ATI-CL13: Transdermal Contraceptive Delivery System (TCDS), Also Known as AG200-15 Patch Arm

• Sponsor: Agile Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01236768
• Collaborator: (none)
• Enrollment: 407
• Locations: 21
• Arms: 2
• Duration (Months): 8
• Patients Per Site: 19.4
• Patients Per Site Per Month: 2.4

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the efficacy and safety of a low dose transdermal contraceptive delivery system containing ethinyl estradiol and levonorgestrel.

Condition or Disease	Intervention/Treatment	Phase
Contraception	Drug: AG200-15; Drug: Levora	Phase 3

Detailed Description

Comparative evaluation of AG200-15 versus OC with regard to safety, contraceptive efficacy, hormone related adverse events, lipid profile, cycle control (bleeding pattern), subject compliance and serum concentrations of EE and LNG. To evaluate TCDS wearability (including adhesion).

Study Design

• Study Type: Interventional
• Actual Enrollment: 407 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: An Open-Label, Randomized, Phase 3 Study of the Contraceptive Efficacy and Safety of Agile Transdermal Contraceptive Delivery System in Comparison to an Oral Contraceptive (OC) Containing 150 mcg LNG and 30 mcg EE
• Study Start Date: Oct 1, 2010
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AG200-15 Thin transdermal contraceptive delivery system (TCDS) that gives systemic exposure of levonorgestrel (LNG) and ethinyl estradiol (EE)	Drug: AG200-15; Contraception; AG200-15 is applied and replaced every 7 days for 3 weeks, followed by a 1-week "patch free" period.; Other Names: Transdermal contraceptive delivery system (TCDS)
Active Comparator: Levora oral contraceptive containing 150mcg of LNG and 30mcg of EE	Drug: Levora; One tablet of Levora will be taken each day for a 28 day cycle.; Other Names: Hormonal oral contraceptive

Outcome Measures

Primary Outcome Measures

1. Pregnancy Reported as Pearl Index [6 months]

   Pearl Index is the number of on-therapy pregnancies times 1300 divided by the number of 28-day on-therapy cycles and is an estimate of the number of pregnancies per 100 woman-years of product use.

Secondary Outcome Measures

1. Safety [6 months]

   Adverse events

Other Outcome Measures

1. Cycle Control [6 months]

   The percentage of cycles with breakthrough bleeding or spotting episodes during all cycles. Numerator is total number of cycles with event, denominator is total number of cycles.

2. Irritation and Itching at Application Site [6 months]

   AG200-15 irritation and itching scores are defined as follows: 0=none mild moderate severe

3. Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE) [3 months and 6 months]

   Measurement of plasma levels of levonorgestrel and ethinyl estradiol.

4. Adhesion at Application Site [6 months]

   Measurement of adhesion of application site is defined as follows: 0: >=90% adhered (no lifting) >=75% adhered but <90% (some edges showing lifting) >=50% adhered but <75% (half of the patch lifts off) <50% (> half of patch lifts off, but not detached) patch completely detached

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• sexually active women requesting contraception

• Regular menses every 24 - 35 days

• In good general health, confirmed by medical history, physical (including gynecologic examination adn screening laboratory values

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Mobile	Alabama	United States	36608
2		Green Valley	Arizona	United States	85614
3		Tucson	Arizona	United States	85712
4		Los Angeles	California	United States	90036
5		Los Angeles	California	United States	90057
6		West Hills	California	United States	91307
7		Boynton Beach	Florida	United States	33472
8		Saint Petersburg	Florida	United States	33709
9		South Miami	Florida	United States	33143
10		Newburgh	Indiana	United States	47630
11		Louisville	Kentucky	United States	40291
12		Las Vegas	Nevada	United States	89109
13		Las Vegas	Nevada	United States	89128
14		Kernersville	North Carolina	United States	27284
15		Englewood	Ohio	United States	45322
16		Tulsa	Oklahoma	United States	74105
17		Mount Pleasant	South Carolina	United States	29464
18		Corpus Christi	Texas	United States	78414
19		Sugar Land	Texas	United States	77479
20		Newport News	Virginia	United States	23606
21		Norfolk	Virginia	United States	23502

