Efficacy and Safety Study of 4 Dose Regimens of Oral Albaconazole in Subjects With Distal Subungual Onychomycosis

Study Overview
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Brief Summary
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Phase 2 study to examine how the study drug works and its side effects in subjects with toenail fungus.

Detailed Description
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A phase 2, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study to investigate the efficacy and safety of 4 dose regimens of ORAL albaconazole in subjects with distal subungual onychomycosis. Subjects will take oral study drug for up to 36 weeks and then will be followed for an additional 16 weeks to determine if the study drug was efficacious. Subjects will have routine blood draws and other safety assessments during the study, as well as regular assessments of their toenail fungus

Official Title
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A Phase 2, Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-ranging Study to Investigate the Efficacy and Safety of 4 Dose Regimens of Oral Albaconazole in Subjects With Distal Subungual Onychomycosis

Conditions
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Onychomycosis

Intervention / Treatment
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* Drug: Albaconazole 100mg
* Drug: Albaconazole 200mg
* Drug: Albaconazole 400mg
* Drug: Albaconazole 400mg
* Drug: Placebo 400 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject aged 18 to 75 years. Diagnosis with distal subungual onychomycosis of the toenails that affects at least one great toe (target toenail). Subject is willing to provide signed and dated written voluntary informed consent (and any local or national authorization requirements) before any protocol-specific procedures are performed. Subject is able to complete the study, comply with study instructions, and take study product orally. Sexually active non-lactating females of childbearing potential participating in the study must agree to use a medically acceptable method of contraception while receiving protocol-assigned product and up to the first menses 60 days following the last dose of study product. Women of childbearing potential must have a negative pregnancy test at enrollment. Subject has screening laboratory parameters and ECG within the normal ranges unless considered to be not clinically relevant by the principal investigator. Exclusion Criteria: Subjects with any of the following conditions or characteristics will be excluded from study enrollment (ie, will not receive study product): Subject has received an investigational drug within 4 weeks of the first dose of study product, or who are scheduled to receive an investigational drug other than the study product during the study. Subject has participated in a clinical trial for the systemic treatment of onychomycosis of the toenails within 6 months prior to the first dose of study product. Subject is receiving any drugs that are known substrates of the 3A4 isozyme of cytochrome P450 (CYP3A4) with QT prolongation potential or any of the concomitant medications listed under prohibited medication section. Subject has a history of known or suspected intolerance to albaconazole or the formulation excipients, or to azole antifungal drugs in general. Subject has previously participated in a clinical study with albaconazole. Subject is not prepared to give up use of any nail cosmetic products for the duration of the study. Subject has any known immunodeficiency or history of malignancy in the last 4 years, excluding nonmelanoma skin cancer. Subject has any known liver disease or a history of liver toxicity with other drugs. Subject is currently suffering from any disease or condition, that could include abnormal laboratory tests, and/or who are currently using medication which in the opinion of the investigator may affect the evaluation of the study product or place the subject at undue risk. Subject has psoriasis, lichen planus, or other abnormalities that could result in a clinically abnormal toenail. Subject has a history of any condition that could possibly affect absorption of drug (eg, gastrectomy), uncontrolled diabetes, clinically significant peripheral vascular disease or peripheral circulatory impairment, or has had any major illness within 30 days prior to the screening examination. Subject has a history of drug, prescription medicine, or alcohol abuse within the past 2 years. Female subjects who are pregnant, trying to become pregnant, or lactating. Employees of Investigator/clinical research organization (CRO) or Stiefel Laboratories, Inc., or an immediate family member (partner, offspring, parents, siblings or sibling's offspring) of an employee.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Albaconazole 100mg<br>Albaconazole for 36 weeks | Drug: Albaconazole 100mg<br>* Albaconazole for 36 weeks<br>|
| Active Comparator: Albaconazole 200mg<br>Albaconazole for 36 weeks | Drug: Albaconazole 200mg<br>* Albaconazole for 36 weeks<br>|
| Active Comparator: Albaconazole 400mg<br>Albaconazole for 36 weeks | Drug: Albaconazole 400mg<br>* Albaconazole for 36 weeks<br>|
| Active Comparator: Albaconazole 400mg 24 weeks, Placebo 12 weeks<br>Albaconazole for 24 weeks, Placebo for 12 weeks | Drug: Albaconazole 400mg<br>* Albaconazole for 24 weeks, Placebo for 12 weeks<br>Drug: Placebo 400 mg<br>* Placebo for 36 weeks<br>|
| Placebo Comparator: Placebo 400 mg<br>Placebo for 36 weeks | Drug: Placebo 400 mg<br>* Placebo for 36 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants Who Achieve Effective Treatment at Week 52 | At each study visit, the investigator assessed the percentage of affected toenail on the target nail by estimating the percent affected nail in each quadrant, summing the percent affected in each quadrant and dividing the sum by 4. Effective treatment was defined as a mycological cure and clear or almost clear nail (distal subungual hyperkeratosis and/or onycholysis leaving less than 10% of nail plate effected). Comparisons were carried out in a sequential step-down fashion, combined with the Holm procedure at step 2. P-value was based on a sequential step-down combined with the Holm procedure. It was assessed on Week 4, 8, 12, 16, 20, 24, 30, 36, 44 and 52. | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants Who Achieve Clinical Cure at Week 52 | At each study visit, the investigator assessed the percentage of affected toenail on the target nail by estimating the percent affected nail in each quadrant, summing the percent affected in each quadrant and dividing the sum by 4. Clinical cure was defined as 100% clear nail. It was assessed on Week 4, 8, 12, 16, 20, 24, 30, 36, 44 and 52. | Week 52 | 
| The Percentage of Participants Who Achieve Mycological Cure at Week 52 | At each study visit, the investigator assessed the percentage of affected toenail on the target nail by estimating the percent affected nail in each quadrant, summing the percent affected in each quadrant and dividing the sum by 4. Mycological cure was defined as negative potassium hydroxide (KOH) and negative cultures for dermatophytes. It was assessed on Week 12, 16, 20, 24, 30, 36, 44 and 52. | Week 52 | 
| The Percentage of Participants Who Achieve Complete Cure at Week 52 | At each study visit, the investigator assessed the percentage of affected toenail on the target nail by estimating the percent affected nail in each quadrant, summing the percent affected in each quadrant and dividing the sum by 4. Complete cure was defined as mycological cure plus clinical cure. It was assessed on Week 4, 8, 12, 16, 20, 24, 30, 36, 44 and 52. | Week 52 | 
| Absolute Change in Unaffected Part of Target Nail From Baseline to Week 52 | Length of the unaffected part of the target nail was measured in millimeters along the midpoint from the nail fold to the proximal border of the affected part (lowest point affected) along the midpoint of the target nail. It was assessed on Week 4, 8, 12, 16, 20, 24, 30, 36, 44 and 52. Baseline values were the observations at Week 0/Day 1 or before. Change from Baseline was a Baseline value subtracted from Week 52 value. P-value was based on analysis of variance (ANOVA) with treatment and pooled center. Statistics is provided for adjusted least square mean. | Baseline (Week 0/Day 1 or before) and up to Week 52 | 
| The Percentage of Participants With a Global Change Score of Cleared or Much Improved at Week 52 | A count of the number of toenails affected, using visual examination, was performed at all study visits (Week 12, 24, 30, 36, 44 and 52). The investigator given a global evaluation of the toenails condition, based on the investigator's assessment of the reduction in extent of nail involvement and improvement in clinical signs as compared with the status at the Baseline visit. The 0-5 rating scale was used: 0: cleared, 1: much improved, 2: minimally improved, 3: unchanged, 4: minimally worse and 5: much worse; where higher score indicates worse condition and lower score indicates clear toenail. | Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Distal, Subungual onychomycosis, onychomycosis, nail fungus, Toenail fungus