SMART GIVES: Multi-Center Study of New Medications to Treat Vaginal Infections

• Sponsor: Curatek Pharmaceuticals, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02308033
• Collaborator: (none)
• Enrollment: 204
• Locations: 35
• Arms: 2
• Actual Duration (Months): 24
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of metronidazole gel in the treatment of vaginal infections.

Condition or Disease	Intervention/Treatment	Phase
Vaginal Infection	Drug: Metronidazole; Drug: Gel vehicle	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 204 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Solubilized Metronidazole And/oR Terconazole Gels Intra-Vaginal Efficacy and Safety
• Actual Study Start Date: Jun 1, 2015
• Actual Primary Completion Date: Jun 1, 2017
• Actual Study Completion Date: Jun 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Metronidazole vaginal gel One applicator full at bedtime	Drug: Metronidazole
Placebo Comparator: Gel vehicle One applicator full at bedtime	Drug: Gel vehicle

Outcome Measures

Primary Outcome Measures

1. Clinical Cure as Assessed by the Investigator at the Test-of-cure Visit [7-14 days after beginning treatment]

   The percentage of participants with clinical cure in each arm was compared. Clinical cure of bacterial vaginosis is defined as 1. discharge has returned to normal/physiologic, 2. the whiff test is negative for any amine "fishy" odor, 3. the saline wet mount is <20% clue cells

Secondary Outcome Measures

1. Improvement of BV Clue Cells [7-14 days after beginning treatment]

   Clue cells on wet mount were assessed and categorized as absent (<20%) or present (>=20%). Absence of clue cells is associated with improvement. The comparison was for percentage between arms for clue cells absent (<20%).

2. Microbiologic Improvement/Cure [7-14 days after beginning treatment]

   For bacterial vaginosis (BV), Gram stain Nugent scores are catergized as normal (0 to 3), intermediate (4 to 6) or BV (7 to 10). Normal scores are associated with BV microbiologic cure. The percentage of participants with normal scores were compared between treatments.

3. Number of Participants Reporting Complete Resolution of Symptoms by Test of Cure Visit [7-14 days after beginning treatment]

   Subjects reported if symptoms completely resolved and the date of resolution. The percentage of participants reporting complete resolution of symptoms was compared between arms.

4. Number of Participants With Treatment Emergent Adverse Events [Any time during study participation (up to 30 days)]

   Adverse events were collected at study visits, from subject diaries and from spontaneous reports

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• A clinical diagnosis of vaginal infection that is confirmed by laboratory testing and:

• Capable of providing written informed consent or assent

• Currently not menstruating and not anticipating menses during treatment

• If heterosexually active, subject must be post-menopausal for ≥ 1 year, surgically sterile, or practicing an acceptable form of birth control

• Negative pregnancy test

• Other criteria as identified in the protocol

Exclusion Criteria:

• Other infectious causes of vulvovaginitis

• Subject has recently used, or is expected to require the concomitant use of prohibited medications/products

• Nursing mother

• Use of any investigational drug within 30 days of enrollment

• History of hypersensitivity to any ingredient/component of the formulations

• Other criteria as identified in the protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35294
2	MomDoc Womens Health Research	Scottsdale	Arizona	United States	85251
3	NEA Baptist Clinic	Jonesboro	Arkansas	United States	72401
4	Gossmont Center for Clinical Research	La Mesa	California	United States	91942
5	Genesis Center for Clinical Research	San Diego	California	United States	92103
6	Medical Center for Clinical Research	San Diego	California	United States	92108
7	Downtown Women's Health Care	Denver	Colorado	United States	80209
8	Red Rocks Ob/Gyn	Lakewood	Colorado	United States	80228
9	Women's Health CT Ob/Gyn	Bridgeport	Connecticut	United States	06606
10	Segal Institute for Clinical Research	North Miami	Florida	United States	33161
11	Discovery Clinical Research	Plantation	Florida	United States	33324
12	Georgia Regents University	Augusta	Georgia	United States	30912
13	Atlanta North Gynecology	Roswell	Georgia	United States	30075
14	Mount Vernon CLinical Research	Sandy Springs	Georgia	United States	30328
15	Rosemark Womens Care Specialists	Idaho Falls	Idaho	United States	83404
16	Women's Health Practice	Champaign	Illinois	United States	61802
17	Women's Healthcare Specialists, PC	Kalamazoo	Michigan	United States	49009
18	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
19	Women's Clinic of Lincoln	Lincoln	Nebraska	United States	68510
20	Legacy Women's Health	Las Vegas	Nevada	United States	89123
21	R. Garn Mabey Jr., MD Gynecology	Las Vegas	Nevada	United States	89128
22	Lawrence Ob/Gyn Clinical Research LLC	Lawrenceville	New Jersey	United States	08648
23	Women's Health Research Center	Plainsboro	New Jersey	United States	08536
24	Suffolk OB/GYN	Port Jefferson	New York	United States	11777
25	East Carolina Women's Center	New Bern	North Carolina	United States	28562
26	Wake Research Associates	Raleigh	North Carolina	United States	27612
27	Radiant Research	Columbus	Ohio	United States	43212
28	Drexel University	Philadelphia	Pennsylvania	United States	19102
29	Philapelphia Clinical Research, LLC	Philadelphia	Pennsylvania	United States	19114
30	Magee-Womens Hospital of UPMC	Pittsburgh	Pennsylvania	United States	15213
31	James T. Martin, MD	North Charleston	South Carolina	United States	29406
32	The Jackson Clinic	Jackson	Tennessee	United States	38305
33	TMC Life Research, Inc.	Houston	Texas	United States	77054
34	Harborview Medical Center	Seattle	Washington	United States	98104
35	Women's Clinical Research Center	Seattle	Washington	United States	98105

