Healthy
Conditions
Keywords
Pharmacokinetic Profile (PK) and Safety, PK analysis of EE and LNG
Brief summary
A study to evaluate pharmacokinetic profile, wearability and safety of AG200-15, transdermal delivery of levonorgestrel (LNG) and ethinyl estradiol (EE), under normal conditions and external conditions of heat, humidity, cold water and exercise.
Detailed description
Normal conditions - average daily living activities, Dry Sauna - 10 minutes at 168.8 - 179.6 degrees Fahrenheit, Whirlpool - 10 minutes at 102.2 - 105.8 degrees Fahrenheit, Treadmill - 20 - 30 minutes at 60-80% max heart rate, Cold Water - 5 - 15 minutes at 71.6 degrees Fahrenheit. There will be three treatment periods. Subjects will be randomly assigned to one of the five conditions for the treatment period. The subject will be exposed daily to the condition assigned while wearing the patch. The study patch will be worn for a 7 day treatment period, followed by a 7 day washout period. The total duration of the study is 6 weeks.
Interventions
DRUGAG200-15
There will be three treatment periods. Subjects will be randomly assigned to one of the five conditions for the treatment period. The subject will be exposed daily to the condition assigned while wearing the patch. The study patch will be worn for a 7 day treatment period, followed by a 7 day washout period. The total duration of the study is 6 weeks.
Sponsors
Agile Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
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)of ≥18 and less than or equal to 32, and weight ≥ 110 lbs. * Willing to use a non-hormonal method of contraception if of childbearing potential, or have already undergone previous bilateral tubal ligation or hysterectomy * Willing to refrain from use of alcohol and grapefruit juice from 48 hours prior to patch application until completion of each treatment period * Willing to give informed consent to participate in study
Exclusion criteria
* Known or suspected pregnancy * Breast-feeding or within 1 month after stopping breast-feeding * Smokers * Any disease that may worsen with hormonal treatment * Hypersensitivity to transdermal preparations or sensitivity to surgical/medical tape
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration Versus Time Curve (AUC) (0-168) Profile of Levonorgestrel (LNG) | 6 weeks | AUC(0-168) profile of LNG for each external condition including dry sauna, normal, whirlpool, cold water, and treadmill exercise. The blood sampling for the pharmacokinetic evaluations was performed at the following time points: 0 hour (immediately prior to dosing) and at 6 hours, 12 hours, 24 hours (1 day), 48 hours (2 days), 72 hours (3 days), 120 hours (5 days), 144 hours (6 days), and 168 hours (7 days) following application of the patch. |
| AUC(0-168) Profile of Ethinyl Estradiol (EE) | 6 weeks | AUC(0-168) profile of EE for external condition including dry sauna, normal, whirlpool, cold water, and treadmill exercise. The blood sampling for the pharmacokinetic evaluations was performed at the following time points: 0 hour (immediately prior to dosing) and at 6 hours, 12 hours, 24 hours (1 day), 48 hours (2 days), 72 hours (3 days), 120 hours (5 days), 144 hours (6 days), and 168 hours (7 days) following application of the patch. |
| Steady-state Concentration (Css) (48-168) Profile of LNG | 6 weeks | Css (48-168) profile of LNG for external condition including dry sauna, normal, whirlpool, cold water, and treadmill exercise. The blood sampling for the pharmacokinetic evaluations was performed at the following time points: 0 hour (immediately prior to dosing) and at 6 hours, 12 hours, 24 hours (1 day), 48 hours (2 days), 72 hours (3 days), 120 hours (5 days), 144 hours (6 days), and 168 hours (7 days) following application of the patch. |
| Css (48-168) Profile of EE | 6 weeks | Css (48-168) profile of EE for external condition including dry sauna, normal, whirlpool, cold water, and treadmill exercise. The blood sampling for the pharmacokinetic evaluations was performed at the following time points: 0 hour (immediately prior to dosing) and at 6 hours, 12 hours, 24 hours (1 day), 48 hours (2 days), 72 hours (3 days), 120 hours (5 days), 144 hours (6 days), and 168 hours (7 days) following application of the patch. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patch Adhesion | 6 weeks | Patch adhesion scores by investigator evaluation by external condition; including dry sauna, whirlpool, treadmill exercise, normal, and cold water conditions; using the following scale: 0: \>90% adhered (essentially no lift off of the skin) 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 Patches were assessed prior to patch removal. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AG200-15 Condition The subject will wear AG200-15 for 7 days and be exposed to one of 5 external conditions (normal, treadmill, cold water, whirlpool, dry sauna). | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | AG200-15 Condition |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants |
| Age, Continuous | 35.13 years STANDARD_DEVIATION 6.469 |
| Region of Enrollment United States | 24 Participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 24 |
| other Total, other adverse events | 23 / 24 |
| serious Total, serious adverse events | 0 / 24 |
Outcome results
Primary
Area Under the Concentration Versus Time Curve (AUC) (0-168) Profile of Levonorgestrel (LNG)
AUC(0-168) profile of LNG for each external condition including dry sauna, normal, whirlpool, cold water, and treadmill exercise. The blood sampling for the pharmacokinetic evaluations was performed at the following time points: 0 hour (immediately prior to dosing) and at 6 hours, 12 hours, 24 hours (1 day), 48 hours (2 days), 72 hours (3 days), 120 hours (5 days), 144 hours (6 days), and 168 hours (7 days) following application of the patch.
