A Multiple-Center Study to Evaluate the Skin Irritation and Sensitization Potential of a Test Estradiol/Levonorgestrel Transdermal Delivery System (Corium TDS)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 250
- 试验地点
- 2
- 主要终点
- Mean Irritation Score (MIS) for the Test and Reference Patches During the 21-Day Continuous Application Period
研究概览
简要总结
The two products used in this study are transdermal patches that contain selegiline. The test drug is the Estradiol/Levonorgestrel Transdermal Delivery System (TDS). The comparator drug is the Climara Pro® TDS.
The purpose of this research study is to compare how the skin tolerates the test TDS and the comparator TDS. The study will evaluate and compare skin irritation and possible allergic-type skin reactions (sensitization) caused by the two products.
The comparison will be based on how the skin responds to repeated applications of each TDS. This includes the assessment of skin irritation during the Induction Period and the evaluation of possible allergic or sensitization reactions after the Challenge Period. In addition, the adhesion of each patch (how well the patch sticks to the skin over time) will be regularly checked, as this is important for both product performance and skin safety.
详细描述
This is a multi-center, evaluator-blinded, randomized phase 1 study evaluating skin irritation and skin sensitization of Estradiol/Levonorgestrel transdermal system in comparison to Climara Pro® transdermal patch in healthy postmenopausal women. The study will consist of a 5 week Screening Phase and a Treatment Phase. The Treatment Phase will consist of the following periods: an Induction Period, a Rest Period followed by a Challenge Period and if needed, a Re-Challenge Period.
Trained study staff will examine the patch application sites at scheduled time points and will score any skin reactions using standardized assessment scales specified within FDA Product Specific Guidance.
Furthermore, the overall safety of the test product will be compared with that of the comparator product by monitoring and recording any adverse events, side effects, or discomfort experienced during the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Naturally or surgically postmenopausal female, with or without an intact uterus, aged 40-75 years, 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.
- •Any participant who meets criteria a) or c) above and has an FSH level that is considered postmenopausal by national lab standards, is eligible for study enrollment.
- •For participants with an intact uterus, has a vaginal ultrasonography and/or MRI (performed at screening or within 3 months before initial patch application) demonstrating inactive endometrial lining with endometrial thickness < 4 mm.
- •A body weight ≤ 90 kg.
- •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 mammogram and/or breast MRI (performed at screening or within 9 months before initial patch application), and a normal clinical breast examination.
- •Total cholesterol level ≤ 275 mg/dL.
- •Triglycerides level ≤ 350 mg/dL.
- •For participants at the US clinical site, the participant will be required to read, understand, sign and date the informed consent form, which meets all criteria of current FDA regulations, and must be able to understand the information and instruction given to them during the study.
- •For participants at the India clinical site, the 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, required study procedures, and visit requirements.
排除标准
- •Male participants.
- •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 or the ability of the evaluator to observe possible irritation.
- •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.
- •Participants with known allergic or immunological disorders (e.g., primary or acquired immunodeficiencies such as human immunodeficiency virus [HIV] positive or AIDS, allergic diseases such as anaphylaxis, asthma or generalized drug reaction, rheumatoid arthritis or systemic lupus erythematosus). Resolved childhood asthma or minor allergic reactions to environmental allergens or foods need not be reason for exclusion.
- •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.
- •Has a scheduled surgery of the type associated with an increased risk of thromboembolism or anticipates periods of prolonged immobilization within 6 weeks after completion of the study.
- •Contraindication to estrogen therapy or is currently taking thyroid hormone replacement therapy or anticipates use during the study.
- •Within 3 weeks of the study start, use of medications or treatments which, in the opinion of the Investigator, could influence or exaggerate responses to the patches or could alter the inflammatory or immune responses.
- •Use of pharmacologic agents or products known to significantly induce or inhibit drug-metabolizing enzymes especially inducers of CYP3A4 and inhibitors of CYP3A4 within 30 days before initial patch application or anticipated use during the study.
