AG200-15 Transdermal Contraceptive Delivery System (TCDS) of Levonorgestrel and Ethinyl Estradiol

• Sponsor: Agile Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01243580
• Collaborator: (none)
• Enrollment: 36
• Location: 1
• Arms: 2
• Duration (Months): 4
• Patients Per Site Per Month: 9

Study Details

Study Description

Brief Summary

Pharmacokinetics and safety of AG200-15 over two consecutive cycles of therapy will be evaluated.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Ortho-Cyclen; Drug: AG200-15	Phase 1

Detailed Description

This is an open-label study comprised of two parts. Part I is a single-arm, run-in cycle with AG200-15 administered to all subjects as a 21-7 day regimen (three consecutive weeks of patch wear followed by a patch-free week).

Part II employs crossover design with subjects randomly assigned to one of the two treatment sequences. Each sequence will include AG200-15 and oral contraceptive (Ortho-Cyclen®) as described below: Sequence 1: AG200-15 (Period 1) followed by oral contraceptive, Ortho-Cyclen® (Period 2); Sequence 2: Oral contraceptive, Ortho-Cyclen® (Period 1) followed by AG200-15 (Period 2) Both AG200-15 and Ortho-Cyclen® will be administered as 21-7 day regimen (three consecutive weeks of drug-taking followed by a drug-free week). Duration of each treatment Period is 28 days (one cycle of therapy).

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Study to Evaluate Pharmacokinetic Profile of Agile TCDS AG200-15 and to Compare Exposure to Ethinyl Estradiol to Oral Contraceptive (Orthocyclen®) in Healthy Female Volunteers
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ortho-Cyclen® Ortho-Cyclen® is a comparator drug intervention	Drug: Ortho-Cyclen; Ortho-Cyclen is an oral contraceptive containing 35 µg of EE and 250 µg of norgestimate (NGM) in a 21 - 7 day regimen.; Other Names: oral contraceptive
Experimental: AG200-15 AG200-15 is an investigational transdermal contraceptive delivery system that is a drug intervention	Drug: AG200-15; AG200-15 is a transdermal contraceptive delivery system delivering 100 - 120 mcg of LNG and 25 - 30 mcg EE; Other Names: transdermal contraception

Outcome Measures

Primary Outcome Measures

1. Comparative Evaluation of Ethinyl Estradiol (EE) Cmax Between AG200-15 and Ortho-Cyclen® in Week 1 [3 months]

   Comparative evaluation of ethinyl estradiol (EE) Cmax between AG200-15 and Ortho-Cyclen® in week 1 for cycle 2 and 3.

2. Comparative Evaluation of EE Cmax Between AG200-15 and Ortho-Cyclen® in Week 3 [3 months]

   Comparative evaluation of EE Cmax between AG200-15 and Ortho-Cyclen® in week 3 for cycles 2 and 3.

3. Comparative Evaluation of EE AUC(0-168hrs Post-first Dose) Between AG200-15 and Ortho-Cyclen® in Week 1 [3 months]

   Comparative evaluation of EE AUC (0-168hrs post-first dose) between AG200-15 and Ortho-Cyclen® in week 1 for cycles 2 and 3.

4. Comparative Evaluation of EE AUC (0-168hrs Post-first Dose) Between AG200-15 and Ortho-Cyclen® in Week 3 [3 months]

   Comparative evaluation of EE AUC (0-168hrs post-first dose) between AG200-15 and Ortho-Cyclen® in week 3 for cycles 2 and 3.

5. Comparative Evaluation of EE Css (1) Between AG200-15 and Ortho-Cyclen® in Week 1 [3 months]

   Comparative evaluation of EE Css (1) between AG200-15 and Ortho-Cyclen® in week 1 for cycles 2 and 3. For Ortho-Cyclen steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For AG200-15 the average concentration within the 48-168 h time-interval was measured.

6. Comparative Evaluation of EE Css (1) Between AG200-15 and Ortho-Cyclen® in Week 3 [3 months]

   Comparative evaluation of EE Css (1) between AG200-15 and Ortho-Cyclen® in week 3 for cycles 2 and 3. For Ortho-Cyclen steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For AG200-15 the average concentration within the 48-168 h time-interval was measured.

7. Comparative Evaluation of EE Css (2) Between AG200-15 and Ortho-Cyclen® in Week 1 [3 months]

   Comparative evaluation of EE Css (2) between AG200-15 and Ortho-Cyclen® in week 1 for cycles 2 and 3. For Ortho-Cyclen steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For Ag200-15, the average concentration at steady-state calculated from trapezoidal AUC within the 48-168h time interval (AUC/time interval).

