Trial Outcomes & Findings for AG200-15 Transdermal Contraceptive Delivery System (TCDS) of Levonorgestrel and Ethinyl Estradiol (NCT NCT01243580)

NCT ID: NCT01243580

Last Updated: 2018-01-23

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 36 participants
• Primary outcome timeframe: 3 months
• Results posted on: 2018-01-23

Participant Flow

Participant milestones

Measure	AG200-15/Ortho-Cyclen® 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.	Ortho-Cyclen®/AG200-15 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.
Overall Study STARTED	18	18
Overall Study COMPLETED	18	16
Overall Study NOT COMPLETED	0	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	AG200-15/Ortho-Cyclen® n=18 Participants Subject applied AG200-15 in cycle 1. Subjects applied AG200-15 (Cycle 2) followed by oral contraceptive, Ortho-Cyclen® (Cycle 3)	Ortho-Cyclen® /AG200-15 n=18 Participants Subject applied AG200-15 in cycle 1. Subjects received Ortho-Cyclen® (Cycle 2) followed by AG200-15 (Cycle 3).	Total n=36 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	37.8 years STANDARD_DEVIATION 5.85 • n=5 Participants	36.2 years STANDARD_DEVIATION 7.66 • n=7 Participants	37 years STANDARD_DEVIATION 6.77 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants

PRIMARY outcome

Timeframe: 3 months

Population: Primary PK population

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

Outcome measures

Measure	Ortho-Cyclen® n=29 Participants 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 n=33 Participants 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
Comparative Evaluation of Ethinyl Estradiol (EE) Cmax Between AG200-15 and Ortho-Cyclen® in Week 1	135 pg/ml Standard Deviation 50.7	45.5 pg/ml Standard Deviation 24.0

PRIMARY outcome

Timeframe: 3 months

Population: Primary PK population

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

Outcome measures

Measure	Ortho-Cyclen® n=32 Participants 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 n=32 Participants 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
Comparative Evaluation of EE Cmax Between AG200-15 and Ortho-Cyclen® in Week 3	131 pg/ml Standard Deviation 45.4	51.3 pg/ml Standard Deviation 17.3

PRIMARY outcome

Timeframe: 3 months

Population: Primary PK population

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

Outcome measures

Measure	Ortho-Cyclen® n=29 Participants 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 n=32 Participants 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
Comparative Evaluation of EE AUC(0-168hrs Post-first Dose) Between AG200-15 and Ortho-Cyclen® in Week 1	7.28 ng.h/ml Standard Deviation 2.66	5.06 ng.h/ml Standard Deviation 2.26

PRIMARY outcome

Timeframe: 3 months

Population: Primary PK population

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

Outcome measures

Measure	Ortho-Cyclen® n=32 Participants 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 n=32 Participants 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
Comparative Evaluation of EE AUC (0-168hrs Post-first Dose) Between AG200-15 and Ortho-Cyclen® in Week 3	6.97 ng.h/ml Standard Deviation 2.25	6.26 ng.h/ml Standard Deviation 2.46

PRIMARY outcome

Timeframe: 3 months

Population: Primary PK population

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.

Outcome measures

Measure	Ortho-Cyclen® n=32 Participants 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 n=32 Participants 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
Comparative Evaluation of EE Css (1) Between AG200-15 and Ortho-Cyclen® in Week 1	43.3 pg/ml Standard Deviation 15.8	31.4 pg/ml Standard Deviation 15.1

PRIMARY outcome

Timeframe: 3 months

Population: Primary PK population

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.

Outcome measures

Measure	Ortho-Cyclen® n=32 Participants 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 n=32 Participants 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
Comparative Evaluation of EE Css (1) Between AG200-15 and Ortho-Cyclen® in Week 3	41.5 pg/ml Standard Deviation 13.4	35.7 pg/ml Standard Deviation 14.5

PRIMARY outcome

Timeframe: 3 months

Population: Primary PK population

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).

Outcome measures

Measure	Ortho-Cyclen® n=32 Participants 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 n=32 Participants 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
Comparative Evaluation of EE Css (2) Between AG200-15 and Ortho-Cyclen® in Week 1	43.3 pg/ml Standard Deviation 15.8	32.0 pg/ml Standard Deviation 16.2

PRIMARY outcome

Timeframe: 3 months

Population: Primary PK population

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).

Outcome measures

Measure	Ortho-Cyclen® n=32 Participants 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 n=32 Participants 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
Comparative Evaluation of EE Css (2) Between AG200-15 and Ortho-Cyclen® in Week 3	41.5 pg/ml Standard Deviation 13.4	35.7 pg/ml Standard Deviation 15.4

PRIMARY outcome

Timeframe: 3 months

Population: Primary PK population

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).

