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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- ProFem GmbH
- 入组人数
- 84
- 试验地点
- 3
- 主要终点
- 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).
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
0,2% Candiplus
Candiplus® 0.2%
干预措施: Candiplus (Drug)
0,3% Candiplus
Candiplus® 0.3%
干预措施: Candiplus (Drug)
0,4% Candiplus
Candiplus® 0.4%
干预措施: Candiplus (Drug)
Clotri mono
Clotrimazole mono
干预措施: Clotrimazole (Drug)
结局指标
主要结局
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).
时间窗: 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.
次要结局
- Time to termination of clinical symptoms(overall study period (max. 65 days))
- Clinical relapse of VVC during follow-up period(follow-up period (from day 8 to day 60))
- 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)
- Time to improvement of symptoms after first intervention(overall study period (max. 65 days))
- Number of patients with local adverse events and serious adverse events (SAEs) with causal relationship to study medication(overall study period (max. 65 days))
- 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)
- 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)
- 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)