8. Comparative Evaluation of EE Css (2) Between AG200-15 and Ortho-Cyclen® in Week 3 [3 months]

   Comparative evaluation of EE Css (2) between AG200-15 and Ortho-Cyclen® in week 3 for cycles 2 and 3. For Ortho-Cyclen steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For Ag200-15, the average concentration at steady-state calculated from trapezoidal AUC within the 48-168h time interval (AUC/time interval).

9. Comparative Evaluation of EE Css (3) Between AG200-15 and Ortho-Cyclen® in Week 1 [3 months]

   Comparative evaluation of EE Css (3) between AG200-15 and Ortho-Cyclen® in week 1 for cycles 2 and 3. For Ortho-Cyclen steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For AG200-15, the average concentration at steady-state calculated from trapezoidal AUC within the 0-168h time interval (AUC/time interval).

10. Comparative Evaluation of EE Css (3) Between AG200-15 and Ortho-Cyclen® in Week 3 [3 months]

    Comparative evaluation of EE Css (3) between AG200-15 and Ortho-Cyclen® in week 3 for cycles 2 and 3. For Ortho-Cyclen steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For AG200-15, the average concentration at steady-state calculated from trapezoidal AUC within the 0-168h time interval (AUC/time interval).

11. Evaluation of LNG Cmax Between AG200-15 in Week 1 and 3 [3 months]

    Evaluation of LNG Cmax Between AG200-15 in Week 1 and 3 for cycles 2 and 3.

12. Evaluation of LNG AUC (0-168hrs Post-first Dose) Between AG200-15 in Week 1 and 3 [3 months]

    Evaluation of LNG AUC (0-168hrs post-first dose) Between AG200-15 in Week 1 and 3 for cycles 2 and 3.

13. Evaluation of LNG Css (1) Between AG200-15 in Week 1 and 3 [3 months]

    Comparative evaluation of EE Css (1) between AG200-15 and Ortho-Cyclen® in week 1 for cycles 2 and 3. For Ortho-Cyclen, steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For Ag200-15, the average concentration at steady-state calculated from trapezoidal AUC within the 48-168h time interval (AUC/time interval).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Healthy women, ages 18-45

• Body mass index (BMI) ≥18 and ≤32, and weight ≥ 110 lbs.

• Willing to use a non-hormonal method of contraception if at risk of pregnancy, OR have already undergone previous bilateral tubal ligation or hysterectomy

• Willing to refrain from use of alcohol and grapefruit juice from 48 hours prior until completion of each treatment period

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

• Smokers

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Miami	Florida	United States	33169

Sponsors and Collaborators

• Agile Therapeutics

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Agile Therapeutics
• ClinicalTrials.gov Identifier: NCT01243580
• Other Study ID Numbers: ATI-CL14
• First Posted: Nov 18, 2010
• Last Update Posted: Jan 23, 2018
• Last Verified: Dec 1, 2017

• Keywords provided by Agile Therapeutics: PK and safety; Pharmacokinetic profile (PK) and safety
• Additional relevant MeSH terms: Moxifloxacin; Contraceptive Agents; Norgestimate, ethinyl estradiol drug combination; Contraceptives, Oral

Study Results

Participant Flow

Arm/Group Title	AG200-15/Ortho-Cyclen®	Ortho-Cyclen®/AG200-15
Arm/Group Description	AG200-15 transdermal contraceptive delivery system, delivering 25-30 mcg ethinyl estradiol/ 100-120 mcg levonorgestrel per day, was applied weekly for 3 consecutive weeks and was removed on the 4th week for a patch free week. This regimen occurred for Cycles 1 and 2. For cycle 3, Ortho-Cyclen® containing 250 mcg norgestimate and 35 mcg ethinyl estradiol was taken daily for 21 days followed by a drug free interval of 7 days.	AG200-15 transdermal contraceptive delivery system, delivering 25-30 mcg ethinyl estradiol and 100-120 mcg levonorgestrel per day, was applied for 3 consecutive weeks and removed on the 4th week for a patch free week. This regimen occurred for Cycle 1 and Cycle 3. Ortho-Cyclen®, containing 250 mcg norgestimate and 35 mcg ethinyl estradiol, was taken daily for 21 days followed by a drug free interval of 7 days for Cycle 2.
Period Title: Overall Study
STARTED	18	18
COMPLETED	18	16
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	AG200-15/Ortho-Cyclen®	Ortho-Cyclen® /AG200-15	Total
Arm/Group Description	Subject applied AG200-15 in cycle 1. Subjects applied AG200-15 (Cycle 2) followed by oral contraceptive, Ortho-Cyclen® (Cycle 3)	Subject applied AG200-15 in cycle 1. Subjects received Ortho-Cyclen® (Cycle 2) followed by AG200-15 (Cycle 3).	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]	37.8 (5.85)	36.2 (7.66)	37 (6.77)
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	Comparative Evaluation of Ethinyl Estradiol (EE) Cmax Between AG200-15 and Ortho-Cyclen® in Week 1
Description	Comparative evaluation of ethinyl estradiol (EE) Cmax between AG200-15 and Ortho-Cyclen® in week 1 for cycle 2 and 3.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Primary PK population

