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ProF-001_Phase IIa

Primary Purpose

Vulvovaginal Candidiasis (VVC)

Status
Completed
Phase
Phase 2
Locations
Austria
Study Type
Interventional
Intervention
Candiplus
Clotrimazole
Sponsored by
ProFem GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Vulvovaginal Candidiasis (VVC) focused on measuring Vulvovaginal candidiasis, Candiplus, Clotrimazole, Safety, Tolerability, Clinical efficacy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Premenopausal female patients ≥ 18 years old

  • Patients suffering from an acute episode of vulvovaginal candidiasis, characterized by:

    • Positive vaginal smear (native, KOH) for budding yeasts and/or fungal (pseudo-) hyphae, normal or intermediate flora (G I and G II)
    • Positive clinical symptoms (itching, burning, irritation, edema, erythema, excoriations), with a subjective symptom score of at least 3 (0=absent, 1=mild, 2=moderate, and 3=severe), with score being at least moderate for at least 1 subjective symptom and itching being present, and a total sign and symptom score of at least 4
  • Readiness for sexual abstinence from start of treatment until test of cure (TOC) - visit
  • Sufficient knowledge of German language to understand trial instructions and rating scales, and ability to comply with treatment
  • Written informed consent prior to enrolment

Exclusion Criteria:

  • Known hypersensitivity to any ingredient of the investigational medicinal product
  • Pregnancy or breast feeding at time of screening
  • Menstrual bleeding (spotting is not an exclusion criterion) during the first three days of treatment
  • Acute cystitis
  • Patients with clinical signs of other infectious causes of vulvovaginitis: bacterial vaginosis (GIII), trichomonas vaginalis, herpes simplex genitalis
  • Treatment with antimycotics (systemic or vaginal) within 7 days of randomization
  • Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs)
  • Patients with other clinical gynecological abnormalities, such as infections of the upper urogenital tract (pelvic inflammatory disease, adnexitis)
  • Subjects with another vaginal or vulvar condition that would confound the interpretation of clinical response (e.g. Lichen sclerosus, neuropathic pain)
  • Subjects who will be under treatment or surgery for gynecological pathologies during the study period, i.e, cervical intraepithelial neoplasia, cervical carcinoma, other neoplasms
  • Known alcohol, drug or medication abuse
  • Any clinically relevant concomitant condition that could compromise the objectives of this study and/ or the patient's compliance (eg. known immune deficiency syndrome with clinical relevance at time of screening)
  • Participation in another interventional clinical trial within the last 30 days
  • Employee at the study site, spouse/partner or relative of any study staff (e.g., investigator, sub-investigators, or study nurse) or relationship to the sponsor

Sites / Locations

  • Medical University Innsbruck
  • Bezirkskrankenhaus Schwaz
  • Medical University Vienna

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Active Comparator

Arm Label

0,2% Candiplus

0,3% Candiplus

0,4% Candiplus

Clotri mono

Arm Description

Candiplus® 0.2%

Candiplus® 0.3%

Candiplus® 0.4%

Clotrimazole mono

Outcomes

Primary Outcome Measures

Combined outcome measure of: Symptom relief within the first 60 minutes (after application of investigational product or active control) and clinical cure at day 7 (± 3 days).
As the primary outcome symptom relief within the first 60 minutes will be documented. A reduction of the subjective symptom score ≥ 2 is expected. Furthermore clinical cure at day 7 will be documented. Clinical cure is defined as absence of signs and symptoms of VVC.

Secondary Outcome Measures

Number of patients with local adverse events and serious adverse events (SAEs) with causal relationship to study medication
All local adverse events and serious adverse events with causal relationship to study medication (drug reaction) will be documented in a descriptive manner.
Symptom relief within the first 60 minutes (after application of investigational product or active control, reduction of the subjective symptom score ≥ 2)
Symptom relief within the first 60 minutes will be documented. A reduction of the subjective symptom score ≥ 2 is expected.
Clinical cure (absence of signs and symptoms of VVC) at the TOC visit (=day 7/ accepted time window ±3days)
Clinical cure at day 7 will be documented. Clinical cure is defined as absence of signs and symptoms of VVC.
Mycological outcome: Vaginal swab culture negative for growth of Candida albicans and/or Candida species at the TOC visit (day 7 / ±3days)
A vaginal swab culture will be taken on day 7 / ±3days. The test result is expected to be negative for growth of Candida albicans and/or Candida species.visit (day 7 / ±3days)
Responder outcome: absence of signs and symptoms plus vaginal swab culture negative for growth of Candida albicans and/or Candida species at the TOC visit (day 7 / ±3days)
Presence or absence of signs and symptoms will be documented. Vaginal swab culture is expected to be negative for growth of Candida albicans and/or Candida species at the TOC visit.
Time to improvement of symptoms after first intervention
The time to improvement of symptoms after the first intervention will be documented.
Time to termination of clinical symptoms
The time to termination of clinical symptoms will be documented.
Clinical relapse of VVC during follow-up period
Every clinical relapse of VVC during the follow-up period will be documented.

