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Trial record 39 of 240 for:    Itraconazole

Itraconazole Tablets Vs. Itraconazole Capsules vs. Placebo in Onychomycosis of the Toenail.

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ClinicalTrials.gov Identifier: NCT00356915
Recruitment Status : Completed
First Posted : July 27, 2006
Results First Posted : January 4, 2012
Last Update Posted : February 9, 2017
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
GlaxoSmithKline ( Stiefel, a GSK Company )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Investigator);   Primary Purpose: Treatment
Condition Onychomycosis
Interventions Drug: Itraconazole 100mg capsules
Drug: Itraconazole 200mg tablets
Drug: Placebo tablets
Enrollment 1381
Recruitment Details Subjects were recruited from clinics in the US, Canada, South America, Ecuador, Dominican Republic, Panama, and Honduras.
Pre-assignment Details Subjects were screened prior to randomization and had to have a positive result from a mycological culture of their toe nail (ie, culture that was positive for dermatophytes). If the culture was negative, they were not randomized to receive treatment and were discontinued from the study.
Arm/Group Title Itraconazole Tablets Itraconazole Capsules Placebo Tablets
Hide Arm/Group Description Itraconazole 200 mg tablets. Subjects took one 200 mg tablet once per day after a full meal. The last dose was taken the day before the Week 12 visit. Itraconazole 100 mg capsules Tablets that were the same as the Itraconazole tables except that they did not contain the active drug (Itraconazole).
Period Title: Overall Study
Started 593 590 198
Completed 517 496 156
Not Completed 76 94 42
Reason Not Completed
Non compliance             1             2             1
Protocol Violation             2             3             2
Withdrawal by Subject             14             14             10
Lack of Efficacy             0             0             3
Lost to Follow-up             27             34             14
Administrative Decision             0             0             1
Physician Decision             0             2             0
Adverse Event             21             31             8
Miscellaneous reasons             11             8             3
Arm/Group Title Itraconazole Tablets Itraconazole Capsules Placebo Tablets Total
Hide Arm/Group Description Itraconazole 200 mg tablets. Subjects took one 200 mg tablet once per day after a full meal. The last dose was taken the day before the Week 12 visit. Itraconazole 100 mg capsules Tablets that were the same as the Itraconazole tables except that they did not contain the active drug (Itraconazole). Total of all reporting groups
Overall Number of Baseline Participants 593 590 198 1381
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 593 participants 590 participants 198 participants 1381 participants
47.1  (11.86) 47  (12.67) 49.2  (11.12) 47.4  (12.13)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 593 participants 590 participants 198 participants 1381 participants
Female
441
  74.4%
440
  74.6%
153
  77.3%
1034
  74.9%
Male
152
  25.6%
150
  25.4%
45
  22.7%
347
  25.1%
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 593 participants 590 participants 198 participants 1381 participants
American Indian or Alaska Native 7 7 4 18
Asian 5 4 2 11
Native Hawaiian or Other Pacific Islander 0 1 0 1
Black or African American 48 48 18 114
White 512 493 169 1174
Unknown or Not Reported 25 41 7 73
[1]
Measure Description: Subjects were permitted to select all choices from the list that apply to them with regard to race; ie, multiracial subjects would have checked more than one box and it would have been reported as such. Therefore the total number of subjects reported for race is greater than the number enrolled.
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 593 participants 590 participants 198 participants 1381 participants
Panama 9 9 3 21
United States 527 523 176 1226
Canada 23 21 8 52
Ecuador 6 8 3 17
Honduras 9 9 3 21
Dominican Republic 7 9 2 18
South Africa 12 11 3 26
[1]
Measure Description: Participants were permitted to select all choices from the list that apply to them with regard to race; ie, multiracial participants would have checked more than one box and it would have been reported as such. Therefore the total number of participants reported for race is greater than the number enrolled.
1.Primary Outcome
Title Clinical and Mycological Cure of Target Toenail
Hide Description

This study was designed to evaluate the superiority of itraconazole tablets to placebo tablets.

Clinical Cure was defined as an IGA score of 0 for the target toenail; Mycological Cure was defined as a negative potassium hydroxide (KOH) exam and a negative culture for dermatophytes of the target toenail.

Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT).
Arm/Group Title Itraconazole Tablets Placebo Tablets
Hide Arm/Group Description:
Itraconazole 200mg tablets
[Not Specified]
Overall Number of Participants Analyzed 593 198
Measure Type: Number
Unit of Measure: Percentage of participants
22.3 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Itraconazole Tablets, Placebo Tablets
Comments P-Value from a Cochran-Mantel-Haenszel test, . The superiority analysis was restricted to the itraconazole 200-mg tablets and placebo tablets dosing groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments This was stratified by analysis center.
2.Primary Outcome
Title Complete Cure - Itraconazole Tablets Compared to Itraconazole Capsules
Hide Description The primary efficacy endpoint was Compete Cure (consisting of a Clinical Cure and a Mycological Cure) at week 52. In this study, Clinical Cure was defined as an Investigator’s Global Assessment (IGA) score of 0 for the target toenail; Mycological Cure was defined as a negative potassium hydroxide (KOH) examination and a negative culture outcome for dermatophytes of the target toenail. The efficacy analyses were conducted to demonstrate the non-inferiority of 1 itraconazole 200-mg tablet to 2 itraconazole 100-mg capsule.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT).
Arm/Group Title Itraconazole Tablets Itraconazole Capsules Placebo Tablets
Hide Arm/Group Description:
Itraconazole 200 mg tablets. Subjects took one 200 mg tablet once per day after a full meal. The last dose was taken the day before the Week 12 visit.
Itraconazole 100 mg capsules
Tablets that were the same as the Itraconazole tables except that they did not contain the active drug (Itraconazole).
Overall Number of Participants Analyzed 593 590 198
Measure Type: Number
Unit of Measure: Percentage of participants
22.3 21.7 1.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Itraconazole Tablets, Itraconazole Capsules
Comments Comparison between the 2 itraconazole groups was based on lower bound of the 97.5% confidence interval for the difference. The non-inferiority analysis was restricted to the active dosing groups.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The non-inferiority was established if the lower limit of the one-sided, 97.5% CI in the observed difference between the proportions of subjects by study drug with Complete Cure at week 52 (itraconazole 200-mg tablets minus itraconazole 100-mg capsules) was greater than -10%. No p-value was calculated for this endpoint.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Wald's CI
Comments The statistical analysis used Wald’s CI with Yates’ continuity correction.
Method of Estimation Estimation Parameter Wald's CI
Estimated Value 0.56
Confidence Interval (1-Sided) 97.5%
-4.3
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Clinical Improvement of the Target Toenail
Hide Description

Clinical Improvement consisted of a mycological cure and an Investigator's Global Assessment (IGA) score less than or equal to 1 at week 52.

The Investigator’s Global Assessment (IGA) assesses the overall severity of onychomycosis on the target toenail and takes into consideration, onycholysis, hyperkeratosis and percent nail involvement.

0 = Clinical Cure: No evidence of onychomycosis.

1 = Clinical Improvement: Minimal evidence of onychomycosis. 2 = Mild: ≤25% dystrophy and/or onycholysis. 3 = Moderate: ≤50% dystrophy with onycholysis. 4 = Severe: >50% dystrophy with onycholysis.

Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Itraconazole Tablets Itraconazole Capsules
Hide Arm/Group Description:
Itraconazole 200mg tablets
Itraconazole 100mg capsules
Overall Number of Participants Analyzed 593 590
Measure Type: Number
Unit of Measure: percentage of participants
33.7 29.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Itraconazole Tablets, Itraconazole Capsules
Comments The test for demonstrating non-inferiority was based on a margin of 10%. Thus, non-inferiority was established if the lower limit of the one-sided, 97.5% CI in the observed difference between the proportions of subjects by study drug with Complete Cure at week 52 (itraconazole 200-mg tablets minus itraconazole 100-mg capsules) was greater than -10%. The non-inferiority analysis was restricted to the active dosing groups.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The assumption was that the Complete Cure rate at week 52 was 35% for the active dosing groups, a sample size of 552 ITT subjects per active group would have had a 93% power for testing the proportion of subjects with Complete Cure. These computations assumed a non inferiority margin of 10% and a one-sided significance level of 0.025. Power computations were performed using nQuery Advisor, Version 5.0.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Wald's CI
Comments The statistical analysis used Wald’s CI with Yates’ continuity correction.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 10
Confidence Interval (1-Sided) 97.5%
-1.1
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Clinical Improvement Compared to Placebo
Hide Description

Clinical Improvement consisted of a mycological cure and an Investigator's Global Assessment (IGA) score less than or equal to 1 at week 52.

The Investigator's Global Assessment(IGA)assesses the overall severity of onychomycosis on the target toenail and takes into consideration, onycholysis, hyperkeratosis and percent nail involvement.

0 = Clinical Cure: No evidence of onychomycosis.

1 = Clinical Improvement: Minimal evidence of onychomycosis. 2 = Mild: ≤25% dystrophy and/or onycholysis. 3 = Moderate: ≤50% dystrophy with onycholysis. 4 = Severe: >50% dystrophy with onycholysis.

Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT)
Arm/Group Title Itraconazole Tablets Placebo Tablets
Hide Arm/Group Description:
Itraconazole 200mg tablets
[Not Specified]
Overall Number of Participants Analyzed 593 198
Measure Type: Number
Unit of Measure: percentage of participants
33.7 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Itraconazole Tablets, Placebo Tablets
Comments The superiority analysis was restricted to the itraconazole 200-mg tablets and placebo tablets dosing groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments This was stratified by analysis center.
Time Frame AEs and SAES are reported for the 12 week treatment period. SAEs are reported for both the treatment & follow-up periods in the Additional Description section.
Adverse Event Reporting Description During the follow-up period, 20 subjects (10, 9, and 1 in the itraconazole 200-mg tablet, itraconazole 100-mg capsule, and placebo tablet dosing groups, respectively) reported SAEs. Because 1 subject experienced a SAE in both periods of the study, 25 individual subjects experienced SAEs during the course of the trial.
 
Arm/Group Title Itraconazole Tablets - Treatment Period Itraconazole Capsules Placebo Tablets Itraconazole Tablets - Follow-up Period Itraconazole Capsules - Follow-up Period Placebo Tablets - Follow-up Period
Hide Arm/Group Description Itraconazole 200mg tablets Adverse events that occurred during the Treatment Period are reported here. Itraconazole 100mg capsules Adverse events that occurred during the Treatment Period are reported here. Adverse events that occurred during the Treatment Period are reported here. Adverse events that occurred during the follow-up (no treatment) period are reported here. Adverse events that occurred during the follow-up (no treatment) period are reported here. Adverse events that occurred during the follow-up (no treatment) period are reported here.
All-Cause Mortality
Itraconazole Tablets - Treatment Period Itraconazole Capsules Placebo Tablets Itraconazole Tablets - Follow-up Period Itraconazole Capsules - Follow-up Period Placebo Tablets - Follow-up Period
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Itraconazole Tablets - Treatment Period Itraconazole Capsules Placebo Tablets Itraconazole Tablets - Follow-up Period Itraconazole Capsules - Follow-up Period Placebo Tablets - Follow-up Period
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/582 (0.34%)      2/581 (0.34%)      2/191 (1.05%)      10/535 (1.87%)      9/515 (1.75%)      1/168 (0.60%)    
Blood and lymphatic system disorders             
Anemia * 1  0/582 (0.00%)  0 0/581 (0.00%)  0 0/191 (0.00%)  0 0/535 (0.00%)  0 1/515 (0.19%)  1 0/168 (0.00%)  0
Cardiac disorders             
Angina Unstable * 1  0/582 (0.00%)  0 0/581 (0.00%)  0 0/191 (0.00%)  0 1/535 (0.19%)  1 0/515 (0.00%)  0 0/168 (0.00%)  0
Coronary artery disease * 1  0/582 (0.00%)  0 0/581 (0.00%)  0 0/191 (0.00%)  0 1/535 (0.19%)  1 0/515 (0.00%)  0 0/168 (0.00%)  0
Cardiac failure congestive * 1  0/582 (0.00%)  0 0/581 (0.00%)  0 0/191 (0.00%)  0 0/535 (0.00%)  0 1/515 (0.19%)  1 0/168 (0.00%)  0
Myocardial infarction * 1  0/582 (0.00%)  0 1/581 (0.17%)  1 0/191 (0.00%)  0 1/535 (0.19%)  1 0/515 (0.00%)  0 0/168 (0.00%)  0
Myocardial ischemia * 1  0/582 (0.00%)  0 0/581 (0.00%)  0 0/191 (0.00%)  0 0/535 (0.00%)  0 1/515 (0.19%)  1 0/168 (0.00%)  0
Gastrointestinal disorders             
Gastric ulcer haemorrhage * 1  0/582 (0.00%)  0 0/581 (0.00%)  0 0/191 (0.00%)  0 0/535 (0.00%)  0 1/515 (0.19%)  1 0/168 (0.00%)  0
Pancreatitis * 1  0/582 (0.00%)  0 0/581 (0.00%)  0 1/191 (0.52%)  1 0/535 (0.00%)  0 0/515 (0.00%)  0 0/168 (0.00%)  0
Hepatobiliary disorders             
Cholelithiasis * 1  1/582 (0.17%)  1 0/581 (0.00%)  0 0/191 (0.00%)  0 0/535 (0.00%)  0 1/515 (0.19%)  1 0/168 (0.00%)  0
Infections and infestations             
Appendicitis * 1  0/582 (0.00%)  0 0/581 (0.00%)  0 0/191 (0.00%)  0 1/535 (0.19%)  1 1/515 (0.19%)  1 0/168 (0.00%)  0
Diverticulitis * 1  0/582 (0.00%)  0 0/581 (0.00%)  0 1/191 (0.52%)  1 0/535 (0.00%)  0 0/515 (0.00%)  0 0/168 (0.00%)  0
Injury, poisoning and procedural complications             
Jaw Fracture * 1  0/582 (0.00%)  0 0/581 (0.00%)  0 0/191 (0.00%)  0 0/535 (0.00%)  0 1/515 (0.19%)  1 0/168 (0.00%)  0
Musculoskeletal and connective tissue disorders             
Neck Pain * 1  0/582 (0.00%)  0 1/581 (0.17%)  1 0/191 (0.00%)  0 0/535 (0.00%)  0 0/515 (0.00%)  0 0/168 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Brain cancer metastatic * 1  0/582 (0.00%)  0 0/581 (0.00%)  0 0/191 (0.00%)  0 1/535 (0.19%)  1 0/515 (0.00%)  0 0/168 (0.00%)  0
Glioblatoma multiforme * 1  0/582 (0.00%)  0 0/581 (0.00%)  0 0/191 (0.00%)  0 0/535 (0.00%)  0 1/515 (0.19%)  1 0/168 (0.00%)  0
Laryngeal cancer * 1  0/582 (0.00%)  0 0/581 (0.00%)  0 0/191 (0.00%)  0 1/535 (0.19%)  1 0/515 (0.00%)  0 0/168 (0.00%)  0
Lung neoplasm malignant * 1  0/582 (0.00%)  0 0/581 (0.00%)  0 0/191 (0.00%)  0 0/535 (0.00%)  0 0/515 (0.00%)  0 1/168 (0.60%)  1
Non-small cenll lung caner stage IV * 1  0/582 (0.00%)  0 0/581 (0.00%)  0 0/191 (0.00%)  0 1/535 (0.19%)  1 0/515 (0.00%)  0 0/168 (0.00%)  0
Prostate Cancer * 1  1/582 (0.17%)  1 0/581 (0.00%)  0 0/191 (0.00%)  0 1/535 (0.19%)  1 0/515 (0.00%)  0 0/168 (0.00%)  0
Thyroid gland cancer * 1  0/582 (0.00%)  0 0/581 (0.00%)  0 0/191 (0.00%)  0 1/535 (0.19%)  1 0/515 (0.00%)  0 0/168 (0.00%)  0
Uterine cancer * 1  0/582 (0.00%)  0 0/581 (0.00%)  0 0/191 (0.00%)  0 1/535 (0.19%)  1 0/515 (0.00%)  0 0/168 (0.00%)  0
Nervous system disorders             
Carteroid artery aneurysm * 1  0/582 (0.00%)  0 0/581 (0.00%)  0 0/191 (0.00%)  0 1/535 (0.19%)  1 0/515 (0.00%)  0 0/168 (0.00%)  0
Cerebrovascular accident * 1  0/582 (0.00%)  0 0/581 (0.00%)  0 0/191 (0.00%)  0 0/535 (0.00%)  0 1/515 (0.19%)  1 0/168 (0.00%)  0
Renal and urinary disorders             
Calculus ureteric * 1  0/582 (0.00%)  0 0/581 (0.00%)  0 0/191 (0.00%)  0 0/535 (0.00%)  0 1/515 (0.19%)  1 0/168 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Pleural effusion * 1  0/582 (0.00%)  0 0/581 (0.00%)  0 0/191 (0.00%)  0 0/535 (0.00%)  0 1/515 (0.19%)  1 0/168 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (9.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Itraconazole Tablets - Treatment Period Itraconazole Capsules Placebo Tablets Itraconazole Tablets - Follow-up Period Itraconazole Capsules - Follow-up Period Placebo Tablets - Follow-up Period
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   19/582 (3.26%)      16/581 (2.75%)      6/191 (3.14%)      19/535 (3.55%)      36/515 (6.99%)      8/168 (4.76%)    
Ear and labyrinth disorders             
Hypoacusis * 1  19/582 (3.26%)  19 16/581 (2.75%)  16 6/191 (3.14%)  6 19/535 (3.55%)  19 36/515 (6.99%)  36 8/168 (4.76%)  8
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (9.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Layout table for additonal information
Responsible Party: GlaxoSmithKline ( Stiefel, a GSK Company )
ClinicalTrials.gov Identifier: NCT00356915     History of Changes
Other Study ID Numbers: BT0300-302-INT
First Submitted: July 25, 2006
First Posted: July 27, 2006
Results First Submitted: October 1, 2010
Results First Posted: January 4, 2012
Last Update Posted: February 9, 2017