Phase 1
N=12
Study to Evaluate Suppression of Ovulation and Pharmacokinetics of Medroxyprogesterone Acetate Following Administration of TV-46046 in Women With Ovulatory Cycle
Pregnancy · Contraception
Bottom Line
View on ClinicalTrials.gov: NCT02817464 ↗Enrolled (actual)
12
Serious AEs
8.3%
Results posted
Feb 2024
Primary outcome: Primary: Part 1: Serum Medroxyprogesterone Acetate (MPA) Concentration at Day 1 — 0.36; 0.67 nanograms (ng)/milliliter (mL)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- TV-46046 - 400 mg/mL (Drug); TV-46046 - 200 mg/mL (Drug)
- Age
- Adult · 18+ yrs
- Sex
- Female
- Sponsor
- Teva Branded Pharmaceutical Products R&D, Inc.
- Primary completion
- Dec 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Serum Medroxyprogesterone Acetate (MPA) Concentration at Day 1 |
0.36; 0.67 | — |
| PRIMARY Part 1: Serum MPA Concentration at Day 7 |
0.37; 0.70 | — |
| PRIMARY Part 1: Serum MPA Concentration at Day 28 |
0.36; 0.69 | — |
| PRIMARY Part 1: Serum MPA Concentration at Day 91 |
0.41; 0.62 | — |
| PRIMARY Part 1: Serum MPA Concentration at Day 182 |
0.22; 0.17 | — |
| PRIMARY Part 1: Serum MPA Concentration at Day 210 |
0.20; 0.12 | — |
| PRIMARY Part 1: Maximum Observed Serum Concentration (Cmax) of MPA |
0.53; 0.97 | — |
| PRIMARY Part 1: Observed Serum Drug Concentration at Day 182 (C182) of MPA |
0.21; 0.14 | — |
| PRIMARY Part 1: Time to Reach Cmax (Tmax) of MPA |
9.49; 47.99 | — |
| PRIMARY Part 1: Area Under the Serum Drug Concentration by Time Curve From Time 0 to Day 182 (AUC0-182) of MPA |
58.61; 97.72 | — |
| PRIMARY Part 1: Area Under the Serum Drug Concentration by Time Curve From Time 0 to Day 210 (AUC0-210) of MPA |
63.91; 103.11 | — |
| PRIMARY Part 1: Area Under the Serum Drug Concentration by Time Curve From Time 0 to Infinity (AUC0-∞) of MPA |
94.56; 114.13 | — |
| PRIMARY Part 1: Apparent Terminal Half-life (t1/2) of MPA |
82.87; 42.34 | — |
| PRIMARY Part 2: Time to Ovulation |
— | — |
| SECONDARY Part 1: Time to Ovulation |
328; 251 | 0.0073 sig |
| SECONDARY Part 2: Cmax of MPA |
— | — |
| SECONDARY Part 2: Tmax of MPA |
— | — |
| SECONDARY Part 2: Observed Serum Drug Concentration at Day 210 (C210) of MPA |
— | — |
| SECONDARY Part 2: C182 of MPA |
— | — |
| SECONDARY Part 2: AUC0-182 of MPA |
— | — |
| SECONDARY Part 2: AUC0-210 of MPA |
— | — |
| SECONDARY Part 2: AUC0-∞ of MPA |
— | — |
| SECONDARY Part 2: Apparent Terminal Half Life (t1/2) of MPA |
— | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |
6; 6 | — |
Summary
The purpose of this pharmacodynamic and pharmacokinetic study is to identify a dose of TV-46046 (within the range 80 to 300 mg) that is both safe and consistent with contraceptive effect when injected every 6 months.
Eligibility Criteria
Inclusion Criteria
- has regular menstrual cycle (24 to 35 days)
- is at low risk of pregnancy (ie, sterilized, in exclusively same-sex partnership, in monogamous relationship with vasectomized partner, or using non-hormonal IUD)
- is in good general health as determined by a medical history and physical examination
- is not pregnant and does not have desire to become pregnant in the subsequent 36 months
- has had a normal mammogram within the last year (for Part 1 only)
- additional criteria apply, please contact the investigator for more information
Exclusion Criteria
- has hypertension:
- systolic blood pressure (BP) ≥160 mm Hg or diastolic BP ≥100 mm Hg
- vascular disease
- has current or history of ischemic heart disease
- has history of stroke
- has history of thromboembolic event
- has systemic lupus erythematosus
- positive (or unknown) antiphospholipid antibodies
- severe thrombocytopenia
- has rheumatoid arthritis on immunosuppressive therapy
- has migraine with aura
- has unexplained vaginal bleeding
- has diabetes
- has strong family history of breast cancer (defined as one or more first degree relatives, breast cancer occurring before menopause in three or more family members, regardless of degree of relationship, and any male family member with breast cancer), or current or history of breast cancer, or undiagnosed mass detected by breast exam
- has current or history of cervical cancer
- has severe cirrhosis (decompensated) or liver tumors
- has known significant renal disease
- used Depo-Provera Contraceptive Injection or Depo-subcutaneous Provera 104 (DMPA) products in the past 12 months
- used any of the following medications within 1 month prior to enrollment:
- any investigational drug
- prohibited drugs per protocol
- oral contraceptives, contraceptive ring or patch
- levonorgestrel intrauterine system (LNG IUS) or contraceptive implant
- used a combined injectable contraceptive in the past 6 months
- less than 3 months since the end of last pregnancy
- currently lactating
- is using or plans to use prohibited drugs per protocol in the next 18 months
- has known sensitivity to MPA or inactive ingredients
- has a plan to move to another location in the next 24 months
- in the opinion of the investigator, potentially at elevated risk of HIV infection (eg, HIV -positive partner, IV drug use by self or by partner)
- additional criteria apply, please contact the investigator for more information
Data sourced from ClinicalTrials.gov (NCT02817464). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.