Pharmacokinetic Study of AG200-15 Transdermal Patch to Three Anatomical Sites in Healthy Females

• Sponsor: Agile Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01422135
• Collaborator: (none)
• Enrollment: 24
• Locations: 2
• Arms: 6
• Duration (Months): 1.9
• Patients Per Site: 12
• Patients Per Site Per Month: 6.2

Study Details

Study Description

Brief Summary

This is a pharmacokinetics and safety study over 3 weekly applications.

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

Detailed Description

Pharmacokinetic study to evaluate the safety and pharmacokinetic profile of AG200-15 following application at three different anatomical sites (abdomen, buttock and upper torso).

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Pharmacokinetic Study of the Agile TCDS AG200-15 Following Weekly Application to Three Anatomical Sites (Abdomen, Buttock and Upper Torso) in Healthy Female Volunteers
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Abdomen, Buttock, Upper Torso Patch was placed on abdomen, buttock then the upper torso excluding breast. Intervention: AG200-15 patch	Drug: AG200-15; A transdermal contraceptive delivery system for levonorgestrel (LNG) and ethinyl estradiol (EE). . A total of 3 patches will be worn during the study. Each patch will be worn for 1 week followed by a patch free week.; Other Names: Transdermal contraceptive delivery system
Experimental: Abdomen, Upper Torso, Buttock Patch was placed on abdomen, upper torso excluding breast then the buttock. Intervention: AG200-15 patch	Drug: AG200-15; A transdermal contraceptive delivery system for levonorgestrel (LNG) and ethinyl estradiol (EE). . A total of 3 patches will be worn during the study. Each patch will be worn for 1 week followed by a patch free week.; Other Names: Transdermal contraceptive delivery system
Experimental: Buttock, Abdomen, Upper Torso Patch was placed on the buttock, abdomen, then the upper torso excluding breast. Intervention: AG200-15 patch	Drug: AG200-15; A transdermal contraceptive delivery system for levonorgestrel (LNG) and ethinyl estradiol (EE). . A total of 3 patches will be worn during the study. Each patch will be worn for 1 week followed by a patch free week.; Other Names: Transdermal contraceptive delivery system
Experimental: Buttock, Upper Torso, Abdomen, Patch was placed on the buttock, upper torso excluding breast then the abdomen Intervention: AG200-15 patch	Drug: AG200-15; A transdermal contraceptive delivery system for levonorgestrel (LNG) and ethinyl estradiol (EE). . A total of 3 patches will be worn during the study. Each patch will be worn for 1 week followed by a patch free week.; Other Names: Transdermal contraceptive delivery system
Experimental: Upper Torso, Abdomen, Buttock Patch was placed on the upper torso excluding breast, abdomen then buttock. Intervention: AG200-15 patch	Drug: AG200-15; A transdermal contraceptive delivery system for levonorgestrel (LNG) and ethinyl estradiol (EE). . A total of 3 patches will be worn during the study. Each patch will be worn for 1 week followed by a patch free week.; Other Names: Transdermal contraceptive delivery system
Experimental: Upper Torso, Buttock, Abdomen Patch was place on the upper torso excluding breast, buttock, then abdomen. Intervention: AG200-15 patch	Drug: AG200-15; A transdermal contraceptive delivery system for levonorgestrel (LNG) and ethinyl estradiol (EE). . A total of 3 patches will be worn during the study. Each patch will be worn for 1 week followed by a patch free week.; Other Names: Transdermal contraceptive delivery system

Outcome Measures

Primary Outcome Measures

1. Steady-State Concentration (Css) (48-168) Profile for LNG [6 weeks]

   Pharmacokinetic (PK) sampling will be done after exposure to each anatomic location. PK evaluations were performed at the following time points: hour (immediately prior to dosing) and at 3 hours, 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. Steady-State Concentration (Css) (48-168) Profile for EE [6 weeks]

   Pharmacokinetic (PK) sampling will be done after exposure to each anatomic location. PK evaluations were performed at the following time points: hour (immediately prior to dosing) and at 3 hours, 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. Area Under the Plasma Concentration Versus Time Curve (AUC) (0-168) Profile for LNG [6 weeks]

   Pharmacokinetic (PK) sampling will be done after exposure to each anatomic location. PK evaluations were performed at the following time points: hour (immediately prior to dosing) and at 3 hours, 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. Area Under the Plasma Concentration Versus Time Curve (AUC) (0-168) Profile for EE [6 weeks]

   Pharmacokinetic (PK) sampling will be done after exposure to each anatomic location. PK evaluations were performed at the following time points: hour (immediately prior to dosing) and at 3 hours, 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.

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 years

• Body mass index 18 - 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

• Hemoglobin within normal range.