Full Information

First Posted
March 13, 2017
Last Updated
March 13, 2019
Sponsor
ProFem GmbH
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1. Study Identification

Unique Protocol Identification Number
NCT03115073
Brief Title
ProF-001_Phase IIa
Official Title
A Phase IIa Randomized, Active-controlled, Double-blind, Dose-escalation Study in Patients With Vulvovaginal Candidiasis to Evaluate Dose Response Relationship of Clinical Efficacy, Safety and Tolerability of Topically Administered ProF-001
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
April 4, 2017 (Actual)
Primary Completion Date
July 30, 2018 (Actual)
Study Completion Date
July 30, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ProFem GmbH

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a multi-center, randomized, prospective, active-controlled, double-blind, dose-escalation study comparing dose response of clinical efficacy, safety, local tolerability of three different doses of ProF-001/Candiplus® (Candiplus® 0.2%, Candiplus® with 0.3%, Candiplus® with 0.4%) to 1% clotrimazole vaginal cream. Patients with acute episode of vulvovaginal candidiasis (VVC) will be randomized to receive a daily dose of either 5 ml (intravaginal) of Candiplus® at three different doses for the first 3 days and 2.5 ml for the remaining 3 days or 5 ml (intravaginal) application of 1% clotrimazole cream over the first 3 days and 2.5 ml for the remaining 3 days according to the following scheme (with each application 2 cm of cream will be applied to the vulvar region): Cohort 1: Candiplus® 0.2% versus clotrimazole mono Cohort 2: Candiplus® 0.3% versus clotrimazole mono Cohort 3: Candiplus® 0.4% versus clotrimazole mono Randomization into the cohorts will occur consecutively from the lowest dose to the highest dose, i.e. patients will be randomized first in cohort 1 and finally in cohort 3. The proposed study is - after a pilot study to assess critical pharmacokinetic data - the second study within a clinical trial program with the objective to develop a new combination therapy for the treatment of vulvovaginal candidiasis. The new combination consists of two registered drug substances.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vulvovaginal Candidiasis (VVC)
Keywords
Vulvovaginal candidiasis, Candiplus, Clotrimazole, Safety, Tolerability, Clinical efficacy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
84 (Actual)

