Contraception
Conditions
Keywords
Contraceptive
Brief summary
The purpose of the study is to evaluate the efficacy and safety of a low dose transdermal contraceptive delivery system containing ethinyl estradiol and levonorgestrel.
Detailed description
Comparative evaluation of AG200-15 versus OC with regard to safety, contraceptive efficacy, cycle control (bleeding pattern), subject compliance and serum concentrations of EE and LNG. To evaluate TCDS wearability (including adhesion).
Interventions
DRUGAG200-15 (cycles 1-13)
AG200-15 containing ethinyl estradiol and levonorgestrel
DRUGLessina crossover to AG200-15
Low dose oral contraceptive containing 20 mcg ethinyl estradiol and 100 mcg Levonorgestrel in 21 day regimen for 6 cycles followed by AG200-15 for 6 cycles.
Sponsors
Agile Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
17 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy females * 17(in states where the legal age of consent to receive contraceptives is 17)-40 years * Regular, consistent menstrual cycles between 25 and 35 days * Sexually active women requesting birth control * In good general health, confirmed by medical history, physical (including gynecologic) examination and screening laboratory values
Exclusion criteria
* Known or suspected pregnancy; * Lactating women * Significant skin reaction to transdermal preparations or sensitivity to surgical / medical tape * Any disease that may worsen under hormonal treatment (cardiovascular, liver, metabolic) * Use of other contraceptive methods than study medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pregnancy | AG200-15: 6 months; Lessina: 6 months; AG200-15: 1 year | Pregnancy outcomes was determine by measuring Pearl index. Pearl Index is the number of on-therapy pregnancies times 1300 divided by the number of 28-day on-therapy cycles and is an estimate of the number of pregnancies per 100 woman-years of product use. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cycle Control | 6 months | Measuring the breakthrough bleeding (BTB) and/or breakthrough spotting (BTS). Measured as a percent of total number of cycles in each Arm/Group with BTB and/or BTS. |
| Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE) | Lessina: 6 months; AG200-15: 1 year; AG200-15: 6 months | Measurement of plasma concentrations of LNG and EE for cycles 2, 6 and 13. |
| Self-reported Irritation at Application Site | 1 year | Evaluation of irritation at application site was determined using the following scores: 0: None 1. Mild 2. Moderate 3. Severe |
| Patch Adhesion by Investigator Evaluation at Each Visit | 1 year | Evaluation of patch adhesion was determined using the following scores: 0: \>= 90% adhered (no lift) 1. \>= 75% adhered but \< 90% (some edges showing lift) 2. \>= 50% adhered but \< 75% (half of system lifts off) 3. \< 50% (\> half of system lifts off, but undetached) 4. patch completely detached |
| Self-reported Itching at Patch Application Site | 1 year | Evaluation of itching at patch application site was determined using the following scores: 0: None 1. Mild 2. Moderate 3. Severe |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AG200-15 Intervention is drug: AG200-15 containing ethinyl estradiol and levonorgestrel for cycles 1-13. | 1,043 |
| Lessina Crossover to AG200-15 Intervention with drug: Lessina containing 20 mcg ethinyl estradiol and 100 mcg levonorgestrel in 21 day regimen cycles 1-6 followed by AG200-15 for cycles 7-13. | 230 |
| Total | 1,273 |
Baseline characteristics
| Characteristic | Total | AG200-15 | Lessina Crossover to AG200-15 |
|---|---|---|---|
| Age, Categorical <=18 years | 7 Participants | 5 Participants | 2 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1266 Participants | 1038 Participants | 228 Participants |
| Age, Continuous | 26.46 years STANDARD_DEVIATION 5.677 | 26.38 years STANDARD_DEVIATION 5.663 | 26.86 years STANDARD_DEVIATION 5.738 |
| Region of Enrollment United States | 1273 participants | 1043 participants | 230 participants |
| Sex: Female, Male Female | 1273 Participants | 1043 Participants | 230 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1,273 | 1 / 344 |
| other Total, other adverse events | 484 / 1,273 | 112 / 344 |
| serious Total, serious adverse events | 14 / 1,273 | 4 / 344 |
Outcome results
Primary
Pregnancy
Pregnancy outcomes was determine by measuring Pearl index. Pearl Index is the number of on-therapy pregnancies times 1300 divided by the number of 28-day on-therapy cycles and is an estimate of the number of pregnancies per 100 woman-years of product use.
Time frame: AG200-15: 6 months; Lessina: 6 months; AG200-15: 1 year
Population: Subjects in the Safety population, age 17-35 with a BMI \<32, were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AG200-15 for Cycle 7-13 | Pregnancy | 5.41 Pearl Index |
| Lessina | Pregnancy | 6.67 Pearl Index |
| AG200-15 for Cycle 1-13 | Pregnancy | 6.43 Pearl Index |
Other Pre-specified
Cycle Control
Measuring the breakthrough bleeding (BTB) and/or breakthrough spotting (BTS). Measured as a percent of total number of cycles in each Arm/Group with BTB and/or BTS.
Time frame: 6 months
Population: Number of subjects with documented cycle information.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AG200-15 for Cycle 7-13 | Cycle Control | 23.9 percentage of cycles with BTB/BTS |
| Lessina | Cycle Control | 21.2 percentage of cycles with BTB/BTS |
p-value: 0.067Chi-squared
Other Pre-specified
Patch Adhesion by Investigator Evaluation at Each Visit
Evaluation of patch adhesion was determined using the following scores: 0: \>= 90% adhered (no lift) 1. \>= 75% adhered but \< 90% (some edges showing lift) 2. \>= 50% adhered but \< 75% (half of system lifts off) 3. \< 50% (\> half of system lifts off, but undetached) 4. patch completely detached
Time frame: 1 year
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AG200-15 for Cycle 7-13 | Patch Adhesion by Investigator Evaluation at Each Visit | 0.29 Score on a scale | Standard Deviation 0.823 |
Other Pre-specified
Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE)
Measurement of plasma concentrations of LNG and EE for cycles 2, 6 and 13.
Time frame: Lessina: 6 months; AG200-15: 1 year; AG200-15: 6 months
Population: Subjects that received contraceptive and were analyzed for LNG and EE.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| AG200-15 for Cycle 7-13 | Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE) | LNG cycle 2 | 2386 pg/ml |
| AG200-15 for Cycle 7-13 | Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE) | EE cycle 6 | 40.1 pg/ml |
| AG200-15 for Cycle 7-13 | Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE) | EE cycle 13 | NA pg/ml |
| AG200-15 for Cycle 7-13 | Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE) | LNG cycle 6 | 2611 pg/ml |
| AG200-15 for Cycle 7-13 | Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE) | EE for cycle 2 | 35.4 pg/ml |
| AG200-15 for Cycle 7-13 | Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE) | LNG cycle 13 | NA pg/ml |
| Lessina | Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE) | EE cycle 13 | 31 pg/ml |
| Lessina | Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE) | LNG cycle 13 | 1590 pg/ml |
| Lessina | Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE) | EE for cycle 2 | 30.5 pg/ml |
| Lessina | Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE) | EE cycle 6 | 36.7 pg/ml |
| Lessina | Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE) | LNG cycle 2 | 1201 pg/ml |
| Lessina | Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE) | LNG cycle 6 | 1753 pg/ml |
| AG200-15 for Cycle 1-13 | Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE) | LNG cycle 6 | NA pg/ml |
| AG200-15 for Cycle 1-13 | Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE) | LNG cycle 2 | NA pg/ml |
| AG200-15 for Cycle 1-13 | Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE) | LNG cycle 13 | 1750 pg/ml |
| AG200-15 for Cycle 1-13 | Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE) | EE cycle 6 | NA pg/ml |
| AG200-15 for Cycle 1-13 | Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE) | EE cycle 13 | 33.4 pg/ml |
| AG200-15 for Cycle 1-13 | Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE) | EE for cycle 2 | NA pg/ml |
Other Pre-specified
Self-reported Irritation at Application Site
Evaluation of irritation at application site was determined using the following scores: 0: None 1. Mild 2. Moderate 3. Severe
Time frame: 1 year
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AG200-15 for Cycle 7-13 | Self-reported Irritation at Application Site | 1.35 Score on scale | Standard Deviation 0.964 |
Other Pre-specified
Self-reported Itching at Patch Application Site
Evaluation of itching at patch application site was determined using the following scores: 0: None 1. Mild 2. Moderate 3. Severe
Time frame: 1 year
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AG200-15 for Cycle 7-13 | Self-reported Itching at Patch Application Site | 1.48 Score on a scale | Standard Deviation 0.948 |