Efficacy and Safety of Natamycin and Lactulose Vaginal Suppositories in Treatment of Vulvovaginal Candidiasis

Efficacy and Safety of Vaginal Suppositories Containing Combination of Natamycin and Lactulose in Treatment of Vulvovaginal Candidiasis: International, Randomized, Controlled, Superiority Clinical Trial

The purpose is to study superior efficacy of combination of Natamycin and Lactulose (Natamycin 100 mg + Lactulose 300 mg vaginal suppositories) compared to Pimafucin (Natamycin 100 mg vaginal suppositories), or Lactulose 300 mg vaginal suppositories. The second objective of the study was to investigate the safety of the combination suppositories in the treatment of vulvovaginal candidiasis in non-pregnant adult females.

Study Overview

• Status: Completed
• Conditions: Vulvovaginal Candidiasis, Genital
• Intervention / Treatment: Combination product: Natamycin + Lactulose 100 mg + 300 mg vaginal suppositories; Drug: Lactulose 300 mg vaginal suppositories; Drug: Pimafucin® (natamycin) 100 mg vaginal suppositories

• Study Type: Interventional
• Enrollment (Actual): 218
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Department of Reproductive Medicine and Surgery at the A.I. Evdokimov Moscow State Medical and Dental University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• two or more of the following signs and symptoms of vulvovaginal candidiasis: white or yellowish-white curd-like, thick or creamy vaginal discharge; vulvar itching, burning and pain; anogenital itching and burning; discomfort in the vulva; itching, burning, painful urination (dysuria);
• yeast cells in the vaginal swab specimen;
• vaginal pH ≤ 4.5.

Exclusion Criteria:

• a clinical and laboratory diagnosis of bacterial vaginosis; vulvovaginitis caused by specific pathogens such as Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhoeae; chronic inflammatory, atrophic, or oncologic diseases of the female genital tract; previous surgery on external or internal genitalia within 6 months; childbirth and abortion within 6 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Natamycin + Lactulose 100 mg + 300 mg vaginal suppositories	Combination product: Natamycin + Lactulose 100 mg + 300 mg vaginal suppositories; 1 suppository once daily at bedtime for 6 days
Active Comparator: Lactulose 300 mg vaginal suppositories	Drug: Lactulose 300 mg vaginal suppositories; 1 suppository once daily at bedtime for 6 days
Active Comparator: Pimafucin® (natamycin) 100 mg vaginal suppositories	Drug: Pimafucin® (natamycin) 100 mg vaginal suppositories; 1 suppository once daily at bedtime for 6 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion (%) of patients who achieved a clinical response (recovery) at Visit 2	The clinical response was considered as the absence of significant signs and symptoms of VVC (white or yellowish-white curd-like, thick, or creamy vaginal discharge; vulvar itching, burning and pain; anogenital itching and burning; discomfort in the vulva; itching, burning, painful urination [dysuria])	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion (%) of patients with the clinical response at Visit 3	The clinical response was considered as the absence of significant signs and symptoms of VVC (white or yellowish-white curd-like, thick, or creamy vaginal discharge; vulvar itching, burning and pain; anogenital itching and burning; discomfort in the vulva; itching, burning, painful urination [dysuria])	24 days
Proportion (%) of patients with microscopic recovery (absence of Candida spp. at Visits 2 and 3	The vaginal culture test for Candida spp. was used for the microscopic assessment	24 days
Proportion of patients with overall (clinical and microscopic) recovery at Visits 2 and 3	The vaginal culture test was used for the microscopic assessment	24 days
Patient's efficacy assessment by the 5-point scale at Visits 2, 3	The patient completed a questionnaire in the presence of the investigating physician as part of the efficacy assessment. The questionnaire contained closed-ended responses ranging from 1 point (no clinical symptoms) to 5 points (severe clinical symptoms)	24 days
Microscopic change in lactobacilli count in vaginal specimens at Visits 2 and 3 compared to baseline (Visit 0)	Microscopic change in lactobacilli count in vaginal specimens at Visits 2 and 3	24 days
Incidence of adverse events	incidence of any adverse events, an incidence of serious adverse events (SAEs), an incidence of AEs and SAEs probably related (in the investigator's opinion) with the study drug at the study dose, and an incidence of AEs and SAEs that led to study drug discontinuation.	24 days

Collaborators and Investigators

• Sponsor: Avva Rus, JSC

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2022
• Primary Completion (Actual): July 26, 2023
• Study Completion (Actual): September 22, 2023

Study Registration Dates

• First Submitted: May 8, 2024
• First Submitted That Met QC Criteria: May 8, 2024
• First Posted (Actual): May 13, 2024

Study Record Updates

• Last Update Posted (Actual): May 13, 2024
• Last Update Submitted That Met QC Criteria: May 8, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: vulvovaginal candidiasis; itching; Lactulose; Natamycin
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Vaginal Diseases; Vulvar Diseases; Vaginitis; Vulvitis; Vulvovaginitis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Candidiasis; Candidiasis, Vulvovaginal; Anti-Infective Agents, Local; Anti-Infective Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Antifungal Agents; Lactulose; Natamycin
• Other Study ID Numbers: 12/21-AVVA RUS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No