follow-up are reported in a separate arm "Follow-up After Treatment".

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products R&D, Inc.

Phone: 1-888-483-8279

Email: [email protected]

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