Title

Study Comparing SUBA™-Itraconazole With SPORANOX® (Itraconazole) in the Treatment of Onychomycosis
A Randomized, Double Blind, Multiple-site, Placebo-Controlled Study, Comparing the Efficacy and Safety of SUBA™-Itraconazole Capsules Compared to SPORANOX® (Itraconazole) Capsules in the Treatment of Onychomycosis of the Toenail
  • Phase

    Phase 2
  • Study Type

    Interventional
  • Intervention/Treatment

    itraconazole ...
  • Study Participants

    175
The objective of this study is to compare the relative efficacy and safety of SUBA™-Itraconazole Capsules (HalcyGen Ltd) to an already marketed oral formulation of itraconazole SPORANOX® (itraconazole) capsules (Janssen Pharma) in the treatment of onychomycosis of the toenail. Both the test and the reference formulations will also be compared to a placebo formulation to test for superiority.
Randomized, Double-Blind, Multiple-Site, Placebo-Controlled, Parallel designed study comparing a dosing regimen of 100 mg approximately 30 minutes prior to breakfast for 12 weeks of SUBA™-Itraconazole 50 mg capsules (HalcyGen Ltd) to the approved dosing regimen of 200 mg taken with breakfast of SPORANOX® (itraconazole) 100 mg capsules (Janssen Pharma). Patients will be randomly assigned in a 3:3:1 ratio to the test product 100 mg once-a-day: reference product 200 mg once-a-day: placebo once-a-day. respectively. The patients will complete 5 visits: baseline/screening (within 28 days of randomization), Day 1 (randomization), Week 6, Week 12 and Week 24.
Study Started
Nov 30
2008
Primary Completion
Jul 31
2010
Study Completion
Dec 31
2010
Results Posted
Aug 25
2020
Last Update
Aug 25
2020

Drug SUBA-itraconazole

100 mg approximately 30 minutes prior to breakfast for 12 weeks of SUBA™-Itraconazole 50 mg capsules (HalcyGen Ltd)

  • Other names: itraconazole 50 mg capsules

Drug Itraconazole

200 mg taken with breakfast of SPORANOX® (itraconazole) 100 mg capsules (Janssen Pharma).

  • Other names: Sporanox

Drug Placebo

Two placebo capsules taken approximately 30 minutes prior to breakfast

  • Other names: placebo capsules

Test Experimental

100 mg approximately 30 minutes prior to breakfast for 12 weeks of SUBA™-Itraconazole 50 mg capsules (HalcyGen Ltd)

Reference Active Comparator

200 mg taken with breakfast of SPORANOX® (itraconazole) 100 mg capsules (Janssen Pharma).

Placebo Placebo Comparator

Two placebo capsules taken approximately 30 minutes prior to breakfast

Criteria

Inclusion Criteria:

Male or non-pregnant, non lactating females 18 years of age or older.
Signed informed consent form, which meets all criteria of current FDA regulations.
If female and of child bearing potential, have a negative urine pregnancy test at the baseline and randomization visits and prepared to abstain from sexual intercourse or use a reliable method of contraception during the study (e.g., condom with spermicide, inter-uterine device, oral, injected, transdermal or implanted hormonal contraceptives).
Clinical diagnosis of onychomycosis of at least one great toenail
Clinical signs and symptoms of onychomycosis of the most severely affected great toenail of at least moderate severity as defined by at least 25% but no more than 75% of the most infected toenail and a combined severity score of at least 4 using the Nail Infection Rating Scale (see Appendix A).
At least 2mm of clear nail on the most affected toe between the proximal nail fold and the deepest extend of the onychomycosis.
Positive potassium hydroxide (KOH) stain for confirmation of fungal nail infection
Positive mycological culture for known fungal dermatophyte consistent with onychomycosis infection of at least one of the great toenails.

Exclusion Criteria:

Females who are pregnant, lactating or likely to become pregnant during the study.
Negative KOH stain
Negative mycological culture for fungal dermatophytes consistent with onychomycosis infection.
Combined score of less than 4 on the Nail Infection Rating Scale for the most severely affected great toenail.
Patient has superficial onychomycosis or significant dystrophy of the target toenail that in the Investigators opinion would impair the evaluation of onychomycosis.
Patient has total dystrophic or proximal subungual onychomycosis of the target toenail.
Presence of mycotic spikes or patient has exclusively lateral groove involvement of the target toenail.
Less than 25% or more than 75% of the most severely infected great toenail affected.
Target toenail thickness is greater than 3mm.
No new nail growth in the target nail over the previous 6 months.
Onychomycosis not caused by a dermatophyte (e.g. mold infection, Candida spp or bacterial infection).
Previous treatment for onychomycosis of the toenail within the last 12 months that was unresponsive to treatment.
Previous treatment within the previous 2 months with any systemic antifungal therapy or within the previous 2 weeks with any topical antifungal therapy.
Significant history or current evidence of chronic infectious disease, system disorder, organ disorder or other medical condition that in the Investigator's opinion would place the study patient at undue risk by participation or could jeopardize the integrity of the study evaluations.
Immunocompromised either because of concomitant disease (e.g. HIV), or ongoing treatment (e.g. chemotherapy).
Current or history of psoriasis within the previous 12 months.
Evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF.
History of diabetes.
Previous hypersensitivity to imidazole or azole compounds.
Liver Function Test results at screening more than twice the upper limit of normal range or other hematology or clinical chemistry test results that would contraindicate dosing with itraconazole.
Use within the previous 3 months or anticipated use during the study of any drugs that are known to affect the bioavailability of oral itraconazole or are otherwise contraindicated to be taken with itraconazole as detailed in the product labeling for SPORANOX® (Appendix B).
Receipt of any drug as part of a research study within 30 days prior to dosing.
Previous dosing in this study.

Summary

Placebo

Test

Reference

All Events

Event Type Organ System Event Term Placebo Test Reference

Non-inferiority Will be Determined by Evaluating the Difference Between the Proportion of Patients in the Test and Reference Treatment Groups Who Are Considered a "Therapeutic Cure" at the End of Study Visit (Week 24)

If the lower bound 95% confidence interval of the difference between the proportion of patients in the Test group compared to the Reference group considered a Therapeutic Cure at Visit 7 was greater than 20 then non-inferiority was considered to have been demonstrated

Placebo

Test

Reference

Non-inferiority Will be Determined by Evaluating the Difference Between the Proportion of Patients in the Test and Reference Treatment Groups Who Are Considered a "Clinical Cure" at the End of Study Visit (Week 24)

If the lower bound 95% confidence interval of the difference between the proportion of patients in the Test group compared to the Reference group considered a Clinical Cure at Visit 7 was greater than 20 then non-inferiority was considered to have been demonstrated

Placebo

Test

Reference

Non-inferiority Will be Determined by Evaluating the Difference Between the Proportion of Patients in the Test and Reference Treatment Groups Who Are Considered a "Mycological Cure" at the End of Study Visit (Week 24)

If the lower bound 95% confidence interval of the difference between the proportion of patients in the Test group compared to the Reference group considered a Mycological Cure at Visit 7 was greater than 20 then non-inferiority was considered to have been demonstrated

Placebo

Test

Reference

The Proportion of Patients in Each Treatment Group Who Are Considered a "Therapeutic Cure" at the End of Treatment Visit (Week 12) 12).

If the lower bound 95% confidence interval of the difference between the proportion of patients in the test group compared to the reference group considered a cure at the visit being analyzed was greater than -20 then non-inferiority was considered to have been demonstrated

Placebo

Test

Reference

Non-inferiority Will be Determined by Evaluating the Difference Between the Proportion of Patients in the Test and Reference Treatment Groups Who Are Considered a "Clinical Cure" at the End of Study Visit (Week 12)

If the lower bound 95% confidence interval of the difference between the proportion of patients in the test group compared to the reference group considered a cure at the visit being analyzed was greater than -20 then non-inferiority was considered to have been demonstrated

Placebo

Test

Reference

Non-inferiority Will be Determined by Evaluating the Difference Between the Proportion of Patients in the Test and Reference Treatment Groups Who Are Considered a "Mycological Cure" at the End of Study Visit (Week 12)

If the lower bound 95% confidence interval of the difference between the proportion of patients in the test group compared to the reference group considered a cure at the visit being analyzed was greater than -20 then non-inferiority was considered to have been demonstrated

Placebo

Test

Reference

Superiority of Test Treatment Over Placebo for Mycological Cure

All primary and secondary endpoints were tested for superiority against Placebo. The intent to treat (ITT) was used for all superiority testing. For the three primary endpoints and all four dichotomous secondary endpoints, if the difference between the proportion of patients considered a cure in the Test or Reference group was statistically greater (p < 0.05) than the proportion of patients considered a cure in the Placebo group, then superiority of that treatment over placebo was considered to have been demonstrated. A one-sided continuity corrected Z-test was used for superiority testing.

Placebo

Test

Reference

Total

175
Participants

Age, Continuous

48.78
years of age (Mean)
Full Range: 21.0 to 78.0

Infecting organism - T.rubrum

165
participants

Percentage of toe infected

58.27
percentage (Mean)
Standard Deviation: 15.56

Presence of infecting organism - T.mentagrophytes

9
participants

Race (NIH/OMB)

Region of Enrollment

Sex: Female, Male

Overall Study

Placebo

Test

Reference