A Phase 1b Study of ZYG24004 in Participants With Tinea Pedis Caused by Dermatophytes

Официальное название

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Different Concentrations of ZYG24004 in Participants With Tinea Pedis Caused by Dermatophytes

Обзор

This is a multicenter, randomized, double-blind, placebo-controlled Phase 1b study in adult participants with tinea pedis caused by dermatophytes. The study will evaluate the safety, local tolerability, and pharmacokinetic profile of two concentrations of ZYG24004 (1% and 3%) after topical administration once or twice (once weekly for two consecutive weeks), and will explore preliminary efficacy.

Подробное описание

The study uses a sequential cohort escalation design from lower to higher concentration and from single to two administrations. Four cohorts are planned: 1% ZYG24004 single administration, 1% ZYG24004 two administrations, 3% ZYG24004 single administration, and 3% ZYG24004 two administrations. Each cohort will enroll 16 participants randomized in a 3:1 ratio to active study drug or placebo (12 active and 4 placebo), for a total of 64 participants. Participants will have clinically diagnosed tinea pedis caused by dermatophytes, with lesions located in the interdigital area and potentially involving the sole and lateral foot, a positive fungal microscopy result at screening, and a target-foot clinical signs and symptoms score of at least 3.

The next cohort may start only after the preceding cohort completes the protocol-specified key safety and local tolerability review. Key safety/local tolerability review is planned at Day 8 +/- 1 after the first administration for single-administration cohorts and at Day 15 +/- 1 after the last administration for two-administration cohorts. The first cohort will also complete all planned pharmacokinetic sampling through Day 15 +/- 1 before the sponsor, investigators, and relevant medical/pharmacokinetic personnel assess whether later cohort pharmacokinetic sampling time points require optimization.

Safety, local tolerability, and pharmacokinetic assessments will be performed throughout the study. Preliminary efficacy will be explored using mycological outcomes and clinical signs and symptoms assessments through Day 43 +/- 2.

Вмешательства

• Препарат ZYG24004 1% topical film-forming formulation
  ZYG24004 1% (4 g:40 mg) topical film-forming formulation. Approximately 2 g will be applied to each foot, with a total dose of approximately 4 g per administration, according to the protocol.
• Препарат ZYG24004 3% topical film-forming formulation
  ZYG24004 3% (4 g:0.12 g) topical film-forming formulation. Approximately 2 g will be applied to each foot, with a total dose of approximately 4 g per administration, according to the protocol.
• Препарат Placebo topical formulation
  Placebo topical formulation matching ZYG24004 in appearance and packaging. Approximately 2 g will be applied to each foot, with a total dose of approximately 4 g per administration, according to the protocol.

Первичные конечные точки

• Incidence of serious adverse events (SAEs) [Срок оценки: From informed consent through Day 43 +/- 2]
• Incidence of Grade 3 or higher treatment-emergent adverse events (TEAEs) or TEAEs leading to withdrawal [Срок оценки: From first administration through Day 43 +/- 2]
• Incidence and severity of local tolerability reactions at the application site [Срок оценки: From first administration through Day 43 +/- 2]
• Plasma concentration-time profile of efinaconazole and metabolite H3 [Срок оценки: Single-administration cohorts: Day 1 through Day 15 +/- 1; two-administration cohorts: Day 1 through Day 22 +/- 1]
• Maximum observed plasma concentration (Cmax) of efinaconazole and metabolite H3 [Срок оценки: Single-administration cohorts: Day 1 through Day 15 +/- 1; two-administration cohorts: Day 1 through Day 22 +/- 1]
• Time to maximum observed plasma concentration (Tmax) of efinaconazole and metabolite H3 [Срок оценки: Single-administration cohorts: Day 1 through Day 15 +/- 1; two-administration cohorts: Day 1 through Day 22 +/- 1]
• Area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUC0-t) [Срок оценки: Single-administration cohorts: Day 1 through Day 15 +/- 1; two-administration cohorts: Day 1 through Day 22 +/- 1]
• Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-inf) [Срок оценки: Single-administration cohorts: Day 1 through Day 15 +/- 1; two-administration cohorts: Day 1 through Day 22 +/- 1]
• Terminal elimination half-life (t1/2) of efinaconazole and metabolite H3 [Срок оценки: Single-administration cohorts: Day 1 through Day 15 +/- 1; two-administration cohorts: Day 1 through Day 22 +/- 1]

