Trial Outcomes & Findings for Efficacy, Safety and Tolerability of Topical 10% Terbinafine Hydrogen Chloride Versus 5% Amorolfine Nail Lacquer in Patients With Mild to Moderate Toenail Onychomycosis (NCT NCT00459537)

NCT ID: NCT00459537

Last Updated: 2011-05-06

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1029 participants
• Primary outcome timeframe: Week 52
• Results posted on: 2011-05-06

Participant Flow

Participant milestones

Measure	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.	Amorolfine 5% amorolfine nail lacquer. Patients applied study medication twice weekly for 48 weeks to all affected toenails.
Overall Study STARTED	507	522
Overall Study Safety Population	493	512
Overall Study COMPLETED	441	446
Overall Study NOT COMPLETED	66	76

Reasons for withdrawal

Measure	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.	Amorolfine 5% amorolfine nail lacquer. Patients applied study medication twice weekly for 48 weeks to all affected toenails.
Overall Study Adverse Event	1	6
Overall Study Lack of Efficacy	10	11
Overall Study Withdrawal by Subject	20	26
Overall Study Lost to Follow-up	27	30
Overall Study Administrative problems	3	0
Overall Study Protocol Violation	4	3
Overall Study Missing	1	0

Baseline Characteristics

Efficacy, Safety and Tolerability of Topical 10% Terbinafine Hydrogen Chloride Versus 5% Amorolfine Nail Lacquer in Patients With Mild to Moderate Toenail Onychomycosis

Baseline characteristics by cohort

Measure	Terbinafine n=507 Participants 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.	Amorolfine n=522 Participants 5% amorolfine nail lacquer. Patients applied study medication twice weekly for 48 weeks to all affected toenails.	Total n=1029 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	425 Participants n=5 Participants	410 Participants n=7 Participants	835 Participants n=5 Participants
Age, Categorical >=65 years	82 Participants n=5 Participants	111 Participants n=7 Participants	193 Participants n=5 Participants
Sex: Female, Male Female	158 Participants n=5 Participants	150 Participants n=7 Participants	308 Participants n=5 Participants
Sex: Female, Male Male	349 Participants n=5 Participants	372 Participants n=7 Participants	721 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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)

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

Outcome measures

Measure	Terbinafine n=507 Participants 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.	Amorolfine n=522 Participants 5% amorolfine nail lacquer. Patients applied study medication twice weekly for 48 weeks to all affected toenails.
Percentage of Participants With Complete Cure at the End of Study After Treating Participants for 48 Weeks	1.18 Percentage of participants	0.96 Percentage of participants

PRIMARY outcome

Timeframe: 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).

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

Outcome measures

Measure	Terbinafine n=260 Participants 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.	Amorolfine n=266 Participants 5% amorolfine nail lacquer. Patients applied study medication twice weekly for 48 weeks to all affected toenails.
Percentage of Participants With Complete Cure at the End of Study After Treating Participants for 48 Weeks.	1.15 Percentage of participants	0.38 Percentage of participants

SECONDARY outcome

Timeframe: Week 52

Population: Intent-to-treat 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.

Outcome measures

Measure	Terbinafine n=507 Participants 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.	Amorolfine n=522 Participants 5% amorolfine nail lacquer. Patients applied study medication twice weekly for 48 weeks to all affected toenails.
Percentage of Participants With Clinical Effectiveness at the End of Study After Treating Patients for 48 Weeks.	4.54 Percentage of participants	3.83 Percentage of participants

SECONDARY outcome

Timeframe: Week 52

Population: Intent-to-treat population, Last Observation Carried Forward (LOCF)

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

Outcome measures

Measure	Terbinafine n=507 Participants 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.	Amorolfine n=522 Participants 5% amorolfine nail lacquer. Patients applied study medication twice weekly for 48 weeks to all affected toenails.
Percentage of Participants With Mycological Cure at End of Study After Treating Patients for 48 Weeks	16.17 Percentage of participants	15.71 Percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Terbinafine n=493 Participants 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.	Amorolfine n=512 Participants 5% amorolfine nail lacquer. Patients applied study medication twice weekly for 48 weeks to all affected toenails.
Safety and Tolerability Assessed by the Number of Participants With Adverse Events At least 1 SAE	9 Participants	18 Participants
Safety and Tolerability Assessed by the Number of Participants With Adverse Events At least 1 AE	285 Participants	291 Participants
Safety and Tolerability Assessed by the Number of Participants With Adverse Events AE suspected related to study drug	11 Participants	7 Participants
Safety and Tolerability Assessed by the Number of Participants With Adverse Events SAE suspected related to study drug	0 Participants	0 Participants
Safety and Tolerability Assessed by the Number of Participants With Adverse Events Death	0 Participants	0 Participants
Safety and Tolerability Assessed by the Number of Participants With Adverse Events Drug discontinuation due to an AE	1 Participants	5 Participants

