A Study to Assess the Bioavailability and Adhesion of Estradiol/Levonorgestrel TDS in Healthy Post-Menopausal Female Participants

NCT07851649 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: P-25-0013
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare the bioequivalence and adhesion performance of a test estradiol/levonorgestrel transdermal delivery system (TDS) with the reference product, Climara Pro® (estradiol/levonorgestrel transdermal system), following a single 7-day application in healthy postmenopausal female participants. The study will also evaluate the safety and tolerability of the test and reference patches.

Conditions

Postmenopause; Healthy Female Participants

Keywords

Healthy female participants; Postmenopause

Outcome Measures

Primary Outcomes (7)

• Maximum Plasma Concentration (Cmax) of Baseline-Corrected Estradiol

  Maximum observed plasma concentration (Cmax) of baseline-corrected estradiol following application of the test and reference transdermal delivery systems.

  Predose through 288 hours after patch application

• Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Baseline-Corrected Estradiol

  Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0-t) for baseline-corrected estradiol

  Predose through 288 hours after patch application

• Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Baseline-Corrected Estradiol

  Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-inf) for baseline-corrected estradiol.

  Predose through 288 hours after patch application

• Maximum Plasma Concentration (Cmax) of Levonorgestrel

  Maximum observed plasma concentration (Cmax) of levonorgestrel following application of the test and reference transdermal delivery systems.

  Predose through 288 hours after patch application

• Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Levonorgestrel

  Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0-t) for levonorgestrel.

  Predose through 288 hours after patch application

• Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Levonorgestrel

  Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-inf) for levonorgestrel.

  Predose through 288 hours after patch application

• Mean Adhesion Score (MAS)

  Mean adhesion score during the 168-hour patch wear period, assessed using the protocol-defined FDA adhesion scoring scale.

  Immediately after patch application through 168 hours after patch application

Secondary Outcomes (1)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  From first patch application through 21 days after the last patch application

Study Arms (2)

Sequence TR (Test → Reference)

EXPERIMENTAL

Participants receive a single application of the Test Estradiol/Levonorgestrel Transdermal Delivery System (0.045 mg/day estradiol and 0.015 mg/day levonorgestrel) during Period 1, followed by a washout interval of at least 21 days between application days, and then receive a single application of the Reference Estradiol/Levonorgestrel Transdermal System (Climara Pro®; 0.045 mg/day estradiol and 0.015 mg/day levonorgestrel) during Period 2. Each patch is applied for 168 hours (7 days).

Drug: Test Estradiol/Levonorgestrel Transdermal Delivery System; Drug: Climara Pro® (Estradiol/Levonorgestrel Transdermal System)

Sequence RT (Reference → Test)

EXPERIMENTAL

Participants receive a single application of the Reference Estradiol/Levonorgestrel Transdermal System (Climara Pro®; 0.045 mg/day estradiol and 0.015 mg/day levonorgestrel) during Period 1, followed by a washout interval of at least 21 days between application days, and then receive a single application of the Test Estradiol/Levonorgestrel Transdermal Delivery System (0.045 mg/day estradiol and 0.015 mg/day levonorgestrel) during Period 2. Each patch is applied for 168 hours (7 days).

Drug: Test Estradiol/Levonorgestrel Transdermal Delivery System; Drug: Climara Pro® (Estradiol/Levonorgestrel Transdermal System)

Interventions

Test Estradiol/Levonorgestrel Transdermal Delivery System DRUG

Investigational estradiol/levonorgestrel transdermal delivery system containing estradiol 0.045 mg/day and levonorgestrel 0.015 mg/day. A single patch is applied to the upper quadrant of the buttock and worn continuously for 168 hours (7 days).

Sequence RT (Reference → Test); Sequence TR (Test → Reference)

Climara Pro® (Estradiol/Levonorgestrel Transdermal System) DRUG

Reference-listed estradiol/levonorgestrel transdermal system (Climara Pro®) containing estradiol 0.045 mg/day and levonorgestrel 0.015 mg/day. A single patch is applied to the upper quadrant of the buttock and worn continuously for 168 hours (7 days).

