ATI-CL21: Study to Evaluate Pharmacokinetics Profile, Wearability, and Safety of 2 Progestin-Only Patches

• Sponsor: Agile Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01623466
• Collaborator: (none)
• Enrollment: 36
• Arms: 2
• Actual Duration (Months): 2

Study Details

Study Description

Brief Summary

Pharmacokinetics, safety and wearability in two size patches of AG890 over eight weeks will be evaluated.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: levonorgestrel	Phase 1/Phase 2

Detailed Description

To evaluate pharmacokinetic (PK) profile, patch wearability (adhesion and skin irritation), and safety of AG890-6.5 and AG890-12.5 TCDS.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-Label, Parallel Group Study To Evaluate Pharmacokinetic Profile, Wearability And Safety of Two Progestin-Only Patches Containing Different Doses Of Levonorgestrel (LNG)
• Actual Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AG890-6.5 Evaluate levonorgestrel delivery in AG890-6.5	Drug: levonorgestrel; transdermal contraceptive delivery system; Other Names: patch, transdermal contraceptive delivery system
Experimental: AG890-12.5 Evaluate levonorgestrel delivery in AG890-12.5	Drug: levonorgestrel; transdermal contraceptive delivery system; Other Names: patch, transdermal contraceptive delivery system

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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) ≥75% adhered but <90% (some edges showing lift) ≥50% adhered but <75% (half of system lifts off) <50% (< half of system lifts off, but undetached) patch completely detached

3. 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 Mild Moderate Severe

4. 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 Mild Moderate Severe

5. Cycle Control [8 weeks]

   Measurement of unscheduled bleeding/spotting days.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Female
• Accepts 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Agile Therapeutics

Investigators

• Study Director: Elizabeth Garner, MD, PHD, Agile Therapeutics

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Agile Therapeutics
• ClinicalTrials.gov Identifier: NCT01623466
• Other Study ID Numbers: ATI-CL21
• First Posted: Jun 20, 2012
• Last Update Posted: Jan 23, 2018
• Last Verified: Dec 1, 2017

• Keywords provided by Agile Therapeutics: PK and Safety
• Additional relevant MeSH terms: Contraceptive Agents; Levonorgestrel

Study Results

Participant Flow

Arm/Group Title	AG890-6.5	AG890-12.5
Arm/Group Description	Evaluate levonorgestrel delivery in AG890-6.5 levonorgestrel: transdermal contraceptive delivery system	Evaluate levonorgestrel delivery in AG890-12.5 levonorgestrel: transdermal contraceptive delivery system
Period Title: Overall Study
STARTED	18	18
COMPLETED	17	18
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	AG890-6.5	AG890-12.5	Total
Arm/Group Description	Evaluate levonorgestrel delivery in AG890-6.5 levonorgestrel: transdermal contraceptive delivery system	Evaluate levonorgestrel delivery in AG890-12.5 levonorgestrel: transdermal contraceptive delivery system	Total of all reporting groups
Overall Participants	18	18	36
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	18 100%	18 100%	36 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	29.83 (8.473)	34.94 (6.673)	32.39 (7.951)
Sex: Female, Male (Count of Participants)
Female	18 100%	18 100%	36 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	18 100%	18 100%	36 100%

Outcome Measures

1. Primary Outcome

Title	Levonorgestrel Pharmacokinetic Profile
Description	The percentage of subjects with a minimal LNG level below pre-specified threshold of 175 pg/mL during the study.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Primary PK population

Arm/Group Title	AG890-6.5	AG890-12.5
Arm/Group Description	Evaluate levonorgestrel delivery in AG890-6.5 levonorgestrel: transdermal contraceptive delivery system	Evaluate levonorgestrel delivery in AG890-12.5 levonorgestrel: transdermal contraceptive delivery system
Measure Participants	17	18
Number [% of subjects below 175 pg/mL]	100	83.3

