Onychomycosis
Conditions
Keywords
Toenail fungus, Onychomycosis, Nail fungus, Toenail fungal infection, Tinea unguium, Dermatophytes, Foot dermatoses
Brief summary
This study will evaluate the efficacy, safety and tolerability of topical 10% terbinafine hydrogen chloride applied daily versus 5% amorolfine nail lacquer applied twice a week in patients with mild to moderate toenail onychomycosis, for a total treatment duration of 48 weeks.
Interventions
DRUGterbinafine hydrogen chloride
10 % terbinafine hydrogen chloride (HCL)
DRUGamorolfine nail lacquer
5 % amorolfine nail lacquer
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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) * The target toenail area must have at least 25% to no more than 75% disease involvement without spikes.
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 * Patients with the target toenail involving the matrix (lunula) or having less than 2mm clear (unaffected) nail plate length beyond the proximal fold. * Presence of dermatophytoma (defined as thick masses of fungal hyphae and necrotic keratin between the nail plate and nail bed) on the target nail. * 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 |
|---|---|---|
| Percentage of Participants With Complete Cure at the End of Study After Treating Participants for 48 Weeks | Week 52 | Complete cure is defined as negative potassium hydroxide (KOH) microscopy and negative culture for dermatophytes and no residual involvement of the target toenail. |
| Percentage of Participants With Complete Cure at the End of Study After Treating Participants for 48 Weeks. | Week 52 | Complete cure is defined as negative potassium hydroxide (KOH) microscopy and negative culture for dermatophytes and no residual involvement of the target toenail. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinical Effectiveness at the End of Study After Treating Patients for 48 Weeks. | Week 52 | Clinical effectiveness is defined as negative KOH microscopy and negative culture for dermatophytes and \<= 10% residual involvement of the target toenail. |
| Percentage of Participants With Mycological Cure at End of Study After Treating Patients for 48 Weeks | Week 52 | Mycological cure is defined as negative KOH microscopy and negative culture for dermatophytes |
| Safety and Tolerability Assessed by the Number of Participants With Adverse Events | Week 52 | Safety and tolerability data as assessed by the number of participants with Adverse Events (AE), Serious Adverse Events, Drug discontinuation due to an AE or SAE and death. Additional details can be found in the Adverse Event Section. |
Countries
Finland, France, Germany, Hungary, Iceland, Norway, Poland, Russia, Spain, Turkey (Türkiye)
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Terbinafine 10% terbinafine hydrogen chloride (72.6 mg/ml nail lacquer). Patients applied one layer of the study medication once daily for 48 weeks, preferably at bedtime, to all affected toenails and allowed to dry. | 507 |
| Amorolfine 5% amorolfine nail lacquer. Patients applied study medication twice weekly for 48 weeks to all affected toenails. | 522 |
| Total | 1,029 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative problems | 3 | 0 |
| Overall Study | Adverse Event | 1 | 6 |
| Overall Study | Lack of Efficacy | 10 | 11 |
| Overall Study | Lost to Follow-up | 27 | 30 |
| Overall Study | Missing | 1 | 0 |
| Overall Study | Protocol Violation | 4 | 3 |
| Overall Study | Withdrawal by Subject | 20 | 26 |
Baseline characteristics
| Characteristic | Terbinafine | Amorolfine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 82 Participants | 111 Participants | 193 Participants |
| Age, Categorical Between 18 and 65 years | 425 Participants | 410 Participants | 835 Participants |
| Sex: Female, Male Female | 158 Participants | 150 Participants | 308 Participants |
| Sex: Female, Male Male | 349 Participants | 372 Participants | 721 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 186 / 493 | 168 / 512 |
| serious Total, serious adverse events | 9 / 493 | 18 / 512 |
Outcome results
Primary
Percentage of Participants With Complete Cure at the End of Study After Treating Participants for 48 Weeks
Complete cure is defined as negative potassium hydroxide (KOH) microscopy and negative culture for dermatophytes and no residual involvement of the target toenail.
Time frame: Week 52
Population: The Intent-to-treat population (ITT) population consisted of all patients who were randomized and dispensed study drug. Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Terbinafine | Percentage of Participants With Complete Cure at the End of Study After Treating Participants for 48 Weeks | 1.18 Percentage of participants |
| Amorolfine | Percentage of Participants With Complete Cure at the End of Study After Treating Participants for 48 Weeks | 0.96 Percentage of participants |
Primary
Percentage of Participants With Complete Cure at the End of Study After Treating Participants for 48 Weeks.
Complete cure is defined as negative potassium hydroxide (KOH) microscopy and negative culture for dermatophytes and no residual involvement of the target toenail.
Time frame: Week 52
Population: The Per-protocol population (PP) consisted of ITT patients who completed the study without protocol deviations that led to exclusion according to criteria defined before database lock The per-protocol population was used to provide confirmation of efficacy findings from the ITT population. Last Observation Carried Forward (LOCF).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Terbinafine | Percentage of Participants With Complete Cure at the End of Study After Treating Participants for 48 Weeks. | 1.15 Percentage of participants |
| Amorolfine | Percentage of Participants With Complete Cure at the End of Study After Treating Participants for 48 Weeks. | 0.38 Percentage of participants |
Secondary
Percentage of Participants With Clinical Effectiveness at the End of Study After Treating Patients for 48 Weeks.
Clinical effectiveness is defined as negative KOH microscopy and negative culture for dermatophytes and \<= 10% residual involvement of the target toenail.
Time frame: Week 52
Population: Intent-to-treat population, Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Terbinafine | Percentage of Participants With Clinical Effectiveness at the End of Study After Treating Patients for 48 Weeks. | 4.54 Percentage of participants |
| Amorolfine | Percentage of Participants With Clinical Effectiveness at the End of Study After Treating Patients for 48 Weeks. | 3.83 Percentage of participants |
Secondary
Percentage of Participants With Mycological Cure at End of Study After Treating Patients for 48 Weeks
Mycological cure is defined as negative KOH microscopy and negative culture for dermatophytes
Time frame: Week 52
Population: Intent-to-treat population, Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Terbinafine | Percentage of Participants With Mycological Cure at End of Study After Treating Patients for 48 Weeks | 16.17 Percentage of participants |
| Amorolfine | Percentage of Participants With Mycological Cure at End of Study After Treating Patients for 48 Weeks | 15.71 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 or SAE and death. Additional details can be found in the Adverse Event Section.
Time frame: Week 52
Population: The Safety population consisted of all patients that received at least one dose of study drug and had at least one post-baseline safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Terbinafine | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | At least 1 AE | 285 Participants |
| Terbinafine | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | AE suspected related to study drug | 11 Participants |
| Terbinafine | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | At least 1 SAE | 9 Participants |
| Terbinafine | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | SAE suspected related to study drug | 0 Participants |
| Terbinafine | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | Death | 0 Participants |
| Terbinafine | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | Drug discontinuation due to an AE | 1 Participants |
| Amorolfine | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | Death | 0 Participants |
| Amorolfine | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | At least 1 AE | 291 Participants |
| Amorolfine | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | SAE suspected related to study drug | 0 Participants |
| Amorolfine | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | AE suspected related to study drug | 7 Participants |
| Amorolfine | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | Drug discontinuation due to an AE | 5 Participants |
| Amorolfine | Safety and Tolerability Assessed by the Number of Participants With Adverse Events | At least 1 SAE | 18 Participants |