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

Primary Purpose

Onychomycosis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Albaconazole 100mg
Albaconazole 200mg
Albaconazole 400mg
Albaconazole 400mg
Placebo 400 mg
Sponsored by
Stiefel, a GSK Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Onychomycosis focused on measuring Distal, Subungual onychomycosis, onychomycosis, nail fungus, Toenail fungus

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Alabama at Birmingham
  • Genova Clinical Research
  • Impact Clinical Trials
  • Northern California Research
  • Center for Dermatology Clinical Research
  • Therapeutics Clinical Research
  • UCSF Dermatology Research
  • Thomas J. Stephens & Associates, Inc. Colorado Research Center
  • Greater Miami Skin & Laser Center
  • International Dermatology Research Inc
  • Miami Dermatology Research Institute LLC
  • MedaPhase, Inc
  • Gwinnett Clinical Research Center, Inc.
  • Welborn Clinic
  • Henry Ford Medical Center
  • Minnesota Clinical Study Center
  • Skin Specialists, Inc
  • NYU Medical Center
  • University of North Carolina at Chapel Hill
  • Oregon Dermatology & Research Centre
  • Oregon Medical
  • The Skin Wellness Center
  • Tennessee Clinical Research
  • DermResearch, Inc.
  • J & S Studies, Inc.
  • Research Across America
  • Center for Clinical Studies
  • DermatologyResearch Center
  • Education and Research Foundation
  • Ultranova Skincare
  • North Bay Dermatology Centre Inc.
  • K. Papp Clinical Research Inc.
  • Dermatology Centre, University of Iceland

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

Albaconazole 100mg

Albaconazole 200mg

Albaconazole 400mg

Albaconazole 400mg 24 weeks, Placebo 12 weeks

Placebo 400 mg

Arm Description

Albaconazole for 36 weeks

Albaconazole for 36 weeks

Albaconazole for 36 weeks

Albaconazole for 24 weeks, Placebo for 12 weeks

Placebo for 36 weeks

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.

Full Information

First Posted
August 4, 2008
Last Updated
February 13, 2018
Sponsor
Stiefel, a GSK Company
Collaborators
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT00730405
Brief Title
Efficacy and Safety Study of 4 Dose Regimens of Oral Albaconazole in Subjects With Distal Subungual Onychomycosis
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
July 16, 2008 (Actual)
Primary Completion Date
February 19, 2010 (Actual)
Study Completion Date
February 19, 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Stiefel, a GSK Company
Collaborators
GlaxoSmithKline

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Onychomycosis
Keywords
Distal, Subungual onychomycosis, onychomycosis, nail fungus, Toenail fungus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
582 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Albaconazole 100mg
Arm Type
Active Comparator
Arm Description
Albaconazole for 36 weeks
Arm Title
Albaconazole 200mg
Arm Type
Active Comparator
Arm Description
Albaconazole for 36 weeks
Arm Title
Albaconazole 400mg
Arm Type
Active Comparator
Arm Description
Albaconazole for 36 weeks
Arm Title
Albaconazole 400mg 24 weeks, Placebo 12 weeks
Arm Type
Active Comparator
Arm Description
Albaconazole for 24 weeks, Placebo for 12 weeks
Arm Title
Placebo 400 mg
Arm Type
Placebo Comparator
Arm Description
Placebo for 36 weeks
Intervention Type
Drug
Intervention Name(s)
Albaconazole 100mg
Intervention Description
Albaconazole for 36 weeks
Intervention Type
Drug
Intervention Name(s)
Albaconazole 200mg
Intervention Description
Albaconazole for 36 weeks
Intervention Type
Drug
Intervention Name(s)
Albaconazole 400mg
Intervention Description
Albaconazole for 36 weeks
Intervention Type
Drug
Intervention Name(s)
Albaconazole 400mg
Intervention Description
Albaconazole for 24 weeks, Placebo for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo 400 mg
Intervention Description
Placebo for 36 weeks
Primary Outcome Measure Information:
Title
The Percentage of Participants Who Achieve Effective Treatment at Week 52
Description
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.
Time Frame
Week 52
Secondary Outcome Measure Information:
Title
The Percentage of Participants Who Achieve Clinical Cure at Week 52
Description
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.
Time Frame
Week 52
Title
The Percentage of Participants Who Achieve Mycological Cure at Week 52
Description
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.
Time Frame
Week 52
Title
The Percentage of Participants Who Achieve Complete Cure at Week 52
Description
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.
Time Frame
Week 52
Title
Absolute Change in Unaffected Part of Target Nail From Baseline to Week 52
Description
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.
Time Frame
Baseline (Week 0/Day 1 or before) and up to Week 52
Title
The Percentage of Participants With a Global Change Score of Cleared or Much Improved at Week 52
Description
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.
Time Frame
Week 52

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Genova Clinical Research
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85791
Country
United States
Facility Name
Impact Clinical Trials
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Facility Name
Northern California Research
City
Carmichael
State/Province
California
ZIP/Postal Code
95608
Country
United States
Facility Name
Center for Dermatology Clinical Research
City
Fremont
State/Province
California
ZIP/Postal Code
94538
Country
United States
Facility Name
Therapeutics Clinical Research
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
UCSF Dermatology Research
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Thomas J. Stephens & Associates, Inc. Colorado Research Center
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80915
Country
United States
Facility Name
Greater Miami Skin & Laser Center
City
Miami Beach
State/Province
Florida
ZIP/Postal Code
33140
Country
United States
Facility Name
International Dermatology Research Inc
City
Miami
State/Province
Florida
ZIP/Postal Code
33144
Country
United States
Facility Name
Miami Dermatology Research Institute LLC
City
North Miami Beach
State/Province
Florida
ZIP/Postal Code
33169
Country
United States
Facility Name
MedaPhase, Inc
City
Newnan
State/Province
Georgia
ZIP/Postal Code
30263
Country
United States
Facility Name
Gwinnett Clinical Research Center, Inc.
City
Snellville
State/Province
Georgia
ZIP/Postal Code
30078
Country
United States
Facility Name
Welborn Clinic
City
Evansville
State/Province
Indiana
ZIP/Postal Code
47713
Country
United States
Facility Name
Henry Ford Medical Center
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Minnesota Clinical Study Center
City
Fridley
State/Province
Minnesota
ZIP/Postal Code
55432
Country
United States
Facility Name
Skin Specialists, Inc
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68144
Country
United States
Facility Name
NYU Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Oregon Dermatology & Research Centre
City
Portland
State/Province
Oregon
ZIP/Postal Code
97210
Country
United States
Facility Name
Oregon Medical
City
Portland
State/Province
Oregon
ZIP/Postal Code
97223
Country
United States
Facility Name
The Skin Wellness Center
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37922
Country
United States
Facility Name
Tennessee Clinical Research
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37215
Country
United States
Facility Name
DermResearch, Inc.
City
Austin
State/Province
Texas
ZIP/Postal Code
78759
Country
United States
Facility Name
J & S Studies, Inc.
City
College Station
State/Province
Texas
ZIP/Postal Code
77845
Country
United States
Facility Name
Research Across America
City
Dallas
State/Province
Texas
ZIP/Postal Code
75234
Country
United States
Facility Name
Center for Clinical Studies
City
Houston
State/Province
Texas
ZIP/Postal Code
77058
Country
United States
Facility Name
DermatologyResearch Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84124
Country
United States
Facility Name
Education and Research Foundation
City
Lynchburg
State/Province
Virginia
ZIP/Postal Code
24501
Country
United States
Facility Name
Ultranova Skincare
City
Barrie
State/Province
Ontario
ZIP/Postal Code
L4M 6L2
Country
Canada
Facility Name
North Bay Dermatology Centre Inc.
City
North Bay
State/Province
Ontario
ZIP/Postal Code
P1B 3Z7
Country
Canada
Facility Name
K. Papp Clinical Research Inc.
City
Waterloo
State/Province
Ontario
ZIP/Postal Code
N2J 1C4
Country
Canada
Facility Name
Dermatology Centre, University of Iceland
City
Hudlaeknaslodin
State/Province
Kopavogur
ZIP/Postal Code
201
Country
Iceland

12. IPD Sharing Statement

Citations:
PubMed Identifier
23706639
Citation
Sigurgeirsson B, van Rossem K, Malahias S, Raterink K. A phase II, randomized, double-blind, placebo-controlled, parallel group, dose-ranging study to investigate the efficacy and safety of 4 dose regimens of oral albaconazole in patients with distal subungual onychomycosis. J Am Acad Dermatol. 2013 Sep;69(3):416-25. doi: 10.1016/j.jaad.2013.03.021. Epub 2013 May 22.
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Efficacy and Safety Study of 4 Dose Regimens of Oral Albaconazole in Subjects With Distal Subungual Onychomycosis

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