Healthy
Conditions
Keywords
PK and safety, Pharmacokinetic profile (PK) and safety
Brief summary
Pharmacokinetics and safety of AG200-15 over two consecutive cycles of therapy will be evaluated.
Detailed description
This is an open-label study comprised of two parts. Part I is a single-arm, run-in cycle with AG200-15 administered to all subjects as a 21-7 day regimen (three consecutive weeks of patch wear followed by a patch-free week). Part II employs crossover design with subjects randomly assigned to one of the two treatment sequences. Each sequence will include AG200-15 and oral contraceptive (Ortho-Cyclen®) as described below: Sequence 1: AG200-15 (Period 1) followed by oral contraceptive, Ortho-Cyclen® (Period 2); Sequence 2: Oral contraceptive, Ortho-Cyclen® (Period 1) followed by AG200-15 (Period 2) Both AG200-15 and Ortho-Cyclen® will be administered as 21-7 day regimen (three consecutive weeks of drug-taking followed by a drug-free week). Duration of each treatment Period is 28 days (one cycle of therapy).
Interventions
DRUGOrtho-Cyclen
Ortho-Cyclen is an oral contraceptive containing 35 µg of EE and 250 µg of norgestimate (NGM) in a 21 - 7 day regimen.
DRUGAG200-15
AG200-15 is a transdermal contraceptive delivery system delivering 100 - 120 mcg of LNG and 25 - 30 mcg EE
Sponsors
Agile Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy women, ages 18-45 * Body mass index (BMI) ≥18 and ≤32, and weight ≥ 110 lbs. * Willing to use a non-hormonal method of contraception if at risk of pregnancy, OR have already undergone previous bilateral tubal ligation or hysterectomy * Willing to refrain from use of alcohol and grapefruit juice from 48 hours prior until completion of each treatment period
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 * Smokers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparative Evaluation of Ethinyl Estradiol (EE) Cmax Between AG200-15 and Ortho-Cyclen® in Week 1 | 3 months | Comparative evaluation of ethinyl estradiol (EE) Cmax between AG200-15 and Ortho-Cyclen® in week 1 for cycle 2 and 3. |
| Comparative Evaluation of EE Cmax Between AG200-15 and Ortho-Cyclen® in Week 3 | 3 months | Comparative evaluation of EE Cmax between AG200-15 and Ortho-Cyclen® in week 3 for cycles 2 and 3. |
| Comparative Evaluation of EE AUC(0-168hrs Post-first Dose) Between AG200-15 and Ortho-Cyclen® in Week 1 | 3 months | Comparative evaluation of EE AUC (0-168hrs post-first dose) between AG200-15 and Ortho-Cyclen® in week 1 for cycles 2 and 3. |
| Comparative Evaluation of EE AUC (0-168hrs Post-first Dose) Between AG200-15 and Ortho-Cyclen® in Week 3 | 3 months | Comparative evaluation of EE AUC (0-168hrs post-first dose) between AG200-15 and Ortho-Cyclen® in week 3 for cycles 2 and 3. |
| Comparative Evaluation of EE Css (1) Between AG200-15 and Ortho-Cyclen® in Week 1 | 3 months | Comparative evaluation of EE Css (1) between AG200-15 and Ortho-Cyclen® in week 1 for cycles 2 and 3. For Ortho-Cyclen steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For AG200-15 the average concentration within the 48-168 h time-interval was measured. |
| Comparative Evaluation of EE Css (1) Between AG200-15 and Ortho-Cyclen® in Week 3 | 3 months | Comparative evaluation of EE Css (1) between AG200-15 and Ortho-Cyclen® in week 3 for cycles 2 and 3. For Ortho-Cyclen steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For AG200-15 the average concentration within the 48-168 h time-interval was measured. |
| Comparative Evaluation of EE Css (2) Between AG200-15 and Ortho-Cyclen® in Week 1 | 3 months | Comparative evaluation of EE Css (2) between AG200-15 and Ortho-Cyclen® in week 1 for cycles 2 and 3. For Ortho-Cyclen steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For Ag200-15, the average concentration at steady-state calculated from trapezoidal AUC within the 48-168h time interval (AUC/time interval). |
| Comparative Evaluation of EE Css (2) Between AG200-15 and Ortho-Cyclen® in Week 3 | 3 months | Comparative evaluation of EE Css (2) between AG200-15 and Ortho-Cyclen® in week 3 for cycles 2 and 3. For Ortho-Cyclen steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For Ag200-15, the average concentration at steady-state calculated from trapezoidal AUC within the 48-168h time interval (AUC/time interval). |
| Comparative Evaluation of EE Css (3) Between AG200-15 and Ortho-Cyclen® in Week 1 | 3 months | Comparative evaluation of EE Css (3) between AG200-15 and Ortho-Cyclen® in week 1 for cycles 2 and 3. For Ortho-Cyclen steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For AG200-15, the average concentration at steady-state calculated from trapezoidal AUC within the 0-168h time interval (AUC/time interval). |
| Comparative Evaluation of EE Css (3) Between AG200-15 and Ortho-Cyclen® in Week 3 | 3 months | Comparative evaluation of EE Css (3) between AG200-15 and Ortho-Cyclen® in week 3 for cycles 2 and 3. For Ortho-Cyclen steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For AG200-15, the average concentration at steady-state calculated from trapezoidal AUC within the 0-168h time interval (AUC/time interval). |
| Evaluation of LNG Cmax Between AG200-15 in Week 1 and 3 | 3 months | Evaluation of LNG Cmax Between AG200-15 in Week 1 and 3 for cycles 2 and 3. |
| Evaluation of LNG AUC (0-168hrs Post-first Dose) Between AG200-15 in Week 1 and 3 | 3 months | Evaluation of LNG AUC (0-168hrs post-first dose) Between AG200-15 in Week 1 and 3 for cycles 2 and 3. |
| Evaluation of LNG Css (1) Between AG200-15 in Week 1 and 3 | 3 months | Comparative evaluation of EE Css (1) between AG200-15 and Ortho-Cyclen® in week 1 for cycles 2 and 3. For Ortho-Cyclen, steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For Ag200-15, the average concentration at steady-state calculated from trapezoidal AUC within the 48-168h time interval (AUC/time interval). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AG200-15/Ortho-Cyclen® Subject applied AG200-15 in cycle 1. Subjects applied AG200-15 (Cycle 2) followed by oral contraceptive, Ortho-Cyclen® (Cycle 3) | 18 |
| Ortho-Cyclen® /AG200-15 Subject applied AG200-15 in cycle 1. Subjects received Ortho-Cyclen® (Cycle 2) followed by AG200-15 (Cycle 3). | 18 |
| Total | 36 |
Baseline characteristics
| Characteristic | Ortho-Cyclen® /AG200-15 | AG200-15/Ortho-Cyclen® | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 18 Participants | 36 Participants |
| Age, Continuous | 36.2 years STANDARD_DEVIATION 7.66 | 37.8 years STANDARD_DEVIATION 5.85 | 37 years STANDARD_DEVIATION 6.77 |
| Region of Enrollment United States | 18 Participants | 18 Participants | 36 Participants |
| Sex: Female, Male Female | 18 Participants | 18 Participants | 36 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 / 34 | 0 / 36 |
| other Total, other adverse events | 3 / 34 | 23 / 36 |
| serious Total, serious adverse events | 0 / 34 | 0 / 36 |
Outcome results
Primary
Comparative Evaluation of EE AUC(0-168hrs Post-first Dose) Between AG200-15 and Ortho-Cyclen® in Week 1
Comparative evaluation of EE AUC (0-168hrs post-first dose) between AG200-15 and Ortho-Cyclen® in week 1 for cycles 2 and 3.
Time frame: 3 months
Population: Primary PK population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ortho-Cyclen® | Comparative Evaluation of EE AUC(0-168hrs Post-first Dose) Between AG200-15 and Ortho-Cyclen® in Week 1 | 7.28 ng.h/ml | Standard Deviation 2.66 |
| AG200-15 | Comparative Evaluation of EE AUC(0-168hrs Post-first Dose) Between AG200-15 and Ortho-Cyclen® in Week 1 | 5.06 ng.h/ml | Standard Deviation 2.26 |
p-value: 0.0001ANOVA
Primary
Comparative Evaluation of EE AUC (0-168hrs Post-first Dose) Between AG200-15 and Ortho-Cyclen® in Week 3
Comparative evaluation of EE AUC (0-168hrs post-first dose) between AG200-15 and Ortho-Cyclen® in week 3 for cycles 2 and 3.
Time frame: 3 months
Population: Primary PK population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ortho-Cyclen® | Comparative Evaluation of EE AUC (0-168hrs Post-first Dose) Between AG200-15 and Ortho-Cyclen® in Week 3 | 6.97 ng.h/ml | Standard Deviation 2.25 |
| AG200-15 | Comparative Evaluation of EE AUC (0-168hrs Post-first Dose) Between AG200-15 and Ortho-Cyclen® in Week 3 | 6.26 ng.h/ml | Standard Deviation 2.46 |
p-value: 0.0532ANOVA
Primary
Comparative Evaluation of EE Cmax Between AG200-15 and Ortho-Cyclen® in Week 3
Comparative evaluation of EE Cmax between AG200-15 and Ortho-Cyclen® in week 3 for cycles 2 and 3.
Time frame: 3 months
Population: Primary PK population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ortho-Cyclen® | Comparative Evaluation of EE Cmax Between AG200-15 and Ortho-Cyclen® in Week 3 | 131 pg/ml | Standard Deviation 45.4 |
| AG200-15 | Comparative Evaluation of EE Cmax Between AG200-15 and Ortho-Cyclen® in Week 3 | 51.3 pg/ml | Standard Deviation 17.3 |
p-value: <0.0001ANOVA
Primary
Comparative Evaluation of EE Css (1) Between AG200-15 and Ortho-Cyclen® in Week 1
Comparative evaluation of EE Css (1) between AG200-15 and Ortho-Cyclen® in week 1 for cycles 2 and 3. For Ortho-Cyclen steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For AG200-15 the average concentration within the 48-168 h time-interval was measured.
Time frame: 3 months
Population: Primary PK population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ortho-Cyclen® | Comparative Evaluation of EE Css (1) Between AG200-15 and Ortho-Cyclen® in Week 1 | 43.3 pg/ml | Standard Deviation 15.8 |
| AG200-15 | Comparative Evaluation of EE Css (1) Between AG200-15 and Ortho-Cyclen® in Week 1 | 31.4 pg/ml | Standard Deviation 15.1 |
p-value: 0.0009ANOVA
Primary
Comparative Evaluation of EE Css (1) Between AG200-15 and Ortho-Cyclen® in Week 3
Comparative evaluation of EE Css (1) between AG200-15 and Ortho-Cyclen® in week 3 for cycles 2 and 3. For Ortho-Cyclen steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For AG200-15 the average concentration within the 48-168 h time-interval was measured.
Time frame: 3 months
Population: Primary PK population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ortho-Cyclen® | Comparative Evaluation of EE Css (1) Between AG200-15 and Ortho-Cyclen® in Week 3 | 41.5 pg/ml | Standard Deviation 13.4 |
| AG200-15 | Comparative Evaluation of EE Css (1) Between AG200-15 and Ortho-Cyclen® in Week 3 | 35.7 pg/ml | Standard Deviation 14.5 |
p-value: 0.0167ANOVA
Primary
Comparative Evaluation of EE Css (2) Between AG200-15 and Ortho-Cyclen® in Week 1
Comparative evaluation of EE Css (2) between AG200-15 and Ortho-Cyclen® in week 1 for cycles 2 and 3. For Ortho-Cyclen steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For Ag200-15, the average concentration at steady-state calculated from trapezoidal AUC within the 48-168h time interval (AUC/time interval).
Time frame: 3 months
Population: Primary PK population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ortho-Cyclen® | Comparative Evaluation of EE Css (2) Between AG200-15 and Ortho-Cyclen® in Week 1 | 43.3 pg/ml | Standard Deviation 15.8 |
| AG200-15 | Comparative Evaluation of EE Css (2) Between AG200-15 and Ortho-Cyclen® in Week 1 | 32.0 pg/ml | Standard Deviation 16.2 |
p-value: 0.0007ANOVA
Primary
Comparative Evaluation of EE Css (2) Between AG200-15 and Ortho-Cyclen® in Week 3
Comparative evaluation of EE Css (2) between AG200-15 and Ortho-Cyclen® in week 3 for cycles 2 and 3. For Ortho-Cyclen steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For Ag200-15, the average concentration at steady-state calculated from trapezoidal AUC within the 48-168h time interval (AUC/time interval).
Time frame: 3 months
Population: Primary PK population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ortho-Cyclen® | Comparative Evaluation of EE Css (2) Between AG200-15 and Ortho-Cyclen® in Week 3 | 41.5 pg/ml | Standard Deviation 13.4 |
| AG200-15 | Comparative Evaluation of EE Css (2) Between AG200-15 and Ortho-Cyclen® in Week 3 | 35.7 pg/ml | Standard Deviation 15.4 |
p-value: 0.0175ANOVA
Primary
Comparative Evaluation of EE Css (3) Between AG200-15 and Ortho-Cyclen® in Week 1
Comparative evaluation of EE Css (3) between AG200-15 and Ortho-Cyclen® in week 1 for cycles 2 and 3. For Ortho-Cyclen steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For AG200-15, the average concentration at steady-state calculated from trapezoidal AUC within the 0-168h time interval (AUC/time interval).