Outcome measures

Measure	Ortho-Cyclen® n=32 Participants 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 n=32 Participants 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
Comparative Evaluation of EE Css (3) Between AG200-15 and Ortho-Cyclen® in Week 1	43.3 pg/ml Standard Deviation 15.8	30.1 pg/ml Standard Deviation 13.4

PRIMARY outcome

Timeframe: 3 months

Population: Primary PK population

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).

Outcome measures

Measure	Ortho-Cyclen® n=32 Participants 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 n=32 Participants 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
Comparative Evaluation of EE Css (3) Between AG200-15 and Ortho-Cyclen® in Week 3	41.5 pg/ml Standard Deviation 13.4	37.3 pg/ml Standard Deviation 14.7

PRIMARY outcome

Timeframe: 3 months

Population: Primary PK population

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

Outcome measures

Measure	Ortho-Cyclen® n=33 Participants 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 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
Evaluation of LNG Cmax Between AG200-15 in Week 1 and 3 Week 1	1370 pg/ml Standard Deviation 908	—
Evaluation of LNG Cmax Between AG200-15 in Week 1 and 3 Week 3	2400 pg/ml Standard Deviation 1140	—

PRIMARY outcome

Timeframe: 3 months

Population: Primary PK population

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

Outcome measures

Measure	Ortho-Cyclen® n=33 Participants 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 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
Evaluation of LNG AUC (0-168hrs Post-first Dose) Between AG200-15 in Week 1 and 3 Week 3	317 ng.h/ml Standard Deviation 159	—
Evaluation of LNG AUC (0-168hrs Post-first Dose) Between AG200-15 in Week 1 and 3 Week 1	160 ng.h/ml Standard Deviation 88.9	—

PRIMARY outcome

Timeframe: 3 months

Population: Primary PK population

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).

Outcome measures

Measure	Ortho-Cyclen® n=33 Participants 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 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
Evaluation of LNG Css (1) Between AG200-15 in Week 1 and 3 Week 1	1060 pg/ml Standard Deviation 631	—
Evaluation of LNG Css (1) Between AG200-15 in Week 1 and 3 Week 3	1847 pg/ml Standard Deviation 930	—

Adverse Events

Ortho-Cyclen®

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

AG200-15

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Ortho-Cyclen® n=34 participants at risk 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 n=36 participants at risk 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
Gastrointestinal disorders Gastointestinal disorders	5.9% 2/34 • Number of events 2 • 3 months Adverse events were analyzed based on Organ System class.	16.7% 6/36 • Number of events 6 • 3 months Adverse events were analyzed based on Organ System class.
General disorders General disorders and application site conditions	2.9% 1/34 • Number of events 1 • 3 months Adverse events were analyzed based on Organ System class.	22.2% 8/36 • Number of events 8 • 3 months Adverse events were analyzed based on Organ System class.
Infections and infestations Infections and infestations	2.9% 1/34 • Number of events 1 • 3 months Adverse events were analyzed based on Organ System class.	8.3% 3/36 • Number of events 3 • 3 months Adverse events were analyzed based on Organ System class.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	0.00% 0/34 • 3 months Adverse events were analyzed based on Organ System class.	2.8% 1/36 • Number of events 1 • 3 months Adverse events were analyzed based on Organ System class.
Musculoskeletal and connective tissue disorders Muscoloskeletal and conncetive tissue disoders	0.00% 0/34 • 3 months Adverse events were analyzed based on Organ System class.	2.8% 1/36 • Number of events 1 • 3 months Adverse events were analyzed based on Organ System class.
Nervous system disorders Nervous system disoders	0.00% 0/34 • 3 months Adverse events were analyzed based on Organ System class.	47.2% 17/36 • Number of events 17 • 3 months Adverse events were analyzed based on Organ System class.
Reproductive system and breast disorders Reproductive system and breast disoders	0.00% 0/34 • 3 months Adverse events were analyzed based on Organ System class.	2.8% 1/36 • Number of events 1 • 3 months Adverse events were analyzed based on Organ System class.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	0.00% 0/34 • 3 months Adverse events were analyzed based on Organ System class.	2.8% 1/36 • Number of events 1 • 3 months Adverse events were analyzed based on Organ System class.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	0.00% 0/34 • 3 months Adverse events were analyzed based on Organ System class.	5.6% 2/36 • Number of events 2 • 3 months Adverse events were analyzed based on Organ System class.

Additional Information

Lisa Flood

Agile Therapeutics

Phone: 609-683-1880

Email: lflood@agiletherapeutics.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER