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| Name | Class |
|---|---|
| FHI 360 | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TV-46046 Undiluted | Experimental | 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 | Experimental | 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 | Placebo Comparator | 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 | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TV-46046 | Drug | TV-46046 will be administered per dose and schedule specified in the arm. |
|
| 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 |
| 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 |
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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
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
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| Name | Affiliation | Role |
|---|---|---|
| Teva Medical Expert, MD | Teva Branded Pharmaceutical Products R&D, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Teva Investigational Site 1 | Santo Domingo | Dominican Republic |
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
The treated analysis set included all participants who received at least 1 of the 4 study drug injections.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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). | 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. | Posted | Count of Participants | Participants | Day 0 (immediately after and 1 hour after the injection) up to Month 18 |
|
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".
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Follow-up After Treatment | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cholelithiasis | Hepatobiliary disorders | MedDRA 21.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain lower | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director, Clinical Research | Teva Branded Pharmaceutical Products R&D, Inc. | 1-888-483-8279 | USMedInfo@tevapharm.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 18, 2020 | Sep 29, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 3, 2019 | Sep 29, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D017258 | Medroxyprogesterone Acetate |
| ID | Term |
|---|---|
| D008525 | Medroxyprogesterone |
| D006908 | Hydroxyprogesterones |
| D011374 | Progesterone |
| D011282 | Pregnenediones |
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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).
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| Depo-subQ 104 | Drug | Depo-subQ 104 will be administered per dose and schedule specified in the arm. |
|
|
| TV-46046 Placebo | Drug | TV-46046 Placebo will be administered per schedule specified in the arm. |
|
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 |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| OG001 |
| TV-46046 Diluted |
Participants received TV-46046 saline-diluted (60 mg/0.3 mL of 200 mg/mL) SC injection as a test formulation. |
| OG002 | TV-46046 Placebo | Participants received TV-46046 placebo (0.3 mL) SC injection. |
| OG003 | Depo-subQ 104 | Participants received Depo-subQ 104 (medroxyprogesterone acetate injectable suspension; 104 mg/0.65 mL) SC injection as a reference formulation. |
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | Day 0 (Immediately after and 1 hour after injection) |
|
|
|
| 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). | 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. | Posted | Number | frequency (number of times) of ranking | Day 0 (1 hour after injection) |
|
|
|
| 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. | The treated analysis set included all participants who received at least 1 of the 4 study drug injections. | Posted | Count of Participants | Participants | Day 0 up to Month 18 |
|
|
|
| 0 |
| 27 |
| 1 |
| 27 |
| 18 |
| 27 |
| EG001 | TV-46046 Undiluted | Participants received TV-46046 undiluted (120mg/0.3 mL of 400 mg/mL) SC injection as a test formulation. | 0 | 27 | 0 | 27 | 0 | 27 |
| EG002 | TV-46046 Diluted | Participants received TV-46046 saline-diluted (60 mg/0.3 mL of 200 mg/mL) SC injection as a test formulation. | 0 | 27 | 0 | 27 | 1 | 27 |
| EG003 | TV-46046 Placebo | Participants received TV-46046 placebo SC injection. | 0 | 27 | 0 | 27 | 2 | 27 |
| EG004 | Depo-subQ 104 | Participants received Depo-subQ 104 (medroxyprogesterone acetate injectable suspension; 104 mg/0.65 mL) SC injection as a reference formulation. | 0 | 27 | 0 | 27 | 0 | 27 |
| Injection site pain | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Acarodermatitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Vulvitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Breast pain | Reproductive system and breast disorders | MedDRA 21.1 | Systematic Assessment |
|
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA 21.1 | Systematic Assessment |
|
Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
| D011283 |
| Pregnenes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| 1 hour after injection |
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| Pain Rank 2 |
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| Pain Rank 3 |
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| Pain Rank 4 |
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