Safety and Equivalence of a Terconazole Vaginal Suppository (Test Product) Compared to the Reference Terconazole Vaginal Suppository in the Treatment of Vulvovaginal Candidiasis

• Sponsor: Padagis LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00803738
• Collaborator: (none)
• Enrollment: 572
• Arms: 2
• Duration (Months): 12

Study Details

Study Description

Brief Summary

The objectives of this study were to demonstrate comparable safety and efficacy of Terconazole Vaginal Suppositories, 80 mg(Test Product) and Terconazole Vaginal Suppositories, 80 mg(Reference Product) in the treatment of subjects with vulvovaginal candidiasis in order to establish bioequivalence.

Condition or Disease	Intervention/Treatment	Phase
Vulvovaginal Candidiasis	Drug: Terconazole Vaginal Suppository; Drug: Terazol Vaginal Suppository	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 572 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: A Multi-center, Randomized, Investigator-blinded, Parallel-group Study, Designed to Evaluate the Safety and Clinical Equivalence of Terconazole Vaginal Suppositories, 80 mg (Test Product) and Terconazole Vaginal Suppositories, 80 mg (Reference Product) in the Treatment of Vulvovaginal Candidiasis Caused by Candida Species
• Study Start Date: Dec 1, 2002
• Actual Primary Completion Date: Dec 1, 2003
• Actual Study Completion Date: Dec 1, 2003

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Test Product Terconazole Vaginal Suppository	Drug: Terconazole Vaginal Suppository; Vaginal Suppository inserted intravaginally once daily before bedtime for 3 consecutive days
Active Comparator: Reference Product Terazol Vaginal Suppository	Drug: Terazol Vaginal Suppository; Vaginal Suppository inserted intravaginally once daily before bedtime for 3 consecutive days; Other Names: Terazol 3 suppository

Outcome Measures

Primary Outcome Measures

1. Proportion of Subjects in Each Treatment Group With Therapeutic Cure [Visit 3: Day 22-31]

   The primary efficacy measure was the proportion of subjects in each treatment group with a therapeutic cure at the Test-of-Cure visit (Visit 3). A subject was considered a therapeutic cure if the subject was a clinical cure with mycological cure.

Secondary Outcome Measures

1. Proportion of Subjects With Mycological Cure [Visit 3: Day 22-31]

   Mycological cure was defined as a negative mycological culture (no growth) for Candida albicans or other relevant baseline yeast organism.

2. Proportion of Subjects With Clinical Cure [Visit 3: Day 22-31]

   A subject was considered a clinical cure if all of the following were satisfied: All signs and symptoms with a score of 1 (mild) or 2 (moderate) at the Screening/Baseline visit were absent (score = 0), and all signs or symptoms with a score of 3 (severe) at Screening/Baseline had a score of 0 or 1. Total signs and symptoms did not worsen at any time following completion of the study treatment. Any new sign or symptom observed during the study period was determined by the Investigator not to be related to VVC. The subject did not require additional vulvovaginal or systemic antifungal therapy at any time during the study period. The subject did not use any topical drug therapy other than the study medication for the treatment of vulvovaginal irritation and/or pruritus such as topical analgesic or corticosteroid products

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Female at least 18 years of age

• Presented with symptomatic vulvovaginitis consistent with a diagnosis of moniliasis

• Willing and able to read and sign an IRB approved ICF, which included agreement to comply with all study requirements as indicated in the protocol.

Exclusion Criteria:

• History of hypersensitivity or allergy to imidazoles

• Female who was pregnant or lactating

• Was menstruating or expected the onset of menses during the treatment days

• Had evidence of any bacterial, viral or protozoal infection

• Had a history of alcoholism, drug abuse, or problems that would likely have made the subject unreliable for the study

• Had any condition or used any medication that, in the opinion of the Investigator, might have interfered with the conduct or results of the study or placed the prospective subject at increased risk

• Had participated in any investigational study within 30 days prior to study enrollment

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Padagis LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Padagis LLC
• ClinicalTrials.gov Identifier: NCT00803738
• Other Study ID Numbers: CPL-202
• First Posted: Dec 8, 2008
• Last Update Posted: Oct 13, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by Padagis LLC: Vulvovaginal Candidiasis; Terconazole
• Additional relevant MeSH terms: Candidiasis; Candidiasis, Vulvovaginal; Terconazole

Study Results

Participant Flow

Recruitment Details	Patients were recruited at 31 dermatology clinical practices.

Arm/Group Title	Terconazole Vaginal Suppositories, 80 mg - Perrigo	Terazol 3 - Terconazole Vaginal Suppositories 80 mg
Arm/Group Description	Terconazole Vaginal Suppositories, 80 mg manufactured by Perrigo applied intravaginally once daily before bedtime for 3 consecutive days	Terazol 3 manufactured by Ortho-McNeil Pharmaceutical, Inc applied intravaginally once daily before bedtime for 3 consecutive daysapplied the study medication intravaginally once daily before bedtime for 3 consecutive days
Period Title: Overall Study
STARTED	286	286
COMPLETED	192	176
NOT COMPLETED	94	110

Baseline Characteristics

Arm/Group Title	Terconazole Vaginal Suppositories, 80 mg - Perrigo	Terazol 3 - Terconazole Vaginal Suppositories 80 mg	Total
Arm/Group Description	Terconazole Vaginal Suppositories, 80 mg manufactured by Perrigo applied intravaginally once daily before bedtime for 3 consecutive days	Terazol 3 manufactured by Ortho-McNeil Pharmaceutical, Inc applied intravaginally once daily before bedtime for 3 consecutive daysapplied the study medication intravaginally once daily before bedtime for 3 consecutive days	Total of all reporting groups
Overall Participants	286	286	572
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	278 97.2%	276 96.5%	554 96.9%
>=65 years	8 2.8%	10 3.5%	18 3.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.4 (13.3)	31.6 (13.1)	32.5 (13.2)
Sex: Female, Male (Count of Participants)
Female	286 100%	286 100%	572 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	286 100%	286 100%	572 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Subjects in Each Treatment Group With Therapeutic Cure
Description	The primary efficacy measure was the proportion of subjects in each treatment group with a therapeutic cure at the Test-of-Cure visit (Visit 3). A subject was considered a therapeutic cure if the subject was a clinical cure with mycological cure.
Time Frame	Visit 3: Day 22-31

Outcome Measure Data

Analysis Population Description

Per Protocol (PP) population

Arm/Group Title	Terconazole Vaginal Suppositories, 80 mg - Perrigo	Terazol 3 - Terconazole Vaginal Suppositories 80 mg
Arm/Group Description	Terconazole Vaginal Suppositories, 80 mg manufactured by Perrigo applied intravaginally once daily before bedtime for 3 consecutive days	Terazol 3 manufactured by Ortho-McNeil Pharmaceutical, Inc applied intravaginally once daily before bedtime for 3 consecutive daysapplied the study medication intravaginally once daily before bedtime for 3 consecutive days
Measure Participants	153	147
Number [participants]	105 36.7%	93 32.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Terconazole Vaginal Suppositories, 80 mg - Perrigo, Terazol 3 - Terconazole Vaginal Suppositories 80 mg
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	For the primary clinical equivalence analysis, a 90% confidence interval was constructed on the difference in the therapeutic cure rates between the Test Product and Reference Product at the Test-of-Cure visit (Visit 3). The interval was calculated using Wald's method with Yates' continuity correction. Clinical equivalence was established if this 90% confidence interval was contained within the interval -0.20 to +0.20 (-20% to +20%).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	proportion of subjects in trtmt groups
	Estimated Value	.05
	Confidence Interval	(2-Sided) 90%; -4.30 to 15.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Proportion of Subjects With Mycological Cure
Description	Mycological cure was defined as a negative mycological culture (no growth) for Candida albicans or other relevant baseline yeast organism.
Time Frame	Visit 3: Day 22-31

