Clinical trial NCT03405818: An Evaluation of the Safety and Pharmacokinetics of Tavaborole Topical Solution for the Treatment of Fungal Disease of the Toenail in Children and Adolescents
Official title: An Open-label Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of Kerydin (Registered) (Tavaborole) Topical Solution, 5% In The Treatment Of Onychomycosis Of The Toenail In Pediatric Subjects Ages 6 To 16 Years And 11 Months
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Onychomycosis
Tinea Unguium
Keywords: Fungal infection of the nail
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2018-01-23
Enrollment: 55
Sex: ALL
Minimum age (years): 72
Maximum age (years): 203
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This was a single group study.
Primary purpose: TREATMENT

Brief summary: This was an open-label study to evaluate the safety and pharmacokinetics of tavaborole 5% topical solution in treating distal subungual onychomycosis (a fungal infection) of the toenail in children and adolescents (ages 6 to 16 years).

Following confirmation of eligibility, including laboratory evidence of a fungal organism in the toenail, tavaborole topical solution was applied once daily to all affected toenails for a 48-week treatment period.

Clinical assessment of the extent of infection and safety assessments were performed periodically throughout the 48-week treatment period, and again at 52 weeks (4 weeks after stopping the treatment).

A subgroup of enrolled subjects applied the topical solution to all 10 toenails and a small area of surrounding skin during the first 28 days. These subjects had blood samples analyzed to evaluate the pharmacokinetics (how the drug moves in the body) of tavaborole topical solution in children and adolescents.

Detailed description: This was an open-label study to evaluate the safety, tolerability, and pharmacokinetics of tavaborole 5% topical solution in treating distal subungual onychomycosis (DSO) of the toenail in pediatric subjects aged 6 to 16 years and 11 months. An eligible subject had a target great toenail (TGT) with at least 20% involvement, with a positive potassium hydroxide (KOH) wet mount and positive fungal culture for T. rubrum or T. mentagrophytes.

Eligible subjects applied tavaborole 5% topical solution, once daily to all affected toenails (the TGT as well as all other toenails having the clinical characteristics of onychomycosis) throughout the 48 week treatment period.

Subjects were evaluated at Screening, Baseline (Day 1), and at Weeks 2, 4, 8, 16, 24, 32, 40, 48, and 52. Each evaluation included a clinical assessment of the AEs and local tolerability evaluation.

Additional procedures were performed as follows:

* Mycology sampling at Screening, Week 24, and Week 52/early termination (ET);
* Clinical disease severity of the TGT at Screening, Week 24, and Week 52/ET;
* Safety laboratory testing at Baseline, Week 24, and Week 52/ET;

In this study, there was a PK subgroup of evaluable subjects aged 12 to 16 years and 11 months studied under maximal use conditions. Subjects in this maximal use subgroup applied the study drug on all 10 toenails, including up to 2 mm of the surrounding skin, for 28 days. On Day 15, a predose PK sample was collected to assess steady state trough level. On Day 29, the study drug application was done at the study site, and PK samples were collected prior to dosing, as well as 4, 6, 8, and 24 hours postdose on Days 29 to 30.

Eligibility criteria: Inclusion Criteria:

* males or females, ages \>/= 6 years and \</= 16 years and 11 months
* clinical diagnosis of distal subungual onychomycosis affecting at least 20% of one of the great toenails (target nail); and with positive KOH and positive culture for T. rubrum or T. mentagrophytes from either great toenail

Exclusion Criteria:

* the target toenail has proximal subungual onychomycosis, onychomycosis involving the nail lunula, superficial white onychomycosis, dermatophytoma, exclusively lateral disease, or yellow or brown spikes, or has co-infection with certain fungi or molds
* anatomic abnormalities of the toes or toenail
* current or past history of chronic moccasin-type tinea pedis
* current or past history of psoriasis or lichen planus
* history of significant chronic fungal disease (other than onychomycosis)
* diabetes
* immunodeficiency

Primary outcomes:
measure: Number of Participants With Local Tolerability Reactions by Severity
timeFrame: Baseline up to Week 52
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 28 days after last dose of study drug (up to Week 52)
measure: Number of Participants With Adverse Events (AEs) By Severity
timeFrame: Baseline up to 28 days after last dose of study drug (up to Week 52)
measure: Change From Baseline in Hematology Parameters (Leukocytes: Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Hematology Parameters (Leukocytes: Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils) at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Hematology Parameter (Hematocrit) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Hematology Parameter (Hematocrit) at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Hematology Parameter (Erythrocytes) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Hematology Parameter (Erythrocytes) at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Hematology Parameters (Hemoglobin) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Hematology Parameters (Hemoglobin) at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Hematology Parameters (Leukocytes and Platelets) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Hematology Parameters (Leukocytes and Platelets) at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Chemistry Parameters (Alanine Aminotransferase, Alkaline Phosphatase and Aspartate Aminotransferase) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Chemistry Parameters (Alanine Aminotransferase, Alkaline Phosphatase and Aspartate Aminotransferase) at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Chemistry Parameters (Albumin and Protein) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Chemistry Parameters (Albumin and Protein) at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Chemistry Parameters (Bilirubin, Creatinine, Glucose [Non-fasting] and Urea Nitrogen) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Chemistry Parameters (Bilirubin, Creatinine, Glucose [Non-fasting] and Urea Nitrogen) at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Chemistry Parameters (Potassium and Sodium) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Chemistry Parameters (Potassium and Sodium) at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Vital Sign (Blood Pressure) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Vital Sign (Blood Pressure) at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Vital Sign (Pulse Rate) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Vital Sign (Pulse Rate) at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Vital Sign (Respiratory Rate) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Vital Sign (Respiratory Rate) at Week 52
timeFrame: Baseline, Week 52
measure: Percentage of Participants With Complete Cure of Target Great Toenail (TGT) at Week 52
timeFrame: Week 52
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Tavaborole
timeFrame: Pre-dose, 4, 6, 8, 24 hours post-dose on Day 29
measure: Time to Maximum Observed Plasma Concentration (Tmax) of Tavaborole
timeFrame: Pre-dose, 4, 6, 8, 24 hours post-dose on Day 29
measure: Area Under the Plasma Concentration-Time Curve From Hour Zero to Hour 24 (AUC24) of Tavaborole
timeFrame: Pre-dose, 4, 6, 8, 24 hours post-dose on Day 29
measure: Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUCinf) of Tavaborole
timeFrame: Pre-dose, 4, 6, 8, 24 hours post-dose on Day 29
measure: Elimination Rate Constant of Tavaborole
timeFrame: Pre-dose, 4, 6, 8, 24 hours post-dose on Day 29
measure: Elimination Half-Life of Tavaborole
timeFrame: Pre-dose, 4, 6, 8, 24 hours post-dose on Day 29
measure: Percentage of Participants With Almost Complete Cure of Target Great Toenail (TGT) at Week 24 and 52
timeFrame: Week 24, 52
measure: Percentage of Participants With Clinical Efficacy of Target Great Toenail (TGT) at Week 24 and 52
timeFrame: Week 24, 52
measure: Percentage of Participants With Mycological Cure of Target Great Toenail (TGT) at Week 24 and 52
timeFrame: Week 24, 52
measure: Percentage of Participants With Negative Fungal Culture of the Target Great Toenail (TGT) at Weeks 24 and 52
timeFrame: Week 24, 52
Other outcomes:
Locations:
city: Madera
country: United States
facility: Madera Family Medical Group
state: California
city: Palo Alto
country: United States
facility: Stanford University School of Medicine
state: California
city: Washington
country: United States
facility: MedStar Health Research Institute - MedStar Georgetown University Hospital
state: District of Columbia
city: South Miami
country: United States
facility: Doctors Research Network
state: Florida
city: Brooklyn
country: United States
facility: University Hospital, SUNY Downstate Medical Center
state: New York
city: New York
country: United States
facility: Skin Specialty Dermatology
state: New York
city: Gresham
country: United States
facility: Cyn3rgy Research
state: Oregon
city: Portland
country: United States
facility: Oregon Dermatology & Research Center
state: Oregon
city: Houston
country: United States
facility: West Houston Clinical Research Services LLC
state: Texas
city: San Antonio
country: United States
facility: Texas Dermatology and Laser Specialists
state: Texas
city: West Jordan
country: United States
facility: Jordan Valley Dermatology Center
state: Utah
city: Burke
country: United States
facility: PI Coor Clinical Research, LLC
state: Virginia
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Rich P, Spellman M, Purohit V, Zang C, Crook TJ. Tavaborole 5% Topical Solution for the Treatment of Toenail Onychomycosis in Pediatric Patients: Results from a Phase 4 Open-Label Study. J Drugs Dermatol. 2019 Feb 1;18(2):190-195.