search
Back to results

A Study to Evaluate Efficacy and Safety of Four Posaconazole Regimens With Placebo and Terbinafine in the Treatment of Toenail Onychomycosis (Study P05082AM2)(COMPLETED)

Primary Purpose

Onychomycosis

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
SCH 56592
SCH 56592
SCH 56592
SCH 56592
Terbinafine
Placebo
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Onychomycosis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • The subject must meet ALL the criteria listed below for entry:

    • Subject must be between 18 and 75 years of age inclusive, of either sex, and of any race;
    • Subject must have distal subungual infection that affects approximately 25% to 75% of at least one great toenail, both clinically and mycologically diagnosed;
    • Subject must have at least 2 mm of the proximal end of the target toenail free of infection;
    • Subject must have a target toenail that is assessed as capable of growing approximately 1 mm/month, (eg, the subject needs to report cutting his or her toenails at least once per month);
    • Subject must have liver function tests within 1.5 x the upper limit of normal (bilirubin and transaminases);
    • Subject must have normal serum creatinine levels;
    • Subject must be able to take study medication orally;
    • Subject must have no history of current narcotic or alcohol addiction;
    • Subject must be willing to give written informed consent and able to adhere to dose, procedures, and visit schedules;
    • Woman of childbearing potential who is currently sexually active must agree to use a medically accepted method of contraception while receiving protocol-specified medication and for 30 days after stopping the medication. Methods include condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed intrauterine device, oral or systemic hormonal contraceptive (plus an additional reliable barrier method), and surgical sterilization (eg, hysterectomy or tubal ligation).

Woman of child-bearing potential who is not currently sexually active must agree to use a medically accepted method of contraception should she become sexually active while participating in the study.

  • Woman of childbearing potential must have a negative serum pregnancy test within 72 hours prior to start of study drug.

Exclusion Criteria:

  • The subject will be excluded from entry if ANY of the criteria listed below are met:

    • Subject with one or more of the following conditions on the target toenail:

      • proximal subungual onychomycosis,
      • white superficial onychomycosis,
      • dermatophytoma or "yellow spike/streak",
      • exclusively lateral disease,
      • inability to become normal in the opinion of the investigator.
    • Subject with psoriasis, severe moccasin-type tinea pedis requiring treatment, symptomatic interdigital tinea pedis, lichen planus, or other abnormalities that could result in a clinically abnormal nail;
    • Subject with peripheral vascular disease or peripheral circulatory impairment;
    • Subject with history of uncontrolled diabetes mellitus;
    • Subject with known chronic or active liver disease;
    • Subject with any known immunodeficiency;
    • Subject with a family history of long QT syndrome;
    • Subject with an electrocardiogram with QTc interval prolongation greater than 450 msec for males and 470 msec for females;
    • Subject with potassium or magnesium lower than the lower limit of normal;
    • Subject with any clinically significant condition or situation, other than the condition being studied that, in the opinion of the investigator, would interfere with study evaluations or optimal participation in the study;
    • Subject who has received systemic antifungal therapy within 3 months or topical antifungal therapy applied to the foot or toenails within 1 month of study entry;
    • Subject who has received radiation therapy, chemotherapy, and/or immunosuppressive drugs within 6 months of Randomization, and/or oral corticosteroids for >1 month within the 6 months of Randomization (exception: inhaled steroids);
    • Subject using medications known to interact with azoles such as terfenadine, pimozide, quinidine, halofantrine, astemizole, alfentanil, cisapride, HMG-Co A (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors that are metabolized by CYP3A4, and ebastine, within 7 days prior to Randomization; and pravastatin within 14 days prior to Randomization;
    • Subject using medications known to lower the serum concentration/efficacy of azoles including rifampin, rifabutin, cimetidine, carbamazepine, phenytoin, barbiturates, and isoniazid, 3 doses or more within 7 days prior to Randomization;
    • Subject with a known sensitivity to azoles, POS and/or its excipients, terbinafine and/or its excipients;
    • Subject who has been previously enrolled in this study or any other POS investigational trial;
    • Subject known to have received treatment with investigational drugs within 30 days prior to enrollment into this study;
    • Woman who is breastfeeding, pregnant, or intends to become pregnant;
    • Subject who is part of the staff personnel directly involved with this study;
    • Subject who is a family member of the investigational study staff.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm 6

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Active Comparator

    Placebo Comparator

    Arm Label

    Posaconazole 100 mg QD for 24 weeks.

    Posaconazole 200 mg QD for 24 weeks.

    Posaconazole 400 mg QD for 24 weeks.

    Posaconazole 400 mg QD for 12 weeks.

    Terbinafine

    Placebo

    Arm Description

    Posaconazole oral suspension (40 mg/mL) 100 mg QD for 24 weeks.