Adverse Events

Terbinafine

Serious events: 9 serious events

Other events: 186 other events

Deaths: 0 deaths

Amorolfine

Serious events: 18 serious events

Other events: 168 other events

Deaths: 0 deaths

Serious adverse events

Measure	Terbinafine n=493 participants at risk 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.	Amorolfine n=512 participants at risk 5% amorolfine nail lacquer. Patients applied study medication twice weekly for 48 weeks to all affected toenails.
Blood and lymphatic system disorders Lymphadenopathy	0.20% 1/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.00% 0/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Cardiac disorders Arteriosclerosis coronary artery	0.00% 0/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.20% 1/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Cardiac disorders Atrial fibrillation	0.00% 0/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.20% 1/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Cardiac disorders Cardiac failure	0.00% 0/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.20% 1/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Cardiac disorders Coronary artery disease	0.00% 0/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.20% 1/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Cardiac disorders Myocardial infarction	0.00% 0/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.59% 3/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Ear and labyrinth disorders Vertigo	0.00% 0/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.20% 1/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Endocrine disorders Thyroid cyst	0.00% 0/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.20% 1/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.20% 1/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Gastrointestinal disorders Enterovesical fistula	0.20% 1/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.00% 0/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Gastrointestinal disorders Oesophagitis	0.00% 0/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.20% 1/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
General disorders Chest pain	0.00% 0/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.20% 1/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.20% 1/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Infections and infestations Appendicitis	0.00% 0/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.20% 1/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Infections and infestations Cystitis	0.20% 1/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.00% 0/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Infections and infestations Diverticulitis	0.20% 1/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.00% 0/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Infections and infestations Erysipelas	0.20% 1/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.00% 0/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Infections and infestations Peritonsillar abscess	0.00% 0/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.20% 1/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Infections and infestations Pneumonia	0.00% 0/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.20% 1/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Infections and infestations Pyelonephritis	0.20% 1/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.00% 0/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Injury, poisoning and procedural complications Ligament rupture	0.00% 0/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.20% 1/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Musculoskeletal and connective tissue disorders Haemarthrosis	0.00% 0/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.20% 1/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Musculoskeletal and connective tissue disorders Intervertebral disc displacement	0.00% 0/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.20% 1/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.20% 1/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.00% 0/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.20% 1/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer metastatic	0.00% 0/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.20% 1/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Nervous system disorders Cerebrovascular accident	0.00% 0/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.20% 1/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Nervous system disorders Transient ischaemic attack	0.00% 0/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.20% 1/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Reproductive system and breast disorders Breast dysplasia	0.00% 0/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.20% 1/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Surgical and medical procedures Cyst removal	0.20% 1/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.00% 0/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Surgical and medical procedures Dupuytren's contracture operation	0.20% 1/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.00% 0/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Vascular disorders Arterial stenosis	0.20% 1/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.00% 0/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Vascular disorders Arteriosclerosis	0.00% 0/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	0.20% 1/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.

Other adverse events

Measure	Terbinafine n=493 participants at risk 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.	Amorolfine n=512 participants at risk 5% amorolfine nail lacquer. Patients applied study medication twice weekly for 48 weeks to all affected toenails.
Infections and infestations Influenza	5.1% 25/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	2.9% 15/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Infections and infestations Nasopharyngitis	14.0% 69/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	12.7% 65/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Infections and infestations Tinea pedis	5.9% 29/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	6.4% 33/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Musculoskeletal and connective tissue disorders Back pain	5.3% 26/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	5.7% 29/512 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Nervous system disorders Headache	19.9% 98/493 • 52 weeks Safety population consisting of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.	13.7% 70/512 • 52 weeks Safety population consisting of all patients who received 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