Arm/Group Title	Ortho-Cyclen®	AG200-15
Arm/Group Description	Ortho-Cyclen® is a comparator drug intervention Ortho-Cyclen: Ortho-Cyclen is an oral contraceptive containing 35 µg of EE and 250 µg of norgestimate (NGM) in a 21 - 7 day regimen.	AG200-15 is an investigational transdermal contraceptive delivery system that is a drug intervention AG200-15: AG200-15 is a transdermal contraceptive delivery system delivering 100 - 120 mcg of levonorgestrel (LNG) and 25 - 30 mcg EE
Measure Participants	29	33
Mean (Standard Deviation) [pg/ml]	135 (50.7)	45.5 (24.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ortho-Cyclen®, AG200-15
	Comments
	Type of Statistical Test	Equivalence
	Comments	Comparing Ortho-Cyclen to Ag200-15
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

2. Primary Outcome

Title	Comparative Evaluation of EE Cmax Between AG200-15 and Ortho-Cyclen® in Week 3
Description	Comparative evaluation of EE Cmax between AG200-15 and Ortho-Cyclen® in week 3 for cycles 2 and 3.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Primary PK population

Arm/Group Title	Ortho-Cyclen®	AG200-15
Arm/Group Description	Ortho-Cyclen® is a comparator drug intervention Ortho-Cyclen: Ortho-Cyclen is an oral contraceptive containing 35 µg of EE and 250 µg of norgestimate (NGM) in a 21 - 7 day regimen.	AG200-15 is an investigational transdermal contraceptive delivery system that is a drug intervention AG200-15: AG200-15 is a transdermal contraceptive delivery system delivering 100 - 120 mcg of LNG and 25 - 30 mcg EE
Measure Participants	32	32
Mean (Standard Deviation) [pg/ml]	131 (45.4)	51.3 (17.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ortho-Cyclen®, AG200-15
	Comments
	Type of Statistical Test	Equivalence
	Comments	Comparison of AG200-15 and Ortho-Cyclen
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

3. Primary Outcome

Title	Comparative Evaluation of EE AUC(0-168hrs Post-first Dose) Between AG200-15 and Ortho-Cyclen® in Week 1
Description	Comparative evaluation of EE AUC (0-168hrs post-first dose) between AG200-15 and Ortho-Cyclen® in week 1 for cycles 2 and 3.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Primary PK population

Arm/Group Title	Ortho-Cyclen®	AG200-15
Arm/Group Description	Ortho-Cyclen® is a comparator drug intervention Ortho-Cyclen: Ortho-Cyclen is an oral contraceptive containing 35 µg of EE and 250 µg of norgestimate (NGM) in a 21 - 7 day regimen.	AG200-15 is an investigational transdermal contraceptive delivery system that is a drug intervention AG200-15: AG200-15 is a transdermal contraceptive delivery system delivering 100 - 120 mcg of LNG and 25 - 30 mcg EE
Measure Participants	29	32
Mean (Standard Deviation) [ng.h/ml]	7.28 (2.66)	5.06 (2.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ortho-Cyclen®, AG200-15
	Comments
	Type of Statistical Test	Equivalence
	Comments	Comparison of AG200-15 and Ortho-Cyclen
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	ANOVA
	Comments

4. Primary Outcome

Title	Comparative Evaluation of EE AUC (0-168hrs Post-first Dose) Between AG200-15 and Ortho-Cyclen® in Week 3
Description	Comparative evaluation of EE AUC (0-168hrs post-first dose) between AG200-15 and Ortho-Cyclen® in week 3 for cycles 2 and 3.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Primary PK population