    Posaconazole oral suspension (40 mg/mL) 200 mg QD for 24 weeks.

    Posaconazole oral suspension (40 mg/mL) 400 mg QD for 24 weeks.

    Posaconazole oral suspension (40 mg/mL) 400 mg QD for 12 weeks.

    Terbinafine 250 mg QD for 12 weeks.

    Placebo for 24 weeks.

    Outcomes

    Primary Outcome Measures

    Complete Cure of Onychomycosis at Week 48.
    Complete cure is defined as negative mycology (negative culture and KOH [potassium hydroxide]) and 0% nail involvement (defined as absence of onycholysis and subungual hyperkeratosis).

    Secondary Outcome Measures

    Effective Treatment of Onychomycosis at Week 48.
    Effective treatment is defined as negative mycology (negative culture and KOH) and either 0% nail involvement or >5 mm growth of unaffected nail
    Treatment Success of Onychomycosis at Week 48
    Treatment success was defined as negative mycology (negative culture and negative KOH) and =<10% nail involvement.

    Full Information

    First Posted
    June 25, 2007
    Last Updated
    March 9, 2017
    Sponsor
    Merck Sharp & Dohme LLC
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT00491764
    Brief Title
    A Study to Evaluate Efficacy and Safety of Four Posaconazole Regimens With Placebo and Terbinafine in the Treatment of Toenail Onychomycosis (Study P05082AM2)(COMPLETED)
    Official Title
    An Investigator-Blinded Study Evaluating the Efficacy and Safety of Four Posaconazole Treatment Regimens With Placebo and Terbinafine in the Treatment of Onychomycosis of the Toenail
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2017
    Overall Recruitment Status
    Completed
    Study Start Date
    June 2007 (undefined)
    Primary Completion Date
    December 2008 (Actual)
    Study Completion Date
    December 2008 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The purpose of this study is to evaluate the efficacy, safety, and tolerability of oral administration of four dosing regimens of posaconazole relative to placebo and terbinafine, in the treatment of toenail onychomycosis.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Onychomycosis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    Investigator
    Allocation
    Randomized
    Enrollment
    218 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Posaconazole 100 mg QD for 24 weeks.
    Arm Type
    Experimental
    Arm Description
    Posaconazole oral suspension (40 mg/mL) 100 mg QD for 24 weeks.
    Arm Title
    Posaconazole 200 mg QD for 24 weeks.
    Arm Type
    Experimental
    Arm Description
    Posaconazole oral suspension (40 mg/mL) 200 mg QD for 24 weeks.
    Arm Title
    Posaconazole 400 mg QD for 24 weeks.
    Arm Type
    Experimental
    Arm Description
    Posaconazole oral suspension (40 mg/mL) 400 mg QD for 24 weeks.
    Arm Title
    Posaconazole 400 mg QD for 12 weeks.
    Arm Type
    Experimental
    Arm Description
    Posaconazole oral suspension (40 mg/mL) 400 mg QD for 12 weeks.
    Arm Title
    Terbinafine
    Arm Type
    Active Comparator
    Arm Description
    Terbinafine 250 mg QD for 12 weeks.
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Placebo for 24 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    SCH 56592
    Other Intervention Name(s)
    Posaconazole, Noxafil
    Intervention Description
    Posaconazole oral suspension (40 mg/mL) 100 mg QD for 24 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    SCH 56592
    Other Intervention Name(s)
    Posaconazole, Noxafil
    Intervention Description
    Posaconazole oral suspension (40 mg/mL) 200 mg QD for 24 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    SCH 56592
    Other Intervention Name(s)
    Posaconazole, Noxafil
    Intervention Description
    Posaconazole oral suspension (40 mg/mL) 400 mg QD for 24 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    SCH 56592
    Other Intervention Name(s)
    Posaconazole, Noxafil
    Intervention Description
    Posaconazole oral suspension (40 mg/mL) 400 mg QD for 12 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    Terbinafine
    Intervention Description
    Terbinafine 250 mg QD for 12 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Placebo for 24 weeks.
    Primary Outcome Measure Information:
    Title
    Complete Cure of Onychomycosis at Week 48.
    Description
    Complete cure is defined as negative mycology (negative culture and KOH [potassium hydroxide]) and 0% nail involvement (defined as absence of onycholysis and subungual hyperkeratosis).
    Time Frame
    Measured at Day 1, Week 2, Week 4, and Every 4 Weeks Thereafter Until Week 48
    Secondary Outcome Measure Information:
    Title
    Effective Treatment of Onychomycosis at Week 48.
    Description
    Effective treatment is defined as negative mycology (negative culture and KOH) and either 0% nail involvement or >5 mm growth of unaffected nail
    Time Frame
    Measured at Day 1, Week 2, Week 4, and Every 4 Weeks Thereafter Until Week 48
    Title
    Treatment Success of Onychomycosis at Week 48
    Description
    Treatment success was defined as negative mycology (negative culture and negative KOH) and =<10% nail involvement.
    Time Frame
    Measured at Day 1, Week 2, Week 4, and Every 4 Weeks Thereafter Until Week 48