Time frame: 6 weeks
Population: Primary PK population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AG200-15 Condition | Area Under the Concentration Versus Time Curve (AUC) (0-168) Profile of Levonorgestrel (LNG) | Normal | 157 ng*hr/mL | Standard Deviation 74 |
| AG200-15 Condition | Area Under the Concentration Versus Time Curve (AUC) (0-168) Profile of Levonorgestrel (LNG) | Dry Sauna | 118 ng*hr/mL | Standard Deviation 51 |
| AG200-15 Condition | Area Under the Concentration Versus Time Curve (AUC) (0-168) Profile of Levonorgestrel (LNG) | Cold water | 153 ng*hr/mL | Standard Deviation 76 |
| AG200-15 Condition | Area Under the Concentration Versus Time Curve (AUC) (0-168) Profile of Levonorgestrel (LNG) | Whirlpool | 137 ng*hr/mL | Standard Deviation 81 |
| AG200-15 Condition | Area Under the Concentration Versus Time Curve (AUC) (0-168) Profile of Levonorgestrel (LNG) | Treadmill | 119 ng*hr/mL | Standard Deviation 46 |
Primary
AUC(0-168) Profile of Ethinyl Estradiol (EE)
AUC(0-168) profile of EE for external condition including dry sauna, normal, whirlpool, cold water, and treadmill exercise. The blood sampling for the pharmacokinetic evaluations was performed at the following time points: 0 hour (immediately prior to dosing) and at 6 hours, 12 hours, 24 hours (1 day), 48 hours (2 days), 72 hours (3 days), 120 hours (5 days), 144 hours (6 days), and 168 hours (7 days) following application of the patch.
Time frame: 6 weeks
Population: Primary PK population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AG200-15 Condition | AUC(0-168) Profile of Ethinyl Estradiol (EE) | Cold water | 4.9 ng*hr/mL | Standard Deviation 2.3 |
| AG200-15 Condition | AUC(0-168) Profile of Ethinyl Estradiol (EE) | Normal | 4.7 ng*hr/mL | Standard Deviation 1.6 |
| AG200-15 Condition | AUC(0-168) Profile of Ethinyl Estradiol (EE) | Dry sauna | 4.3 ng*hr/mL | Standard Deviation 2 |
| AG200-15 Condition | AUC(0-168) Profile of Ethinyl Estradiol (EE) | Whirlpool | 4.3 ng*hr/mL | Standard Deviation 1.4 |
| AG200-15 Condition | AUC(0-168) Profile of Ethinyl Estradiol (EE) | Treadmill | 3.9 ng*hr/mL | Standard Deviation 1.1 |
Primary
Css (48-168) Profile of EE
Css (48-168) profile of EE for external condition including dry sauna, normal, whirlpool, cold water, and treadmill exercise. The blood sampling for the pharmacokinetic evaluations was performed at the following time points: 0 hour (immediately prior to dosing) and at 6 hours, 12 hours, 24 hours (1 day), 48 hours (2 days), 72 hours (3 days), 120 hours (5 days), 144 hours (6 days), and 168 hours (7 days) following application of the patch.
Time frame: 6 weeks
Population: Primary PK population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AG200-15 Condition | Css (48-168) Profile of EE | Normal | 30 pg/mL | Standard Deviation 12 |
| AG200-15 Condition | Css (48-168) Profile of EE | Treadmill | 24 pg/mL | Standard Deviation 8 |
| AG200-15 Condition | Css (48-168) Profile of EE | Dry Sauna | 28 pg/mL | Standard Deviation 13 |
| AG200-15 Condition | Css (48-168) Profile of EE | Cold water | 29 pg/mL | Standard Deviation 14 |
| AG200-15 Condition | Css (48-168) Profile of EE | Whirlpool | 27 pg/mL | Standard Deviation 9 |
Primary
Steady-state Concentration (Css) (48-168) Profile of LNG
Css (48-168) profile of LNG for external condition including dry sauna, normal, whirlpool, cold water, and treadmill exercise. The blood sampling for the pharmacokinetic evaluations was performed at the following time points: 0 hour (immediately prior to dosing) and at 6 hours, 12 hours, 24 hours (1 day), 48 hours (2 days), 72 hours (3 days), 120 hours (5 days), 144 hours (6 days), and 168 hours (7 days) following application of the patch.
Time frame: 6 weeks
Population: Primary PK population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AG200-15 Condition | Steady-state Concentration (Css) (48-168) Profile of LNG | Normal | 1068 pg/mL | Standard Deviation 494 |
| AG200-15 Condition | Steady-state Concentration (Css) (48-168) Profile of LNG | Dry Sauna | 793 pg/mL | Standard Deviation 317 |
| AG200-15 Condition | Steady-state Concentration (Css) (48-168) Profile of LNG | Cold water | 1033 pg/mL | Standard Deviation 518 |
| AG200-15 Condition | Steady-state Concentration (Css) (48-168) Profile of LNG | Whirlpool | 918 pg/mL | Standard Deviation 512 |
| AG200-15 Condition | Steady-state Concentration (Css) (48-168) Profile of LNG | Treadmill | 814 pg/mL | Standard Deviation 333 |
Secondary
Patch Adhesion
Patch adhesion scores by investigator evaluation by external condition; including dry sauna, whirlpool, treadmill exercise, normal, and cold water conditions; using the following scale: 0: \>90% adhered (essentially no lift off of the skin) 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 Patches were assessed prior to patch removal.
Time frame: 6 weeks
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AG200-15 Condition | Patch Adhesion | Normal | 0.08 Score | Standard Deviation 0.282 |
| AG200-15 Condition | Patch Adhesion | Dry Sauna | 0.08 Score | Standard Deviation 0.289 |
| AG200-15 Condition | Patch Adhesion | Cold water | 0 Score | Standard Deviation 0 |
| AG200-15 Condition | Patch Adhesion | Whirlpool | 0 Score | Standard Deviation 0 |
| AG200-15 Condition | Patch Adhesion | Treadmill | 0.17 Score | Standard Deviation 0.577 |