Arm/Group Title	Ortho-Cyclen®	AG200-15
Arm/Group Description	Ortho-Cyclen® is a comparator drug intervention Ortho-Cyclen: Ortho-Cyclen is an oral contraceptive containing 35 µg of EE and 250 µg of norgestimate (NGM) in a 21 - 7 day regimen.	AG200-15 is an investigational transdermal contraceptive delivery system that is a drug intervention AG200-15: AG200-15 is a transdermal contraceptive delivery system delivering 100 - 120 mcg of LNG and 25 - 30 mcg EE
Measure Participants	32	32
Mean (Standard Deviation) [ng.h/ml]	6.97 (2.25)	6.26 (2.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ortho-Cyclen®, AG200-15
	Comments
	Type of Statistical Test	Equivalence
	Comments	Comparison of Ortho-Cylen and AG200-15
Statistical Test of Hypothesis	p-Value	0.0532
	Comments
	Method	ANOVA
	Comments

5. Primary Outcome

Title	Comparative Evaluation of EE Css (1) Between AG200-15 and Ortho-Cyclen® in Week 1
Description	Comparative evaluation of EE Css (1) between AG200-15 and Ortho-Cyclen® in week 1 for cycles 2 and 3. For Ortho-Cyclen steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For AG200-15 the average concentration within the 48-168 h time-interval was measured.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Primary PK population

Arm/Group Title	Ortho-Cyclen®	AG200-15
Arm/Group Description	Ortho-Cyclen® is a comparator drug intervention Ortho-Cyclen: Ortho-Cyclen is an oral contraceptive containing 35 µg of EE and 250 µg of norgestimate (NGM) in a 21 - 7 day regimen.	AG200-15 is an investigational transdermal contraceptive delivery system that is a drug intervention AG200-15: AG200-15 is a transdermal contraceptive delivery system delivering 100 - 120 mcg of LNG and 25 - 30 mcg EE
Measure Participants	32	32
Mean (Standard Deviation) [pg/ml]	43.3 (15.8)	31.4 (15.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ortho-Cyclen®, AG200-15
	Comments
	Type of Statistical Test	Equivalence
	Comments	Comparison of Ortho-Cyclen and AG200-15
Statistical Test of Hypothesis	p-Value	0.0009
	Comments
	Method	ANOVA
	Comments

6. Primary Outcome

Title	Comparative Evaluation of EE Css (1) Between AG200-15 and Ortho-Cyclen® in Week 3
Description	Comparative evaluation of EE Css (1) between AG200-15 and Ortho-Cyclen® in week 3 for cycles 2 and 3. For Ortho-Cyclen steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For AG200-15 the average concentration within the 48-168 h time-interval was measured.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Primary PK population

Arm/Group Title	Ortho-Cyclen®	AG200-15
Arm/Group Description	Ortho-Cyclen® is a comparator drug intervention Ortho-Cyclen: Ortho-Cyclen is an oral contraceptive containing 35 µg of EE and 250 µg of norgestimate (NGM) in a 21 - 7 day regimen.	AG200-15 is an investigational transdermal contraceptive delivery system that is a drug intervention AG200-15: AG200-15 is a transdermal contraceptive delivery system delivering 100 - 120 mcg of LNG and 25 - 30 mcg EE
Measure Participants	32	32
Mean (Standard Deviation) [pg/ml]	41.5 (13.4)	35.7 (14.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ortho-Cyclen®, AG200-15
	Comments
	Type of Statistical Test	Equivalence
	Comments	Comparison of Ortho-Cyclen and AG200-15
Statistical Test of Hypothesis	p-Value	0.0167
	Comments
	Method	ANOVA
	Comments

7. Primary Outcome

Title	Comparative Evaluation of EE Css (2) Between AG200-15 and Ortho-Cyclen® in Week 1
Description	Comparative evaluation of EE Css (2) between AG200-15 and Ortho-Cyclen® in week 1 for cycles 2 and 3. For Ortho-Cyclen steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For Ag200-15, the average concentration at steady-state calculated from trapezoidal AUC within the 48-168h time interval (AUC/time interval).
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Primary PK population

