Evaluation of Pharmacodynamic Effects on Ovulation and Cycle Control

Phase 2

Completed

• Conditions: Ovulation Suppression
• Interventions: Drug: levonorgestrel and ethinyl estradiol

• Registration Number: NCT01250210
• Lead Sponsor: Agile Therapeutics

Brief Summary

Evaluate the adequacy of ovulation suppression, cycle control, and safety of three transdermal contraceptive delivery systems (TCDSs).

Detailed Description

The primary objective was to evaluate the adequacy of ovulation suppression, cycle control, and safety of three transdermal contraceptive delivery systems (TCDSs) containing 2 different doses of levonorgestrel (LNG) and 3 different doses of ethinyl estradiol (EE) during 3 consecutive cycles of administration of each treatment.

Study Timeline

• Study Start: 2007-09
• Primary Completion: 2008-02
• Study Completion: 2008-02
• Study First Submitted: 2010-11-29
• Study First Submitted QC: 2010-11-29
• Study First Posted: 2010-11-30
• Results First Submitted: 2013-01-22
• Status Verified: 2018-07
• Results First Submitted QC: 2018-07-03
• Last Update Submitted: 2018-07-03
• Results First Posted: 2018-07-05
• Last Update Posted: 2018-07-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 123

Inclusion Criteria

1. Healthy adult women, ages 18-45.
2. Cycles with a usual duration between 21 and 35 days and an individual variation of +/ 3 days.
3. Normotensive (blood pressure < 140/90 mm Hg at rest) at screening and randomization visits (Visits 1 and 2).
4. Willing to use a non-hormonal method of contraception for the entire duration of the study, or
5. Have already undergone previous bilateral tubal ligation OR vasectomized partner OR not at risk of pregnancy.
6. Willing to refrain from excessive use of alcohol during the entire duration of the study.
7. Willing to give informed consent to participate in the study.

Exclusion Criteria

1. History of significant medical illness or seizures.
2. Positive hepatitis B or C antibody or positive human immunodeficiency virus (HIV) antibody.
3. Known or suspected pregnancy.
4. A recent abnormal cervical smear - low-grade squamous intraepithelial lesion (SIL) or higher in the Bethesda System - which has not been resolved or treated.
5. Any disorder that contraindicates the use of contraceptive steroids i.e., history of heart attack and stroke, blood clots in the legs, lungs or eyes, history of blood clots in the deep veins of the legs, known or suspected breast cancer, hepatitis or yellowing of the whites of the eyes or the skin (jaundice) during pregnancy or during previous use of hormonal contraceptives, headaches with neurological symptoms, disease of heart valves with complications.
6. Uncontrolled thyroid disorder.
7. History of or existing thromboembolic disorder, vascular disease, cerebral vascular, or coronary artery disease.
8. Undiagnosed abnormal genital bleeding.
9. Known or suspected breast carcinoma, endometrial carcinoma, or estrogen-dependent neoplasia.
10. History or presence of dermal hypersensitivity in response to topical application.
11. Use of an injectable hormonal contraceptive (e.g. Depo-Provera®) within 6 months prior to Day 1.
12. Use of a contraceptive implant (e.g. Implanon® or Jadelle®) or hormone-medicated intrauterine device within 2 months (60 days) prior to Day 1.
13. Use of OCs or other sex steroid hormones within 60 days prior to Day 1.
14. Women who are breast-feeding or are within 2 months of stopping breast-feeding.
15. Status post-partum or post-abortion within a period of 2 months prior to Day 1.
16. Chronic use of any medication that might interfere with the metabolism of hormone contraceptives (e.g., rifampin, barbiturates, phenytoin, primidone, topiramate, carbamazepine, phenylbutazone, ritonavir, modafinil, St John's Wort etc.) or use within the past 3 months prior to Day 1.
17. Administration of investigational drug within 30 days prior to Day 1.
18. A history (within prior 12 months) of drug or alcohol abuse.
19. Women who smoke more than 4-5 cigarettes daily.
20. History of skin sensitivity to adhesives.
21. Use of over-the-counter medications or herbals that might interfere with the metabolism of hormone contraceptives within 3 days prior to wearing the first patch.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AG200LE	levonorgestrel and ethinyl estradiol	Drug intervention with levonorgestrel and ethinyl estradiol: AG200LE a transdermal contraceptive system containing 2.17 mg of levonorgestrel and 1.28 mg of ethinyl estradiol.
AG200	levonorgestrel and ethinyl estradiol	Drug intervention with levonorgestrel and ethinyl estradiol: AG200 a transdermal contraceptive system containing 2.17 mg of levonorgestrel and 1.92 of ethinyl estradiol.
AG200-15	levonorgestrel and ethinyl estradiol	Drug intervention with levonorgestrel and ethinyl estradiol : AG200-15 a transdermal contraceptive system containing 2.60 mg of levonorgestrel and 2.30 mg of ethinyl estradiol.

Primary Outcome Measures

Name	Time	Method
Ovulation Suppression in Three Treatment Groups Over 3 Cycles	3 months	Ovulation suppression measured by possible ovulation. Possible ovulation is defined as cycles with greatest progesterone level ≥4.7 ng/mL across Cycles 1-3 combined for each Arm/Group. The following four primary analysis datasets are: Intent-to-treat (ITT): At least 1 study patch was applied and at least 1 progesterone measurement is available at 1 of the nominal data collection points.; Complete progesterone: At least 1 study patch was applied and at least 3 progesterone measurements are available across any of the data collection points.; Perfect compliance: If no patch has been off \>1 day and no more than 1 day has elapsed between patch changes.; Verifiable compliance: is a cycle during which at least 1 study patch was applied and where LNG and EE measurements were available at each of the nominal data collection points of Days 8, 15, and 22, and all values were above the lower detection limit.
Cycle Control	3 months	The incidence of breakthrough bleeding (BTB) and/or spotting (S) episodes in Cycle 3 for ITT cycles. A BTB/S episode was defined as any number of days with BTB and/or BTS preceded and followed by at least 2 bleeding-free days.