Outcome Measure Data

Analysis Population Description

Per protocol population

Arm/Group Title	Terconazole Vaginal Suppositories, 80 mg - Perrigo	Terazol 3 - Terconazole Vaginal Suppositories 80 mg
Arm/Group Description	Terconazole Vaginal Suppositories, 80 mg manufactured by Perrigo applied intravaginally once daily before bedtime for 3 consecutive days	Terazol 3 manufactured by Ortho-McNeil Pharmaceutical, Inc applied intravaginally once daily before bedtime for 3 consecutive daysapplied the study medication intravaginally once daily before bedtime for 3 consecutive days
Measure Participants	153	147
Number [participants]	127 44.4%	117 40.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Terconazole Vaginal Suppositories, 80 mg - Perrigo, Terazol 3 - Terconazole Vaginal Suppositories 80 mg
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	A 90% confidence interval was constructed on the difference in the mycological cure rates between the Test Product and Reference Product at the Test-of-Cure visit (Visit 3). The interval was calculated using Wald's method with Yates' continuity correction. Clinical equivalence was established if this 90% confidence interval was contained within the interval -0.20 to +0.20 (-20% to +20%).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	proportion of subjects in trtmt groups
	Estimated Value	.05
	Confidence Interval	(2-Sided) 90%; -4.66 to 11.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Proportion of Subjects With Clinical Cure
Description	A subject was considered a clinical cure if all of the following were satisfied: All signs and symptoms with a score of 1 (mild) or 2 (moderate) at the Screening/Baseline visit were absent (score = 0), and all signs or symptoms with a score of 3 (severe) at Screening/Baseline had a score of 0 or 1. Total signs and symptoms did not worsen at any time following completion of the study treatment. Any new sign or symptom observed during the study period was determined by the Investigator not to be related to VVC. The subject did not require additional vulvovaginal or systemic antifungal therapy at any time during the study period. The subject did not use any topical drug therapy other than the study medication for the treatment of vulvovaginal irritation and/or pruritus such as topical analgesic or corticosteroid products
Time Frame	Visit 3: Day 22-31

Outcome Measure Data

Analysis Population Description

per protocol population

Arm/Group Title	Terconazole Vaginal Suppositories, 80 mg - Perrigo	Terazol 3 - Terconazole Vaginal Suppositories 80 mg
Arm/Group Description	Terconazole Vaginal Suppositories, 80 mg manufactured by Perrigo applied intravaginally once daily before bedtime for 3 consecutive days	Terazol 3 manufactured by Ortho-McNeil Pharmaceutical, Inc applied intravaginally once daily before bedtime for 3 consecutive daysapplied the study medication intravaginally once daily before bedtime for 3 consecutive days
Measure Participants	153	147
Number [participants]	117 40.9%	101 35.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Terconazole Vaginal Suppositories, 80 mg - Perrigo, Terazol 3 - Terconazole Vaginal Suppositories 80 mg
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	A 90% confidence interval was constructed on the difference in the clinical cure rates between the Test Product and Reference Product at the Test-of-Cure visit (Visit 3). The interval was calculated using Wald's method with Yates' continuity correction. Clinical equivalence was established if this 90% confidence interval was contained within the interval -0.20 to +0.20 (-20% to +20%).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	proportion of subjects in trtmt groups
	Estimated Value	.05
	Confidence Interval	(2-Sided) 90%; -1.35 to 16.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Up to day 31
Adverse Event Reporting Description	Incidence of AEs during the study was summarized by treatment group. Frequency of all AEs was tabulated by treatment group, COSTART body system, severity, and relationship to the study medication. The differences between the treatment groups were compared using statistical measures. The analyses were conducted in the ITT population only.
Arm/Group Title	Terconazole Vaginal Suppositories, 80 mg - Perrigo		Terazol 3 - Terconazole Vaginal Suppositories 80 mg
Arm/Group Description	Terconazole Vaginal Suppositories, 80 mg manufactured by Perrigo applied intravaginally once daily before bedtime for 3 consecutive days		Terazol 3 manufactured by Ortho-McNeil Pharmaceutical, Inc applied intravaginally once daily before bedtime for 3 consecutive daysapplied the study medication intravaginally once daily before bedtime for 3 consecutive days
All Cause Mortality
	Terconazole Vaginal Suppositories, 80 mg - Perrigo		Terazol 3 - Terconazole Vaginal Suppositories 80 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Terconazole Vaginal Suppositories, 80 mg - Perrigo		Terazol 3 - Terconazole Vaginal Suppositories 80 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/282 (0%)		1/275 (0.4%)
Infections and infestations
appendicitis	0/282 (0%)	0	1/275 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Terconazole Vaginal Suppositories, 80 mg - Perrigo		Terazol 3 - Terconazole Vaginal Suppositories 80 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	48/282 (17%)		54/275 (19.6%)
Infections and infestations
infection	12/282 (4.3%)	12	15/275 (5.5%)	15
Nervous system disorders
headache	36/282 (12.8%)	36	39/275 (14.2%)	39

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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