Healthy
Conditions
Keywords
PK and Safety
Brief summary
Pharmacokinetics, safety and wearability in two size patches of AG890 over eight weeks will be evaluated.
Detailed description
To evaluate pharmacokinetic (PK) profile, patch wearability (adhesion and skin irritation), and safety of AG890-6.5 and AG890-12.5 TCDS.
Interventions
DRUGlevonorgestrel
transdermal contraceptive delivery system
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
* Body mass index (BMI) greater than or equal to 18. * 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 excessive use of alcohol from 48 hours prior to patch application through completion of the study.
Exclusion criteria
* Known or suspected pregnancy * Lactating women * Status post-partum or post-abortion within a period of 2 months prior to the start of study medication * 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) * Valvular heart disease with complications * ECG (in women with BMI ≥35 kg/m2) with clinically significant findings * Diabetes Mellitus * History of headaches with focal neurological symptoms * Uncontrolled thyroid disorder * Sickle cell anemia * Current or history of clinically significant depression in the last year * Known disturbance of lipid metabolism * Acute or chronic hepatocellular disease with abnormal liver function * Hepatic adenoma or carcinoma * Cholestatic jaundice of pregnancy or jaundice with prior hormonal contraceptive use * Plans for major surgery * History of or existing venous and arterial thrombotic and thromboembolic disorder, vascular disease, cerebral vascular, or coronary artery disease * Undiagnosed abnormal genital bleeding * Known or suspected breast carcinoma, endometrial carcinoma, or estrogen-dependent neoplasia * History or presence of dermal hypersensitivity in response to topical applications (bandages, surgical tape, etc.) * Use of an injectable hormonal contraceptive within the past 10 months prior to the screening visit * Use of a contraceptive implant or hormone-medicated intrauterine device (IUD) within 1 month prior to the screening visit * Use of oral contraceptives or other sex steroid hormones within 2 months prior to the screening visit * 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 * A recent history (within prior 2 years ) of drug or alcohol abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cycle Control | 8 weeks | Measurement of unscheduled bleeding/spotting days. |
| Levonorgestrel Pharmacokinetic Profile | 8 weeks | The percentage of subjects with a minimal LNG level below pre-specified threshold of 175 pg/mL during the study. |
| Evaluation of Patch Adhesion | 8 weeks | Evaluation of worst patch adhesion score for each subject using a 5-point adhesion scale: 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 |
| Evaluation of Irritation at Patch Application Site | 8 weeks | Self-reported worst skin irritation score at patch application site for each subject using a 4-point irritation scale: 0: None 1. Mild 2. Moderate 3. Severe |
| Evaluation of Itching at Patch Application Site | 8 weeks | Self-reported worst skin itching at patch application site by subject using a 4-point scale: 0\. None 1. Mild 2. Moderate 3. Severe |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AG890-6.5 Evaluate levonorgestrel delivery in AG890-6.5
levonorgestrel: transdermal contraceptive delivery system | 18 |
| AG890-12.5 Evaluate levonorgestrel delivery in AG890-12.5
levonorgestrel: transdermal contraceptive delivery system | 18 |
| Total | 36 |
Baseline characteristics
| Characteristic | Total | AG890-6.5 | AG890-12.5 |
|---|---|---|---|
| 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 | 36 Participants | 18 Participants | 18 Participants |
| Age, Continuous | 32.39 years STANDARD_DEVIATION 7.951 | 29.83 years STANDARD_DEVIATION 8.473 | 34.94 years STANDARD_DEVIATION 6.673 |
| Region of Enrollment United States | 36 Participants | 18 Participants | 18 Participants |
| Sex: Female, Male Female | 36 Participants | 18 Participants | 18 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 / 18 | 0 / 18 |
| other Total, other adverse events | 11 / 18 | 9 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 |
Outcome results
Primary
Cycle Control
Measurement of unscheduled bleeding/spotting days.
Time frame: 8 weeks
Population: Completed subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AG890-6.5 | Cycle Control | 8.4 days | Standard Deviation 4.81 |
| AG890-12.5 | Cycle Control | 8.3 days | Standard Deviation 4.23 |
Primary
Evaluation of Irritation at Patch Application Site
Self-reported worst skin irritation score at patch application site for each subject using a 4-point irritation scale: 0: None 1. Mild 2. Moderate 3. Severe
Time frame: 8 weeks
Population: Safety population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AG890-6.5 | Evaluation of Irritation at Patch Application Site | 0.11 Score on a scale | Standard Deviation 0.471 |
| AG890-12.5 | Evaluation of Irritation at Patch Application Site | 0.06 Score on a scale | Standard Deviation 0.236 |
Primary
Evaluation of Itching at Patch Application Site
Self-reported worst skin itching at patch application site by subject using a 4-point scale: 0\. None 1. Mild 2. Moderate 3. Severe
Time frame: 8 weeks
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AG890-6.5 | Evaluation of Itching at Patch Application Site | 0.33 Score | Standard Deviation 0.594 |
| AG890-12.5 | Evaluation of Itching at Patch Application Site | 0.39 Score | Standard Deviation 0.502 |
Primary
Evaluation of Patch Adhesion
Evaluation of worst patch adhesion score for each subject using a 5-point adhesion scale: 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: 8 weeks
Population: Safety population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AG890-6.5 | Evaluation of Patch Adhesion | 0.41 Score on a scale | Standard Deviation 1.004 |
| AG890-12.5 | Evaluation of Patch Adhesion | 0.78 Score on a scale | Standard Deviation 1.517 |
Primary
Levonorgestrel Pharmacokinetic Profile
The percentage of subjects with a minimal LNG level below pre-specified threshold of 175 pg/mL during the study.
Time frame: 8 weeks
Population: Primary PK population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AG890-6.5 | Levonorgestrel Pharmacokinetic Profile | 100 % of subjects below 175 pg/mL |
| AG890-12.5 | Levonorgestrel Pharmacokinetic Profile | 83.3 % of subjects below 175 pg/mL |