Trial Outcomes & Findings for Efficacy Safety, and Tolerability of Topical Terbinafine in Patients With Mild to Moderate Toenail Fungus of the Big Toenail (NCT NCT00443820)

Last Updated: 2011-04-19

Results Overview

Complete cure is defined as negative KOH microscopy and negative culture for dermatophytes and no residual involvement of the target toenail.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

526 participants

Primary outcome timeframe

52 weeks

Results posted on

2011-04-19

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Terbinafine 24 Weeks Terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) for 24 weeks	Vehicle 24 Weeks Vehicle (placebo) for 24 weeks	Terbinafine 48 Weeks Terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) for 48 weeks	Vehicle 48 Weeks Vehicle (placebo) for 48 weeks
Overall Study STARTED	133	130	135	128
Overall Study Safety Population	131	129	134	126
Overall Study COMPLETED	112	111	117	111
Overall Study NOT COMPLETED	21	19	18	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Terbinafine 24 Weeks Terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) for 24 weeks	Vehicle 24 Weeks Vehicle (placebo) for 24 weeks	Terbinafine 48 Weeks Terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) for 48 weeks	Vehicle 48 Weeks Vehicle (placebo) for 48 weeks
Overall Study Adverse Event	1	1	0	0
Overall Study Lack of Efficacy	3	2	1	1
Overall Study Protocol Violation	2	1	2	1
Overall Study Withdrawal by Subject	6	7	8	9
Overall Study Lost to Follow-up	9	8	6	5
Overall Study Administrative problems	0	0	0	1
Overall Study Death	0	0	1	0

Baseline Characteristics

Efficacy Safety, and Tolerability of Topical Terbinafine in Patients With Mild to Moderate Toenail Fungus of the Big Toenail

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Terbinafine 24 Weeks n=133 Participants Terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) for 24 weeks	Vehicle 24 Weeks n=130 Participants Vehicle (placebo) for 24 weeks	Terbinafine 48 Weeks n=135 Participants Terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) for 48 weeks	Vehicle 48 Weeks n=128 Participants Vehicle (placebo) for 48 weeks	Total n=526 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants	1 Participants n=31 Participants
Age, Categorical Between 18 and 65 years	93 Participants n=99 Participants	103 Participants n=107 Participants	95 Participants n=206 Participants	97 Participants n=7 Participants	388 Participants n=31 Participants
Age, Categorical >=65 years	40 Participants n=99 Participants	27 Participants n=107 Participants	40 Participants n=206 Participants	30 Participants n=7 Participants	137 Participants n=31 Participants
Sex: Female, Male Female	34 Participants n=99 Participants	39 Participants n=107 Participants	41 Participants n=206 Participants	35 Participants n=7 Participants	149 Participants n=31 Participants
Sex: Female, Male Male	99 Participants n=99 Participants	91 Participants n=107 Participants	94 Participants n=206 Participants	93 Participants n=7 Participants	377 Participants n=31 Participants

PRIMARY outcome

Timeframe: 52 weeks

Population: Intent to treat (ITT) population, Last observation carried forward (LOCF)

Complete cure is defined as negative KOH microscopy and negative culture for dermatophytes and no residual involvement of the target toenail.

Outcome measures

Outcome measures
Measure	Terbinafine 24 Weeks n=133 Participants Terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) for 24 weeks	Vehicle 24 Weeks n=130 Participants Vehicle (placebo) for 24 weeks	Terbinafine 48 Weeks n=135 Participants Terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) for 48 weeks	Vehicle 48 Weeks n=128 Participants Vehicle (placebo) for 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	1.50 Percentage of participants Interval -1.82 to 3.29	0.77 Percentage of participants Interval -1.82 to 3.29	2.96 Percentage of participants Interval 0.1 to 5.82	0 Percentage of participants Interval 0.1 to 5.82

SECONDARY outcome

Timeframe: 52 weeks

Population: Intent to treat (ITT) population, Last observation carried forward (LOCF)

Mycological cure is defined as negative KOH microscopy and negative culture for dermatophytes.

