Healthy
Conditions
Keywords
PK and safety, Pharmacokinetic profile (PK) and safety
Brief summary
This is a pharmacokinetics and safety study over 3 weekly applications.
Detailed description
Pharmacokinetic study to evaluate the safety and pharmacokinetic profile of AG200-15 following application at three different anatomical sites (abdomen, buttock and upper torso).
Interventions
DRUGAG200-15
A transdermal contraceptive delivery system for levonorgestrel (LNG) and ethinyl estradiol (EE). . A total of 3 patches will be worn during the study. Each patch will be worn for 1 week followed by a patch free week.
Sponsors
Agile Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
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 years * Body mass index 18 - 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 * Hemoglobin within normal range.
Exclusion criteria
* Known or suspected pregnancy * A cervical cytology smear of Papanicolaou (Pap) class III or greater or a Bethesda System report of low grade squamous intraepithelial lesions (SIL) or greater * Smoking * Hypertension (blood pressure \>140 mm Hg systolic and/or \>90 mm Hg diastolic) * Diabetes Mellitus * History of headaches with focal neurological symptoms * Current or history of clinically significant depression in the last year * Acute or chronic hepatocellular disease with abnormal liver function * History of or existing venous and arterial thrombotic and thromboembolic disorder, vascular disease, cerebral vascular, or coronary artery disease * Chronic use of any medication that might interfere with the efficacy of hormone contraceptives (including barbiturates, bosentan, carbamazepine, felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, St. John's Wort, topiramate, and HIV protease inhibitors), OR use of these medications within the past 3 months prior to screening visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Steady-State Concentration (Css) (48-168) Profile for LNG | 6 weeks | Pharmacokinetic (PK) sampling will be done after exposure to each anatomic location. PK evaluations were performed at the following time points: hour (immediately prior to dosing) and at 3 hours, 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 for EE | 6 weeks | Pharmacokinetic (PK) sampling will be done after exposure to each anatomic location. PK evaluations were performed at the following time points: hour (immediately prior to dosing) and at 3 hours, 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. |
| Area Under the Plasma Concentration Versus Time Curve (AUC) (0-168) Profile for LNG | 6 weeks | Pharmacokinetic (PK) sampling will be done after exposure to each anatomic location. PK evaluations were performed at the following time points: hour (immediately prior to dosing) and at 3 hours, 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. |
| Area Under the Plasma Concentration Versus Time Curve (AUC) (0-168) Profile for EE | 6 weeks | Pharmacokinetic (PK) sampling will be done after exposure to each anatomic location. PK evaluations were performed at the following time points: hour (immediately prior to dosing) and at 3 hours, 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AG200-15 Subjects will be randomly assigned to one of six treatment (site of application) sequences. Each sequence will include three patch application sites: abdomen, buttock, or upper torso excluding breasts.
AG200-15: A transdermal contraceptive delivery system for levonorgestrel (LNG) and ethinyl estradiol (EE). A total of 3 patches will be worn during the study. Each patch will be worn for 1 week followed by a patch free week. | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | AG200-15 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants |
| Age, Continuous | 32.2 years STANDARD_DEVIATION 8.32 |
| 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 | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 23 | 0 / 23 |
| other Total, other adverse events | 19 / 22 | 23 / 23 | 21 / 23 |
| serious Total, serious adverse events | 0 / 22 | 0 / 23 | 0 / 23 |
Outcome results
Primary
Area Under the Plasma Concentration Versus Time Curve (AUC) (0-168) Profile for EE
Pharmacokinetic (PK) sampling will be done after exposure to each anatomic location. PK evaluations were performed at the following time points: hour (immediately prior to dosing) and at 3 hours, 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 | Area Under the Plasma Concentration Versus Time Curve (AUC) (0-168) Profile for EE | Abdomen | 5.8 ng*hr/mL | Standard Deviation 2.8 |
| AG200-15 | Area Under the Plasma Concentration Versus Time Curve (AUC) (0-168) Profile for EE | Buttock | 7.12 ng*hr/mL | Standard Deviation 2.85 |
| AG200-15 | Area Under the Plasma Concentration Versus Time Curve (AUC) (0-168) Profile for EE | Upper torso | 6.86 ng*hr/mL | Standard Deviation 2.53 |
Primary
Area Under the Plasma Concentration Versus Time Curve (AUC) (0-168) Profile for LNG
Pharmacokinetic (PK) sampling will be done after exposure to each anatomic location. PK evaluations were performed at the following time points: hour (immediately prior to dosing) and at 3 hours, 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 | Area Under the Plasma Concentration Versus Time Curve (AUC) (0-168) Profile for LNG | Abdomen | 182 ng*hr/mL | Standard Deviation 135 |
| AG200-15 | Area Under the Plasma Concentration Versus Time Curve (AUC) (0-168) Profile for LNG | Buttock | 197 ng*hr/mL | Standard Deviation 116 |
| AG200-15 | Area Under the Plasma Concentration Versus Time Curve (AUC) (0-168) Profile for LNG | Upper torso | 206 ng*hr/mL | Standard Deviation 106 |
Primary
Steady-State Concentration (Css) (48-168) Profile for EE
Pharmacokinetic (PK) sampling will be done after exposure to each anatomic location. PK evaluations were performed at the following time points: hour (immediately prior to dosing) and at 3 hours, 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 | Steady-State Concentration (Css) (48-168) Profile for EE | Buttock | 40.7 pg/mL | Standard Deviation 16.4 |
| AG200-15 | Steady-State Concentration (Css) (48-168) Profile for EE | Abdomen | 35.8 pg/mL | Standard Deviation 19.9 |
| AG200-15 | Steady-State Concentration (Css) (48-168) Profile for EE | Upper torso | 42.3 pg/mL | Standard Deviation 17 |
Primary
Steady-State Concentration (Css) (48-168) Profile for LNG
Pharmacokinetic (PK) sampling will be done after exposure to each anatomic location. PK evaluations were performed at the following time points: hour (immediately prior to dosing) and at 3 hours, 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 | Steady-State Concentration (Css) (48-168) Profile for LNG | Abdomen | 1256 pg/mL | Standard Deviation 998 |
| AG200-15 | Steady-State Concentration (Css) (48-168) Profile for LNG | Buttock | 1246 pg/mL | Standard Deviation 725 |
| AG200-15 | Steady-State Concentration (Css) (48-168) Profile for LNG | Upper torso | 1384 pg/mL | Standard Deviation 728 |