8. Arms, Groups, and Interventions

Arm Title
0,2% Candiplus
Arm Type
Experimental
Arm Description
Candiplus® 0.2%
Arm Title
0,3% Candiplus
Arm Type
Experimental
Arm Description
Candiplus® 0.3%
Arm Title
0,4% Candiplus
Arm Type
Experimental
Arm Description
Candiplus® 0.4%
Arm Title
Clotri mono
Arm Type
Active Comparator
Arm Description
Clotrimazole mono
Intervention Type
Drug
Intervention Name(s)
Candiplus
Intervention Description
Administration of Candiplus
Intervention Type
Drug
Intervention Name(s)
Clotrimazole
Intervention Description
Administration of Clotrimazole
Primary Outcome Measure Information:
Title
Combined outcome measure of: Symptom relief within the first 60 minutes (after application of investigational product or active control) and clinical cure at day 7 (± 3 days).
Description
As the primary outcome symptom relief within the first 60 minutes will be documented. A reduction of the subjective symptom score ≥ 2 is expected. Furthermore clinical cure at day 7 will be documented. Clinical cure is defined as absence of signs and symptoms of VVC.
Time Frame
within 60 minutes after application and at day 7 (± 3 days) after drug application
Secondary Outcome Measure Information:
Title
Number of patients with local adverse events and serious adverse events (SAEs) with causal relationship to study medication
Description
All local adverse events and serious adverse events with causal relationship to study medication (drug reaction) will be documented in a descriptive manner.
Time Frame
overall study period (max. 65 days)
Title
Symptom relief within the first 60 minutes (after application of investigational product or active control, reduction of the subjective symptom score ≥ 2)
Description
Symptom relief within the first 60 minutes will be documented. A reduction of the subjective symptom score ≥ 2 is expected.
Time Frame
within 60 minutes after drug application
Title
Clinical cure (absence of signs and symptoms of VVC) at the TOC visit (=day 7/ accepted time window ±3days)
Description
Clinical cure at day 7 will be documented. Clinical cure is defined as absence of signs and symptoms of VVC.
Time Frame
day 7 ±3 days after drug application
Title
Mycological outcome: Vaginal swab culture negative for growth of Candida albicans and/or Candida species at the TOC visit (day 7 / ±3days)
Description
A vaginal swab culture will be taken on day 7 / ±3days. The test result is expected to be negative for growth of Candida albicans and/or Candida species.visit (day 7 / ±3days)
Time Frame
day 7 ±3 days after drug application
Title
Responder outcome: absence of signs and symptoms plus vaginal swab culture negative for growth of Candida albicans and/or Candida species at the TOC visit (day 7 / ±3days)
Description
Presence or absence of signs and symptoms will be documented. Vaginal swab culture is expected to be negative for growth of Candida albicans and/or Candida species at the TOC visit.
Time Frame
day 7 ±3 days after drug application
Title
Time to improvement of symptoms after first intervention
Description
The time to improvement of symptoms after the first intervention will be documented.
Time Frame
overall study period (max. 65 days)
Title
Time to termination of clinical symptoms
Description
The time to termination of clinical symptoms will be documented.
Time Frame
overall study period (max. 65 days)
Title
Clinical relapse of VVC during follow-up period
Description
Every clinical relapse of VVC during the follow-up period will be documented.
Time Frame
follow-up period (from day 8 to day 60)

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Premenopausal female patients ≥ 18 years old Patients suffering from an acute episode of vulvovaginal candidiasis, characterized by: Positive vaginal smear (native, KOH) for budding yeasts and/or fungal (pseudo-) hyphae, normal or intermediate flora (G I and G II) Positive clinical symptoms (itching, burning, irritation, edema, erythema, excoriations), with a subjective symptom score of at least 3 (0=absent, 1=mild, 2=moderate, and 3=severe), with score being at least moderate for at least 1 subjective symptom and itching being present, and a total sign and symptom score of at least 4 Readiness for sexual abstinence from start of treatment until test of cure (TOC) - visit Sufficient knowledge of German language to understand trial instructions and rating scales, and ability to comply with treatment Written informed consent prior to enrolment Exclusion Criteria: Known hypersensitivity to any ingredient of the investigational medicinal product Pregnancy or breast feeding at time of screening Menstrual bleeding (spotting is not an exclusion criterion) during the first three days of treatment Acute cystitis Patients with clinical signs of other infectious causes of vulvovaginitis: bacterial vaginosis (GIII), trichomonas vaginalis, herpes simplex genitalis Treatment with antimycotics (systemic or vaginal) within 7 days of randomization Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) Patients with other clinical gynecological abnormalities, such as infections of the upper urogenital tract (pelvic inflammatory disease, adnexitis) Subjects with another vaginal or vulvar condition that would confound the interpretation of clinical response (e.g. Lichen sclerosus, neuropathic pain) Subjects who will be under treatment or surgery for gynecological pathologies during the study period, i.e, cervical intraepithelial neoplasia, cervical carcinoma, other neoplasms Known alcohol, drug or medication abuse Any clinically relevant concomitant condition that could compromise the objectives of this study and/ or the patient's compliance (eg. known immune deficiency syndrome with clinical relevance at time of screening) Participation in another interventional clinical trial within the last 30 days Employee at the study site, spouse/partner or relative of any study staff (e.g., investigator, sub-investigators, or study nurse) or relationship to the sponsor
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Herbert Kiss, Ao.Univ.Prof.Dr.
Organizational Affiliation
Medical University of Vienna
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical University Innsbruck
City
Innsbruck
Country
Austria
Facility Name
Bezirkskrankenhaus Schwaz
City
Schwaz
Country
Austria
Facility Name
Medical University Vienna
City
Vienna
Country
Austria

12. IPD Sharing Statement

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Voltarol Suppositories 12.5 mg, 25 mg, 50 mg, 100 mg, UK SmPC 2013

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ProF-001_Phase IIa

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