Arm/Group Title	Ortho-Cyclen®	AG200-15
Arm/Group Description	Ortho-Cyclen® is a comparator drug intervention Ortho-Cyclen: Ortho-Cyclen is an oral contraceptive containing 35 µg of EE and 250 µg of norgestimate (NGM) in a 21 - 7 day regimen.	AG200-15 is an investigational transdermal contraceptive delivery system that is a drug intervention AG200-15: AG200-15 is a transdermal contraceptive delivery system delivering 100 - 120 mcg of LNG and 25 - 30 mcg EE
Measure Participants	32	32
Mean (Standard Deviation) [pg/ml]	43.3 (15.8)	32.0 (16.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ortho-Cyclen®, AG200-15
	Comments
	Type of Statistical Test	Equivalence
	Comments	Comparison of Ortho-Cyclen and AG200-15
Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	ANOVA
	Comments

8. Primary Outcome

Title	Comparative Evaluation of EE Css (2) Between AG200-15 and Ortho-Cyclen® in Week 3
Description	Comparative evaluation of EE Css (2) between AG200-15 and Ortho-Cyclen® in week 3 for cycles 2 and 3. For Ortho-Cyclen steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For Ag200-15, the average concentration at steady-state calculated from trapezoidal AUC within the 48-168h time interval (AUC/time interval).
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Primary PK population

Arm/Group Title	Ortho-Cyclen®	AG200-15
Arm/Group Description	Ortho-Cyclen® is a comparator drug intervention Ortho-Cyclen: Ortho-Cyclen is an oral contraceptive containing 35 µg of EE and 250 µg of norgestimate (NGM) in a 21 - 7 day regimen.	AG200-15 is an investigational transdermal contraceptive delivery system that is a drug intervention AG200-15: AG200-15 is a transdermal contraceptive delivery system delivering 100 - 120 mcg of LNG and 25 - 30 mcg EE
Measure Participants	32	32
Mean (Standard Deviation) [pg/ml]	41.5 (13.4)	35.7 (15.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ortho-Cyclen®, AG200-15
	Comments
	Type of Statistical Test	Equivalence
	Comments	Comparison of Ortho-Cyclen and AG200-15
Statistical Test of Hypothesis	p-Value	0.0175
	Comments
	Method	ANOVA
	Comments

9. Primary Outcome

Title	Comparative Evaluation of EE Css (3) Between AG200-15 and Ortho-Cyclen® in Week 1
Description	Comparative evaluation of EE Css (3) between AG200-15 and Ortho-Cyclen® in week 1 for cycles 2 and 3. For Ortho-Cyclen steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For AG200-15, the average concentration at steady-state calculated from trapezoidal AUC within the 0-168h time interval (AUC/time interval).
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Primary PK population

Arm/Group Title	Ortho-Cyclen®	AG200-15
Arm/Group Description	Ortho-Cyclen® is a comparator drug intervention Ortho-Cyclen: Ortho-Cyclen is an oral contraceptive containing 35 µg of EE and 250 µg of norgestimate (NGM) in a 21 - 7 day regimen.	AG200-15 is an investigational transdermal contraceptive delivery system that is a drug intervention AG200-15: AG200-15 is a transdermal contraceptive delivery system delivering 100 - 120 mcg of LNG and 25 - 30 mcg EE
Measure Participants	32	32
Mean (Standard Deviation) [pg/ml]	43.3 (15.8)	30.1 (13.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ortho-Cyclen®, AG200-15
	Comments
	Type of Statistical Test	Equivalence
	Comments	Comparison of Ortho-Cyclen and AG200-15
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	ANOVA
	Comments

10. Primary Outcome

Title	Comparative Evaluation of EE Css (3) Between AG200-15 and Ortho-Cyclen® in Week 3
Description	Comparative evaluation of EE Css (3) between AG200-15 and Ortho-Cyclen® in week 3 for cycles 2 and 3. For Ortho-Cyclen steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For AG200-15, the average concentration at steady-state calculated from trapezoidal AUC within the 0-168h time interval (AUC/time interval).
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Primary PK population

Arm/Group Title	Ortho-Cyclen®	AG200-15
Arm/Group Description	Ortho-Cyclen® is a comparator drug intervention Ortho-Cyclen: Ortho-Cyclen is an oral contraceptive containing 35 µg of EE and 250 µg of norgestimate (NGM) in a 21 - 7 day regimen.	AG200-15 is an investigational transdermal contraceptive delivery system that is a drug intervention AG200-15: AG200-15 is a transdermal contraceptive delivery system delivering 100 - 120 mcg of LNG and 25 - 30 mcg EE
Measure Participants	32	32
Mean (Standard Deviation) [pg/ml]	41.5 (13.4)	37.3 (14.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ortho-Cyclen®, AG200-15
	Comments
	Type of Statistical Test	Equivalence
	Comments	Comparison of Ortho-Cyclen and AG200-15
Statistical Test of Hypothesis	p-Value	0.0532
	Comments
	Method	ANOVA
	Comments

