Trial Outcomes & Findings for Efficacy, Safety, and Tolerability of Topical Terbinafine in Patients With Mild to Moderate Toenail Fungus of the Big Toenail (NCT NCT00443898)

Last Updated: 2012-05-03

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

518 participants

Primary outcome timeframe

52 weeks

Results posted on

2012-05-03

Participant Flow

Participant milestones

Participant milestones
Measure	Terbinafine 24 w Active terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) applied once daily for 24 weeks	Vehicle 24 w vehicle (placebo) applied once daily for 24 weeks	Terbinafine 48 w Active terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) applied once daily for 48 weeks	Vehicle 48 w vehicle (placebo) applied once daily for 48 weeks
Overall Study STARTED	126	128	136	128
Overall Study COMPLETED	102	103	107	110
Overall Study NOT COMPLETED	24	25	29	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Terbinafine 24 w Active terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) applied once daily for 24 weeks	Vehicle 24 w vehicle (placebo) applied once daily for 24 weeks	Terbinafine 48 w Active terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) applied once daily for 48 weeks	Vehicle 48 w vehicle (placebo) applied once daily for 48 weeks
Overall Study Adverse Event	0	0	1	1
Overall Study Lack of Efficacy	2	3	3	1
Overall Study Protocol Violation	1	1	1	0
Overall Study Withdrawal by Subject	11	10	10	6
Overall Study Lost to Follow-up	10	10	14	10
Overall Study Death	0	1	0	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 w n=126 Participants Active terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) applied once daily for 24 weeks	Vehicle 24 w n=128 Participants vehicle (placebo) applied once daily for 24 weeks	Terbinafine 48 w n=136 Participants Active terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) applied once daily for 48 weeks	Vehicle 48 w n=128 Participants vehicle (placebo) applied once daily for 48 weeks	Total n=518 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	107 Participants n=5 Participants	101 Participants n=7 Participants	116 Participants n=5 Participants	100 Participants n=4 Participants	424 Participants n=21 Participants
Age, Categorical >=65 years	19 Participants n=5 Participants	27 Participants n=7 Participants	20 Participants n=5 Participants	28 Participants n=4 Participants	94 Participants n=21 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	29 Participants n=7 Participants	26 Participants n=5 Participants	27 Participants n=4 Participants	107 Participants n=21 Participants
Sex: Female, Male Male	101 Participants n=5 Participants	99 Participants n=7 Participants	110 Participants n=5 Participants	101 Participants n=4 Participants	411 Participants n=21 Participants

PRIMARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Terbinafine 24 w n=126 Participants Active terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) applied once daily for 24 weeks	Vehicle 24 w n=128 Participants vehicle (placebo) applied once daily for 24 weeks	Terbinafine 48 w n=136 Participants Active terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) applied once daily for 48 weeks	Vehicle 48 w n=128 Participants vehicle (placebo) applied once daily for 48 weeks
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 Interval -2.16 to 2.19	0.78 Percentage of Participants Interval -2.16 to -2.16	1.47 Percentage of Participants Interval -0.55 to 3.49	0.00 Percentage of Participants Interval -0.55 to 3.49

SECONDARY outcome

Timeframe: 52 weeks

Mycological cure is defined as negative KOH microscopy and negative culture for dermatophytes. Mycological cure was a composite binary variable defined as "Yes"if : * Negative microscopy and * Negative culture for dermatophytes "No" if otherwise.

Outcome measures

Outcome measures
Measure	Terbinafine 24 w n=126 Participants Active terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) applied once daily for 24 weeks	Vehicle 24 w n=128 Participants vehicle (placebo) applied once daily for 24 weeks	Terbinafine 48 w n=136 Participants Active terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) applied once daily for 48 weeks	Vehicle 48 w n=128 Participants vehicle (placebo) applied once daily for 48 weeks
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 Interval -2.7 to 10.83	6.25 Percentage of Participants Interval -2.7 to 10.83	15.44 Percentage of Participants Interval 5.54 to 19.1	3.13 Percentage of Participants Interval 5.54 to 19.1

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Terbinafine 24 w n=126 Participants Active terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) applied once daily for 24 weeks	Vehicle 24 w n=128 Participants vehicle (placebo) applied once daily for 24 weeks	Terbinafine 48 w n=136 Participants Active terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) applied once daily for 48 weeks	Vehicle 48 w n=128 Participants vehicle (placebo) applied once daily for 48 weeks
Efficacy Assessed by Clinical Efficacy at the End of Study After Treating Patients for 24 or 48 Weeks.	1.59 Percentage of Participants	2.34 Percentage of Participants	3.68 Percentage of Participants	1.56 Percentage of Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Terbinafine 24 w n=126 Participants Active terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) applied once daily for 24 weeks	Vehicle 24 w n=124 Participants vehicle (placebo) applied once daily for 24 weeks	Terbinafine 48 w n=135 Participants Active terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) applied once daily for 48 weeks	Vehicle 48 w n=128 Participants vehicle (placebo) applied once daily for 48 weeks
Number of Participants Assessed With Adverse Events and Serious Adverse Events	126 Participants	124 Participants	135 Participants	128 Participants

Adverse Events

Terbinafine 24 w

Serious events: 2 serious events

Other events: 35 other events

Deaths: 0 deaths

Vehicle 24 w

Serious events: 7 serious events

Other events: 38 other events

Deaths: 0 deaths

Terbinafine 48 w

Serious events: 7 serious events

Other events: 47 other events

Deaths: 0 deaths

Vehicle 48 w

Serious events: 4 serious events

Other events: 56 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Terbinafine 24 w n=126 participants at risk Active terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) applied once daily for 24 weeks	Vehicle 24 w n=124 participants at risk vehicle (placebo) applied once daily for 24 weeks	Terbinafine 48 w n=135 participants at risk Active terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) applied once daily for 48 weeks	Vehicle 48 w n=128 participants at risk vehicle (placebo) applied once daily for 48 weeks
General disorders Influenza like illness	1.6% 2/126 • 52 weeks 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.	0.81% 1/124 • 52 weeks 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.	0.00% 0/135 • 52 weeks 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.	6.2% 8/128 • 52 weeks 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.
Infections and infestations Nasopharyngitis	5.6% 7/126 • 52 weeks 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.	7.3% 9/124 • 52 weeks 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.	13.3% 18/135 • 52 weeks 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.	14.1% 18/128 • 52 weeks 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.
Infections and infestations Upper respiratory tract infection	3.2% 4/126 • 52 weeks 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.	4.8% 6/124 • 52 weeks 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.	5.9% 8/135 • 52 weeks 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.	6.2% 8/128 • 52 weeks 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.
Musculoskeletal and connective tissue disorders Back pain	5.6% 7/126 • 52 weeks 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.	5.6% 7/124 • 52 weeks 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.	6.7% 9/135 • 52 weeks 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.	7.8% 10/128 • 52 weeks 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.
Nervous system disorders Headache	18.3% 23/126 • 52 weeks 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.	19.4% 24/124 • 52 weeks 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.	17.0% 23/135 • 52 weeks 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.	22.7% 29/128 • 52 weeks 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.

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