Sequence RT (Reference → Test); Sequence TR (Test → Reference)

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Naturally or surgically postmenopausal female, with or without an intact uterus, aged 45-65 years, living in and around Ahmedabad city or western part of India. inclusive. Postmenopausal is defined by FDA Draft Guidance as:
• At least 12 months natural spontaneous amenorrhea; or
• ≥ 6 months and \< 12 months natural spontaneous amenorrhea with serum FSH levels \> 40 mIU/mL at screening; or
• At least 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
• Only participants that meet one of the above criteria and have their postmenopausal status confirmed by a serum FSH level \> 40 mIU/mL are eligible for study enrollment.
• Serum FSH level \> 40 mIU/mL; determined at screening.
• For participants with an intact uterus, has a vaginal ultrasonography demonstrating inactive endometrial lining with endometrial thickness \< 4 mm.
• A body weight ≤ 90 kg. Page 36 of 59
• Seated vital signs measurements, determined at screening, as specified below (inclusive): Temperature (T) 96.5-99.4°F, Respiration Rate (RR) 12-20 breaths per minute, Pulse Rate (PR) 50-100 beats per minute, Blood Pressure (BP) 90-140 (systolic)/60-90 (diastolic) mmHg
• Total cholesterol level ≤ 275 mg/dL.
• Triglycerides level ≤ 350 mg/dL.
• Good health as determined by lack of clinically significant abnormalities in the participant's medical history or health assessments performed at screening (as applicable), as determined by the Investigator (or designee), including a negative screening mammogram and/or Breast MRI and a normal clinical breast examination.
• Participant is able to understand and comply with the study procedures, in the opinion of the Investigator, and able to give voluntary written consent for participation in the study.
• Able and willing to comply with protocol restrictions and required study procedures and visit requirements.
• Serum estradiol level should be clinically acceptable.

You may not qualify if:

• Male Participant.
• Participants who are premenopausal or perimenopausal, as determined by the Investigator, or pregnant, lactating or likely to become pregnant during the study.
• History of allergy (e.g., anaphylactic reaction), hypersensitivity, or angioedema (including hereditary angioedema) to Climara Pro® or any of its components, including glues/adhesives, or history of any drug hypersensitivity or intolerance that, in the opinion of the Investigator, would compromise the safety of the participant or integrity of the study.
• Presence of any current dermatological condition at the application site(s) (e.g., atopy, psoriasis, eczema, chronic or atopic dermatitis, vitiligo, urticaria) or conditions known to alter skin appearance or physiologic response (e.g., diabetes, porphyria) or history of allergic, sensitization or skin sensitivity that would compromise the integrity of the study data.
• Excessive hair or other compounding factors (e.g., tattoos, scar tissue, recently shaved skin, uneven or obvious difference in skin condition or coloration, sunburn, open sores, moles, body piercings, etc.) at the application sites that, in the opinion of the Investigator, would compromise the ability of the patch to be applied.
• History of or current evidence of hypertension, as determined by the Investigator, or has a seated systolic blood pressure \> 140 mmHg or diastolic blood pressure \> 90 mmHg; determined at screening.
• Significant history or current evidence, as determined by the Investigator, of chronic infectious disease, system disorders, organ dysfunction especially renal disorders, hepatic impairment or disease (especially prior cholestatic jaundice of pregnancy, jaundice with prior estrogen use, or hepatic hemangiomas), gallbladder disease, pancreatitis or hypertriglyceridemia, hypercalcemia, thyroid disorders (especially hypoparathyroidism), residual endometriosis post-hysterectomy, epilepsy, migraine, porphyria, or cardiovascular disorders (especially coronary heart disease).
• Has any risk factors, as determined by the Investigator, for arterial vascular disease/arterial thrombosis (e.g., hypertension, diabetes, tobacco use, or hypercholesterolemia) or venous thromboembolism (VTE) including retinal vascular thrombosis (e.g., personal history or immediate family history of VTE, or systemic lupus erythematosus).
• History or current evidence (i.e., active) of deep venous thrombosis (DVT) or pulmonary embolism (PE), as determined by the Investigator.
• History or current evidence (i.e., active) of arterial thromboembolic disease (e.g., stroke, myocardial infarction, etc.), as determined by the Investigator.
• Known or significant family history (as determined by the Investigator) of coagulation disorders (i.e., bleeding or clotting disorders) such as excessive/prolonged bleeding from cuts, bruising easily, blood clots, etc.
• Known, suspected, significant family history (as determined by the Investigator), or history of breast cancer, bone metastases, endometrial cancer, or ovarian cancer.
• Known or suspected (as determined by the Investigator based on participant's provided medical history) estrogen-dependent neoplasia.
• Known or suspected (as determined by the Investigator based on participant's provided medical history) protein C, protein S, or antithrombin deficiency, or other thrombophilic disorders.
• Undiagnosed persistent or recurring abnormal genital bleeding with unknown etiology.

Sponsors & Collaborators

• Corium Innovations, Inc.: lead

Study Sites (1)

Lambda Therapeutic Research Ltd.

Ahmedabad, Gujarat, 382481, India

Location

MeSH Terms

Interventions

Estradiol

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Niraj Vasisht

  Corium Innovations

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2026
• First Posted: October 1, 2026
• Study Start: July 1, 2026
• Primary Completion: September 8, 2026
• Study Completion: September 26, 2026
• Last Updated: October 1, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)