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
Active terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) once daily for 48 weeks
DRUGPlacebo
vehicle (placebo) applied 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 terbinifine 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 Complete Cure Rate 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. The complete cure was a composite binary variable defined as Yes if: * Mycological cure (negative KOH and negative culture for dermatophytes) and * No residual involvement of the target toenail No if otherwise |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy Assessed by Mycological Cure (Negative Culture and Negative KOH Microscopy) at the End of Study After Treating Patients for 24 or 48 Weeks. | 52 weeks | Mycological cure is defined as negative KOH microscopy and negative culture for dermatophytes. Mycological cure was a composite binary variable defined as Yesif : * Negative microscopy and * Negative culture for dermatophytes No if otherwise. |
| Efficacy Assessed by Clinical Efficacy at the End of Study After Treating Patients 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 * Mycological cure (negative KOH and negative culture for dermatophytes) and * = 10% residual involvement of the target toenail No if otherwise |
| Number of Participants Assessed With Adverse Events and Serious Adverse Events | 52 weeks | An adverse event (AE) is any adverse change in health or side effect that occurs while the participant is receiving the treatment or within a previously specified period of time after the treatment has been completed. A Serious Adverse Event (SAE) is any untoward medical occurrence that results in death, is life-threatening requires, inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage. |
Countries
Canada, Iceland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Terbinafine 24 w Active terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) applied once daily for 24 weeks | 126 |
| Vehicle 24 w vehicle (placebo) applied once daily for 24 weeks | 128 |
| Terbinafine 48 w Active terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) applied once daily for 48 weeks | 136 |
| Vehicle 48 w vehicle (placebo) applied once daily for 48 weeks | 128 |
| Total | 518 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 1 |
| Overall Study | Death | 0 | 1 | 0 | 0 |
| Overall Study | Lack of Efficacy | 2 | 3 | 3 | 1 |
| Overall Study | Lost to Follow-up | 10 | 10 | 14 | 10 |
| Overall Study | Protocol Violation | 1 | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 11 | 10 | 10 | 6 |
Baseline characteristics
| Characteristic | Terbinafine 24 w | Vehicle 24 w | Terbinafine 48 w | Vehicle 48 w | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 19 Participants | 27 Participants | 20 Participants | 28 Participants | 94 Participants |
| Age, Categorical Between 18 and 65 years | 107 Participants | 101 Participants | 116 Participants | 100 Participants | 424 Participants |
| Sex: Female, Male Female | 25 Participants | 29 Participants | 26 Participants | 27 Participants | 107 Participants |
| Sex: Female, Male Male | 101 Participants | 99 Participants | 110 Participants | 101 Participants | 411 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 | 35 / 126 | 38 / 124 | 47 / 135 | 56 / 128 |
| serious Total, serious adverse events | 2 / 126 | 7 / 124 | 7 / 135 | 4 / 128 |
Outcome results
Primary
Efficacy Assessed by Complete Cure Rate 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. The complete cure was a composite binary variable defined as Yes if: * Mycological cure (negative KOH and negative culture for dermatophytes) and * No residual involvement of the target toenail No if otherwise
Time frame: 52 weeks
Population: All participants were included in the intention to treat (ITT) population, defined as all participants who were randomized and received study drug. The Last Observation was Carried Forward (LOCF).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Terbinafine 24 w | Efficacy Assessed by Complete Cure Rate at the End of Study (Week 52) After Treating for 24 or 48 Weeks. | 0.79 Percentage of Participants |
| Vehicle 24 w | Efficacy Assessed by Complete Cure Rate at the End of Study (Week 52) After Treating for 24 or 48 Weeks. | 0.78 Percentage of Participants |
| Terbinafine 48 w | Efficacy Assessed by Complete Cure Rate at the End of Study (Week 52) After Treating for 24 or 48 Weeks. | 1.47 Percentage of Participants |
| Vehicle 48 w | Efficacy Assessed by Complete Cure Rate at the End of Study (Week 52) After Treating for 24 or 48 Weeks. | 0.00 Percentage of Participants |
Secondary
Efficacy Assessed by Clinical Efficacy at the End of Study After Treating Patients 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 * 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: All participants were included in the intention to treat (ITT) population, defined as all participants who were randomized and received study drug. The Last Observation was Carried Forward (LOCF).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Terbinafine 24 w | Efficacy Assessed by Clinical Efficacy at the End of Study After Treating Patients for 24 or 48 Weeks. | 1.59 Percentage of Participants |
| Vehicle 24 w | Efficacy Assessed by Clinical Efficacy at the End of Study After Treating Patients for 24 or 48 Weeks. | 2.34 Percentage of Participants |
| Terbinafine 48 w | Efficacy Assessed by Clinical Efficacy at the End of Study After Treating Patients for 24 or 48 Weeks. | 3.68 Percentage of Participants |
| Vehicle 48 w | Efficacy Assessed by Clinical Efficacy at the End of Study After Treating Patients for 24 or 48 Weeks. | 1.56 Percentage of Participants |
Secondary
Efficacy Assessed by Mycological Cure (Negative Culture and Negative KOH Microscopy) at the End of Study After Treating Patients for 24 or 48 Weeks.
Mycological cure is defined as negative KOH microscopy and negative culture for dermatophytes. Mycological cure was a composite binary variable defined as Yesif : * Negative microscopy and * Negative culture for dermatophytes No if otherwise.
Time frame: 52 weeks
Population: All participants were included in the intention to treat (ITT) population, defined as all participants who were randomized and received study drug. The Last Observation was Carried Forward (LOCF).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Terbinafine 24 w | Efficacy Assessed by Mycological Cure (Negative Culture and Negative KOH Microscopy) at the End of Study After Treating Patients for 24 or 48 Weeks. | 10.32 Percentage of Participants |
| Vehicle 24 w | Efficacy Assessed by Mycological Cure (Negative Culture and Negative KOH Microscopy) at the End of Study After Treating Patients for 24 or 48 Weeks. | 6.25 Percentage of Participants |
| Terbinafine 48 w | Efficacy Assessed by Mycological Cure (Negative Culture and Negative KOH Microscopy) at the End of Study After Treating Patients for 24 or 48 Weeks. | 15.44 Percentage of Participants |
| Vehicle 48 w | Efficacy Assessed by Mycological Cure (Negative Culture and Negative KOH Microscopy) at the End of Study After Treating Patients for 24 or 48 Weeks. | 3.13 Percentage of Participants |
Secondary
Number of Participants Assessed With Adverse Events and Serious Adverse Events
An adverse event (AE) is any adverse change in health or side effect that occurs while the participant is receiving the treatment or within a previously specified period of time after the treatment has been completed. A Serious Adverse Event (SAE) is any untoward medical occurrence that results in death, is life-threatening requires, inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage.
Time frame: 52 weeks
Population: Safety Population was defined as all participants who received at least one dose of study drug and had at least one post-baseline safety assessment. All except 4 participants who were randomized to the vehicle 24 w group and one participant randomized to the terbinafine 48 w group, were included in the safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Terbinafine 24 w | Number of Participants Assessed With Adverse Events and Serious Adverse Events | 126 Participants |
| Vehicle 24 w | Number of Participants Assessed With Adverse Events and Serious Adverse Events | 124 Participants |
| Terbinafine 48 w | Number of Participants Assessed With Adverse Events and Serious Adverse Events | 135 Participants |
| Vehicle 48 w | Number of Participants Assessed With Adverse Events and Serious Adverse Events | 128 Participants |