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

• Sponsor: Onxeo (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00390780
• Collaborator: (none)
• Enrollment: 578
• Locations: 27
• Arms: 2
• Duration (Months): 18
• Patients Per Site: 21.4
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: miconazole Lauriad; Drug: Clotrimazole	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 578 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Jul 1, 2006
• Actual Primary Completion Date: Dec 1, 2007
• Actual Study Completion Date: Jan 1, 2008

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 [17 to 22 days]

   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.

Secondary Outcome Measures

1. Clinical Cure at Day 7 (Using Murray Scoring Scale) [7 days]

   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.

2. Clinical Success at Test-of-cure Visit (Day 17-22) (Using Murray Scoring Scale) [17 to 22 days]

   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.

3. Clinical Success at Day 7 (Using Murray Scoring Scale) [7 days]

   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.

4. Partial Response at Test of Cure Visit (Days 17-22) Using Murray Scoring Scale [17 to 22 days]

   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

5. Mycological Cure at the Test of Cure Visit (Day 17-22) [17 to 22 days]

   Mycological cure was defined as a patient who had "no yeast isolated" when oral specimens were cultured for fungi.

6. Relapse at the Late Post-Therapy Visit (Day 35-38) [35 to 38 days]

   "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".

7. Oral Discomfort Using Visual Analog Scale (VAS) [14 days]

   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)

8. General and Local Tolerability and Oral Discomfort [14 days]

   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.

9. Duration of Adhesion of Miconazole Lauriad 50 mg Mucoadhesive Buccal Tablet [14 days]

   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

10. Systemic Exposure of Miconazole Lauriad 50 mg Bioadhesive Buccal Tablet [7 days]

    Number of patients with detectable plasma concentration at Visit 3 (day 7)

11. Susceptibility of Candida Species by Microdilution Test [Initiation of treatment to Day 17 to 22]

    minimum inhibitory concentration (MIC) in nonresponders at test-of-cure visit

12. Treatment Compliance [Initiation of treatment to Day 14]

    Number of patients who were 100% compliant with the treatment regimen

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama, Department of diagnostic Sciences School of Dentistry	Birmingham	Alabama	United States	35294-00007
2	L.A. Gay & Lesbian center, Health & Mental, health services	Los Angeles	California	United States	90028
3	East Bay AIDS Center	Oakland	California	United States	94609
4	1401 Noth Palm Canyon	Palm Springs	California	United States	92262
5	University of Connecticut, School of dental medicine	Farmington	Connecticut	United States	06030
6	Therafirst Medical Center	Fort Lauderdale	Florida	United States	33308
7		Fort Lauderdale	Florida	United States
8	Ryan White Title III Clinic	Labelle	Florida	United States	33935
9	University of Miami	Miami	Florida	United States	33136
10	Triple O Medical Services	West Palm Beach	Florida	United States	21201
11	Department of oral medicine and diagnostic sciences UIC college of dentistry	Chicago	Illinois	United States	60612-7213
12	Plus Clinic, University of Maryland Dental school	Baltimore	Maryland	United States	21201
13	Henry Ford Hospital and Wayne State University, Division of infectious diseases	Detroit	Michigan	United States	48202
14	AIDS Community Research Initiative of America	New-York	New York	United States	10018
15	Department Diagnostics Sciences, UNC	Chapel Hill	North Carolina	United States	27599-7450
16	East Carolina University, Brody School of Medicine	Greenville	North Carolina	United States	27858
17	University of Oklahoma, College of medicine	Tulsa	Oklahoma	United States	74129
18	Lehigh Valley Hospital Clinical Research Department of Medicine	Allentown	Pennsylvania	United States	18102
19	Roger Williams Medical Center	Providence	Rhode Island	United States	02908
20	Bering Omega Dental Clinic	Houston	Texas	United States	77006
21	Eastern Virginia Medical Center, Center for comprehensive care of immune deficiency	Norfolk	Virginia	United States	23507
22	Downtown Infectious Disease Clinic	Vancouver	British Columbia	Canada
23	Providence Health Center British Columbia Centre for excellence in HIV/AIDS	Vancouver	British Columbia	Canada
24	Health Sciences Center	Winnipeg	Manitoba	Canada	GG441-820
25	University of Ottawa Health Services	Ottawa	Ontario	Canada
26	Montreal Chest Institutes immunodeficiency clinic	Montreal	Quebec	Canada	H2x2P4
27	Montreal General Hospital	Montreal	Quebec	Canada	H3G 1A4

Sponsors and Collaborators

• Onxeo

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Onxeo
• ClinicalTrials.gov Identifier: NCT00390780
• Other Study ID Numbers: BA/2004/01/04
• First Posted: Oct 20, 2006
• Last Update Posted: Sep 16, 2013
• Last Verified: Feb 1, 2013

• Keywords provided by Onxeo: Miconazole Lauriad; Oropharyngeal candidiasis; HIV patients; Mycology; Clinical picture of Oropharyngeal candidiasis; Candida culture positive; Treatment Experienced
• Additional relevant MeSH terms: Candidiasis; Clotrimazole; Miconazole

Study Results

Participant Flow

Recruitment Details	Recruitment from 25 July 06 to 27 December 07 A total of 30 clinical sites (private practice and hospitals) in US, Canada and South Africa screened patients for this study, and 28 sites randomized patients
Pre-assignment Detail	There were no significant events or approaches following participant enrollment and prior to group assignment

Arm/Group Title	Miconazole Lauriad Buccal Tablet	Clotrimazole Troches
Arm/Group Description	Miconazole Lauriad 50 mg mucoadhesive buccal tablet, once daily, for 14 days	Clotrimazole troches, 10 mg, 5 times per day, for 14 days
Period Title: Overall Study
STARTED	291	287
Treatment	290	287
COMPLETED	268	260
NOT COMPLETED	23	27

Baseline Characteristics

Arm/Group Title	Miconazole Lauriad Buccal Tablet	Clotrimazole Troches	Total
Arm/Group Description	Miconazole Lauriad 50 mg mucoadhesive buccal tablet, once daily, for 14 days	Clotrimazole troches, 10 mg, 5 times per day for 14 days	Total of all reporting groups
Overall Participants	290	287	577
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	37.5 (9.7)	36.5 (9.1)	37.0 (9.4)
Sex: Female, Male (Count of Participants)
Female	173 59.7%	168 58.5%	341 59.1%
Male	117 40.3%	119 41.5%	236 40.9%
Region of Enrollment (participants) [Number]
United States	67 23.1%	62 21.6%	129 22.4%
Canada	3 1%	3 1%	6 1%
South Africa	220 75.9%	222 77.4%	442 76.6%

Outcome Measures

1. Primary Outcome

Title	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
Description	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.
Time Frame	17 to 22 days

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT, all randomized patients who took at least 1 dose of study medication) Per Protocol (PP, all patients in ITT without major protocol deviation, with positive fungal culture, completed at least 10 days of treatment, had main efficacy criteria at test of cure, compliant within 71.4% to 120%, and no forbidden medications taken)

