Pharmacokinetic Study Of AGILE AG200-15 After Weekly Application Under Various Conditions in Healthy Female Volunteers

• Sponsor: Agile Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01375946
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arm: 1
• Duration (Months): 1
• Patients Per Site Per Month: 23.6

Study Details

Study Description

Brief Summary

A study to evaluate pharmacokinetic profile, wearability and safety of AG200-15, transdermal delivery of levonorgestrel (LNG) and ethinyl estradiol (EE), under normal conditions and external conditions of heat, humidity, cold water and exercise.

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

Detailed Description

Normal conditions - average daily living activities, Dry Sauna - 10 minutes at 168.8 - 179.6 degrees Fahrenheit, Whirlpool - 10 minutes at 102.2 - 105.8 degrees Fahrenheit, Treadmill - 20 - 30 minutes at 60-80% max heart rate, Cold Water - 5 - 15 minutes at 71.6 degrees Fahrenheit.

There will be three treatment periods. Subjects will be randomly assigned to one of the five conditions for the treatment period. The subject will be exposed daily to the condition assigned while wearing the patch. The study patch will be worn for a 7 day treatment period, followed by a 7 day washout period. The total duration of the study is 6 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Pharmacokinetic And Wearability Study of the Agile TCDS AG200-15 Following Weekly Application Under Various External Conditions in Healthy Female Volunteers
• Study Start Date: May 1, 2011
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: AG200-15 location The subject will wear AG200-15 for 7 days and be exposed to one of 5 external conditions (normal, treadmill, cold water, whirlpool, dry sauna).

Drug: AG200-15; There will be three treatment periods. Subjects will be randomly assigned to one of the five conditions for the treatment period. The subject will be exposed daily to the condition assigned while wearing the patch. The study patch will be worn for a 7 day treatment period, followed by a 7 day washout period. The total duration of the study is 6 weeks.; Other Names: transdermal contraceptive delivery system, patch

Outcome Measures

Primary Outcome Measures

1. Area Under the Concentration Versus Time Curve (AUC) (0-168) Profile of Levonorgestrel (LNG) [6 weeks]

   AUC(0-168) profile of LNG for each external condition including dry sauna, normal, whirlpool, cold water, and treadmill exercise. The blood sampling for the pharmacokinetic evaluations was performed at the following time points: 0 hour (immediately prior to dosing) and at 6 hours, 12 hours, 24 hours (1 day), 48 hours (2 days), 72 hours (3 days), 120 hours (5 days), 144 hours (6 days), and 168 hours (7 days) following application of the patch.

2. AUC(0-168) Profile of Ethinyl Estradiol (EE) [6 weeks]

   AUC(0-168) profile of EE for external condition including dry sauna, normal, whirlpool, cold water, and treadmill exercise. The blood sampling for the pharmacokinetic evaluations was performed at the following time points: 0 hour (immediately prior to dosing) and at 6 hours, 12 hours, 24 hours (1 day), 48 hours (2 days), 72 hours (3 days), 120 hours (5 days), 144 hours (6 days), and 168 hours (7 days) following application of the patch.

3. Steady-state Concentration (Css) (48-168) Profile of LNG [6 weeks]

   Css (48-168) profile of LNG for external condition including dry sauna, normal, whirlpool, cold water, and treadmill exercise. The blood sampling for the pharmacokinetic evaluations was performed at the following time points: 0 hour (immediately prior to dosing) and at 6 hours, 12 hours, 24 hours (1 day), 48 hours (2 days), 72 hours (3 days), 120 hours (5 days), 144 hours (6 days), and 168 hours (7 days) following application of the patch.

4. Css (48-168) Profile of EE [6 weeks]

   Css (48-168) profile of EE for external condition including dry sauna, normal, whirlpool, cold water, and treadmill exercise. The blood sampling for the pharmacokinetic evaluations was performed at the following time points: 0 hour (immediately prior to dosing) and at 6 hours, 12 hours, 24 hours (1 day), 48 hours (2 days), 72 hours (3 days), 120 hours (5 days), 144 hours (6 days), and 168 hours (7 days) following application of the patch.