Outcome measures

Outcome measures
Measure	Terbinafine 24 Weeks n=133 Participants Terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) for 24 weeks	Vehicle 24 Weeks n=130 Participants Vehicle (placebo) for 24 weeks	Terbinafine 48 Weeks n=135 Participants Terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) for 48 weeks	Vehicle 48 Weeks n=128 Participants Vehicle (placebo) for 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	15.04 Percentage of participants Interval 1.54 to 16.23	6.15 Percentage of participants Interval 1.54 to 16.23	22.22 Percentage of participants Interval 6.0 to 22.82	7.81 Percentage of participants Interval 6.0 to 22.82

SECONDARY outcome

Timeframe: 52 weeks

Population: Intent to treat (ITT) population, Last observation carried forward (LOCF)

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

Outcome measures

Outcome measures
Measure	Terbinafine 24 Weeks n=133 Participants Terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) for 24 weeks	Vehicle 24 Weeks n=130 Participants Vehicle (placebo) for 24 weeks	Terbinafine 48 Weeks n=135 Participants Terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) for 48 weeks	Vehicle 48 Weeks n=128 Participants Vehicle (placebo) for 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	3.01 Percentage of participants	0.77 Percentage of participants	5.93 Percentage of participants	0.78 Percentage of participants

SECONDARY outcome

Timeframe: 52 weeks

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	Terbinafine 24 Weeks n=131 Participants Terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) for 24 weeks	Vehicle 24 Weeks n=129 Participants Vehicle (placebo) for 24 weeks	Terbinafine 48 Weeks n=134 Participants Terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) for 48 weeks	Vehicle 48 Weeks n=126 Participants Vehicle (placebo) for 48 weeks
Safety and Tolerability Assessed by the Number of Participants With Adverse Events At least 1 AE	80 Number of participants	72 Number of participants	94 Number of participants	87 Number of participants
Safety and Tolerability Assessed by the Number of Participants With Adverse Events At least 1 SAE	8 Number of participants	3 Number of participants	9 Number of participants	7 Number of participants
Safety and Tolerability Assessed by the Number of Participants With Adverse Events Study drug discontinued due to an AE	0 Number of participants	1 Number of participants	1 Number of participants	0 Number of participants
Safety and Tolerability Assessed by the Number of Participants With Adverse Events Death	0 Number of participants	0 Number of participants	1 Number of participants	0 Number of participants

Adverse Events

Terbinafine 24 Weeks

Serious events: 8 serious events

Other events: 37 other events

Deaths: 0 deaths

Vehicle 24 Weeks

Serious events: 3 serious events

Other events: 38 other events

Deaths: 0 deaths

Terbinafine 48 Weeks

Serious events: 9 serious events

Other events: 54 other events

Deaths: 0 deaths

Vehicle 48 Weeks

Serious events: 7 serious events

Other events: 52 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Terbinafine 24 Weeks n=131 participants at risk Terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) for 24 weeks	Vehicle 24 Weeks n=129 participants at risk Vehicle (placebo) for 24 weeks	Terbinafine 48 Weeks n=134 participants at risk Terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) for 48 weeks	Vehicle 48 Weeks n=126 participants at risk Vehicle (placebo) for 48 weeks
Infections and infestations Influenza	1.5% 2/131 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.	0.78% 1/129 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.	9.7% 13/134 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.	7.9% 10/126 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.
Infections and infestations Nasopharyngitis	9.9% 13/131 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.	8.5% 11/129 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.	11.2% 15/134 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.	11.9% 15/126 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.
Infections and infestations Sinusitis	2.3% 3/131 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.	0.00% 0/129 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.	3.0% 4/134 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.	5.6% 7/126 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.
Infections and infestations Upper respiratory tract infection	3.1% 4/131 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.	3.1% 4/129 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.	3.0% 4/134 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.	7.9% 10/126 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.
Musculoskeletal and connective tissue disorders Back pain	6.1% 8/131 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.	5.4% 7/129 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.	4.5% 6/134 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.	9.5% 12/126 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.
Nervous system disorders Headache	16.0% 21/131 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.	16.3% 21/129 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.	20.9% 28/134 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.	18.3% 23/126 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.
Vascular disorders Hypertension	0.76% 1/131 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.	2.3% 3/129 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.	6.0% 8/134 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.	3.2% 4/126 • 52 weeks Safety population consisting of all participants who had at least one dose of study drug and had at least one post-baseline safety assessment.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER