An Evaluation of the Safety and Pharmacokinetics of Tavaborole Topical Solution for the Treatment of Fungal Disease of the Toenail in Children and Adolescents

NCT03405818 | Completed Phase 4 Results

• 2 other identifiers: TAV-ONYC-401C3371003
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 12

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.

Conditions

Onychomycosis; Tinea Unguium

Keywords

Fungal infection of the nail

Outcome Measures

Primary Outcomes (28)

• Number of Participants With Local Tolerability Reactions by Severity

  Local tolerability reactions consisted of burning/stinging, induration/edema, oozing and crusting, pruritus, erythema, and scaling. Here 0 indicates None, 1 (Mild), 2 (Moderate) and 3 (severe). Grading details are as follows: Burning/Stinging (0: no stinging/burning, 1: slight warm, 2: definite warm, 3: hot); Induration/Edema (0: no elevation, 1: barely perceptible elevation, 2: clearly perceptible elevation but not extensive, 3: marked and extensive elevation); Oozing and Crusting (0: absent, 1: faint signs of oozing, 2: definite oozing, 3: marked and extensive oozing); Pruritus (0: no pruritus, 1: occasional, slight itching, 2: constant itching which is not disturbing sleep, 3: severe bothersome itching/scratching which is disturbing sleep); Erythema (0: no redness present, 1: faintly detectable erythema; very light pink, 2: dull red, 3: deep/dark red); Scaling (0: no scaling, 1: barely perceptible shedding, 2: obvious but not profuse scaling, 3: heavy scale production).

  Baseline up to Week 52

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious AEs.

  Baseline up to 28 days after last dose of study drug (up to Week 52)

• Number of Participants With Adverse Events (AEs) By Severity

  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs were classified as mild, moderate and severe based on severity assessment by investigator and defined as: Mild = symptoms barely noticeable to the participant or does not make the participant uncomfortable; moderate = symptoms of a sufficient severity to make the participant uncomfortable; severe = symptoms of a sufficient severity to cause the participant severe discomfort.

  Baseline up to 28 days after last dose of study drug (up to Week 52)

• Change From Baseline in Hematology Parameters (Leukocytes: Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils) at Week 24

  Baseline, Week 24

• Change From Baseline in Hematology Parameters (Leukocytes: Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils) at Week 52

  Baseline, Week 52

• Change From Baseline in Hematology Parameter (Hematocrit) at Week 24

  Baseline, Week 24

• Change From Baseline in Hematology Parameter (Hematocrit) at Week 52

  Baseline, Week 52

• Change From Baseline in Hematology Parameter (Erythrocytes) at Week 24

  Baseline, Week 24

• Change From Baseline in Hematology Parameter (Erythrocytes) at Week 52

  Baseline, Week 52

• Change From Baseline in Hematology Parameters (Hemoglobin) at Week 24

  Baseline, Week 24

• Change From Baseline in Hematology Parameters (Hemoglobin) at Week 52

  Baseline, Week 52

• Change From Baseline in Hematology Parameters (Leukocytes and Platelets) at Week 24

  Baseline, Week 24

• Change From Baseline in Hematology Parameters (Leukocytes and Platelets) at Week 52

  Baseline, Week 52

• Change From Baseline in Chemistry Parameters (Alanine Aminotransferase, Alkaline Phosphatase and Aspartate Aminotransferase) at Week 24

  Baseline, Week 24

• Change From Baseline in Chemistry Parameters (Alanine Aminotransferase, Alkaline Phosphatase and Aspartate Aminotransferase) at Week 52

  Baseline, Week 52

• Change From Baseline in Chemistry Parameters (Albumin and Protein) at Week 24

  Baseline, Week 24

• Change From Baseline in Chemistry Parameters (Albumin and Protein) at Week 52

  Baseline, Week 52

• Change From Baseline in Chemistry Parameters (Bilirubin, Creatinine, Glucose [Non-fasting] and Urea Nitrogen) at Week 24

  Baseline, Week 24

• Change From Baseline in Chemistry Parameters (Bilirubin, Creatinine, Glucose [Non-fasting] and Urea Nitrogen) at Week 52

  Baseline, Week 52

• Change From Baseline in Chemistry Parameters (Potassium and Sodium) at Week 24

  Baseline, Week 24

• Change From Baseline in Chemistry Parameters (Potassium and Sodium) at Week 52

  Baseline, Week 52

• Change From Baseline in Vital Sign (Blood Pressure) at Week 24

  Baseline, Week 24

• Change From Baseline in Vital Sign (Blood Pressure) at Week 52

  Baseline, Week 52

• Change From Baseline in Vital Sign (Pulse Rate) at Week 24

  Pulse rate was defined as the number of pulsations noted in a peripheral artery per minute after participant rested supine for 5 minutes.