Time frame: 3 months
Population: Primary PK population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ortho-Cyclen® | Comparative Evaluation of EE Css (3) Between AG200-15 and Ortho-Cyclen® in Week 1 | 43.3 pg/ml | Standard Deviation 15.8 |
| AG200-15 | Comparative Evaluation of EE Css (3) Between AG200-15 and Ortho-Cyclen® in Week 1 | 30.1 pg/ml | Standard Deviation 13.4 |
p-value: 0.0001ANOVA
Primary
Comparative Evaluation of EE Css (3) Between AG200-15 and Ortho-Cyclen® in Week 3
Comparative evaluation of EE Css (3) between AG200-15 and Ortho-Cyclen® in week 3 for cycles 2 and 3. For Ortho-Cyclen steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For AG200-15, the average concentration at steady-state calculated from trapezoidal AUC within the 0-168h time interval (AUC/time interval).
Time frame: 3 months
Population: Primary PK population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ortho-Cyclen® | Comparative Evaluation of EE Css (3) Between AG200-15 and Ortho-Cyclen® in Week 3 | 41.5 pg/ml | Standard Deviation 13.4 |
| AG200-15 | Comparative Evaluation of EE Css (3) Between AG200-15 and Ortho-Cyclen® in Week 3 | 37.3 pg/ml | Standard Deviation 14.7 |
p-value: 0.0532ANOVA
Primary
Comparative Evaluation of Ethinyl Estradiol (EE) Cmax Between AG200-15 and Ortho-Cyclen® in Week 1
Comparative evaluation of ethinyl estradiol (EE) Cmax between AG200-15 and Ortho-Cyclen® in week 1 for cycle 2 and 3.
Time frame: 3 months
Population: Primary PK population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ortho-Cyclen® | Comparative Evaluation of Ethinyl Estradiol (EE) Cmax Between AG200-15 and Ortho-Cyclen® in Week 1 | 135 pg/ml | Standard Deviation 50.7 |
| AG200-15 | Comparative Evaluation of Ethinyl Estradiol (EE) Cmax Between AG200-15 and Ortho-Cyclen® in Week 1 | 45.5 pg/ml | Standard Deviation 24 |
p-value: <0.0001ANOVA
Primary
Evaluation of LNG AUC (0-168hrs Post-first Dose) Between AG200-15 in Week 1 and 3
Evaluation of LNG AUC (0-168hrs post-first dose) Between AG200-15 in Week 1 and 3 for cycles 2 and 3.
Time frame: 3 months
Population: Primary PK population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ortho-Cyclen® | Evaluation of LNG AUC (0-168hrs Post-first Dose) Between AG200-15 in Week 1 and 3 | Week 1 | 160 ng.h/ml | Standard Deviation 88.9 |
| Ortho-Cyclen® | Evaluation of LNG AUC (0-168hrs Post-first Dose) Between AG200-15 in Week 1 and 3 | Week 3 | 317 ng.h/ml | Standard Deviation 159 |
Primary
Evaluation of LNG Cmax Between AG200-15 in Week 1 and 3
Evaluation of LNG Cmax Between AG200-15 in Week 1 and 3 for cycles 2 and 3.
Time frame: 3 months
Population: Primary PK population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ortho-Cyclen® | Evaluation of LNG Cmax Between AG200-15 in Week 1 and 3 | Week 1 | 1370 pg/ml | Standard Deviation 908 |
| Ortho-Cyclen® | Evaluation of LNG Cmax Between AG200-15 in Week 1 and 3 | Week 3 | 2400 pg/ml | Standard Deviation 1140 |
Primary
Evaluation of LNG Css (1) Between AG200-15 in Week 1 and 3
Comparative evaluation of EE Css (1) between AG200-15 and Ortho-Cyclen® in week 1 for cycles 2 and 3. For Ortho-Cyclen, steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For Ag200-15, the average concentration at steady-state calculated from trapezoidal AUC within the 48-168h time interval (AUC/time interval).
Time frame: 3 months
Population: Primary PK population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ortho-Cyclen® | Evaluation of LNG Css (1) Between AG200-15 in Week 1 and 3 | Week 1 | 1060 pg/ml | Standard Deviation 631 |
| Ortho-Cyclen® | Evaluation of LNG Css (1) Between AG200-15 in Week 1 and 3 | Week 3 | 1847 pg/ml | Standard Deviation 930 |