Pharmacokinetics and Safety Study of ME1111 in Moderate to Severe Onychomycosis Patients

A Phase 1 Randomized, Double-Blind, Vehicle-Controlled, Multiple-Dose Study of the Safety, Absorption and Systemic Pharmacokinetics of ME1111 Topical Agent Applied to All Toenails of Adult Moderate to Severe Onychomycosis Patients for 28 Days

This study is Randomized, Double-Blind, Vehicle-Controlled, Multiple-Dose Study.

The purpose is to determine the safety, tolerability, systemic exposure and pharmacokinetics of ME1111 after repeated daily topical application of ME1111 in a maximal use setting in adults with distal subungual onychomycosis of the toenails.

Study Overview

• Status: Completed
• Conditions: Onychomycosis
• Intervention / Treatment: Drug: ME1111 solution; Drug: Vehicle Solution

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States
    • College Station, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female of any race and between the ages of 18 and 70 inclusive
2. Clinically diagnosed onychomycosis of the target nail
3. Presence of moderate to severe distal subungual onychomycosis
4. A positive potassium hydroxide(KOH) microscopy test result
5. A positive fungal culture for a dermatophyte
6. Females of childbearing potential must be using a highly effective method of birth control and be willing to remain on the same method of birth control throughout the study
7. Good general health as determined by the Investigator based on the subject's medical history and physical examination

Exclusion Criteria:

1. Clinical significant laboratory abnormalities that would interfere with the conduct or interpretation of the study or jeopardize subject's safety
2. Subjects with a history of diabetes mellitus
3. Unwilling to refrain from the use of nail cosmetics such as clear and/or colored nail solutions
4. Females who are nursing, pregnant, or planning a pregnancy during the study
5. Failure to complete the specified washout period(s) for the following topical medications: Antifungals drugs within 4 weeks; Anti-inflammatory drugs, corticosteroids, immunomodulators within 2 weeks
6. Failure to complete the specified washout period(s) for the following systemic medications: Corticosteroids within 2 weeks; Antifungals for treatment of onychomycosis or any antifungal with known activity against dermatophyte within the previous 24 weeks or 5 half-lives of the drug, whichever is longer; Immunomodulators within 4 weeks
7. History of cardiac disease and cardiac arrhythmic activity, or prolonged QT interval
8. Received treatment for any type of cancer within the last 6 months
9. History of any significant disease or disorder that might put subjects at risk by participating in study or influence results of study
10. Nail or anatomic abnormalities of the toe
11. Positive test for HIV, Hepatitis B or Hepatitis C
12. History of street drug or alcohol abuse
13. Donated or lost blood or participated in a clinical study which involved the withdrawal of a large volume of blood (500 mL or more), within the last 6-week
14. Participated in any other trial of an investigational drug or device within 30 days or 5 half-lives of the investigational drug or participation in a research study concurrent with this study
15. Unable to communicate or cooperate with the Investigator due to comprehension, mental development, or impaired cerebral function
16. Presence of any underlying disease that the Investigator deems uncontrolled, and poses a concern for the subjects safety while participating on the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ME1111 solution	Drug: ME1111 solution; Once a day for 28 days
PLACEBO_COMPARATOR: Vehicle Solution	Drug: Vehicle Solution; Once a day for 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The number of adverse events observed throughout the study period.	from Baseline to Day 57
Application site reactions will be evaluated using categorical scales for signs and symptoms throughout the study period.	from Baseline to Day 57
Area under the plasma concentration of ME1111 will be assessed based on the analysis of blood samples over 24 hours	Day 1, 28
Urinary excretion rate will be assessed based on the analysis of urinary samples over 24 hours	Day 1, 28
Plasma trough levels of ME1111	Day 4, 8, 15, 22, 25, 43, 57

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under the nail concentration of ME1111	Day 2, 15, 29, 57
The proportion of subjects who achieve negative KOH microscopy testing results	Day 29, 57
The proportion of subjects who achieve negative fungal culture results	Day 29, 57
The change from baseline in linear toenail growth at Days 29 and 57 will be analyzed	Day 1, 29, 57

Collaborators and Investigators

• Sponsor: Meiji Seika Pharma Co., Ltd.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (ACTUAL): August 1, 2013

Study Registration Dates

• First Submitted: April 18, 2013
• First Submitted That Met QC Criteria: April 24, 2013
• First Posted (ESTIMATE): April 29, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): December 17, 2013
• Last Update Submitted That Met QC Criteria: December 15, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Infections; Bacterial Infections and Mycoses; Skin Diseases, Infectious; Mycoses; Tinea; Dermatomycoses; Nail Diseases; Onychomycosis; Pharmaceutical Solutions
• Other Study ID Numbers: ME1111-1