  Baseline, Week 24

• Change From Baseline in Vital Sign (Pulse Rate) at Week 52

  Pulse rate was defined as the number of pulsations noted in a peripheral artery per minute after participant rested supine for 5 minutes.

  Baseline, Week 52

• Change From Baseline in Vital Sign (Respiratory Rate) at Week 24

  Respiratory rate was defined as the number of inspirations per minute.

  Baseline, Week 24

• Change From Baseline in Vital Sign (Respiratory Rate) at Week 52

  Respiratory rate was defined as the number of inspirations per minute.

  Baseline, Week 52

• Percentage of Participants With Complete Cure of Target Great Toenail (TGT) at Week 52

  Complete cure was defined as completely clear nail, negative fungal culture and negative potassium hydroxide (KOH) wet mount.

  Week 52

Secondary Outcomes (10)

• Maximum Observed Plasma Concentration (Cmax) of Tavaborole

  Pre-dose, 4, 6, 8, 24 hours post-dose on Day 29

• Time to Maximum Observed Plasma Concentration (Tmax) of Tavaborole

  Pre-dose, 4, 6, 8, 24 hours post-dose on Day 29

• Area Under the Plasma Concentration-Time Curve From Hour Zero to Hour 24 (AUC24) of Tavaborole

  Pre-dose, 4, 6, 8, 24 hours post-dose on Day 29

• Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUCinf) of Tavaborole

  Pre-dose, 4, 6, 8, 24 hours post-dose on Day 29

• Elimination Rate Constant of Tavaborole

  Pre-dose, 4, 6, 8, 24 hours post-dose on Day 29

Study Arms (1)

Tavaborole 5% Topical Solution

EXPERIMENTAL

All study participants apply study drug

Drug: Tavaborole 5% Topical Solution

Interventions

Tavaborole 5% Topical Solution DRUG

topical solution for application to toenails

Also known as: Kerydin

Tavaborole 5% Topical Solution

Eligibility Criteria

• Age: 72 Months - 203 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (12)

Madera Family Medical Group

Madera, California, 93637, United States

Location

Stanford University School of Medicine

Palo Alto, California, 94304, United States

Location

MedStar Health Research Institute - MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20016, United States

Location

Doctors Research Network

South Miami, Florida, 33143, United States

Location

University Hospital, SUNY Downstate Medical Center

Brooklyn, New York, 11203, United States

Location

Skin Specialty Dermatology

New York, New York, 10155, United States

Location

Cyn3rgy Research

Gresham, Oregon, 97030, United States

Location

Oregon Dermatology & Research Center

Portland, Oregon, 97210, United States

Location

West Houston Clinical Research Services LLC

Houston, Texas, 77055, United States

Location

Texas Dermatology and Laser Specialists

San Antonio, Texas, 78218, United States

Location

Jordan Valley Dermatology Center

West Jordan, Utah, 84088, United States

Location

PI Coor Clinical Research, LLC

Burke, Virginia, 22015, United States

Location

Related Publications (1)

• 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.

  PMID: 30811142 DERIVED

MeSH Terms

Conditions

Onychomycosis

Interventions

tavaborole; Solutions

Condition Hierarchy (Ancestors)

Tinea; Dermatomycoses; Mycoses; Bacterial Infections and Mycoses; Infections; Skin Diseases, Infectious; Nail Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This was a single group study.

Study Record Dates

• First Submitted: January 3, 2018
• First Posted: January 23, 2018
• Study Start: October 22, 2015
• Primary Completion: July 27, 2017
• Study Completion: July 27, 2017
• Last Updated: April 17, 2018
• Results First Posted: April 17, 2018

Record last verified: 2018-03

Locations

US (12)