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
| Registry | NCT03115073 |
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| Status | Completed |
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| Phase | Phase 2 / Phase 3 |
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| Study type | Interventional; randomized, parallel, masking: triple, treatment |
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| Enrollment | 84 (Actual) |
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| Sponsor | ProFem GmbH (Industry) |
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| Conditions | Vulvovaginal Candidiasis (VVC) |
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| Interventions | Candiplus, Clotrimazole (Drug) |
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| Dates | start 2017-04-04, primary completion 2018-07-30, completion 2018-07-30, first posted 2017-04-14, last updated 2019-03-14 |
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| Locations | 3 sites in Austria |
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-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.
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+Arms and interventions
| Arm | Type | Interventions | Description |
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| 0,2% Candiplus | Experimental | Drug: Candiplus | Candiplus® 0.2% |
| 0,3% Candiplus | Experimental | Drug: Candiplus | Candiplus® 0.3% |
| 0,4% Candiplus | Experimental | Drug: Candiplus | Candiplus® 0.4% |
| Clotri mono | Active comparator | Drug: Clotrimazole | Clotrimazole mono |
- Candiplus (Drug): Administration of Candiplus
- Clotrimazole (Drug): Administration of Clotrimazole
+Outcome measures
Primary outcomes
- 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). [within 60 minutes after application and at day 7 (± 3 days) after drug application]: 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 outcomes
- Number of patients with local adverse events and serious adverse events (SAEs) with causal relationship to study medication [overall study period (max. 65 days)]: 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) [within 60 minutes after drug application]: 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) [day 7 ±3 days after drug application]: 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) [day 7 ±3 days after drug application]: 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) [day 7 ±3 days after drug application]: 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 [overall study period (max. 65 days)]: The time to improvement of symptoms after the first intervention will be documented.
- Time to termination of clinical symptoms [overall study period (max. 65 days)]: The time to termination of clinical symptoms will be documented.
- Clinical relapse of VVC during follow-up period [follow-up period (from day 8 to day 60)]: Every clinical relapse of VVC during the follow-up period will be documented.
+Eligibility
Sex: Female, ages: 18 Years to any
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
+Locations (3)
| Facility | City | Country | Status |
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| Medical University Innsbruck | Innsbruck | Austria | |
| Bezirkskrankenhaus Schwaz | Schwaz | Austria | |
| Medical University Vienna | Vienna | Austria | |
+Publications
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+Investigators