Sigurgeirsson 2013.

Methods	Design: randomised, double‐blind, placebo‐controlled, parallel group study
Participants	Number of participants randomised: 582 Sex (M/F): 441/141 Mean age: 48.6 years (range 19‐74) Number included in analysis: 582 Number completing treatment: 482 Inclusion criteria: distal subungual onychomycosis affecting at least 1 great toenail (target toenail) with > 25% nail involvement, > 2 mm of unaffected toenail at the proximal end, and microscopic (KOH, calcofluor) and culture confirmation of dermatophytes. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and total bilirubin levels that were < 1.5 times the upper normal limit. Baseline ECG normal or clinically insignificant. Duration of infection: not specified Exclusion criteria: women who were pregnant, trying to become pregnant or breastfeeding, receipt of an investigational drug within 4 weeks before the first dose of the study product, an investigational drug treatment for onychomycosis within 6 months before the first dose of the study product; schedule receipt of any other investigational drug during the study; receipt of any known substrate of the 3A4 isozyme of cytochrome P450 (CYP3A4) with QT prolongation potential; concomitant use of prohibited medications, a history of any condition that could possibly affect drug absorption (e.g. gastrectomy), uncontrolled diabetes, clinically significant peripheral vascular disease or circulatory impairment, any major illness within 30 days before screening, ECG abnormalities deemed clinically significant. Washout period: 4 weeks Setting: 26 centres in the USA, 3 in Canada and 1 in Iceland Comorbidities: not stated
Interventions	Placebo capsule once weekly for 36 weeks Albaconazole capsule 100 mg once weekly for 36 weeks Albaconazole capsule 200 mg once weekly for 36 weeks Albaconazole capsule 400 mg once weekly for 36 weeks Albaconazole capsule 400 mg (24 weeks plus 12 weeks of placebo)
Outcomes	Duration of follow‐up: 52 weeks Outcomes measured: mycological and clinical cure, adverse events Safety and tolerability assessed by: clinical laboratory indicators, vital signs and physical examination results and ECG measurements
Source of funding	Supported by Stiefel, a GSK company
Conflict of interest	Dr Sigurgeirsson was a sponsored investigator on this study and a member of an advisory board that assisted in the planning and design of the study. He also has served as a consultant and investigator for and received honoraria from Arpedia, Celtic, deCode, Galderma, Novartis, Prostrakan, Stiefel, TLT, Topica, and Vertex. Dr van Rossem, Mr Malahias, and Ms Raterink are employees of Stiefel, a GSK company
Notes	—
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote "independently randomized (with a 1:1:1:1:1 schedule) using a computer‐generated schedule to 1 of the 5 study groups"
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote "Investigators, study centre personnel, patients, study monitors, and statisticians were unaware of the assigned study treatment", "placebo‐matched capsules"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "[i]nvestigators, study centre personnel, participants, study monitors, and statisticians were unaware of the assigned study treatment." Comment: outcome assessment was blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	High completion rate (82%‐98%) and very low loss to follow‐up
Selective reporting (reporting bias)	Low risk	All results presented as set out in the Methods. All prespecified outcomes appear to be reported.
Other bias	Low risk	No other source of bias seen