Efficacy and Safety Study of Miconazole Lauriad to Treat Oropharyngeal Candidiasis in HIV Patients

A Comparative Randomized, Double-blind, Double-Dummy, Multicenter Study of the Efficacy and Safety of Miconazole Lauriad 50mg Administered Once a Day and Mycelex Troches (Clotrimazole 10mg) Administered Five Times a Day in the Treatment of Oropharyngeal Candidiasis in Immunocompromised Patients

The purpose of this study is to evaluate the clinical cure of miconazole Lauriad 50 mg (1x50mg) Bioadhesive buccal tablets compared with clotrimazole troches (5x10mg) after 14 days of treatment (at the test of cure visit, at Day 17-19).

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Clotrimazole; Drug: miconazole Lauriad

• Study Type: Interventional
• Enrollment (Actual): 578
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Downtown Infectious Disease Clinic
    • Vancouver, British Columbia, Canada
      • Providence Health Center British Columbia Centre for excellence in HIV/AIDS
  • Manitoba
    • Winnipeg, Manitoba, Canada, GG441-820
      • Health Sciences Center
  • Ontario
    • Ottawa, Ontario, Canada
      • University of Ottawa Health Services
  • Quebec
    • Montreal, Quebec, Canada, H3G 1A4
      • Montreal General Hospital
    • Montreal, Quebec, Canada, H2x2P4
      • Montreal Chest Institutes immunodeficiency clinic
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-00007
      • University of Alabama, Department of diagnostic Sciences School of Dentistry
  • California
    • Los Angeles, California, United States, 90028
      • L.A. Gay & Lesbian center, Health & Mental, health services
    • Oakland, California, United States, 94609
      • East Bay AIDS Center
    • Palm Springs, California, United States, 92262
      • 1401 Noth Palm Canyon
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • University of Connecticut, School of dental medicine
  • Florida
    • Fort Lauderdale, Florida, United States
    • Fort Lauderdale, Florida, United States, 33308
      • Therafirst Medical Center
    • Labelle, Florida, United States, 33935
      • Ryan White Title III Clinic
    • Miami, Florida, United States, 33136
      • University of Miami
    • West Palm Beach, Florida, United States, 21201
      • Triple O Medical Services
  • Illinois
    • Chicago, Illinois, United States, 60612-7213
      • Department of oral medicine and diagnostic sciences UIC college of dentistry
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Plus Clinic, University of Maryland Dental school
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital and Wayne State University, Division of infectious diseases
  • New York
    • New-York, New York, United States, 10018
      • AIDS Community Research Initiative of America
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7450
      • Department Diagnostics Sciences, UNC
    • Greenville, North Carolina, United States, 27858
      • East Carolina University, Brody School of Medicine
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74129
      • University of Oklahoma, College of medicine
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18102
      • Lehigh Valley Hospital Clinical Research Department of Medicine
  • Rhode Island
    • Providence, Rhode Island, United States, 02908
      • Roger Williams Medical Center
  • Texas
    • Houston, Texas, United States, 77006
      • Bering Omega Dental Clinic
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Eastern Virginia Medical Center, Center for comprehensive care of immune deficiency

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients with clinical picture of oropharyngeal candidiasis
• Confirmation of oropharyngeal candidiasis by candida culture positive
• HIV-positive patients
• Patients 18 years of age

Exclusion Criteria:

• Patients with signs or symptoms of systemic candidiasis
• Patients with signs or symptoms of esophagitis
• Pregnant or breast-feeding women
• Patients who have taken systemic antifungals within the past 30 days
• Patients who have taken local antifungals within the past 7 days

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Clotrimazole; Clotrimazole troches, 10 mg, 5 times per day for 14 days	Drug: Clotrimazole; 10mg troches administered Five Times a Day for 14 days
EXPERIMENTAL: miconazole Lauriad; Miconazole Lauriad 50 mg mucoadhesive buccal tablet, once daily, for 14 days	Drug: miconazole Lauriad; 50 mg buccal tablet once a day for 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Cure (Defined as a Complete Resolution of Signs and Symptoms) After 14 Days of Treatment at the Test of Cure Visit (Day 17-Day 22) Using Murray Scoring Scale	Murray scoring scale range: extent of oral lesions (signs) 0 (none) to 3 (extensive or confluent), ordinal; symptoms (soreness/burning) 0 (absent) to 3 (severe), ordinal. Clinical cure was defined as a complete resolution of signs and symptoms (extent of oral lesions score = 0, symptoms score = 0). Clinical failure was defined as any patient who failed to be clinically cured by the treatment.	17 to 22 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Cure at Day 7 (Using Murray Scoring Scale)	Murray scoring scale range: extent of oral lesions (signs) 0 (none) to 3 (extensive or confluent), ordinal; symptoms (soreness/burning) 0 (absent) to 3 (severe), ordinal. Clinical cure was defined as a complete resolution of signs and symptoms (extent of oral lesions score = 0, symptoms score = 0). Clinical failure was defined as any patient who failed to be clinically cured by the treatment.	7 days
Clinical Success at Test-of-cure Visit (Day 17-22) (Using Murray Scoring Scale)	Murray scoring scale range: extent of oral lesions (signs) 0 (none) to 3 (extensive or confluent), ordinal; symptoms (soreness/burning) 0 (absent) to 3 (severe), ordinal. Clinical success was defined as clinical cure or clinical improvement. Clinical cure was defined as a complete resolution of signs and symptoms (extent of oral lesions score = 0, symptoms score = 0). Clinical improvement was defined as having no visible lesion (extent of lesions score = 0) and minimal symptoms (soreness/burning score <2). Clinical failure was defined as any patient who failed to be clinically cured by the treatment.	17 to 22 days
Clinical Success at Day 7 (Using Murray Scoring Scale)	Murray scoring scale range: extent of oral lesions (signs) 0 (none) to 3 (extensive or confluent), ordinal; symptoms (soreness/burning) 0 (absent) to 3 (severe), ordinal. Clinical success was defined as clinical cure or clinical improvement. Clinical cure was defined as a complete resolution of signs and symptoms (extent of oral lesions score = 0, symptoms score = 0). Clinical improvement was defined as having no visible lesion (extent of lesions score = 0) and minimal symptoms (soreness/burning score <2). Clinical failure was defined as any patient who failed to be clinically cured by the treatment.	7 days
Partial Response at Test of Cure Visit (Days 17-22) Using Murray Scoring Scale	Murray scoring scale range: extent of oral lesions (signs) 0 (none) to 3 (extensive or confluent), ordinal; symptoms (soreness/burning) 0 (absent) to 3 (severe), ordinal. Clinical success was defined as clinical cure or clinical improvement. Partial response is having decrease in Murray extent of oral lesions score by at least 1 level and a stable Murray symptoms score, with partial symptom response defined as having a decrease in the Murray symptoms (soreness/burning) score by at least 1 level and a stable Murray extent of oral lesions score, and partial clinical/symptom response defined as decrease in Murray extent of oral lesions score by at least 1 level and a decrease in the Murray symptoms (soreness/burning) score by at least 1 level	17 to 22 days
Mycological Cure at the Test of Cure Visit (Day 17-22)	Mycological cure was defined as a patient who had "no yeast isolated" when oral specimens were cultured for fungi.	17 to 22 days
Relapse at the Late Post-Therapy Visit (Day 35-38)	"Number of patients" represents the number of participants who completed visit 6 (the late post-therapy visit on Days 35-38) and had been a clinical success at test-of-cure visit (visit 5). For this subset of participants, relapse was defined as a patient who responded to treatment by clinical cure or improvement (i.e., "clinical success") on Days 17-22 at the test-of-cure visit (visit 5) and subsequently had an increase in the extent of oral lesions or symptoms, as assessed at the late post-therapy visit on Days 35-38 (visit 6). No relapse indicates participants who were considered a "clinical success" at visit 5 and did not have a subsequent increase in the extent of oral lesions or symptoms, as assessed at the late post-therapy visit (visit 6). The remaining number of participants in the Intent-to-Treat population who did not meet the criteria for relapse assessment at visit 6 is listed under "Not Analyzed-ITT".	35 to 38 days
Oral Discomfort Using Visual Analog Scale (VAS)	Visual analog scale was used by the patient in the patient diary. The scale ranged from 0 (no oral discomfort) to 10 (maximum oral discomfort)	14 days
General and Local Tolerability and Oral Discomfort	Overall local adverse reactions, including gingival inflammation, gum pain, alterations in taste of food when eating, alterations in taste when not eating, and dry mouth. Visit 4 occurred on Day 14.	14 days
Duration of Adhesion of Miconazole Lauriad 50 mg Mucoadhesive Buccal Tablet	The mean durations of adhesion from initiation of treatment to Day 14 of miconazole Lauriad 50 mg mucoadhesive buccal tablet (or, in the case of the Clotrimazole troches treatment arm, the placebo mucoadhesive buccal tablet) were rounded to the nearest hour	14 days
Systemic Exposure of Miconazole Lauriad 50 mg Bioadhesive Buccal Tablet	Number of patients with detectable plasma concentration at Visit 3 (day 7)	7 days
Susceptibility of Candida Species by Microdilution Test	minimum inhibitory concentration (MIC) in nonresponders at test-of-cure visit	Initiation of treatment to Day 17 to 22
Treatment Compliance	Number of patients who were 100% compliant with the treatment regimen	Initiation of treatment to Day 14

Collaborators and Investigators

• Sponsor: Onxeo

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (ACTUAL): December 1, 2007
• Study Completion (ACTUAL): January 1, 2008

Study Registration Dates

• First Submitted: October 19, 2006
• First Submitted That Met QC Criteria: October 19, 2006
• First Posted (ESTIMATE): October 20, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): September 16, 2013
• Last Update Submitted That Met QC Criteria: September 5, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: Treatment Experienced; Miconazole Lauriad; Oropharyngeal candidiasis; HIV patients; Mycology; Clinical picture of Oropharyngeal candidiasis; Candida culture positive
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Candidiasis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents, Local; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Clotrimazole; Miconazole
• Other Study ID Numbers: BA/2004/01/04