Exclusion Criteria:

• Known or suspected pregnancy

• A cervical cytology smear of Papanicolaou (Pap) class III or greater or a Bethesda System report of low grade squamous intraepithelial lesions (SIL) or greater

• Smoking

• Hypertension (blood pressure >140 mm Hg systolic and/or >90 mm Hg diastolic)

• Diabetes Mellitus

• History of headaches with focal neurological symptoms

• Current or history of clinically significant depression in the last year

• Acute or chronic hepatocellular disease with abnormal liver function

• History of or existing venous and arterial thrombotic and thromboembolic disorder, vascular disease, cerebral vascular, or coronary artery disease

• Chronic use of any medication that might interfere with the efficacy of hormone contraceptives (including barbiturates, bosentan, carbamazepine, felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, St. John's Wort, topiramate, and HIV protease inhibitors), OR use of these medications within the past 3 months prior to screening visit

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Lincoln	Nebraska	United States	68502
2		Neptune	New Jersey	United States	07753

Sponsors and Collaborators

• Agile Therapeutics

Investigators

• Study Director: Elizabeth Garner, MD, Agile Therapeutics

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Agile Therapeutics
• ClinicalTrials.gov Identifier: NCT01422135
• Other Study ID Numbers: ATI-CL15
• First Posted: Aug 23, 2011
• Last Update Posted: Dec 31, 2018
• Last Verified: Jul 1, 2018

• Keywords provided by Agile Therapeutics: PK and safety; Pharmacokinetic profile (PK) and safety
• Additional relevant MeSH terms: Contraceptive Agents

Study Results

Participant Flow

Arm/Group Title	Lower Abdomen, Buttock, Upper Torso Excluding Breast	Lower Abdomen, Upper Torso Excluding Breast, Buttock	Buttock, Lower Abdomen, Upper Torso Excluding Breast	Buttock, Upper Torso Excluding Breast, Lower Abdomen	Upper Torso Excluding Breast, Lower Abdomen, Buttock	Upper Torso Excluding Breast, Buttock, Lower Abdomen
Arm/Group Description	Subjects applied AG200-15 to Abdomen, Buttock, then Upper Torso excluding Breast	Subjects applied AG200-15 to Abdomen, Upper Torso excluding Breast, then Buttock	Subjects applied AG200-15 to Buttock, Abdomen, then Upper Torso excluding Breast	Subjects applied AG200-15 to Buttock, Upper Torso excluding Breast, then Lower Abdomen.	Subjects applied AG200-15 to Upper Torso excluding Breast, Lower Abdomen, then Buttock	Subjects applied AG200-15 to Upper Torso excluding Breast, Buttock, then Lower Abdomen
Period Title: Overall Study
STARTED	4	4	4	4	4	4
COMPLETED	4	4	3	4	4	3
NOT COMPLETED	0	0	1	0	0	1

Baseline Characteristics

Arm/Group Title	AG200-15
Arm/Group Description	Subjects will be randomly assigned to one of six treatment (site of application) sequences. Each sequence will include three patch application sites: abdomen, buttock, or upper torso excluding breasts. AG200-15: A transdermal contraceptive delivery system for levonorgestrel (LNG) and ethinyl estradiol (EE). A total of 3 patches will be worn during the study. Each patch will be worn for 1 week followed by a patch free week.
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]	32.2 (8.32)
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	Steady-State Concentration (Css) (48-168) Profile for LNG
Description	Pharmacokinetic (PK) sampling will be done after exposure to each anatomic location. PK evaluations were performed at the following time points: hour (immediately prior to dosing) and at 3 hours, 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
Arm/Group Description	Subjects will be randomly assigned to one of six treatment (site of application) sequences. Each sequence will include three patch application sites: abdomen, buttock, or upper torso excluding breasts. AG200-15: A transdermal contraceptive delivery system for LNG and EE. A total of 3 patches will be worn during the study. Each patch will be worn for 1 week followed by a patch free week.
Measure Participants	22
Abdomen	1256 (998)
Buttock	1246 (725)
Upper torso	1384 (728)

2. Primary Outcome

Title	Steady-State Concentration (Css) (48-168) Profile for EE
Description	Pharmacokinetic (PK) sampling will be done after exposure to each anatomic location. PK evaluations were performed at the following time points: hour (immediately prior to dosing) and at 3 hours, 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
Arm/Group Description	Subjects will be randomly assigned to one of six treatment (site of application) sequences. Each sequence will include three patch application sites: abdomen, buttock, or upper torso excluding breasts. AG200-15: A transdermal contraceptive delivery system for LNG and EE. A total of 3 patches will be worn during the study. Each patch will be worn for 1 week followed by a patch free week.
Measure Participants	22
Abdomen	35.8 (19.9)
Buttock	40.7 (16.4)
Upper torso	42.3 (17.0)