Secondary Outcome Measures

1. Patch Adhesion [6 weeks]

   Patch adhesion scores by investigator evaluation by external condition; including dry sauna, whirlpool, treadmill exercise, normal, and cold water conditions; using the following scale: 0: >90% adhered (essentially no lift off of the skin) >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 Patches were assessed prior to patch removal.

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)of ≥18 and less than or equal to 32, and weight ≥ 110 lbs.

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

• Willing to give informed consent to participate in study

Exclusion Criteria:

• Known or suspected pregnancy

• Breast-feeding or within 1 month after stopping breast-feeding

• Smokers

• Any disease that may worsen with hormonal treatment

• Hypersensitivity to transdermal preparations or sensitivity to surgical/medical tape

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Pharmacology of Miami, Inc.	Miami	Florida	United States	33014

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: NCT01375946
• Other Study ID Numbers: ATI-CL16
• First Posted: Jun 20, 2011
• Last Update Posted: Jul 31, 2018
• Last Verified: Jul 1, 2018

• Keywords provided by Agile Therapeutics: Pharmacokinetic Profile (PK) and Safety; PK analysis of EE and LNG
• Additional relevant MeSH terms: Contraceptive Agents

Study Results

Participant Flow

Arm/Group Title	AG200-15 Condition (NDC)	AG200-15 Condition (CNW)	AG200-15 Condition (WTN)	AG200-15 Condition (NCD)	AG200-15 Condition (DNT)	AG200-15 Condition (TWN)
Arm/Group Description	The subject will wear AG200-15 for 7 days and be exposed to normal (N), dry sauna (D) then cold water (C)conditions	The subject will wear AG200-15 for 7 days and be exposed to cold water (C), normal (N) then whirlpool (W)conditions	The subject will wear AG200-15 for 7 days and be exposed to whirlpool (W), treadmill (T) then normal (N)conditions	The subject will wear AG200-15 for 7 days and be exposed to normal (N), cold water (C) then dry sauna (D)conditions	The subject will wear AG200-15 for 7 days and be exposed to dry sauna (D), normal (N) then treadmill (T)conditions	The subject will wear AG200-15 for 7 days and be exposed to treadmill (T), whirlpool (W) then normal (N) conditions
Period Title: Overall Study
STARTED	4	4	4	4	4	4
COMPLETED	4	4	4	4	4	4
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	AG200-15 Condition
Arm/Group Description	The subject will wear AG200-15 for 7 days and be exposed to one of 5 external conditions (normal, treadmill, cold water, whirlpool, dry sauna).
Overall Participants	24
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	24 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.13 (6.469)
Sex: Female, Male (Count of Participants)
Female	24 100%
Male	0 0%
Region of Enrollment (Count of Participants)
United States	24 100%

Outcome Measures

1. Primary Outcome

Title	Area Under the Concentration Versus Time Curve (AUC) (0-168) Profile of Levonorgestrel (LNG)
Description	AUC(0-168) profile of LNG for each external condition including dry sauna, normal, whirlpool, cold water, and treadmill exercise. The blood sampling for the pharmacokinetic evaluations was performed at the following time points: 0 hour (immediately prior to dosing) and at 6 hours, 12 hours, 24 hours (1 day), 48 hours (2 days), 72 hours (3 days), 120 hours (5 days), 144 hours (6 days), and 168 hours (7 days) following application of the patch.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Primary PK population

Arm/Group Title	AG200-15 Condition
Arm/Group Description	The subject will wear AG200-15 for 7 days and be exposed to one of 5 external conditions (normal, treadmill, cold water, whirlpool, dry sauna).
Measure Participants	24
Normal	157 (74)
Dry Sauna	118 (51)
Cold water	153 (76)
Whirlpool	137 (81)
Treadmill	119 (46)

2. Primary Outcome

Title	AUC(0-168) Profile of Ethinyl Estradiol (EE)
Description	AUC(0-168) profile of EE for external condition including dry sauna, normal, whirlpool, cold water, and treadmill exercise. The blood sampling for the pharmacokinetic evaluations was performed at the following time points: 0 hour (immediately prior to dosing) and at 6 hours, 12 hours, 24 hours (1 day), 48 hours (2 days), 72 hours (3 days), 120 hours (5 days), 144 hours (6 days), and 168 hours (7 days) following application of the patch.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Primary PK population