Sponsors and Collaborators

• Agile Therapeutics

Investigators

• Study Director: Marie Foegh, MD, Agile Therapeutics

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Agile Therapeutics
• ClinicalTrials.gov Identifier: NCT01236768
• Other Study ID Numbers: ATI-CL13
• First Posted: Nov 9, 2010
• Last Update Posted: Sep 15, 2017
• Last Verified: Aug 1, 2017

• Keywords provided by Agile Therapeutics: Contraceptive
• Additional relevant MeSH terms: Contraceptive Agents; Contraceptives, Oral; Contraceptives, Oral, Hormonal

Study Results

Participant Flow

Arm/Group Title	AG200-15	Levora
Arm/Group Description	Transdermal contraceptive delivery system (TCDS)	hormonal oral contraceptive
Period Title: Overall Study
STARTED	201	206
COMPLETED	112	145
NOT COMPLETED	89	61

Baseline Characteristics

Arm/Group Title	AG200-15	Levora	Total
Arm/Group Description	Thin transdermal contraceptive delivery system (TCDS) that gives systemic exposure of levonorgestrel (LNG) and ethinyl estradiol (EE) AG200-15: Contraception; AG200-15 is applied and replaced every 7 days for 3 weeks, followed by a 1-week "patch free" period.	hormonal oral contraceptive	Total of all reporting groups
Overall Participants	177	188	365
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	177 100%	188 100%	365 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	177 100%	188 100%	365 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	177 100%	188 100%	365 100%

Outcome Measures

1. Primary Outcome

Title	Pregnancy Reported as Pearl Index
Description	Pearl Index is the number of on-therapy pregnancies times 1300 divided by the number of 28-day on-therapy cycles and is an estimate of the number of pregnancies per 100 woman-years of product use.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Intent-to-treat population ages 18-35.

Arm/Group Title	AG200-15	Levora
Arm/Group Description	Thin transdermal contraceptive delivery system (TCDS) that gives systemic exposure of levonorgestrel (LNG) and ethinyl estradiol (EE) AG200-15: Contraception; AG200-15 is applied and replaced every 7 days for 3 weeks, followed by a 1-week "patch free" period.	hormonal oral contraceptive
Measure Participants	147	163
Number (95% Confidence Interval) [Pearl Index]	8.19	6.80

2. Secondary Outcome

Title	Safety
Description	Adverse events
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Any subject who applied a patch.

Arm/Group Title	AG200-15	Levora
Arm/Group Description	Thin transdermal contraceptive delivery system (TCDS) that gives systemic exposure of levonorgestrel (LNG) and ethinyl estradiol (EE) AG200-15: Contraception; AG200-15 is applied and replaced every 7 days for 3 weeks, followed by a 1-week "patch free" period.	oral contraceptive containing 150mcg of LNG and 30mcg of EE Levora: One tablet of Levora will be taken each day for a 28 day cycle.
Measure Participants	177	188
Number [Events]	85	88

3. Other Pre-specified Outcome

Title	Cycle Control
Description	The percentage of cycles with breakthrough bleeding or spotting episodes during all cycles. Numerator is total number of cycles with event, denominator is total number of cycles.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Subjects with relevant breakthrough bleeding (BTB) and/or spotting (BTS), and drug information for a cycle.

Arm/Group Title	AG200-15	Levora
Arm/Group Description	Thin transdermal contraceptive delivery system (TCDS) that gives systemic exposure of levonorgestrel (LNG) and ethinyl estradiol (EE) AG200-15: Contraception; AG200-15 is applied and replaced every 7 days for 3 weeks, followed by a 1-week "patch free" period.	oral contraceptive containing 150mcg of LNG and 30mcg of EE Levora: One tablet of Levora will be taken each day for a 28 day cycle.
Measure Participants	162	182
Number [percent cycles with BTB or BTS]	24.5	21

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AG200-15, Levora
	Comments	Comparative evaluation of AG200-15 and Levora
	Type of Statistical Test	Equivalence
	Comments	Comparative analysis of AG200-15 and Levora for breakthrough bleeding and/or spotting.
Statistical Test of Hypothesis	p-Value	0.089
	Comments
	Method	Chi-squared
	Comments

4. Other Pre-specified Outcome

Title	Irritation and Itching at Application Site
Description	AG200-15 irritation and itching scores are defined as follows: 0=none mild moderate severe
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Subject self-reported worse irritation score in a cycle.

Arm/Group Title	AG200-15
Arm/Group Description	Thin transdermal contraceptive delivery system (TCDS) that gives systemic exposure of levonorgestrel (LNG) and ethinyl estradiol (EE) AG200-15: Contraception; AG200-15 is applied and replaced every 7 days for 3 weeks, followed by a 1-week "patch free" period.
Measure Participants	170
Irritation Score (cycles 1-6 combined)	1.15 (0.914)
Itching Score (cycles 1-6 combined)	1.31 (0.851)

5. Other Pre-specified Outcome

Title	Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE)
Description	Measurement of plasma levels of levonorgestrel and ethinyl estradiol.
Time Frame	3 months and 6 months

Outcome Measure Data

Analysis Population Description

Number of subjects with available LNG data for cycle 3 or cycle 6

Arm/Group Title	AG200-15	Levora
Arm/Group Description	Thin transdermal contraceptive delivery system (TCDS) that gives systemic exposure of levonorgestrel (LNG) and ethinyl estradiol (EE) AG200-15: Contraception; AG200-15 is applied and replaced every 7 days for 3 weeks, followed by a 1-week "patch free" period.	oral contraceptive containing 150mcg of LNG and 30mcg of EE Levora: One tablet of Levora will be taken each day for a 28 day cycle.
Measure Participants	111	140
LNG cycle 3	2244	3474
LNG cycle 6	1743	3682
EE cycle 3	44.5	50.6
EE cycle 6	34.7	54.7

6. Other Pre-specified Outcome

Title	Adhesion at Application Site
Description	Measurement of adhesion of application site is defined as follows: 0: >=90% adhered (no lifting) >=75% adhered but <90% (some edges showing lifting) >=50% adhered but <75% (half of the patch lifts off) <50% (> half of patch lifts off, but not detached) patch completely detached
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Subjects that have documented adhesion scores.

Arm/Group Title	AG200-15
Arm/Group Description	Thin transdermal contraceptive delivery system (TCDS) that gives systemic exposure of levonorgestrel (LNG) and ethinyl estradiol (EE) AG200-15: Contraception; AG200-15 is applied and replaced every 7 days for 3 weeks, followed by a 1-week "patch free" period.
Measure Participants	159
Mean (Standard Deviation) [Score]	0.46 (1.118)

Adverse Events

Time Frame	6 months
Arm/Group Title	AG200-15		Levora
Arm/Group Description	Thin transdermal contraceptive delivery system (TCDS) that gives systemic exposure of levonorgestrel (LNG) and ethinyl estradiol (EE) AG200-15: Contraception; AG200-15 is applied and replaced every 7 days for 3 weeks, followed by a 1-week "patch free" period.		oral contraceptive containing 150mcg of LNG and 30mcg of EE Levora: One tablet of Levora will be taken each day for a 28 day cycle.
All Cause Mortality
	AG200-15		Levora
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/177 (0%)		0/188 (0%)
Serious Adverse Events
	AG200-15		Levora
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/177 (0%)		2/188 (1.1%)
Infections and infestations
Murine Typhus	0/177 (0%)	0	1/188 (0.5%)	1
Nervous system disorders
Convulsion	0/177 (0%)	0	1/188 (0.5%)	1
Other (Not Including Serious) Adverse Events
	AG200-15		Levora
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/177 (23.7%)		45/188 (23.9%)
Gastrointestinal disorders
Nausea	5/177 (2.8%)	5	11/188 (5.9%)	11
Infections and infestations
Sinusitis	7/177 (4%)	7	5/188 (2.7%)	5
Nasopharyngitis	9/177 (5.1%)	9	8/188 (4.3%)	8
Reproductive system and breast disorders
Cervical dysplasia	10/177 (5.6%)	10	11/188 (5.9%)	11
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection	4/177 (2.3%)	4	8/188 (4.3%)	8
Sinus Congestion	7/177 (4%)	7	2/188 (1.1%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Review and approval by Agile Therapeutics, Inc. of any publication, including oral presentations and abstracts, utilizing data or any information from the ATI-CL13 study is required prior to publication submission.