Clinical trial NCT02092571: A Pharmacokinetic Study to Evaluate the Bioequivalence of 2 Progesterone Vaginal Rings in Postmenopausal Women
Official title: An Open-Label, Single-Dose, Randomized, 2-Treatment, 2-Period Crossover Pharmacokinetic Study to Evaluate the Bioequivalence of 2 Progesterone Vaginal Rings 20% (w/w) in Postmenopausal Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacokinetics
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2014-03-20
Enrollment: 56
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: A study to assess the pharmacokinetics of 2 progesterone vaginal rings in postmenopausal women


Eligibility criteria: Inclusion:

1. Naturally postmenopausal woman with an intact uterus, 40 to 70 years of age, inclusive.
2. The subject has serum estradiol and FSH levels that are consistent with the subject being postmenopausal.
3. The subject has no clinically significant abnormality findings observed during pelvic, breast, and vaginal examination or based on mammogram and Pap smear evaluations.
4. The subject will agree to be treated with 1 mg/day estradiol oral tablets for at least 28 days before insertion of the first vaginal ring and throughout the study.

Exclusion:

1. The subject has a history or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, urologic, gynecologic, immunologic, dermatologic, neurologic, or psychiatric disease.
2. The subject has a history of toxic shock syndrome.
3. The subject has a history of jaundice associated with previous use of oral contraceptives.
4. The subject has contraindications to the use of estrogen or progesterone that include, but are not limited to, the following:

   * known sensitivity to estrogen or progesterone or related drugs
   * known hypersensitivity to study medication ingredients, including FD\&C Yellow No. 5 (tartrazine) present in estradiol tablets
   * undiagnosed vaginal bleeding or high risk for endometrial cancer
   * breast mass on examination
   * known, suspected, or family history of estrogen- or progesterone-dependent neoplasia (now or in the past)
5. The subject has low-grade squamous intraepithelial lesion (LSIL) or worse as observed in the Pap smear at screening. Any other abnormal finding on the Pap smear that the investigator considers clinically significant (such as atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion \[HSIL; ASC-H\], atypical glandular cells \[AGC\]); or any Pap result that would necessitate further evaluation by biopsy and/or colposcopy.
6. The subject has any abnormal finding or condition deemed clinically significant by the investigator at screening that is a contraindication to the use of progestins, estrogen, or a vaginal ring.
7. The subject has a positive pregnancy test at screening or at any time during the study.
8. Current treatment with progesterone, other progestins, or estrogen (other than estradiol 1-mg tablets, progesterone 200-mg capsules, or medroxyprogesterone acetate 10-mg tablets required for this study purpose).
9. Use of any of the following medications within the time frames noted below before the start of estrogen treatment:

   * vaginal hormonal products (rings, creams, or gels) within 7 days
   * transdermal estrogen alone or estrogen/progestin products within 28 days
   * oral estrogen or progestin therapy within 56 days
   * intrauterine progestin therapy within 56 days
   * progestin implants or estrogen alone injectable drug therapy within 3 months
   * estrogen pellet therapy or progestin injectable therapy within 6 months
10. The subject has a vaginal ultrasonography at screening that confirms an active endometrial lining and/or an endometrial thickness of ≥4 mm.

Primary outcomes:
measure: baseline-adjusted AUCt
timeFrame: 16 weeks
measure: baseline-adjusted AUC∞
timeFrame: 16 weeks
measure: baseline-adjusted Cmax
timeFrame: 16 weeks
Secondary outcomes:
measure: baseline-adjusted tmax
timeFrame: 16 weeks
measure: baseline-unadjusted AUCt
timeFrame: 16 weeks
measure: baseline-adjusted λz
timeFrame: 16 weeks
measure: baseline-adjusted t½
timeFrame: 16 weeks
measure: baseline-unadjusted AUC∞
timeFrame: 16 weeks
measure: baseline-unadjusted Cmax
timeFrame: 16 weeks
measure: baseline-unadjusted tmax
timeFrame: 16 weeks
measure: baseline-unadjusted λz
timeFrame: 16 weeks
measure: baseline-unadjusted t½
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Miami
country: United States
facility: Teva Investigational Site 12355
state: Florida
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Medical Expert, MD
role: STUDY_DIRECTOR
References: