Ovulation Suppression
Conditions
Keywords
contraception, pregnancy prevention
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.
Interventions
pregnancy prevention
Sponsors
Agile Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
Planned enrollment included: approximately 30 subjects in the AG200LE treatment group, 30 subjects in the AG200 treatment group and 20 to 30 subjects in the AG200 15 treatment group. Actual enrollment included: 45 subjects in the AG200 treatment group; 45 subjects in the AG200LE treatment group; and 33 subjects in the AG200-15 treatment group.
Pre-assignment details
: Subjects enrolled were healthy adult women aged 18-45 years with a history of regular menstrual cycles (i.e., lasting between 21 and 35 days) and no disorders precluding hormonal contraceptive use.
Participants by arm
| Arm | Count |
|---|---|
| AG200LE Transdermal Contraceptive Delivery System a 12.5 cm2 patch (Lot #27621) containing 2.17 LNG/1.28 EE mg (designed to deliver approximately: 0.075 LNG/0.015 EE mg/day). | 43 |
| AG200 Transdermal Contraceptive Delivery System a 12.5 cm2 patch (Lot #27620) containing 2.17 LNG/1.92 EE mg (designed to deliver approximately: 0.1 LNG/0.02 EE mg/day). | 44 |
| AG200-15 Transdermal Contraceptive System a 15 cm2 patch (Lot #27620) containing 2.60 LNG/2.30 EE mg (designed to deliver approximately: 0.12 LNG/0.025 EE mg/day). | 31 |
| Total | 118 |
Baseline characteristics
| Characteristic | AG200 Transdermal Contraceptive Delivery System | AG200-15 Transdermal Contraceptive System | AG200LE Transdermal Contraceptive Delivery System | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 44 Participants | 31 Participants | 43 Participants | 118 Participants |
| Age, Continuous | 31 years STANDARD_DEVIATION 6.9 | 32.1 years STANDARD_DEVIATION 7.8 | 31.7 years STANDARD_DEVIATION 7.4 | 31.6 years STANDARD_DEVIATION 7.3 |
| Region of Enrollment United States | 44 Participants | 31 Participants | 43 Participants | 118 Participants |
| Sex: Female, Male Female | 44 Participants | 31 Participants | 43 Participants | 118 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 44 | 0 / 31 |
| other Total, other adverse events | 19 / 43 | 29 / 44 | 19 / 31 |
| serious Total, serious adverse events | 0 / 43 | 0 / 44 | 0 / 31 |
Outcome results
Primary
Cycle Control
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.
Time frame: 3 months
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AG200LE | Cycle Control | 0.29 number of episodes | Standard Deviation 0.46 |
| AG200 | Cycle Control | 0.29 number of episodes | Standard Deviation 0.46 |
| AG200-15 | Cycle Control | 0.15 number of episodes | Standard Deviation 0.36 |
Primary
Ovulation Suppression in Three Treatment Groups Over 3 Cycles
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.
Time frame: 3 months
Population: ITT, perfect compliance, complete progesterone, verifiable compliance
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AG200LE | Ovulation Suppression in Three Treatment Groups Over 3 Cycles | ITT, perfect compliance | 36.5 %of cycles with possible ovulation |
| AG200LE | Ovulation Suppression in Three Treatment Groups Over 3 Cycles | Complete progesterone, perfect compliance | 36.9 %of cycles with possible ovulation |
| AG200LE | Ovulation Suppression in Three Treatment Groups Over 3 Cycles | ITT, verifiable compliance | 32.5 %of cycles with possible ovulation |
| AG200LE | Ovulation Suppression in Three Treatment Groups Over 3 Cycles | Complete progesterone, verifiable compliance | 32.5 %of cycles with possible ovulation |
| AG200 | Ovulation Suppression in Three Treatment Groups Over 3 Cycles | Complete progesterone, verifiable compliance | 14.9 %of cycles with possible ovulation |
| AG200 | Ovulation Suppression in Three Treatment Groups Over 3 Cycles | ITT, perfect compliance | 20.7 %of cycles with possible ovulation |
| AG200 | Ovulation Suppression in Three Treatment Groups Over 3 Cycles | ITT, verifiable compliance | 14.9 %of cycles with possible ovulation |
| AG200 | Ovulation Suppression in Three Treatment Groups Over 3 Cycles | Complete progesterone, perfect compliance | 20.7 %of cycles with possible ovulation |
| AG200-15 | Ovulation Suppression in Three Treatment Groups Over 3 Cycles | Complete progesterone, verifiable compliance | 12.0 %of cycles with possible ovulation |
| AG200-15 | Ovulation Suppression in Three Treatment Groups Over 3 Cycles | Complete progesterone, perfect compliance | 11.7 %of cycles with possible ovulation |
| AG200-15 | Ovulation Suppression in Three Treatment Groups Over 3 Cycles | ITT, verifiable compliance | 12.0 %of cycles with possible ovulation |
| AG200-15 | Ovulation Suppression in Three Treatment Groups Over 3 Cycles | ITT, perfect compliance | 11.5 %of cycles with possible ovulation |