Sponsors and Collaborators

• Curatek Pharmaceuticals, LLC

Investigators

• Study Director: Robert J Borgman, Ph.D., Curatek Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Mar 12, 2015
• Statistical Analysis Plan - May 1, 2018

More Information

Publications

None provided.

• Responsible Party: Curatek Pharmaceuticals, LLC
• ClinicalTrials.gov Identifier: NCT02308033
• Other Study ID Numbers: MTC-001 (Trial 2)
• First Posted: Dec 4, 2014
• Last Update Posted: Jul 27, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Infections; Metronidazole

Study Results

Participant Flow

Arm/Group Title	Metronidazole Vaginal Gel	Gel Vehicle
Arm/Group Description	One applicator full at bedtime Metronidazole	One applicator full at bedtime Gel vehicle
Period Title: Overall Study
STARTED	102	102
COMPLETED	76	83
NOT COMPLETED	26	19

Baseline Characteristics

Arm/Group Title	Metronidazole Vaginal Gel	Gel Vehicle	Total
Arm/Group Description	One applicator full at bedtime Metronidazole	One applicator full at bedtime Gel vehicle	Total of all reporting groups
Overall Participants	76	83	159
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.1 (8.76)	35.8 (10.48)	34.5 (9.76)
Sex: Female, Male (Count of Participants)
Female	76 100%	83 100%	159 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	9 11.8%	9 10.8%	18 11.3%
Not Hispanic or Latino	67 88.2%	74 89.2%	141 88.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.3%	0 0%	1 0.6%
Asian	0 0%	2 2.4%	2 1.3%
Native Hawaiian or Other Pacific Islander	0 0%	1 1.2%	1 0.6%
Black or African American	47 61.8%	45 54.2%	92 57.9%
White	25 32.9%	32 38.6%	57 35.8%
More than one race	3 3.9%	3 3.6%	6 3.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	76 100%	83 100%	159 100%

Outcome Measures

1. Primary Outcome

Title	Clinical Cure as Assessed by the Investigator at the Test-of-cure Visit
Description	The percentage of participants with clinical cure in each arm was compared. Clinical cure of bacterial vaginosis is defined as 1. discharge has returned to normal/physiologic, 2. the whiff test is negative for any amine "fishy" odor, 3. the saline wet mount is <20% clue cells
Time Frame	7-14 days after beginning treatment

Outcome Measure Data

Analysis Population Description

mITT population (Baseline Gram stain Nugent score of 4 or more and used at least one dose of study medication)

Arm/Group Title	Metronidazole Vaginal Gel	Gel Vehicle
Arm/Group Description	One applicator full at bedtime Metronidazole	One applicator full at bedtime Gel vehicle
Measure Participants	76	83
Count of Participants [Participants]	47 61.8%	18 21.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Metronidazole Vaginal Gel, Gel Vehicle
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Chi-squared, Corrected
	Comments

2. Secondary Outcome

Title	Improvement of BV Clue Cells
Description	Clue cells on wet mount were assessed and categorized as absent (<20%) or present (>=20%). Absence of clue cells is associated with improvement. The comparison was for percentage between arms for clue cells absent (<20%).
Time Frame	7-14 days after beginning treatment

Outcome Measure Data

Analysis Population Description

mITT population (Baseline Gram stain Nugent score of 4 or more and used at least one dose of study medication)

Arm/Group Title	Metronidazole Vaginal Gel	Gel Vehicle
Arm/Group Description	One applicator full at bedtime Metronidazole	One applicator full at bedtime Gel vehicle
Measure Participants	76	83
Clue cells absent	52 68.4%	19 22.9%
Clue cells present	17 22.4%	58 69.9%
Data missing	7 9.2%	6 7.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Metronidazole Vaginal Gel, Gel Vehicle
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Chi-squared, Corrected
	Comments

3. Secondary Outcome

Title	Microbiologic Improvement/Cure
Description	For bacterial vaginosis (BV), Gram stain Nugent scores are catergized as normal (0 to 3), intermediate (4 to 6) or BV (7 to 10). Normal scores are associated with BV microbiologic cure. The percentage of participants with normal scores were compared between treatments.
Time Frame	7-14 days after beginning treatment

Outcome Measure Data

Analysis Population Description

mITT population (Baseline Gram stain Nugent score of 4 or more and used at least one dose of study medication)

Arm/Group Title	Metronidazole Vaginal Gel	Gel Vehicle
Arm/Group Description	One applicator full at bedtime Metronidazole	One applicator full at bedtime Gel vehicle
Measure Participants	76	83
Normal Nugent score	38 50%	7 8.4%
Intermediate Nugent score	16 21.1%	11 13.3%
BV Nugent score	15 19.7%	59 71.1%
Not taken	7 9.2%	6 7.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Metronidazole Vaginal Gel, Gel Vehicle
	Comments	Comparison of normal Nugent scores at 7-14 days
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Chi-squared, Corrected
	Comments

4. Secondary Outcome

Title	Number of Participants Reporting Complete Resolution of Symptoms by Test of Cure Visit
Description	Subjects reported if symptoms completely resolved and the date of resolution. The percentage of participants reporting complete resolution of symptoms was compared between arms.
Time Frame	7-14 days after beginning treatment

Outcome Measure Data

Analysis Population Description

mITT population (Baseline Gram stain Nugent score of 4 or more and used at least one dose of study medication)

Arm/Group Title	Metronidazole Vaginal Gel	Gel Vehicle
Arm/Group Description	One applicator full at bedtime Metronidazole	One applicator full at bedtime Gel vehicle
Measure Participants	76	83
Count of Participants [Participants]	43 56.6%	32 38.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Metronidazole Vaginal Gel, Gel Vehicle
	Comments	Comparison of the number of subjects whose reported their symptoms completely resolved
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.034
	Comments
	Method	Chi-squared, Corrected
	Comments

5. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events
Description	Adverse events were collected at study visits, from subject diaries and from spontaneous reports
Time Frame	Any time during study participation (up to 30 days)

Outcome Measure Data

Analysis Population Description

The safety population includes all subjects randomized to treatment and administered at least one dose of study drug.

Arm/Group Title	Metronidazole Vaginal Gel	Gel Vehicle
Arm/Group Description	One applicator full at bedtime Metronidazole	One applicator full at bedtime Gel vehicle
Measure Participants	96	97
Count of Participants [Participants]	42 55.3%	31 37.3%

Adverse Events

Time Frame	Adverse events were collected over the entire course of the study (up to 30 days after beginning treatment).
Adverse Event Reporting Description	Adverse events were collected through direct questioning at each post-baseline visit, by participant diaries, and by spontaneous reporting. The safety population includes all participants randomized to treatment and administered at least one dose of study drug, and includes subjects who had a normal gram stain Nugent score at the baseline visit.
Arm/Group Title	Metronidazole Vaginal Gel		Gel Vehicle
Arm/Group Description	One applicator full at bedtime Metronidazole		One applicator full at bedtime Gel vehicle
All Cause Mortality
	Metronidazole Vaginal Gel		Gel Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/96 (0%)		0/97 (0%)
Serious Adverse Events
	Metronidazole Vaginal Gel		Gel Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/96 (0%)		0/97 (0%)
Other (Not Including Serious) Adverse Events
	Metronidazole Vaginal Gel		Gel Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/96 (26%)		10/97 (10.3%)
Infections and infestations
Vulvovaginal candidiasis	7/96 (7.3%)	7	1/97 (1%)	1
Vulvovaginal mycotic infection	5/96 (5.2%)	5	1/97 (1%)	1
Nervous system disorders
Headache	5/96 (5.2%)	5	2/97 (2.1%)	2
Reproductive system and breast disorders
Vulvovaginal pruritis	8/96 (8.3%)	8	6/97 (6.2%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Investigators have the right to disclose and publish results of the Study conducted by them; provided that, in order to protect any Sponsor confidential information, Investigator shall submit to Sponsor manuscripts at least 30 days before submission for publication or 10 days before public presentation. After that time, Investigator is free to submit the manuscript for publication or deliver the presentation, provided Investigator removes any confidential information as directed by Sponsor