Residual Drug Amount of EE and LNGPhase 4NCT07739589

A Postmarketing Open-Label Study to Assess Residual Levonorgestrel (LNG) and Ethinyl Estradiol (EE) Content of TWIRLA® (Levonorgestrel and Ethinyl Estradiol) Transdermal System

A Phase 4 study testing Twirla® (Levonorgestrel/Ethinyl Estradiol) Transdermal System in people with Residual Drug Amount of EE and LNG, run by Insud Pharma at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The objective of this open-label study was to assess residual EE and LNG content on used Twirla® TDSs, packaging, and the skin surface at the application site after 7 full days of wear and the estimate EE and LNG loaded on control TDSs using valid analytical methods. Read more about this study

Who is it for?: Ages 18 to 40 years, women onlyHealthy volunteers can take part
Conditions the study is for: Residual Drug Amount of EE and LNG
What is being tested?: Twirla® (Levonorgestrel/Ethinyl Estradiol) Transdermal System
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 28 participants
Where: 1 siteUnited States
Study dates: 25 Oct 2021to 16 Nov 2021
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 40 years
Women only
Healthy volunteers accepted
Adult

Who may be able to join

Willing and able to give signed informed consent
No evidence of Coronavirus Disease 2019 (COVID-19) infection based on Centers for Disease Control and Prevention (CDC) testing and/or screening procedures
Healthy woman, 18 to 40 years of age
Body mass index (BMI) ≥ 18 kg/m² and < 30 kg/m²
Willing to refrain from use of alcohol and grapefruit juice from 48 hours prior until completion of the follow-up period
In good general health, confirmed by medical history, physical examination, and laboratory testing
Willing to not use other hormonal contraception including oral contraceptive, TDS, or vaginal ring, for the treatment and follow-up period

Who cannot join

Known or suspected pregnancy
Breast-feeding or within 1 month after stopping breast-feeding
User of injectable contraceptives (e.g., depot-medroxyprogesterone acetate) and less than 3 months since last injection
User of progestin intrauterine device (IUD) and less than 3 months since last IUD insertion
Recent pregnancy (within 2 months), including vaginal or cesarean delivery, surgical or medically induced abortion, spontaneous abortion, or ectopic pregnancy
Unexplained vaginal bleeding

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Undiagnosed abnormal genital bleeding
Diagnosis of sickle cell
Known hypersensitivity to, or intolerance of, progestins or estrogens (leading to discontinuation), including hormonal contraception; or history of serious or severe adverse event (SAE) related to progestins or estrogens, including hormonal contraception (e.g., worsening of a disease or condition while on hormonal contraception)
History of dermal hypersensitivity in response to medicated TDSs (e.g., nicotine TDS) or topical applications (bandages, surgical tape, etc.); known hypersensitivity to any components of the Twirla®, or prior difficulties with transdermal methods for any indication
Presence on the lower abdomen of skin changes that, at the discretion of the Investigator, would have potentially interfered with TDS adhesion or TDS application site assessment, including for example tattoos, striae, scarring or other skin damage, skin lesions, skin irritation, diffuse skin disease (e.g., psoriasis, eczema, rash, or any etiology), excessive stretch marks, or excess hair at the TDS application site
Preclusion of TDS placement, at the discretion of the Investigator, on the lower abdomen
Has a contraindication to combined estrogen-progestin contraceptive use (as defined by a category 3 or 4 condition of the 2016 U.S. Medical Eligibility Criteria for Contraceptive Use), including:
Personal history of or DVT or venous thromboembolism
History of stroke, vascular or cerebral vascular disease including TIAs or coronary artery disease
Known inherited or acquired hypercoagulopathy, including thrombogenic mutations (e.g., factor V Leiden; prothrombin mutation; protein S, protein C, or antithrombin deficiency)
Systemic Lupus Erythematosus with positive or unknown antiphospholipid antibodies
Known or suspected carcinoma of the breast, including past personal history of breast cancer
Jaundice with prior CHC use
Hepatocellular adenoma or carcinoma
Severe cirrhosis
Symptomatic current gallbladder disease
Current smokers 35 years of age or over, or smoker who would have turned 35 years old during the course of the trial (Smoking includes cigarettes, cigars, smokeless tobacco, e-cigarettes, hookah, etc.)
Headaches with focal neurological symptoms (i.e., migraines with auras)
Migraines of any type in women over 35 years of age
Diabetes mellitus with nephropathy, neuropathy, retinopathy, or other vascular disease; diabetes mellitus of ˃20 year's duration
Elevated blood pressure, defined as screening sitting blood pressure ≥ 140 mm Hg systolic or ≥ 90 mm Hg diastolic; or hypertension with known vascular disease
History of peripartum cardiomyopathy
Known thrombophilia, including antiphospholipid antibody syndrome
History of any other condition that in the Investigator's opinion suggests an elevated risk of arterial or venous thromboembolic disease
Carcinoma of the endometrium, ovary, fallopian tubes, or other known or suspected estrogen-dependent malignant or pre-malignant neoplasia
Other active malignancy, excluding non-melanoma skin cancer
Known history of acute or chronic hepatocellular disease with a history of significantly abnormal liver function, or liver function tests (LFTs) ≥ 2x normal
Known history of Triglycerides ≥ 350 mg/dL
Thrombogenic valvular or thrombogenic rhythm diseases of the heart (e.g., subacute bacterial endocarditis with valvular disease or atrial fibrillation).
Uncontrolled diabetes mellitus; participants with a history of gestational diabetes are eligible for the study if they are currently euglycemic
Uncontrolled thyroid disorder
Known HIV and/or hepatitis B or C infection
History of suicidal ideation or attempt, or history of severe depression requiring hospitalization within the past year
Recent history (within prior 12 months) of drug or alcohol abuse or at Investigator discretion, history greater than 12 months prior and at risk for noncompliance
Positive urine drug screen for Cocaine, Methamphetamine, Opiates, Phencyclidine unless there is a documented prescription with supporting medical history and diagnosis
Administration of any investigational drug and/or experimental device within 30 days prior to enrollment; planned administration of an experimental drug or device during the duration of the study; current participation in any investigational studies
In the Investigator's judgement, woman was unsuitable for participation in the study or who could not comply with study procedures
Participant was a dependent of (e.g., relative or family member) and/or was a member of the Investigator's staff.

