Tinea Pedis
Conditions
Keywords
ZYG24004, tinea pedis, Phase 1b, topical film-forming formulation
Brief summary
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.
Detailed description
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.
Interventions
DRUGZYG24004 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.
DRUGZYG24004 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.
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.
Sponsors
Sinomune Pharmaceutical Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. 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. 2. Clinically diagnosed tinea pedis, with lesions located in the interdigital area and possibly involving the sole and lateral foot. 3. Positive mycological test of the target foot at screening, based on fungal microscopy. 4. Target-foot clinical signs and symptoms score \>=3. 5. In generally good health, with no serious or uncontrolled systemic disease, and considered by the investigator to be suitable for participation. 6. 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. 7. Willing and able to comply with scheduled visits and protocol requirements, and able to understand and sign the informed consent form.
Exclusion criteria
1. Hyperkeratotic tinea pedis, or tinea pedis accompanied by erosion, exudation, or ulceration. 2. Concomitant onychomycosis of the feet or other active fungal disease. 3. 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. 4. History of dermatophyte infection that was ineffective to prior antifungal therapy. 5. Use of systemic antifungal drugs within 3 months before enrollment. 6. 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. 7. Use of topical antibacterial drugs, disinfectants, keratolytic agents such as salicylic acid, or other topical treatment on the feet within 2 weeks before enrollment. 8. Use of oral antihistamines within 1 week before enrollment. 9. Use of systemic corticosteroids or immunosuppressive drugs within 4 weeks before enrollment. 10. Serious or uncontrolled cardiovascular, hepatic, renal, neurological, psychiatric, or immune system disease. 11. History of diabetes mellitus or fasting blood glucose above the upper limit of normal. 12. Clinically significant abnormalities in physical examination, hematology, blood chemistry, urinalysis, 12-lead electrocardiogram, infectious disease screening, coagulation function, or other assessments. 13. 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. 14. Known severe allergy or intolerance to ZYG24004 or any excipients of the formulation, including film-forming polymers or ethanol. 15. Addiction to smoking, defined as \>10 cigarettes per day. 16. Diagnosis of alcohol dependence or drug dependence within the past 12 months, or any situation judged by the investigator to affect compliance. 17. Any other condition that, in the investigator's opinion, may interfere with study results or make participation unsafe.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of serious adverse events (SAEs) | From informed consent through Day 43 +/- 2 | The type and proportion of participants experiencing any SAE will be summarized, including investigator-assessed causal relationship to study drug. |
| Incidence of Grade 3 or higher treatment-emergent adverse events (TEAEs) or TEAEs leading to withdrawal | From first administration through Day 43 +/- 2 | The proportion of participants with CTCAE Version 6.0 Grade \>=3 TEAEs or TEAEs leading to withdrawal will be summarized by event type, severity, and relationship to study drug. |
| Incidence and severity of local tolerability reactions at the application site | From first administration through Day 43 +/- 2 | Local tolerability reactions include erythema, edema, burning/stinging, pruritus, blisters, pain, and other local symptoms. Frequency, type, severity, duration, and the proportion of participants with local tolerability reactions leading to treatment interruption or discontinuation will be summarized. |
| Plasma concentration-time profile of efinaconazole and metabolite H3 | Single-administration cohorts: Day 1 through Day 15 +/- 1; two-administration cohorts: Day 1 through Day 22 +/- 1 | Plasma concentrations of efinaconazole and its major metabolite H3 will be measured at protocol-specified pharmacokinetic time points. |
| Maximum observed plasma concentration (Cmax) of efinaconazole and metabolite H3 | Single-administration cohorts: Day 1 through Day 15 +/- 1; two-administration cohorts: Day 1 through Day 22 +/- 1 | Cmax will be calculated using non-compartmental analysis where data permit. |
| Time to maximum observed plasma concentration (Tmax) of efinaconazole and metabolite H3 | Single-administration cohorts: Day 1 through Day 15 +/- 1; two-administration cohorts: Day 1 through Day 22 +/- 1 | Tmax will be calculated using non-compartmental analysis where data permit. |
| Area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUC0-t) | Single-administration cohorts: Day 1 through Day 15 +/- 1; two-administration cohorts: Day 1 through Day 22 +/- 1 | AUC0-t will be calculated using non-compartmental analysis where data permit. |
| Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-inf) | Single-administration cohorts: Day 1 through Day 15 +/- 1; two-administration cohorts: Day 1 through Day 22 +/- 1 | AUC0-inf will be calculated using non-compartmental analysis where data permit. |
| Terminal elimination half-life (t1/2) of efinaconazole and metabolite H3 | Single-administration cohorts: Day 1 through Day 15 +/- 1; two-administration cohorts: Day 1 through Day 22 +/- 1 | t1/2 will be calculated using non-compartmental analysis where data permit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mycological cure rate of the target area | Week 1, Week 2, Week 4, and Week 6 after first administration | Mycological cure is defined as both fungal microscopy and fungal culture being negative for the target area. |
| Time to mycological negativity | From first administration through Week 6 | Time from first administration to the first visit at which mycological testing is negative. Mycological negativity is based on negative fungal microscopy and negative fungal culture. |
| Change from baseline in clinical signs and symptoms score | Week 2, Week 4, and Week 6 after first administration | Clinical signs and symptoms include scaling, erythema, pruritus, crusting, maceration, fissures, pustules, and blisters, each scored on a 0 to 3 scale, where 0 = absent and 3 = severe. |
| Treatment success rate at Week 6 | Week 6 after first administration | Treatment success is defined as mycological cure and a total clinical signs and symptoms score \<=2, with crusting, fissures, pustules, and blisters each scored 0 and scaling, erythema, maceration, and pruritus each scored 0 or 1. |
Countries
China
Contacts
CONTACTYaheng Wang
PRINCIPAL_INVESTIGATORRuoyu Li, MD
Peking University First Hospital
Outcome results
None listed