2. Primary Outcome

Title	Evaluation of Patch Adhesion
Description	Evaluation of worst patch adhesion score for each subject using a 5-point adhesion scale: 0: ≥90% adhered (no lift) ≥75% adhered but <90% (some edges showing lift) ≥50% adhered but <75% (half of system lifts off) <50% (< half of system lifts off, but undetached) patch completely detached
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	AG890-6.5	AG890-12.5
Arm/Group Description	Evaluate levonorgestrel delivery in AG890-6.5 levonorgestrel: transdermal contraceptive delivery system	Evaluate levonorgestrel delivery in AG890-12.5 levonorgestrel: transdermal contraceptive delivery system
Measure Participants	17	18
Mean (Standard Deviation) [Score on a scale]	0.41 (1.004)	0.78 (1.517)

3. Primary Outcome

Title	Evaluation of Irritation at Patch Application Site
Description	Self-reported worst skin irritation score at patch application site for each subject using a 4-point irritation scale: 0: None Mild Moderate Severe
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	AG890-6.5	AG890-12.5
Arm/Group Description	Evaluate levonorgestrel delivery in AG890-6.5 levonorgestrel: transdermal contraceptive delivery system	Evaluate levonorgestrel delivery in AG890-12.5 levonorgestrel: transdermal contraceptive delivery system
Measure Participants	18	18
Mean (Standard Deviation) [Score on a scale]	0.11 (0.471)	0.06 (0.236)

4. Primary Outcome

Title	Evaluation of Itching at Patch Application Site
Description	Self-reported worst skin itching at patch application site by subject using a 4-point scale: 0. None Mild Moderate Severe
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	AG890-6.5	AG890-12.5
Arm/Group Description	Evaluate levonorgestrel delivery in AG890-6.5 levonorgestrel: transdermal contraceptive delivery system	Evaluate levonorgestrel delivery in AG890-12.5 levonorgestrel: transdermal contraceptive delivery system
Measure Participants	18	18
Mean (Standard Deviation) [Score]	0.33 (0.594)	0.39 (0.502)

5. Primary Outcome

Title	Cycle Control
Description	Measurement of unscheduled bleeding/spotting days.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Completed subjects

Arm/Group Title	AG890-6.5	AG890-12.5
Arm/Group Description	Evaluate levonorgestrel delivery in AG890-6.5 levonorgestrel: transdermal contraceptive delivery system	Evaluate levonorgestrel delivery in AG890-12.5 levonorgestrel: transdermal contraceptive delivery system
Measure Participants	17	18
Mean (Standard Deviation) [days]	8.4 (4.81)	8.3 (4.23)

Adverse Events

Arm/Group Title	AG890-6.5		AG890-12.5
Arm/Group Description	Evaluate levonorgestrel delivery in AG890-6.5 levonorgestrel: transdermal contraceptive delivery system		Evaluate levonorgestrel delivery in AG890-12.5 levonorgestrel: transdermal contraceptive delivery system
All Cause Mortality
	AG890-6.5		AG890-12.5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/18 (0%)
Serious Adverse Events
	AG890-6.5		AG890-12.5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	AG890-6.5		AG890-12.5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/18 (61.1%)		9/18 (50%)
Gastrointestinal disorders
Gastrointestinal Disorders	1/18 (5.6%)	1	1/18 (5.6%)	2
Immune system disorders
Immune system disorders	1/18 (5.6%)	1	0/18 (0%)	0
Metabolism and nutrition disorders
Metabolism and nutrition disorders	2/18 (11.1%)	2	2/18 (11.1%)	2
Nervous system disorders
Nervous system disorders	9/18 (50%)	9	5/18 (27.8%)	5
Psychiatric disorders
Psychiatric disorders	1/18 (5.6%)	1	2/18 (11.1%)	2
Reproductive system and breast disorders
Reproductive system ad breast disorders	3/18 (16.7%)	3	5/18 (27.8%)	5
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders	1/18 (5.6%)	1	0/18 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

All publications must be reviewed and approved by sponsor