A Pharmacokinetic Study to Evaluate the Bioequivalence of 2 Progesterone Vaginal Rings in Postmenopausal Women

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

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

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics
• Intervention / Treatment: Drug: Progesterone vaginal ring,

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States
      • Teva Investigational Site 12355

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A; 1 ring intravaginal for 7 days, produced from the new process	Drug: Progesterone vaginal ring,; Participants will be randomized to receive treatments in 1 of 2 treatment sequences (AB or BA); Other Names: Treatment A - DR-201, progesterone vaginal ring, 20% (w/w),; 11 mg/day, produced from the NEW process and; Treatment B - DR-201, progesterone vaginal ring, 20% (w/w),; 11 mg/day, produced from the LEGACY process
Experimental: Treatment B; 1 ring intravaginal for 7 days, produced from the legacy process	Drug: Progesterone vaginal ring,; Participants will be randomized to receive treatments in 1 of 2 treatment sequences (AB or BA); Other Names: Treatment A - DR-201, progesterone vaginal ring, 20% (w/w),; 11 mg/day, produced from the NEW process and; Treatment B - DR-201, progesterone vaginal ring, 20% (w/w),; 11 mg/day, produced from the LEGACY process

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
baseline-adjusted AUCt	16 weeks
baseline-adjusted AUC∞	16 weeks
baseline-adjusted Cmax	16 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
baseline-adjusted tmax	16 weeks
baseline-unadjusted AUCt	16 weeks
baseline-adjusted λz	16 weeks
baseline-adjusted t½	16 weeks
baseline-unadjusted AUC∞	16 weeks
baseline-unadjusted Cmax	16 weeks
baseline-unadjusted tmax	16 weeks
baseline-unadjusted λz	16 weeks
baseline-unadjusted t½	16 weeks

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
• Investigators: Study Director: Medical Expert, MD, Teva Branded Pharmaceutical Products R&D, Inc.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: February 28, 2014
• First Submitted That Met QC Criteria: March 18, 2014
• First Posted (Estimate): March 20, 2014

Study Record Updates

• Last Update Posted (Actual): November 9, 2021
• Last Update Submitted That Met QC Criteria: November 6, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: DR201-BE-10021

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No