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

NCT07739589 | Completed Phase 4 FDA Drug

• 1 other identifier: ATI-CL28
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Residual Drug Amount of EE and LNG

Keywords

Residual Drug Levels; transdermal patch; contraceptive; levonorgestrel; ethinyl estradiol; Twirla; contraception; transdermal system; TDS

Outcome Measures

Primary Outcomes (2)

• The sum of means for EE and LNG content on used TDSs, storage pouches, release liners, and skin swabs

  7 days

• The sum and means for EE and LNG content on control TDSs, storage pouches, and release liners

  7 days

Study Arms (1)

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.

Drug: Twirla® (Levonorgestrel/Ethinyl Estradiol) Transdermal System

Interventions

Twirla® (Levonorgestrel/Ethinyl Estradiol) Transdermal System DRUG

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.

Twirla® Transdermal System

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Insud Pharma: lead
• Agile Therapeutics: collaborator
• TKL Research, Inc.: collaborator

Study Sites (1)

TKL Research Inc.

Fair Lawn, New Jersey, 07410, United States

Location

MeSH Terms

Interventions

Ethinyl Estradiol-Norgestrel Combination; Levonorgestrel; Ethinyl Estradiol; Transdermal Patch

Intervention Hierarchy (Ancestors)

Norpregnatrienes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Norgestrel; Norpregnenes; Estrogenic Steroids, Alkylated; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Equipment and Supplies

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2026
• First Posted: July 31, 2026
• Study Start: October 25, 2021
• Primary Completion: November 16, 2021
• Study Completion: November 16, 2021
• Last Updated: July 31, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)