Вторичные конечные точки (4)

• Mycological cure rate of the target area [Срок оценки: Week 1, Week 2, Week 4, and Week 6 after first administration]
• Time to mycological negativity [Срок оценки: From first administration through Week 6]
• Change from baseline in clinical signs and symptoms score [Срок оценки: Week 2, Week 4, and Week 6 after first administration]
• Treatment success rate at Week 6 [Срок оценки: Week 6 after first administration]

Критерии участия

Критерии включения

• Male or female participants aged 18 to 65 years; body weight >=50 kg for males and >=45 kg for females; body mass index (BMI) 18.5 to 28.0 kg/m2, inclusive.
• Clinically diagnosed tinea pedis, with lesions located in the interdigital area and possibly involving the sole and lateral foot.
• Positive mycological test of the target foot at screening, based on fungal microscopy.
• Target-foot clinical signs and symptoms score >=3.
• In generally good health, with no serious or uncontrolled systemic disease, and considered by the investigator to be suitable for participation.
• The participant or the participant's partner is not pregnant or breastfeeding, and the participant agrees to use reliable contraception throughout the study and for 3 months after the last administration.
• Willing and able to comply with scheduled visits and protocol requirements, and able to understand and sign the informed consent form.

Критерии исключения

• Hyperkeratotic tinea pedis, or tinea pedis accompanied by erosion, exudation, or ulceration.
• Concomitant onychomycosis of the feet or other active fungal disease.
• Bacterial or viral skin infection of the feet, or severe skin disease judged by the investigator to affect study assessments, such as severe eczema, psoriasis, atopic dermatitis, or chronic dermatitis.
• History of dermatophyte infection that was ineffective to prior antifungal therapy.
• Use of systemic antifungal drugs within 3 months before enrollment.
• Use of topical antifungal drugs, such as terbinafine cream, butenafine cream, ciclopirox, clotrimazole, or miconazole, or topical corticosteroid-containing drugs within 4 weeks before enrollment.
• Use of topical antibacterial drugs, disinfectants, keratolytic agents such as salicylic acid, or other topical treatment on the feet within 2 weeks before enrollment.
• Use of oral antihistamines within 1 week before enrollment.
• Use of systemic corticosteroids or immunosuppressive drugs within 4 weeks before enrollment.
• Serious or uncontrolled cardiovascular, hepatic, renal, neurological, psychiatric, or immune system disease.
• History of diabetes mellitus or fasting blood glucose above the upper limit of normal.
• Clinically significant abnormalities in physical examination, hematology, blood chemistry, urinalysis, 12-lead electrocardiogram, infectious disease screening, coagulation function, or other assessments.
• Currently participating in another clinical trial, or participation in another clinical trial within 30 days before the baseline visit or within 5 half-lives of the investigational product, whichever is longer.
• Known severe allergy or intolerance to ZYG24004 or any excipients of the formulation, including film-forming polymers or ethanol.
• Addiction to smoking, defined as >10 cigarettes per day.
• Diagnosis of alcohol dependence or drug dependence within the past 12 months, or any situation judged by the investigator to affect compliance.
• Any other condition that, in the investigator's opinion, may interfere with study results or make participation unsafe.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Peking University First Hospital — Пекин

Идентификаторы

NCT: NCT07668999 · ZYG-24004-Ⅰ-01-2025-03 · CTR20262184

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)
• NMPA/CDE CTR20262184 (платформа chinadrugtrials.org.cn)

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