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: The subject must meet ALL the criteria listed below for entry: Subject must be between 18 and 75 years of age inclusive, of either sex, and of any race; Subject must have distal subungual infection that affects approximately 25% to 75% of at least one great toenail, both clinically and mycologically diagnosed; Subject must have at least 2 mm of the proximal end of the target toenail free of infection; Subject must have a target toenail that is assessed as capable of growing approximately 1 mm/month, (eg, the subject needs to report cutting his or her toenails at least once per month); Subject must have liver function tests within 1.5 x the upper limit of normal (bilirubin and transaminases); Subject must have normal serum creatinine levels; Subject must be able to take study medication orally; Subject must have no history of current narcotic or alcohol addiction; Subject must be willing to give written informed consent and able to adhere to dose, procedures, and visit schedules; Woman of childbearing potential who is currently sexually active must agree to use a medically accepted method of contraception while receiving protocol-specified medication and for 30 days after stopping the medication. Methods include condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed intrauterine device, oral or systemic hormonal contraceptive (plus an additional reliable barrier method), and surgical sterilization (eg, hysterectomy or tubal ligation). Woman of child-bearing potential who is not currently sexually active must agree to use a medically accepted method of contraception should she become sexually active while participating in the study. Woman of childbearing potential must have a negative serum pregnancy test within 72 hours prior to start of study drug. Exclusion Criteria: The subject will be excluded from entry if ANY of the criteria listed below are met: Subject with one or more of the following conditions on the target toenail: proximal subungual onychomycosis, white superficial onychomycosis, dermatophytoma or "yellow spike/streak", exclusively lateral disease, inability to become normal in the opinion of the investigator. Subject with psoriasis, severe moccasin-type tinea pedis requiring treatment, symptomatic interdigital tinea pedis, lichen planus, or other abnormalities that could result in a clinically abnormal nail; Subject with peripheral vascular disease or peripheral circulatory impairment; Subject with history of uncontrolled diabetes mellitus; Subject with known chronic or active liver disease; Subject with any known immunodeficiency; Subject with a family history of long QT syndrome; Subject with an electrocardiogram with QTc interval prolongation greater than 450 msec for males and 470 msec for females; Subject with potassium or magnesium lower than the lower limit of normal; Subject with any clinically significant condition or situation, other than the condition being studied that, in the opinion of the investigator, would interfere with study evaluations or optimal participation in the study; Subject who has received systemic antifungal therapy within 3 months or topical antifungal therapy applied to the foot or toenails within 1 month of study entry; Subject who has received radiation therapy, chemotherapy, and/or immunosuppressive drugs within 6 months of Randomization, and/or oral corticosteroids for >1 month within the 6 months of Randomization (exception: inhaled steroids); Subject using medications known to interact with azoles such as terfenadine, pimozide, quinidine, halofantrine, astemizole, alfentanil, cisapride, HMG-Co A (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors that are metabolized by CYP3A4, and ebastine, within 7 days prior to Randomization; and pravastatin within 14 days prior to Randomization; Subject using medications known to lower the serum concentration/efficacy of azoles including rifampin, rifabutin, cimetidine, carbamazepine, phenytoin, barbiturates, and isoniazid, 3 doses or more within 7 days prior to Randomization; Subject with a known sensitivity to azoles, POS and/or its excipients, terbinafine and/or its excipients; Subject who has been previously enrolled in this study or any other POS investigational trial; Subject known to have received treatment with investigational drugs within 30 days prior to enrollment into this study; Woman who is breastfeeding, pregnant, or intends to become pregnant; Subject who is part of the staff personnel directly involved with this study; Subject who is a family member of the investigational study staff.

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    21967490
    Citation
    Elewski B, Pollak R, Ashton S, Rich P, Schlessinger J, Tavakkol A. A randomized, placebo- and active-controlled, parallel-group, multicentre, investigator-blinded study of four treatment regimens of posaconazole in adults with toenail onychomycosis. Br J Dermatol. 2012 Feb;166(2):389-98. doi: 10.1111/j.1365-2133.2011.10660.x. Epub 2011 Dec 6.
    Results Reference
    derived

    Learn more about this trial

    A Study to Evaluate Efficacy and Safety of Four Posaconazole Regimens With Placebo and Terbinafine in the Treatment of Toenail Onychomycosis (Study P05082AM2)(COMPLETED)

    We'll reach out to this number within 24 hrs