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

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ClinicalTrials.gov Identifier: NCT03405818
Recruitment Status : Completed
First Posted : January 23, 2018
Results First Posted : April 17, 2018
Last Update Posted : April 17, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

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.


Condition or disease Intervention/treatment Phase
Onychomycosis Tinea Unguium Drug: Tavaborole 5% Topical Solution Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 55 participants
Intervention Model: Single Group Assignment
Intervention Model Description: This was a single group study.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 22, 2015
Actual Primary Completion Date : July 27, 2017
Actual Study Completion Date : July 27, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Tavaborole

Arm Intervention/treatment
Experimental: Tavaborole 5% Topical Solution
All study participants apply study drug
Drug: Tavaborole 5% Topical Solution
topical solution for application to toenails
Other Name: Kerydin




Primary Outcome Measures :
  1. Number of Participants With Local Tolerability Reactions by Severity [ Time Frame: Baseline up to Week 52 ]
    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).

  2. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 28 days after last dose of study drug (up to Week 52) ]
    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.

  3. Number of Participants With Adverse Events (AEs) By Severity [ Time Frame: Baseline up to 28 days after last dose of study drug (up to Week 52) ]
    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.

  4. Change From Baseline in Hematology Parameters (Leukocytes: Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils) at Week 24 [ Time Frame: Baseline, Week 24 ]
  5. Change From Baseline in Hematology Parameters (Leukocytes: Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils) at Week 52 [ Time Frame: Baseline, Week 52 ]
  6. Change From Baseline in Hematology Parameter (Hematocrit) at Week 24 [ Time Frame: Baseline, Week 24 ]
  7. Change From Baseline in Hematology Parameter (Hematocrit) at Week 52 [ Time Frame: Baseline, Week 52 ]
  8. Change From Baseline in Hematology Parameter (Erythrocytes) at Week 24 [ Time Frame: Baseline, Week 24 ]
  9. Change From Baseline in Hematology Parameter (Erythrocytes) at Week 52 [ Time Frame: Baseline, Week 52 ]
  10. Change From Baseline in Hematology Parameters (Hemoglobin) at Week 24 [ Time Frame: Baseline, Week 24 ]
  11. Change From Baseline in Hematology Parameters (Hemoglobin) at Week 52 [ Time Frame: Baseline, Week 52 ]
  12. Change From Baseline in Hematology Parameters (Leukocytes and Platelets) at Week 24 [ Time Frame: Baseline, Week 24 ]
  13. Change From Baseline in Hematology Parameters (Leukocytes and Platelets) at Week 52 [ Time Frame: Baseline, Week 52 ]
  14. Change From Baseline in Chemistry Parameters (Alanine Aminotransferase, Alkaline Phosphatase and Aspartate Aminotransferase) at Week 24 [ Time Frame: Baseline, Week 24 ]
  15. Change From Baseline in Chemistry Parameters (Alanine Aminotransferase, Alkaline Phosphatase and Aspartate Aminotransferase) at Week 52 [ Time Frame: Baseline, Week 52 ]
  16. Change From Baseline in Chemistry Parameters (Albumin and Protein) at Week 24 [ Time Frame: Baseline, Week 24 ]
  17. Change From Baseline in Chemistry Parameters (Albumin and Protein) at Week 52 [ Time Frame: Baseline, Week 52 ]
  18. Change From Baseline in Chemistry Parameters (Bilirubin, Creatinine, Glucose [Non-fasting] and Urea Nitrogen) at Week 24 [ Time Frame: Baseline, Week 24 ]
  19. Change From Baseline in Chemistry Parameters (Bilirubin, Creatinine, Glucose [Non-fasting] and Urea Nitrogen) at Week 52 [ Time Frame: Baseline, Week 52 ]
  20. Change From Baseline in Chemistry Parameters (Potassium and Sodium) at Week 24 [ Time Frame: Baseline, Week 24 ]
  21. Change From Baseline in Chemistry Parameters (Potassium and Sodium) at Week 52 [ Time Frame: Baseline, Week 52 ]
  22. Change From Baseline in Vital Sign (Blood Pressure) at Week 24 [ Time Frame: Baseline, Week 24 ]
  23. Change From Baseline in Vital Sign (Blood Pressure) at Week 52 [ Time Frame: Baseline, Week 52 ]
  24. Change From Baseline in Vital Sign (Pulse Rate) at Week 24 [ Time Frame: Baseline, 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.

  25. Change From Baseline in Vital Sign (Pulse Rate) at Week 52 [ Time Frame: Baseline, 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.

  26. Change From Baseline in Vital Sign (Respiratory Rate) at Week 24 [ Time Frame: Baseline, Week 24 ]
    Respiratory rate was defined as the number of inspirations per minute.

  27. Change From Baseline in Vital Sign (Respiratory Rate) at Week 52 [ Time Frame: Baseline, Week 52 ]
    Respiratory rate was defined as the number of inspirations per minute.

  28. Percentage of Participants With Complete Cure of Target Great Toenail (TGT) at Week 52 [ Time Frame: Week 52 ]
    Complete cure was defined as completely clear nail, negative fungal culture and negative potassium hydroxide (KOH) wet mount.


Secondary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) of Tavaborole [ Time Frame: Pre-dose, 4, 6, 8, 24 hours post-dose on Day 29 ]
  2. Time to Maximum Observed Plasma Concentration (Tmax) of Tavaborole [ Time Frame: Pre-dose, 4, 6, 8, 24 hours post-dose on Day 29 ]
  3. Area Under the Plasma Concentration-Time Curve From Hour Zero to Hour 24 (AUC24) of Tavaborole [ Time Frame: Pre-dose, 4, 6, 8, 24 hours post-dose on Day 29 ]
    AUC24 was defined as the area under the plasma concentration-time curve from hour 0 to hour 24. AUC24 was calculated using the linear trapezoidal rule.

  4. Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUCinf) of Tavaborole [ Time Frame: Pre-dose, 4, 6, 8, 24 hours post-dose on Day 29 ]
  5. Elimination Rate Constant of Tavaborole [ Time Frame: Pre-dose, 4, 6, 8, 24 hours post-dose on Day 29 ]
    Elimination rate constant was defined as the rate at which a drug was removed from the body.

  6. Elimination Half-Life of Tavaborole [ Time Frame: Pre-dose, 4, 6, 8, 24 hours post-dose on Day 29 ]
    Elimination half-life (t1/2) was defined as the time required for the body to eliminate half of the drug than its original concentration.

  7. Percentage of Participants With Almost Complete Cure of Target Great Toenail (TGT) at Week 24 and 52 [ Time Frame: Week 24, 52 ]
    Almost complete cure was defined as almost clear nail and negative mycology (negative mycology was defined as negative fungal culture and negative KOH wet mount).

  8. Percentage of Participants With Clinical Efficacy of Target Great Toenail (TGT) at Week 24 and 52 [ Time Frame: Week 24, 52 ]
    Clinical efficacy target great toenail (TGT) was defined as completely clear nail or almost clear nail.

  9. Percentage of Participants With Mycological Cure of Target Great Toenail (TGT) at Week 24 and 52 [ Time Frame: Week 24, 52 ]
    Mycological cure was defined as negative mycology of the TGT. Negative mycology was defined as negative fungal culture and negative potassium hydroxide (KOH) wet mount. Participants with only one result for either fungal culture or KOH were excluded from this analysis.

  10. Percentage of Participants With Negative Fungal Culture of the Target Great Toenail (TGT) at Weeks 24 and 52 [ Time Frame: Week 24, 52 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   72 Months to 203 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03405818


Locations
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United States, California
Madera Family Medical Group
Madera, California, United States, 93637
Stanford University School of Medicine
Palo Alto, California, United States, 94304
United States, District of Columbia
MedStar Health Research Institute - MedStar Georgetown University Hospital
Washington, District of Columbia, United States, 20016
United States, Florida
Doctors Research Network
South Miami, Florida, United States, 33143
United States, New York
University Hospital, SUNY Downstate Medical Center
Brooklyn, New York, United States, 11203
Skin Specialty Dermatology
New York, New York, United States, 10155
United States, Oregon
Cyn3rgy Research
Gresham, Oregon, United States, 97030
Oregon Dermatology & Research Center
Portland, Oregon, United States, 97210
United States, Texas
West Houston Clinical Research Services LLC
Houston, Texas, United States, 77055
Texas Dermatology and Laser Specialists
San Antonio, Texas, United States, 78218
United States, Utah
Jordan Valley Dermatology Center
West Jordan, Utah, United States, 84088
United States, Virginia
PI Coor Clinical Research, LLC
Burke, Virginia, United States, 22015
Sponsors and Collaborators
Pfizer
Investigators
Layout table for investigator information
Study Director: Pfizer CT.gov Call Center Pfizer
  Study Documents (Full-Text)

Documents provided by Pfizer:
Study Protocol  [PDF] March 28, 2016
Statistical Analysis Plan  [PDF] June 2, 2017


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03405818     History of Changes
Other Study ID Numbers: TAV-ONYC-401
C3371003 ( Other Identifier: Alias Study Number )
First Posted: January 23, 2018    Key Record Dates
Results First Posted: April 17, 2018
Last Update Posted: April 17, 2018
Last Verified: March 2018

Keywords provided by Pfizer:
Fungal infection of the nail

Additional relevant MeSH terms:
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Onychomycosis
Tinea
Dermatomycoses
Skin Diseases, Infectious
Infection
Mycoses
Nail Diseases
Skin Diseases
Pharmaceutical Solutions
Tavaborole
Antifungal Agents
Anti-Infective Agents