11. Primary Outcome

Title	Evaluation of LNG Cmax Between AG200-15 in Week 1 and 3
Description	Evaluation of LNG Cmax Between AG200-15 in Week 1 and 3 for cycles 2 and 3.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Primary PK population

Arm/Group Title	AG200-15
Arm/Group Description	AG200-15 is an investigational transdermal contraceptive delivery system that is a drug intervention AG200-15: AG200-15 is a transdermal contraceptive delivery system delivering 100 - 120 mcg of LNG and 25 - 30 mcg EE
Measure Participants	33
Week 1	1370 (908)
Week 3	2400 (1140)

12. Primary Outcome

Title	Evaluation of LNG AUC (0-168hrs Post-first Dose) Between AG200-15 in Week 1 and 3
Description	Evaluation of LNG AUC (0-168hrs post-first dose) Between AG200-15 in Week 1 and 3 for cycles 2 and 3.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Primary PK population

Arm/Group Title	AG200-15
Arm/Group Description	AG200-15 is an investigational transdermal contraceptive delivery system that is a drug intervention AG200-15: AG200-15 is a transdermal contraceptive delivery system delivering 100 - 120 mcg of LNG and 25 - 30 mcg EE
Measure Participants	33
Week 1	160 (88.9)
Week 3	317 (159)

13. Primary Outcome

Title	Evaluation of LNG Css (1) Between AG200-15 in Week 1 and 3
Description	Comparative evaluation of EE Css (1) between AG200-15 and Ortho-Cyclen® in week 1 for cycles 2 and 3. For Ortho-Cyclen, steady-state concentration calculated as average concentration at steady-state from the 24-hour trapezoidal AUC (AUC0-24h/24). For Ag200-15, the average concentration at steady-state calculated from trapezoidal AUC within the 48-168h time interval (AUC/time interval).
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Primary PK population

Arm/Group Title	AG200-15
Arm/Group Description	AG200-15 is an investigational transdermal contraceptive delivery system that is a drug intervention AG200-15: AG200-15 is a transdermal contraceptive delivery system delivering 100 - 120 mcg of LNG and 25 - 30 mcg EE
Measure Participants	33
Week 1	1060 (631)
Week 3	1847 (930)

Adverse Events

Time Frame	3 months
Adverse Event Reporting Description	Adverse events were analyzed based on Organ System class.
Arm/Group Title	Ortho-Cyclen®		AG200-15
Arm/Group Description	Ortho-Cyclen® is a comparator drug intervention Ortho-Cyclen: Ortho-Cyclen is an oral contraceptive containing 35 µg of EE and 250 µg of norgestimate (NGM) in a 21 - 7 day regimen.		AG200-15 is an investigational transdermal contraceptive delivery system that is a drug intervention AG200-15: AG200-15 is a transdermal contraceptive delivery system delivering 100 - 120 mcg of LNG and 25 - 30 mcg EE
All Cause Mortality
	Ortho-Cyclen®		AG200-15
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/36 (0%)
Serious Adverse Events
	Ortho-Cyclen®		AG200-15
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/36 (0%)
Other (Not Including Serious) Adverse Events
	Ortho-Cyclen®		AG200-15
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/34 (8.8%)		23/36 (63.9%)
Gastrointestinal disorders
Gastointestinal disorders	2/34 (5.9%)	2	6/36 (16.7%)	6
General disorders
General disorders and application site conditions	1/34 (2.9%)	1	8/36 (22.2%)	8
Infections and infestations
Infections and infestations	1/34 (2.9%)	1	3/36 (8.3%)	3
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications	0/34 (0%)	0	1/36 (2.8%)	1
Musculoskeletal and connective tissue disorders
Muscoloskeletal and conncetive tissue disoders	0/34 (0%)	0	1/36 (2.8%)	1
Nervous system disorders
Nervous system disoders	0/34 (0%)	0	17/36 (47.2%)	17
Reproductive system and breast disorders
Reproductive system and breast disoders	0/34 (0%)	0	1/36 (2.8%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders	0/34 (0%)	0	1/36 (2.8%)	1
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders	0/34 (0%)	0	2/36 (5.6%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Approval by Agile Therapeutics, Inc. of any publication, including oral presentations and abstracts, utilizing data or any information from the ATI-CL14 study is required prior to publication submission.