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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Ortho-Cyclen; Drug: AG200-15

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 Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33169

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparative Evaluation of Ethinyl Estradiol (EE) Cmax Between AG200-15 and Ortho-Cyclen® in Week 1	Comparative evaluation of ethinyl estradiol (EE) Cmax between AG200-15 and Ortho-Cyclen® in week 1 for cycle 2 and 3.	3 months
Comparative Evaluation of EE Cmax Between AG200-15 and Ortho-Cyclen® in Week 3	Comparative evaluation of EE Cmax between AG200-15 and Ortho-Cyclen® in week 3 for cycles 2 and 3.	3 months
Comparative Evaluation of EE AUC(0-168hrs Post-first Dose) Between AG200-15 and Ortho-Cyclen® in Week 1	Comparative evaluation of EE AUC (0-168hrs post-first dose) between AG200-15 and Ortho-Cyclen® in week 1 for cycles 2 and 3.	3 months
Comparative Evaluation of EE AUC (0-168hrs Post-first Dose) Between AG200-15 and Ortho-Cyclen® in Week 3	Comparative evaluation of EE AUC (0-168hrs post-first dose) between AG200-15 and Ortho-Cyclen® in week 3 for cycles 2 and 3.	3 months
Comparative Evaluation of EE Css (1) Between AG200-15 and Ortho-Cyclen® in Week 1	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.	3 months
Comparative Evaluation of EE Css (1) Between AG200-15 and Ortho-Cyclen® in Week 3	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.	3 months
Comparative Evaluation of EE Css (2) Between AG200-15 and Ortho-Cyclen® in Week 1	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).	3 months
Comparative Evaluation of EE Css (2) Between AG200-15 and Ortho-Cyclen® in Week 3	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).	3 months
Comparative Evaluation of EE Css (3) Between AG200-15 and Ortho-Cyclen® in Week 1	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).	3 months
Comparative Evaluation of EE Css (3) Between AG200-15 and Ortho-Cyclen® in Week 3	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).	3 months
Evaluation of LNG Cmax Between AG200-15 in Week 1 and 3	Evaluation of LNG Cmax Between AG200-15 in Week 1 and 3 for cycles 2 and 3.	3 months
Evaluation of LNG AUC (0-168hrs Post-first Dose) Between AG200-15 in Week 1 and 3	Evaluation of LNG AUC (0-168hrs post-first dose) Between AG200-15 in Week 1 and 3 for cycles 2 and 3.	3 months
Evaluation of LNG Css (1) Between AG200-15 in Week 1 and 3	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).	3 months

Collaborators and Investigators

• Sponsor: Agile Therapeutics

Publications and helpful links

General Publications

• Archer DF, Stanczyk FZ, Rubin A, Foegh M. Ethinyl estradiol and levonorgestrel pharmacokinetics with a low-dose transdermal contraceptive delivery system, AG200-15: a randomized controlled trial. Contraception. 2012 Jun;85(6):595-601. doi: 10.1016/j.contraception.2011.10.006. Epub 2011 Nov 30.

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: November 16, 2010
• First Submitted That Met QC Criteria: November 17, 2010
• First Posted (Estimate): November 18, 2010

Study Record Updates

• Last Update Posted (Actual): January 23, 2018
• Last Update Submitted That Met QC Criteria: December 21, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: PK and safety; Pharmacokinetic profile (PK) and safety
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Contraceptive Agents, Hormonal; Reproductive Control Agents; Contraceptives, Oral, Combined; Contraceptive Agents, Female; Moxifloxacin; Norgestimate, ethinyl estradiol drug combination; Contraceptive Agents; Contraceptives, Oral
• Other Study ID Numbers: ATI-CL14