Clinical trial NCT02817464: Study to Evaluate Suppression of Ovulation and Pharmacokinetics of Medroxyprogesterone Acetate Following Administration of TV-46046 in Women With Ovulatory Cycle
Official title: A Two-part, Phase 1, Exploratory and Dose-range Finding Study to Evaluate Suppression of Ovulation and Pharmacokinetics of Medroxyprogesterone Acetate Following a Single Subcutaneous Administration of TV-46046 in Women With Ovulatory Cycle
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pregnancy
Contraception
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
Collaborators: name: FHI 360
First posted: 2016-06-29
Enrollment: 12
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief 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

Primary outcomes:
measure: Part 1: Serum Medroxyprogesterone Acetate (MPA) Concentration at Day 1
timeFrame: Day 1
measure: Part 1: Serum MPA Concentration at Day 7
timeFrame: Day 7
measure: Part 1: Serum MPA Concentration at Day 28
timeFrame: Day 28
measure: Part 1: Serum MPA Concentration at Day 91
timeFrame: Day 91
measure: Part 1: Serum MPA Concentration at Day 182
timeFrame: Day 182
measure: Part 1: Serum MPA Concentration at Day 210
timeFrame: Day 210
measure: Part 1: Maximum Observed Serum Concentration (Cmax) of MPA
timeFrame: Day 0 up to Week 52
measure: Part 1: Observed Serum Drug Concentration at Day 182 (C182) of MPA
timeFrame: Day 182
measure: Part 1: Time to Reach Cmax (Tmax) of MPA
timeFrame: Day 0 up to Week 52
measure: Part 1: Area Under the Serum Drug Concentration by Time Curve From Time 0 to Day 182 (AUC0-182) of MPA
timeFrame: Day 0 up to Day 182
measure: Part 1: Area Under the Serum Drug Concentration by Time Curve From Time 0 to Day 210 (AUC0-210) of MPA
timeFrame: Day 0 up to Day 210
measure: Part 1: Area Under the Serum Drug Concentration by Time Curve From Time 0 to Infinity (AUC0-∞) of MPA
timeFrame: Day 0 up to Week 52
measure: Part 1: Apparent Terminal Half-life (t1/2) of MPA
timeFrame: Day 0 up to Week 52
measure: Part 2: Time to Ovulation
timeFrame: Day 0 up to Week 78
Secondary outcomes:
measure: Part 1: Time to Ovulation
timeFrame: Day 0 up to Week 78
measure: Part 2: Cmax of MPA
timeFrame: Day 0 up to Week 52
measure: Part 2: Tmax of MPA
timeFrame: Day 0 up to Week 52
measure: Part 2: Observed Serum Drug Concentration at Day 210 (C210) of MPA
timeFrame: Day 0 up to Day 210
measure: Part 2: C182 of MPA
timeFrame: Day 0 up to Day 182
measure: Part 2: AUC0-182 of MPA
timeFrame: Day 0 up to Day 182
measure: Part 2: AUC0-210 of MPA
timeFrame: Day 0 up to Day 210
measure: Part 2: AUC0-∞ of MPA
timeFrame: Day 0 up to Week 52
measure: Part 2: Apparent Terminal Half Life (t1/2) of MPA
timeFrame: Day 0 up to Week 52
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Day 0 up to Week 78
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Teva Investigational Site 001
state: Pennsylvania
city: Norfolk
country: United States
facility: Teva Investigational Site 002
state: Virginia
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Teva Medical Expert, MD
role: STUDY_DIRECTOR
References: