Onychomycosis
Conditions
Keywords
Toenail fungus, Onychomycosis, Nail fungus, Toenail fungal infection, Tinea unguium, Dermatophytes, Foot dermatoses
Brief summary
This study is designed to assess the efficacy, safety and tolerability of a topical formulation of terbinafine solution applied daily in patients with toenail fungus. This trial will study patients with mild to moderate toenail fungus disease of the big toenail and their responses to two treatment durations, 24 or 48 weeks.
Interventions
DRUGterbinafine
Terbinafine hydrochloride (HCl) 10 % nail solution for onychomycosis (NSO) once daily for 48 weeks
DRUGPlacebo
Vehicle (placebo) once daily for 48 weeks
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male and females 12 - 75 years of age * Fungal toenail infection of one or both of the large (great) toenails * The nail infection must be due to a dermatophyte, (mixed infections dermatophyte and non-dermatophyte\] are not allowed)
Exclusion criteria
* Target foot must not have severe plantar (moccasin) tinea pedis that would require systemic therapy. Mild to moderate tinea pedis (athlete's foot) infection should be treated with terbinafine prior to baseline or at any time during the trial. Other topical treatments for athlete's foot may be recommended at the discretion of the investigator. * Subjects must not have abnormalities of the nail that could prevent a normal appearing nail if clearing of infection is achieved * No administration of systemic antifungal medications within 6 months prior to screening visit * No application of prescription topical antifungal medications for toenail fungus within 3 months or other commercially available topical medications for toenail fungus applied directly to the toenails within 1 month prior to screening visit * No professional pedicures or application of any nail polish product or nail cosmetic to the toenails after the screening visit * Known pregnancy or lactation at time of enrollment Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy Assessed by the Percentage of Participants With Complete Cure at the End of Study (Week 52) After Treating for 24 or 48 Weeks | 52 weeks | Complete cure is defined as negative KOH microscopy and negative culture for dermatophytes and no residual involvement of the target toenail. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy Assessed by the Percentage of Participants With Mycological Cure at the End of Study After Treating Participants for 24 or 48 Weeks | 52 weeks | Mycological cure is defined as negative KOH microscopy and negative culture for dermatophytes. |
| Efficacy Assessed by the Percentage of Participants With Clinical Effectiveness at the End of Study After Treating Participants for 24 or 48 Weeks | 52 weeks | Clinical effectiveness is defined as negative KOH microscopy and negative culture for dermatophytes and \<= 10% residual involvement of the target toenail. Clinical effectiveness was a composite binary variable defined as Yes if: * If mycological cure (negative KOH and negative culture for dermatophytes) and * = 10% residual involvement of the target toenail No if otherwise |
| Safety and Tolerability Assessed by the Number of Participants With Adverse Events | 52 weeks | Safety and tolerability data as assessed by the number of participants with Adverse Events (AE), Serious Adverse Events, Drug discontinuation due to an AE and death. Additional details can be found in the Adverse Event Section. |
Countries
France, Germany, United States
Participant flow
Recruitment details
This randomized, double -blind, vehicle -controlled, multicenter, parallel group study was designed to assess the efficacy, safety and tolerability of a topical formulation of terbinafine hydrogen chloride 10% topical solution (TTS10%) applied daily in patients with toenail onychomycosis. Started 07 DEC 2006 and ending 27 JUN 2008.
Participants by arm
| Arm | Count |
|---|---|
| Terbinafine 24 Weeks Terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) for 24 weeks | 133 |
| Vehicle 24 Weeks Vehicle (placebo) for 24 weeks | 130 |
| Terbinafine 48 Weeks Terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) for 48 weeks | 135 |
| Vehicle 48 Weeks Vehicle (placebo) for 48 weeks | 128 |
| Total | 526 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Administrative problems | 0 | 0 | 0 | 1 |
| Overall Study | Adverse Event | 1 | 1 | 0 | 0 |
| Overall Study | Death | 0 | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 3 | 2 | 1 | 1 |
| Overall Study | Lost to Follow-up | 9 | 8 | 6 | 5 |
| Overall Study | Protocol Violation | 2 | 1 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 7 | 8 | 9 |
Baseline characteristics
| Characteristic | Terbinafine 24 Weeks | Vehicle 24 Weeks | Terbinafine 48 Weeks | Vehicle 48 Weeks | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 40 Participants | 27 Participants | 40 Participants | 30 Participants | 137 Participants |
| Age, Categorical Between 18 and 65 years | 93 Participants | 103 Participants | 95 Participants | 97 Participants | 388 Participants |
| Sex: Female, Male Female | 34 Participants | 39 Participants | 41 Participants | 35 Participants | 149 Participants |
| Sex: Female, Male Male | 99 Participants | 91 Participants | 94 Participants | 93 Participants | 377 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 37 / 131 | 38 / 129 | 54 / 134 | 52 / 126 |
| serious Total, serious adverse events | 8 / 131 | 3 / 129 | 9 / 134 | 7 / 126 |
Outcome results
Primary
Efficacy Assessed by the Percentage of Participants With Complete Cure at the End of Study (Week 52) After Treating for 24 or 48 Weeks
Complete cure is defined as negative KOH microscopy and negative culture for dermatophytes and no residual involvement of the target toenail.
Time frame: 52 weeks
Population: Intent to treat (ITT) population, Last observation carried forward (LOCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Terbinafine 24 Weeks | Efficacy Assessed by the Percentage of Participants With Complete Cure at the End of Study (Week 52) After Treating for 24 or 48 Weeks | 1.50 Percentage of participants |
| Vehicle 24 Weeks | Efficacy Assessed by the Percentage of Participants With Complete Cure at the End of Study (Week 52) After Treating for 24 or 48 Weeks | 0.77 Percentage of participants |
| Terbinafine 48 Weeks | Efficacy Assessed by the Percentage of Participants With Complete Cure at the End of Study (Week 52) After Treating for 24 or 48 Weeks | 2.96 Percentage of participants |
| Vehicle 48 Weeks | Efficacy Assessed by the Percentage of Participants With Complete Cure at the End of Study (Week 52) After Treating for 24 or 48 Weeks | 0 Percentage of participants |
Secondary
Efficacy Assessed by the Percentage of Participants With Clinical Effectiveness at the End of Study After Treating Participants for 24 or 48 Weeks
Clinical effectiveness is defined as negative KOH microscopy and negative culture for dermatophytes and \<= 10% residual involvement of the target toenail. Clinical effectiveness was a composite binary variable defined as Yes if: * If mycological cure (negative KOH and negative culture for dermatophytes) and * = 10% residual involvement of the target toenail No if otherwise
Time frame: 52 weeks
Population: Intent to treat (ITT) population, Last observation carried forward (LOCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Terbinafine 24 Weeks | Efficacy Assessed by the Percentage of Participants With Clinical Effectiveness at the End of Study After Treating Participants for 24 or 48 Weeks | 3.01 Percentage of participants |
| Vehicle 24 Weeks | Efficacy Assessed by the Percentage of Participants With Clinical Effectiveness at the End of Study After Treating Participants for 24 or 48 Weeks | 0.77 Percentage of participants |
| Terbinafine 48 Weeks | Efficacy Assessed by the Percentage of Participants With Clinical Effectiveness at the End of Study After Treating Participants for 24 or 48 Weeks | 5.93 Percentage of participants |
| Vehicle 48 Weeks | Efficacy Assessed by the Percentage of Participants With Clinical Effectiveness at the End of Study After Treating Participants for 24 or 48 Weeks | 0.78 Percentage of participants |
Secondary
Efficacy Assessed by the Percentage of Participants With Mycological Cure at the End of Study After Treating Participants for 24 or 48 Weeks
Mycological cure is defined as negative KOH microscopy and negative culture for dermatophytes.
Time frame: 52 weeks
Population: Intent to treat (ITT) population, Last observation carried forward (LOCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Terbinafine 24 Weeks | Efficacy Assessed by the Percentage of Participants With Mycological Cure at the End of Study After Treating Participants for 24 or 48 Weeks | 15.04 Percentage of participants |
| Vehicle 24 Weeks | Efficacy Assessed by the Percentage of Participants With Mycological Cure at the End of Study After Treating Participants for 24 or 48 Weeks | 6.15 Percentage of participants |
| Terbinafine 48 Weeks | Efficacy Assessed by the Percentage of Participants With Mycological Cure at the End of Study After Treating Participants for 24 or 48 Weeks | 22.22 Percentage of participants |
| Vehicle 48 Weeks | Efficacy Assessed by the Percentage of Participants With Mycological Cure at the End of Study After Treating Participants for 24 or 48 Weeks | 7.81 Percentage of participants |
Secondary
Safety and Tolerability Assessed by the Number of Participants With Adverse Events
Safety and tolerability data as assessed by the number of participants with Adverse Events (AE), Serious Adverse Events, Drug discontinuation due to an AE and death. Additional details can be found in the Adverse Event Section.
Time frame: 52 weeks
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Terbinafine 24 Weeks | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | At least 1 AE | 80 Number of participants |
| Terbinafine 24 Weeks | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | Death | 0 Number of participants |
| Terbinafine 24 Weeks | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | At least 1 SAE | 8 Number of participants |
| Terbinafine 24 Weeks | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | Study drug discontinued due to an AE | 0 Number of participants |
| Vehicle 24 Weeks | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | At least 1 SAE | 3 Number of participants |
| Vehicle 24 Weeks | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | At least 1 AE | 72 Number of participants |
| Vehicle 24 Weeks | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | Study drug discontinued due to an AE | 1 Number of participants |
| Vehicle 24 Weeks | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | Death | 0 Number of participants |
| Terbinafine 48 Weeks | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | At least 1 SAE | 9 Number of participants |
| Terbinafine 48 Weeks | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | At least 1 AE | 94 Number of participants |
| Terbinafine 48 Weeks | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | Study drug discontinued due to an AE | 1 Number of participants |
| Terbinafine 48 Weeks | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | Death | 1 Number of participants |
| Vehicle 48 Weeks | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | At least 1 SAE | 7 Number of participants |
| Vehicle 48 Weeks | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | At least 1 AE | 87 Number of participants |
| Vehicle 48 Weeks | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | Death | 0 Number of participants |
| Vehicle 48 Weeks | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | Study drug discontinued due to an AE | 0 Number of participants |