Arm/Group Title	Miconazole Lauriad Buccal Tablet	Clotrimazole Troches
Arm/Group Description	Miconazole Lauriad 50 mg mucoadhesive buccal tablet, once daily, for 14 days	Clotrimazole troches, 10 mg, 5 times per day for 14 days
Measure Participants	290	287
Clinical Cure-ITT	176 60.7%	187 65.2%
Clinical Failure-ITT	114 39.3%	100 34.8%
Clinical Cure-PP	164 56.6%	175 61%
Clinical Failure-PP	76 26.2%	61 21.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Miconazole Lauriad Buccal Tablet, Clotrimazole Troches
	Comments	Analyses for ITT and PP populations: H0: clinical cure rate for miconazole Lauriad minus clinical cure rate for clotrimazole troches is less than or equal to -0.15 H1: clinical cure rate for miconazole Lauriad minus clinical cure rate for Mycelex troches is greater than -0.15
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non inferiority assumptions: Type of test: one-sided Inferiority margin: -15% Expected cure rate: 70% Type I error: 2.5% Type II error: 5%
Statistical Test of Hypothesis	p-Value	>0.025
	Comments	Significance level was <0.025
	Method	one-sided test
	Comments
Method of Estimation	Estimation Parameter	comparison of proportion clinical cure
	Estimated Value	0.15
	Confidence Interval	(1-Sided) 95%; -0.15 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Clinical Cure at Day 7 (Using Murray Scoring Scale)
Description	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.
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

ITT (all randomized patients who took at least 1 dose of study medication) PP (all patients in ITT without major protocol deviation, with positive fungal culture, completed at least 10 days of treatment, had main efficacy criteria at test of cure, compliant within 71.4% to 120%, and no forbidden medications taken)

Arm/Group Title	Miconazole Lauriad Buccal Tablet	Clotrimazole Troches
Arm/Group Description	Miconazole Lauriad 50 mg mucoadhesive buccal tablet, once daily, for 14 days	Clotrimazole troches, 10 mg, 5 times per day for 14 days
Measure Participants	290	287
Clinical Cure-ITT	67 23.1%	71 24.7%
Clinical Failure-ITT	210 72.4%	202 70.4%
Data Missing-ITT	13 4.5%	14 4.9%
Clinical Cure-PP	60 20.7%	63 22%
Clinical Failure-PP	180 62.1%	173 60.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Miconazole Lauriad Buccal Tablet, Clotrimazole Troches
	Comments	Analysis for ITT and PP populations: H0: clinical cure rate for miconazole Lauriad minus clinical cure rate for clotrimazole troches is less than or equal to -0.15 H1: clinical cure rate for miconazole Lauriad minus clinical cure rate for Mycelex troches is greater than -0.15
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non inferiority assumptions: Type of test: one-sided Inferiority margin: -15% Expected cure rate: 70% Type I error: 2.5% Type II error: 5%
Statistical Test of Hypothesis	p-Value	>0.025
	Comments	Significance level was <0.025.
	Method	one-sided noninferiority test
	Comments
Method of Estimation	Estimation Parameter	comparison of proportion clinical cure
	Estimated Value	0.15
	Confidence Interval	(1-Sided) 95%; -0.15 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Clinical Success at Test-of-cure Visit (Day 17-22) (Using Murray Scoring Scale)
Description	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.
Time Frame	17 to 22 days

Outcome Measure Data

Analysis Population Description

ITT (all randomized patients who took at least 1 dose of study medication) PP (all patients in ITT without major protocol deviation, with positive fungal culture, completed at least 10 days of treatment, had main efficacy criteria at test of cure, compliant within 71.4% to 120%, and no forbidden medications taken)

Arm/Group Title	Miconazole Lauriad Buccal Tablet	Clotrimazole Troches
Arm/Group Description	Miconazole Lauriad 50 mg mucoadhesive buccal tablet, once daily, for 14 days	Clotrimazole troches, 10 mg, 5 times per day for 14 days
Measure Participants	290	287
Clinical Success-ITT	188 64.8%	199 69.3%
Clinical Failure-ITT	80 27.6%	61 21.3%
Data Missing-ITT	22 7.6%	27 9.4%
Clinical Failure-PP	67 23.1%	51 17.8%
Clinical Success-PP	173 59.7%	185 64.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Miconazole Lauriad Buccal Tablet, Clotrimazole Troches
	Comments	Analysis for ITT population: H0: clinical success rate for miconazole Lauriad minus clinical success rate for clotrimazole troches is less than or equal to -0.15 H1: clinical success rate for miconazole Lauriad minus clinical success rate for Mycelex troches is greater than -0.15
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non inferiority assumptions: Type of test: one-sided Inferiority margin: -15% Type I error: 2.5% Type II error: 5%
Statistical Test of Hypothesis	p-Value	0.0974
	Comments	Significance level was <0.025.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	compare proportion of clinical success
	Estimated Value	0.15
	Confidence Interval	(1-Sided) 95%; -0.15 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Miconazole Lauriad Buccal Tablet, Clotrimazole Troches
	Comments	Analysis for PP population: H0: clinical success rate for miconazole Lauriad minus clinical success rate for clotrimazole troches is less than or equal to -0.15 H1: clinical success rate for miconazole Lauriad minus clinical success rate for Mycelex troches is greater than -0.15
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non inferiority assumptions: Type of test: one-sided Inferiority margin: -15% Type I error: 2.5% Type II error: 5%
Statistical Test of Hypothesis	p-Value	0.1115
	Comments	Significance level was <0.025.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Compare proportion of clinical success
	Estimated Value	0.15
	Confidence Interval	(1-Sided) 95%; -0.15 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Clinical Success at Day 7 (Using Murray Scoring Scale)
Description	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.
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

ITT (all randomized patients who took at least 1 dose of study medication) PP (all patients in ITT without major protocol deviation, with positive fungal culture, completed at least 10 days of treatment, had main efficacy criteria at test of cure, compliant within 71.4% to 120%, and no forbidden medications taken)

Arm/Group Title	Miconazole Lauriad Buccal Tablet	Clotrimazole Troches
Arm/Group Description	Miconazole Lauriad 50 mg mucoadhesive buccal tablet, once daily, for 14 days	Clotrimazole troches, 10 mg, 5 times per day for 14 days
Measure Participants	290	287
Clinical Success-ITT	92 31.7%	89 31%
Clinical Failure-ITT	185 63.8%	184 64.1%
Data Missing-ITT	13 4.5%	14 4.9%
Clinical Success-PP	82 28.3%	78 27.2%
Clinical Failure-PP	158 54.5%	158 55.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Miconazole Lauriad Buccal Tablet, Clotrimazole Troches
	Comments	Analysis for ITT population: H0: clinical success rate for miconazole Lauriad minus clinical success rate for clotrimazole troches is less than or equal to -0.15 H1: clinical success rate for miconazole Lauriad minus clinical success rate for Mycelex troches is greater than -0.15
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non inferiority assumptions: Type of test: one-sided Inferiority margin: -15% Type I error: 2.5% Type II error: 5%
Statistical Test of Hypothesis	p-Value	0.8787
	Comments	Significance level was <0.025.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	compare proportion of clinical success
	Estimated Value	0.15
	Confidence Interval	(1-Sided) 95%; -0.15 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Miconazole Lauriad Buccal Tablet, Clotrimazole Troches
	Comments	Analysis for PP population: H0: clinical success rate for miconazole Lauriad minus clinical success rate for clotrimazole troches is less than or equal to -0.15 H1: clinical success rate for miconazole Lauriad minus clinical success rate for Mycelex troches is greater than -0.15
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non inferiority assumptions: Type of test: one-sided Inferiority margin: -15% Type I error: 2.5% Type II error: 5%
Statistical Test of Hypothesis	p-Value	0.7969
	Comments	Significance level was <0.025.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	compare proportion of clinical success
	Estimated Value	0.15
	Confidence Interval	(1-Sided) 95%; -0.15 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Partial Response at Test of Cure Visit (Days 17-22) Using Murray Scoring Scale
Description	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
Time Frame	17 to 22 days

Outcome Measure Data

Analysis Population Description

ITT (all randomized patients who took at least 1 dose of study medication) PP (all patients in ITT without major protocol deviation, with positive fungal culture, completed at least 10 days of treatment, had main efficacy criteria at test of cure, compliant within 71.4% to 120%, and no forbidden medications taken)