3. Primary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve (AUC) (0-168) Profile for LNG
Description	Pharmacokinetic (PK) sampling will be done after exposure to each anatomic location. PK evaluations were performed at the following time points: hour (immediately prior to dosing) and at 3 hours, 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
Arm/Group Description	Subjects will be randomly assigned to one of six treatment (site of application) sequences. Each sequence will include three patch application sites: abdomen, buttock, or upper torso excluding breasts. AG200-15: A transdermal contraceptive delivery system for LNG and EE. A total of 3 patches will be worn during the study. Each patch will be worn for 1 week followed by a patch free week.
Measure Participants	22
Abdomen	182 (135)
Buttock	197 (116)
Upper torso	206 (106)

4. Primary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve (AUC) (0-168) Profile for EE
Description	Pharmacokinetic (PK) sampling will be done after exposure to each anatomic location. PK evaluations were performed at the following time points: hour (immediately prior to dosing) and at 3 hours, 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
Arm/Group Description	Subjects will be randomly assigned to one of six treatment (site of application) sequences. Each sequence will include three patch application sites: abdomen, buttock, or upper torso excluding breasts. AG200-15: A transdermal contraceptive delivery system for LNG and EE. A total of 3 patches will be worn during the study. Each patch will be worn for 1 week followed by a patch free week.
Measure Participants	22
Abdomen	5.8 (2.8)
Buttock	7.12 (2.85)
Upper torso	6.86 (2.53)

Adverse Events

Time Frame	6 weeks
Arm/Group Title	AG200-15 on Lower Abdomen		AG200-15 on Buttock		AG200-15 on Upper Torso Excluding Breast
Arm/Group Description	Subjects will be randomly assigned to one of six treatment (site of application) sequences. Each sequence will include three patch application sites: abdomen, buttock, or upper torso excluding breasts. AG200-15: A transdermal contraceptive delivery system for LNG and EE. A total of 3 patches will be worn during the study. Each patch will be worn for 1 week followed by a patch free week.		Subjects will be randomly assigned to one of six treatment (site of application) sequences. Each sequence will include three patch application sites: abdomen, buttock, or upper torso excluding breasts. AG200-15: A transdermal contraceptive delivery system for LNG and EE. A total of 3 patches will be worn during the study. Each patch will be worn for 1 week followed by a patch free week.		Subjects will be randomly assigned to one of six treatment (site of application) sequences. Each sequence will include three patch application sites: abdomen, buttock, or upper torso excluding breasts. AG200-15: A transdermal contraceptive delivery system for LNG and EE. A total of 3 patches will be worn during the study. Each patch will be worn for 1 week followed by a patch free week.
All Cause Mortality
	AG200-15 on Lower Abdomen		AG200-15 on Buttock		AG200-15 on Upper Torso Excluding Breast
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/23 (0%)		0/23 (0%)
Serious Adverse Events
	AG200-15 on Lower Abdomen		AG200-15 on Buttock		AG200-15 on Upper Torso Excluding Breast
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/23 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	AG200-15 on Lower Abdomen		AG200-15 on Buttock		AG200-15 on Upper Torso Excluding Breast
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/22 (86.4%)		23/23 (100%)		21/23 (91.3%)
Gastrointestinal disorders
Gastrointestinal disorders	6/22 (27.3%)	6	12/23 (52.2%)	12	10/23 (43.5%)	10
General disorders
General disorders and adminstration site conditions	7/22 (31.8%)	7	7/23 (30.4%)	7	13/23 (56.5%)	13
Metabolism and nutrition disorders
Metabolism and nutrition disorders	2/22 (9.1%)	2	2/23 (8.7%)	2	0/23 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders	1/22 (4.5%)	1	2/23 (8.7%)	2	2/23 (8.7%)	2
Nervous system disorders
Nervous system disorders	8/22 (36.4%)	8	11/23 (47.8%)	11	7/23 (30.4%)	7
Psychiatric disorders
Psychiatric disorders	3/22 (13.6%)	3	3/23 (13%)	3	1/23 (4.3%)	1
Reproductive system and breast disorders
Reproductive system and breast disorders	9/22 (40.9%)	9	13/23 (56.5%)	13	10/23 (43.5%)	10
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders	2/22 (9.1%)	2	0/23 (0%)	0	1/23 (4.3%)	1
Vascular disorders
Vascular disorders	1/22 (4.5%)	1	1/23 (4.3%)	1	0/23 (0%)	0

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-CL15 study is required prior to publication submission.