Contraception
Conditions
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.
Interventions
DRUGTV-46046
TV-46046 will be administered per dose and schedule specified in the arm.
DRUGDepo-subQ 104
Depo-subQ 104 will be administered per dose and schedule specified in the arm.
DRUGTV-46046 Placebo
TV-46046 Placebo will be administered per schedule specified in the arm.
Sponsors
FHI 360
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Masking description
The study will be partially blinded due to differences in appearance and volume of the treatments. Designated unblinded study staff will conduct randomization procedures. The staff preparing and administering injections will also be unblinded to treatment sequence but will be trained to shield the syringe prior to and at the time of injection from view of the participant and study staff assessing injection site reactions (ISRs).
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Dominican Republic
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Study 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. | 27 |
| Total | 27 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 35.7 years STANDARD_DEVIATION 6.2 |
| Race/Ethnicity, Customized Race Biracial | 26 Participants |
| Race/Ethnicity, Customized Race Black or African American | 1 Participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 27 | 0 / 27 | 0 / 27 | 0 / 27 |
| other Total, other adverse events | 18 / 27 | 0 / 27 | 1 / 27 | 2 / 27 | 0 / 27 |
| serious Total, serious adverse events | 1 / 27 | 0 / 27 | 0 / 27 | 0 / 27 | 0 / 27 |
Outcome results
Primary
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).
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TV-46046 Undiluted | Number of Participants With Injection Site Reactions (ISRs) (Excluding Injection Site Pain) | 12 Participants |
| TV-46046 Diluted | Number of Participants With Injection Site Reactions (ISRs) (Excluding Injection Site Pain) | 6 Participants |
| TV-46046 Placebo | Number of Participants With Injection Site Reactions (ISRs) (Excluding Injection Site Pain) | 0 Participants |
| Depo-subQ 104 | Number of Participants With Injection Site Reactions (ISRs) (Excluding Injection Site Pain) | 8 Participants |
Secondary
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TV-46046 Undiluted | Injection Site Pain Score, as Assessed by Numerical Rating Scale (NRS) | Immediately after injection | 2.1 units on a scale | Standard Deviation 1.72 |
| TV-46046 Undiluted | Injection Site Pain Score, as Assessed by Numerical Rating Scale (NRS) | 1 hour after injection | 0.2 units on a scale | Standard Deviation 0.5 |
| TV-46046 Diluted | Injection Site Pain Score, as Assessed by Numerical Rating Scale (NRS) | 1 hour after injection | 0.2 units on a scale | Standard Deviation 0.5 |
| TV-46046 Diluted | Injection Site Pain Score, as Assessed by Numerical Rating Scale (NRS) | Immediately after injection | 1.9 units on a scale | Standard Deviation 1.46 |
| TV-46046 Placebo | Injection Site Pain Score, as Assessed by Numerical Rating Scale (NRS) | Immediately after injection | 3.3 units on a scale | Standard Deviation 2.15 |
| TV-46046 Placebo | Injection Site Pain Score, as Assessed by Numerical Rating Scale (NRS) | 1 hour after injection | 0.6 units on a scale | Standard Deviation 1 |
| Depo-subQ 104 | Injection Site Pain Score, as Assessed by Numerical Rating Scale (NRS) | Immediately after injection | 1.2 units on a scale | Standard Deviation 1.4 |
| Depo-subQ 104 | Injection Site Pain Score, as Assessed by Numerical Rating Scale (NRS) | 1 hour after injection | 0.1 units on a scale | Standard Deviation 0.29 |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TV-46046 Undiluted | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 23 Participants |
Secondary
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).
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TV-46046 Undiluted | 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 |
| TV-46046 Undiluted | 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 |
| TV-46046 Undiluted | 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 |
| TV-46046 Undiluted | 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 |
| TV-46046 Diluted | Participant's Perception of Pain, as Assessed by an Overall Ranking of the 4 Study Injections From Least to Most Painful | Pain Rank 4 | 4 frequency (number of times) of ranking |
| TV-46046 Diluted | 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 |
| TV-46046 Diluted | 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 |
| TV-46046 Diluted | Participant's Perception of Pain, as Assessed by an Overall Ranking of the 4 Study Injections From Least to Most Painful | Pain Rank 1 | 5 frequency (number of times) of ranking |
| TV-46046 Placebo | Participant's Perception of Pain, as Assessed by an Overall Ranking of the 4 Study Injections From Least to Most Painful | Pain Rank 3 | 6 frequency (number of times) of ranking |
| TV-46046 Placebo | Participant's Perception of Pain, as Assessed by an Overall Ranking of the 4 Study Injections From Least to Most Painful | Pain Rank 4 | 12 frequency (number of times) of ranking |
| TV-46046 Placebo | Participant's Perception of Pain, as Assessed by an Overall Ranking of the 4 Study Injections From Least to Most Painful | Pain Rank 2 | 0 frequency (number of times) of ranking |
| TV-46046 Placebo | 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 |
| Depo-subQ 104 | Participant's Perception of Pain, as Assessed by an Overall Ranking of the 4 Study Injections From Least to Most Painful | Pain Rank 4 | 1 frequency (number of times) of ranking |
| Depo-subQ 104 | Participant's Perception of Pain, as Assessed by an Overall Ranking of the 4 Study Injections From Least to Most Painful | Pain Rank 1 | 9 frequency (number of times) of ranking |
| Depo-subQ 104 | Participant's Perception of Pain, as Assessed by an Overall Ranking of the 4 Study Injections From Least to Most Painful | Pain Rank 2 | 5 frequency (number of times) of ranking |
| Depo-subQ 104 | Participant's Perception of Pain, as Assessed by an Overall Ranking of the 4 Study Injections From Least to Most Painful | Pain Rank 3 | 7 frequency (number of times) of ranking |