Trial locations and contacts

1 site in 1 country.

United States1 site

TKL Research Inc.
Fair Lawn, New Jersey, 07410

Other trials in United States

About this study

Read the detailed description

Twirla® (levonorgestrel and ethinyl estradiol) transdermal system is an FDA-approved transdermal delivery system (TDS) indicated as a method of contraception for use in women of reproductive potential with a body mass index (BMI) < 30 kg/m² for whom a combined hormonal contraceptive is appropriate. The 28-day TDS regimen is worn for 7 days for 3 consecutive weeks, followed by a 7-day TDS-free period.

Study ATI-CL28 measured residual EE and LNG content on Twirla® packaging (including storage pouches and release liners), Twirla® TDSs worn for 7 full days, and application site stratum corneum (SC) per Postmarketing Commitment 3785-2. Validated analytical methods were used in this study to measure residual EE and LNG.

Conditions: Residual Drug Amount of EE and LNG
Being tested: Twirla® (Levonorgestrel/Ethinyl Estradiol) Transdermal System
Keywords: Residual Drug Levels, transdermal patch, contraceptive, levonorgestrel, ethinyl estradiol, Twirla, contraception, transdermal system, TDS

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Twirla® (Levonorgestrel/Ethinyl Estradiol) Transdermal SystemDrug
Twirla® is a transdermal delivery system that delivers levonorgestrel and ethinyl estradiol. In this study, participants applied a single transdermal system and wore it continuously for 7 days.

Study groups in NCT07739589
Study group	Role	What they receive
Twirla® Transdermal System	Experimental	Participants applied a single Twirla® transdermal system and wore it continuously for 7 days. After patch removal, residual levonorgestrel and ethinyl estradiol content was measured in the used transdermal system, packaging components, and application-site stratum corneum. Receives: Drug: Twirla® (Levonorgestrel/Ethinyl Estradiol) Transdermal System

What is being measured

The primary outcome is the main question the study is designed to answer.

The Sum of Means for EE and LNG Content on Used TDSs, Storage Pouches, Release Liners, and Skin Swabs
Measurements of Residual Ethinyl Estradiol and Levonorgestrel (μg) Per Protocol Population Post 7-Day Wear
Measured: 7 days
The Sum and Means for EE and LNG Content on Control TDSs, Storage Pouches, and Release Liners
Measurements of Ethinyl Estradiol and Levonorgestrel (μg) in Controls
Measured: 7 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

25 Oct 202116 Nov 2021

First posted31 Jul 2026
Study start25 Oct 2021
Primary completion16 Nov 2021
Study completion16 Nov 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Residual Drug Amount of EE and LNGStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 28 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07739589
Sponsor's protocol ID: ATI-CL28
Status last verified: Aug 2026
First submitted: 28 Jul 2026
Last updated: 27 Aug 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Study at a glance

From the registry record, last updated by the sponsor on 27 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Postmarketing Open-Label Study to Assess Residual Levonorgestrel (LNG) and Ethinyl Estradiol (EE) Content of TWIRLA® (Levonorgestrel and Ethinyl Estradiol) Transdermal System
ClinicalTrials.gov ID: NCT07739589
Acronym / sponsor ID: ATI-CL28
Conditions: Residual Drug Amount of EE and LNG
Keywords: Residual Drug Levels, transdermal patch, contraceptive, levonorgestrel, ethinyl estradiol, Twirla, contraception, transdermal system
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 28 participants (actual)
Lead sponsor: Insud PharmaIndustry (pharma, biotech, devices)
Collaborators: Agile Therapeutics, TKL Research, Inc.
Study start: 25 Oct 2021 (actual)
Primary completion: 16 Nov 2021 (actual)
Study completion: 16 Nov 2021 (actual)
First posted: 31 Jul 2026 (actual)
Results: Posted 27 Aug 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Twirla® Transdermal System	Experimental	Drug: Twirla® (Levonorgestrel/Ethinyl Estradiol) Transdermal SystemParticipants applied a single Twirla® transdermal system and wore it continuously for 7 days. After patch removal, residual levonorgestrel and ethinyl estradiol content was measured in the used transdermal system, packaging components, and application-site stratum corneum.

Who may qualify

Ages: 18 to 40 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (7 listed)

Willing and able to give signed informed consent
No evidence of Coronavirus Disease 2019 (COVID-19) infection based on Centers for Disease Control and Prevention (CDC) testing and/or screening procedures
Healthy woman, 18 to 40 years of age
Body mass index (BMI) ≥ 18 kg/m² and < 30 kg/m²
Willing to refrain from use of alcohol and grapefruit juice from 48 hours prior until completion of the follow-up period

Key exclusion criteria (44 listed)

Known or suspected pregnancy
Breast-feeding or within 1 month after stopping breast-feeding
User of injectable contraceptives (e.g., depot-medroxyprogesterone acetate) and less than 3 months since last injection
User of progestin intrauterine device (IUD) and less than 3 months since last IUD insertion
Recent pregnancy (within 2 months), including vaginal or cesarean delivery, surgical or medically induced abortion, spontaneous abortion, or ectopic pregnancy

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Twirla® (Levonorgestrel/Ethinyl Estradiol) Transdermal SystemTwirla® is a transdermal delivery system that delivers levonorgestrel and ethinyl estradiol. In this study, participants applied a single transdermal system and wore it continuously for 7 days.	Drug	Twirla® Transdermal System

Primary outcome

The Sum of Means for EE and LNG Content on Used TDSs, Storage Pouches, Release Liners, and Skin Swabs
Time frame: 7 days
Measurements of Residual Ethinyl Estradiol and Levonorgestrel (μg) Per Protocol Population Post 7-Day Wear
The Sum and Means for EE and LNG Content on Control TDSs, Storage Pouches, and Release Liners
Time frame: 7 days
Measurements of Ethinyl Estradiol and Levonorgestrel (μg) in Controls

Results and safety

Results posted to the registry on 27 Aug 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Twirla® Transdermal System	28	26

Primary outcome: The Sum of Means for EE and LNG Content on Used TDSs, Storage Pouches, Release Liners, and Skin Swabs

Time frame: 7 days. Mean (Standard Deviation). Unit: (μg)

Measure	Twirla® Transdermal System n = 26
Ethinyl Estradiol (μg)	2028.7 (43.01)
Levonorgestrel (μg)	2189.6 (62.35)

Population analysed: Per Protocol Population

Primary outcome: The Sum and Means for EE and LNG Content on Control TDSs, Storage Pouches, and Release Liners

Time frame: 7 days. Mean (Standard Deviation). Unit: (μg)

Measure	Controls to Assess Drug Loaded for EE and LNG n = 5
Ethinyl Estradiol (μg)	2102.0 (85.26)
Levonorgestrel (μg)	2454.0 (93.70)

Population analysed: Five (5) controls were used to assess drug loaded for EE and LNG.

Adverse events

Time frame: Adverse events were monitored from the time of written informed consent to 7 days following TDS removal. Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Twirla® Transdermal System	0 of 28 (0%)	9 of 28 (32.1%)	0 of 28

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Twirla® (Levonorgestrel/Ethinyl Estradiol) Transdermal System in people with Residual Drug Amount of EE and LNG, run by Insud Pharma at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 44 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Sum of Means for EE and LNG Content on Used TDSs, Storage Pouches, Release Liners, and Skin Swabs (time frame: 7 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07739589.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2026.