Arm/Group Title	Miconazole Lauriad Buccal Tablet	Clotrimazole Troches
Arm/Group Description	Miconazole Lauriad 50 mg mucoadhesive buccal tablet, once daily, for 14 days	Clotrimazole troches, 10 mg, 5 times per day for 14 days
Measure Participants	290	287
Partial response-ITT	139 47.9%	140 48.8%
Partial response-PP	120 41.4%	123 42.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Miconazole Lauriad Buccal Tablet, Clotrimazole Troches
	Comments	Analysis for ITT population: H0: partial response rate for miconazole Lauriad minus partial response rate for clotrimazole troches is less than or equal to -0.15 H1: partial response rate for miconazole Lauriad minus partial response rate for Mycelex troches is greater than -0.15
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non inferiority assumptions: Type of test: one-sided Inferiority margin: -15% Type I error: 2.5% Type II error: 5%
Statistical Test of Hypothesis	p-Value	0.8820
	Comments	Significance level was <0.025.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	compare proportion of partial response
	Estimated Value	0.15
	Confidence Interval	(1-Sided) 95%; -0.15 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Miconazole Lauriad Buccal Tablet, Clotrimazole Troches
	Comments	Analysis for PP population: H0: partial response rate for miconazole Lauriad minus partial response rate for clotrimazole troches is less than or equal to -0.15 H1: partial response rate for miconazole Lauriad minus partial response rate for Mycelex troches is greater than -0.15
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non inferiority assumptions: Type of test: one-sided Inferiority margin: -15% Type I error: 2.5% Type II error: 5%
Statistical Test of Hypothesis	p-Value	0.9033
	Comments	Significance level was <0.025.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	compare proportion of partial response
	Estimated Value	0.15
	Confidence Interval	(1-Sided) 95%; -0.15 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Mycological Cure at the Test of Cure Visit (Day 17-22)
Description	Mycological cure was defined as a patient who had "no yeast isolated" when oral specimens were cultured for fungi.
Time Frame	17 to 22 days

Outcome Measure Data

Analysis Population Description

ITT (all randomized patients who took at least 1 dose of study medication) PP (all patients in ITT without major protocol deviation, with positive fungal culture, completed at least 10 days of treatment, had main efficacy criteria at test of cure, compliant within 71.4% to 120%, and no forbidden medications taken)

Arm/Group Title	Miconazole Lauriad Buccal Tablet	Clotrimazole Troches
Arm/Group Description	Miconazole Lauriad 50 mg mucoadhesive buccal tablet, once daily, for 14 days	Clotrimazole troches, 10 mg, 5 times per day for 14 days
Measure Participants	290	287
Mycological Cure-ITT	79 27.2%	71 24.7%
Mycological Failure-ITT	185 63.8%	185 64.5%
Data Missing-ITT	26 9%	31 10.8%
Mycological Cure-PP	73 25.2%	64 22.3%
Mycological Failure-PP	164 56.6%	168 58.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Miconazole Lauriad Buccal Tablet, Clotrimazole Troches
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority statistical analysis for ITT population.
Statistical Test of Hypothesis	p-Value	0.5816
	Comments	Significance level was <0.025.
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	difference in proportion mycologic cure
	Estimated Value	0.15
	Confidence Interval	(1-Sided) 95%; -0.15 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Miconazole Lauriad Buccal Tablet, Clotrimazole Troches
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority statistical analysis for PP population
Statistical Test of Hypothesis	p-Value	0.4439
	Comments	Significance level was <0.025.
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	difference in proportion mycologic cure
	Estimated Value	0.15
	Confidence Interval	(1-Sided) 95%; -0.15 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Relapse at the Late Post-Therapy Visit (Day 35-38)
Description	"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".
Time Frame	35 to 38 days

Outcome Measure Data

Analysis Population Description

ITT (all randomized patients who took at least 1 dose of study medication) PP (all patients in ITT without major protocol deviation, with positive fungal culture, completed at least 10 days of treatment, had main efficacy criteria at test of cure, compliant within 71.4% to 120%, and no forbidden medications taken)

Arm/Group Title	Miconazole Lauriad Buccal Tablet	Clotrimazole Troches
Arm/Group Description	Miconazole Lauriad 50 mg mucoadhesive buccal tablet, once daily, for 14 days	Clotrimazole troches, 10 mg, 5 times per day for 14 days
Measure Participants	290	287
Number of patients-ITT	183 63.1%	197 68.6%
Relapse-ITT	51 17.6%	53 18.5%
No relapse-ITT	132 45.5%	144 50.2%
Not Analyzed-ITT	107 36.9%	90 31.4%
Number of patients-PP	168 57.9%	184 64.1%
Relapse-PP	45 15.5%	49 17.1%
No relapse-PP	123 42.4%	135 47%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Miconazole Lauriad Buccal Tablet, Clotrimazole Troches
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority statistical analysis for ITT population.
Statistical Test of Hypothesis	p-Value	0.8330
	Comments	Significance level is <0.025.
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	difference in proportion relapsed
	Estimated Value	0.15
	Confidence Interval	(1-Sided) 95%; -0.15 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Miconazole Lauriad Buccal Tablet, Clotrimazole Troches
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority statistical analysis for PP population.
Statistical Test of Hypothesis	p-Value	0.9738
	Comments	Significance level is <0.025.
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	difference in proportion relapsed
	Estimated Value	0.15
	Confidence Interval	(1-Sided) 95%; -0.15 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Oral Discomfort Using Visual Analog Scale (VAS)
Description	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)
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT, all randomized patients who took at least 1 dose of study medication)

Arm/Group Title	Miconazole Lauriad Buccal Tablet	Clotrimazole Troches
Arm/Group Description	Miconazole Lauriad 50 mg mucoadhesive buccal tablet, once daily, for 14 days	Clotrimazole troches, 10 mg, 5 times per day for 14 days
Measure Participants	290	287
Mean (Full Range) [units on a scale]	0.8	0.4

9. Secondary Outcome

Title	General and Local Tolerability and Oral Discomfort
Description	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.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

Safety Population (same as ITT population, includes all randomized patients who took at least one dose of the study medication)

Arm/Group Title	Miconazole Lauriad Buccal Tablet	Clotrimazole Troches
Arm/Group Description	Miconazole Lauriad 50 mg mucoadhesive buccal tablet, once daily, for 14 days	Clotrimazole troches, 10 mg, 5 times per day for 14 days
Measure Participants	290	287
Gingival Inflammation-Visit 4 (R canine fossa)	34 11.7%	26 9.1%
No Gingival Inflammation-Visit 4 (R canine fossa)	235 81%	233 81.2%
Data Missing (Inflammation)-Visit 4 (R fossa)	21 7.2%	28 9.8%
Gingival Inflammation-Visit 4 (L canine fossa)	30 10.3%	24 8.4%
No Gingival Inflammation-Visit 4 (L canine fossa)	239 82.4%	236 82.2%
Data Missing (Inflammation)-Visit 4 (L fossa)	21 7.2%	27 9.4%
Gum Pain-Visit 4	32 11%	24 8.4%
No Gum Pain-Visit 4	240 82.8%	236 82.2%
Data Missing (Gum Pain)-Visit 4	18 6.2%	27 9.4%
Taste of Food Alteration-Visit 4	63 21.7%	54 18.8%
No Taste of Food Alteration-Visit 4	209 72.1%	206 71.8%
Data Missing (Taste of Food Alteration)-Visit 4	18 6.2%	27 9.4%
Taste When Not Eating Alteration-Visit 4	63 21.7%	52 18.1%
No Taste When Not Eating Alteration-Visit 4	209 72.1%	208 72.5%
Data Missing (Taste When Not Eating)-Visit 4	18 6.2%	27 9.4%
Dry Mouth-Visit 4	57 19.7%	67 23.3%
No Dry Mouth-Visit 4	215 74.1%	193 67.2%
Data Missing (Dry Mouth)-Visit 4	18 6.2%	27 9.4%

10. Secondary Outcome

Title	Duration of Adhesion of Miconazole Lauriad 50 mg Mucoadhesive Buccal Tablet
Description	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
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

ITT (all randomized patients who took at least 1 dose of study medication)

Arm/Group Title	Miconazole Lauriad Buccal Tablet	Clotrimazole Troches
Arm/Group Description	Miconazole Lauriad 50 mg mucoadhesive buccal tablet, once daily, for 14 days	Clotrimazole troches, 10 mg, 5 times per day for 14 days
Measure Participants	290	287
Mean (Full Range) [hours]	13	13

11. Secondary Outcome

Title	Systemic Exposure of Miconazole Lauriad 50 mg Bioadhesive Buccal Tablet
Description	Number of patients with detectable plasma concentration at Visit 3 (day 7)
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

ITT (all randomized patients who took at least 1 dose of study medication)

Arm/Group Title	Miconazole Lauriad Buccal Tablet	Clotrimazole Troches
Arm/Group Description	Miconazole Lauriad 50 mg mucoadhesive buccal tablet, once daily, for 14 days	Clotrimazole troches, 10 mg, 5 times per day for 14 days
Measure Participants	290	287
Number [participants]	0 0%	0 0%

12. Secondary Outcome

Title	Susceptibility of Candida Species by Microdilution Test
Description	minimum inhibitory concentration (MIC) in nonresponders at test-of-cure visit
Time Frame	Initiation of treatment to Day 17 to 22

Outcome Measure Data

Analysis Population Description

ITT (all randomized patients who took at least 1 dose of study medication), nonresponders (participants with progression to a higher visible lesion extent score or no reduction in oral lesion extent score at the test of cure [Day 17 to 22] visit)

Arm/Group Title	Miconazole Lauriad Buccal Tablet	Clotrimazole Troches
Arm/Group Description	Miconazole Lauriad 50 mg mucoadhesive buccal tablet, once daily, for 14 days	Clotrimazole troches, 10 mg, 5 times per day for 14 days
Measure Participants	290	287
Clotrimazole MIC for C. albicans (n=9, 7)	0.0099 (0.0040)	0.0073 (0.0039)
Miconazole MIC for C. albicans (n=9, 7)	0.0764 (0.0995)	0.1664 (0.3679)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Miconazole Lauriad Buccal Tablet, Clotrimazole Troches
	Comments	Analysis for Clotrimazole minimum inhibitory concentration (MIC) between treatment groups
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1860
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Miconazole Lauriad Buccal Tablet, Clotrimazole Troches
	Comments	Analysis for Miconazole minimum inhibitory concentration (MIC) between treatment groups
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9564
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

13. Secondary Outcome

Title	Treatment Compliance
Description	Number of patients who were 100% compliant with the treatment regimen
Time Frame	Initiation of treatment to Day 14

Outcome Measure Data

Analysis Population Description

ITT (all randomized patients who took at least 1 dose of study medication)

Arm/Group Title	Miconazole Lauriad Buccal Tablet	Clotrimazole Troches
Arm/Group Description	Miconazole Lauriad 50 mg mucoadhesive buccal tablet, once daily, for 14 days	Clotrimazole troches, 10 mg, 5 times per day for 14 days
Measure Participants	290	287
Number [participants compliant]	253 87.2%	250 87.1%

Adverse Events

Time Frame	14 days study treatment, then 21 days of follow-up
Arm/Group Title	Miconazole Lauriad Buccal Tablet		Clotrimazole Troches
Arm/Group Description	Miconazole Lauriad 50 mg mucoadhesive buccal tablet, once daily, for 14 days		Clotrimazole troches, 10 mg, 5 times per day for 14 days
All Cause Mortality
	Miconazole Lauriad Buccal Tablet		Clotrimazole Troches
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Miconazole Lauriad Buccal Tablet		Clotrimazole Troches
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/290 (3.4%)		9/287 (3.1%)
Blood and lymphatic system disorders
Anaemia	3/290 (1%)	3	0/287 (0%)	0
Disseminated intravascular coagulation	1/290 (0.3%)	1	0/287 (0%)	0
General disorders
Death	0/290 (0%)	0	1/287 (0.3%)	1
Hepatobiliary disorders
Liver disorder	1/290 (0.3%)	1	0/287 (0%)	0
Infections and infestations
AIDS dementia complex	1/290 (0.3%)	2	0/287 (0%)	0
Disseminated tuberculosis	0/290 (0%)	0	1/287 (0.3%)	1
Gastroenteritis	0/290 (0%)	0	1/287 (0.3%)	1
Lower respiratory tract infection	2/290 (0.7%)	2	1/287 (0.3%)	1
Meningitis	0/290 (0%)	0	1/287 (0.3%)	1
Meningitis cryptococcal	1/290 (0.3%)	1	0/287 (0%)	0
Pneumocystis jiroveci pneumonia	1/290 (0.3%)	1	1/287 (0.3%)	1
Pneumonia	0/290 (0%)	0	2/287 (0.7%)	2
Pulmonary tuberculosis	0/290 (0%)	0	1/287 (0.3%)	1
Retroviral infection	1/290 (0.3%)	1	0/287 (0%)	0
Sepsis	0/290 (0%)	0	1/287 (0.3%)	1
Shigella infection	1/290 (0.3%)	1	0/287 (0%)	0
Injury, poisoning and procedural complications
Fall	1/290 (0.3%)	1	0/287 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/290 (0.3%)	1	1/287 (0.3%)	1
Musculoskeletal and connective tissue disorders
Muscular weakness	1/290 (0.3%)	1	0/287 (0%)	0
Renal and urinary disorders
Renal failure	1/290 (0.3%)	1	0/287 (0%)	0
Reproductive system and breast disorders
Menorrhagia	1/290 (0.3%)	1	0/287 (0%)	0
Other (Not Including Serious) Adverse Events
	Miconazole Lauriad Buccal Tablet		Clotrimazole Troches
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	85/290 (29.3%)		84/287 (29.3%)
Blood and lymphatic system disorders
Anaemia	8/290 (2.8%)	8	5/287 (1.7%)	6
Lymphopenia	5/290 (1.7%)	5	6/287 (2.1%)	6
Neutropenia	2/290 (0.7%)	2	6/287 (2.1%)	6
Gastrointestinal disorders
Diarrhea	26/290 (9%)	30	23/287 (8%)	28
Nausea	19/290 (6.6%)	25	22/287 (7.7%)	28
Vomiting	11/290 (3.8%)	11	9/287 (3.1%)	10
Abdominal pain upper	5/290 (1.7%)	5	8/287 (2.8%)	10
Dry mouth	8/290 (2.8%)	8	5/287 (1.7%)	5
General disorders
Fatigue	8/290 (2.8%)	9	6/287 (2.1%)	7
Pain	3/290 (1%)	3	8/287 (2.8%)	9
Infections and infestations
Gastroenteritis	4/290 (1.4%)	4	8/287 (2.8%)	8
Upper respiratory tract infection	6/290 (2.1%)	6	7/287 (2.4%)	7
Investigations
GGT increased	3/290 (1%)	3	8/287 (2.8%)	8
Nervous system disorders
Headache	22/290 (7.6%)	25	19/287 (6.6%)	23
Ageusia	7/290 (2.4%)	9	1/287 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	8/290 (2.8%)	8	5/287 (1.7%)	5
Pharyngolaryngeal pain	2/290 (0.7%)	2	7/287 (2.4%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.