Arm/Group Title	AG200-15 Condition
Arm/Group Description	The subject will wear AG200-15 for 7 days and be exposed to one of 5 external conditions (normal, treadmill, cold water, whirlpool, dry sauna).
Measure Participants	24
Normal	4.7 (1.6)
Dry sauna	4.3 (2.0)
Cold water	4.9 (2.3)
Whirlpool	4.3 (1.4)
Treadmill	3.9 (1.1)

3. Primary Outcome

Title	Steady-state Concentration (Css) (48-168) Profile of LNG
Description	Css (48-168) profile of LNG for external condition including dry sauna, normal, whirlpool, cold water, and treadmill exercise. The blood sampling for the pharmacokinetic evaluations was performed at the following time points: 0 hour (immediately prior to dosing) and at 6 hours, 12 hours, 24 hours (1 day), 48 hours (2 days), 72 hours (3 days), 120 hours (5 days), 144 hours (6 days), and 168 hours (7 days) following application of the patch.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Primary PK population

Arm/Group Title	AG200-15 Condition
Arm/Group Description	The subject will wear AG200-15 for 7 days and be exposed to one of 5 external conditions (normal, treadmill, cold water, whirlpool, dry sauna).
Measure Participants	24
Normal	1068 (494)
Dry Sauna	793 (317)
Cold water	1033 (518)
Whirlpool	918 (512)
Treadmill	814 (333)

4. Primary Outcome

Title	Css (48-168) Profile of EE
Description	Css (48-168) profile of EE for external condition including dry sauna, normal, whirlpool, cold water, and treadmill exercise. The blood sampling for the pharmacokinetic evaluations was performed at the following time points: 0 hour (immediately prior to dosing) and at 6 hours, 12 hours, 24 hours (1 day), 48 hours (2 days), 72 hours (3 days), 120 hours (5 days), 144 hours (6 days), and 168 hours (7 days) following application of the patch.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Primary PK population

Arm/Group Title	AG200-15 Condition
Arm/Group Description	The subject will wear AG200-15 for 7 days and be exposed to one of 5 external conditions (normal, treadmill, cold water, whirlpool, dry sauna).
Measure Participants	24
Normal	30 (12)
Dry Sauna	28 (13)
Cold water	29 (14)
Whirlpool	27 (9)
Treadmill	24 (8)

5. Secondary Outcome

Title	Patch Adhesion
Description	Patch adhesion scores by investigator evaluation by external condition; including dry sauna, whirlpool, treadmill exercise, normal, and cold water conditions; using the following scale: 0: >90% adhered (essentially no lift off of the skin) >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 Patches were assessed prior to patch removal.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	AG200-15 Condition
Arm/Group Description	The subject will wear AG200-15 for 7 days and be exposed to one of 5 external conditions (normal, treadmill, cold water, whirlpool, dry sauna).
Measure Participants	24
Normal	0.08 (0.282)
Dry Sauna	0.08 (0.289)
Cold water	0 (0)
Whirlpool	0 (0)
Treadmill	0.17 (0.577)

Adverse Events

Time Frame	6 weeks
Arm/Group Title	AG200-15 Condition
Arm/Group Description	The subject will wear AG200-15 for 7 days and be exposed to one of 5 external conditions (normal, treadmill, cold water, whirlpool, dry sauna).
All Cause Mortality
	AG200-15 Condition
	Affected / at Risk (%)	# Events
Total	0/24 (0%)
Serious Adverse Events
	AG200-15 Condition
	Affected / at Risk (%)	# Events
Total	0/24 (0%)
Other (Not Including Serious) Adverse Events
	AG200-15 Condition
	Affected / at Risk (%)	# Events
Total	23/24 (95.8%)
Gastrointestinal disorders
Gastrointestinal disorders	12/24 (50%)	12
General disorders
General disorders and administration site conditions	13/24 (54.2%)	13
Infections and infestations
Infections and infestations	2/24 (8.3%)	2
Metabolism and nutrition disorders
Metabolism and nutrition disorders	4/24 (16.7%)	4
Nervous system disorders
Nervous system disorders	14/24 (58.3%)	14
Reproductive system and breast disorders
Reproductive system and breast disorders	16/24 (66.7%)	16
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders	2/24 (8.3%)	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-CL16 study is required prior to publication submission.