- •Use of any of the following within the noted times before initial patch application or anticipated use during the study:
- •Estrogen pellet therapy or progestin injectable drug therapy within 6 months before initial patch application.
- •Progestin implants and estrogen alone injectable drug therapy within 3 months before initial patch application.
- •Oral estrogen and/or oral or intrauterine progestin therapy within 8 weeks before initial patch application.
- •Transdermal estrogen alone or transdermal estrogen/progestin products within 4 weeks before initial patch application.
- •Vaginal hormonal products (e.g., rings, creams, gels) within 1 week before initial patch application.
- •Use of prescription or over-the-counter (OTC) antihypertensives (e.g., diuretics, ACE inhibitors, angiotensin II receptor blockers, beta-blockers), pressor agents (e.g., midodrine, vasopressin, norepinephrine, epinephrine, phenylephrine, decongestants, NSAIDs like ibuprofen and naproxen), and estrogens (other than the study drug) from the time screening to initial patch application or anticipated use during the study.
- •Use of antihistamines or use of topical drugs at application site within 72 hours before the first patch application.
- •Use of any cosmetics, moisturizers, powders, and sunscreen or other topical products (e.g., makeup, oil, lotion, creams sprays, powders, etc.) at the patch application sites within 24 hours before the first patch application.
- •Receipt of any drug as part of a research study within at least 30 days before initial dosing.
- •Any history of narcotic abuse, drug abuse or alcohol addiction.
- •Positive test results for HIV, Hepatitis B surface antigen, or Hepatitis C antibody.
- •Positive test results for drugs of abuse or alcohol at screening.
- •Positive pregnancy test at screening.
- •Use of tobacco- or nicotine-containing products within 30 days before initial patch application or anticipated use during the study.
研究组 & 干预措施
1/2 patch Estradiol/Levonorgestrel TDS on left buttock, 1/2 patch Climara Pro® TDS on right buttock
干预措施: Estradiol/Levonorgestrel Transdermal System (Drug)
1/2 patch Estradiol/Levonorgestrel TDS on right buttock, 1/2 patch Climara Pro® TDS on left buttock
干预措施: Estradiol/Levonorgestrel Transdermal System (Drug)
结局指标
主要结局
Mean Irritation Score (MIS) for the Test and Reference Patches During the 21-Day Continuous Application Period
时间窗: From Day 1 through Day 22 (21-day continuous application period; assessments 30 minutes [+10 minutes] after patch removal on Days 8, 15, and 22)
For each participant and patch, an Irritation Score is calculated by adding the Dermal Response Score and the numerical Other Effects Score. The Dermal Response Score ranges from 0 to 7 and the Other Effects Score ranges from 0 to 3, resulting in a combined Irritation Score ranging from 0 to 10; higher scores indicate greater skin irritation. The Mean Irritation Score is calculated separately for the Test Patch and Reference Patch as the sum of the Irritation Scores obtained 30 minutes (+10 minutes) after patch removal on Days 8, 15, and 22, divided by the number of irritation assessments. The baseline assessment is excluded. The primary non-inferiority comparison is based on the difference in overall mean MIS between the Test and Reference Patches (Test minus Reference), using a non-inferiority margin of 0.20.
Number of Participants With a Potential Sensitization Response to the Test or Reference Patch
时间窗: At the last evaluation more than 24 hours after challenge patch removal (48 or 72 hours); for rechallenged participants, at the last evaluation more than 24 hours after rechallenge patch removal (48 or 72 hours)
Potential sensitization is evaluated separately for the Test Patch and Reference Patch in the Per Protocol Population for Sensitization. A participant is considered to have a potential sensitization response to a patch if the combined Irritation Score (Dermal Response Score plus Other Effects Score) is at least 2 at the participant's last evaluation occurring more than 24 hours after patch removal, such as the 48- or 72-hour evaluation, during the challenge phase and the rechallenge phase if rechallenge is performed.
次要结局
未报告次要终点