A Pivotal, Randomized, Double-blind, Vehicle-controlled Study to Evaluate WR 279,396 and Paromomycin Alone to Treat Cutaneous Leishmaniasis (in Tunisia)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 375
- 试验地点
- 1
- 主要终点
- Final Clinical Cure Rate
研究概览
简要总结
This study will test the ability of the topical cream WR 279,396 to treat the skin lesions caused by the parasite called leishmania. WR 279,396 is an antibiotic preparation that contains paromomycin + gentamicin. This cream will be compared to the effect of a topical cream containing paromomycin alone and to a placebo cream that contains no antibiotics. Therefore, this study will have three groups of patients, and they will be assigned to one of these treatments randomly. The study will be carried out without the patient or the physician knowing which cream is being used for which patient. The goal is to determine if WR 279,396 cream or the paromomycin cream is better than placebo, and if WR 279,396 is better than paromomycin alone.
详细描述
This is an efficacy study to test the ability of WR 279,396 topical cream to treat uncomplicated cutaneous leishmaniasis caused primarily by Leishmania major in adults and children in Tunisia where the disease in endemic. A total of 375 volunteers will be randomized to the three arms described above to determine product efficacy. Safety data in all three arms will also be collected.
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
- 5 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The subject was age 5 years or older, but less than 65 years.
- •The subject was able to understand the information provided to him/her and give written informed consent. Consent was obtained from the parent/guardian of subjects who were < 18 years old. Children 12 to < 18 years old were asked to sign the written assent form. Witnessed verbal assent was obtained from subjects 5 to 11 years old.
- •The subject was a male or female who was generally healthy.
- •The subject had cutaneous lesions diagnosed as leishmaniasis in the index lesion by: (1) the identification of promastigotes in a culture of an aspirated lesion, or (2) the microscopic identification of Leishmania amastigotes on a DifQuik or Giemsa stained smear obtained from a lesion scraping.
- •The subject had five or fewer cutaneous lesions.
- •The subject had one lesion, which would be designated as the index lesion, that was ≥ 1 and < 5 cm in its greatest diameter and primarily ulcerative, ie, not purely verrucous or nodular.
- •The subject was willing to forego other forms of treatment for CL, including other investigational treatment during the study.
- •In the opinion of the principal investigator, the subject or subject's parent/guardian was capable of understanding and complying with the protocol
- •Exclusion Criteria
- •The subject received previous treatment for leishmaniasis (including WR 279,396) within the last 6-months, with the exception of mercurochrome.
- •The subject had difficulty complying with instructions on maintaining the dressing, eg, due to life style activities or age.
- •The subject had only a single lesion whose characteristics included any of the following: verrucous or nodular lesion, ≥ 5 cm in its greatest diameter, < 1 cm or located on the ear, or other location that in the opinion of the principal investigator would be difficult to maintain application of study drug topically.
- •The subject had a lesion due to Leishmania that involved the mucosa.
- •The subject had signs or symptoms of disseminated disease, ie, clinically significant lymphadenitis with nodules that were painful and > 1 cm in the lymphatic drainage of the ulcer.
- •The subject was a female with a positive urine pregnancy test, or who was breast feeding or lactating.
- •The subject had an active malignancy or had a history of a solid, metastatic or hematologic malignancy, with the exception of a basal or squamous cell carcinoma of the skin that had been removed.
- •The subject had a significant organ abnormality or chronic disease that, in the opinion of the investigator, would warrant exclusion of the subject from the study or would prevent the subject from completing the study.
- •The subject was receiving any of the following medications: any medication containing pentavalent antimony, including stibogluconate sodium (Pentostam®) and meglumine antimoniate (Glucantime®); amphotericin B, including liposomal amphotericin B and amphotericin B deoxycholate; other medications containing paromomycin (administered IV or topically); methylbenzethonium chloride, fluconazole, ketoconazole, itraconazole; pentamidine; or allopurinol.
- •The subject or the subject's parent/guardian was unable to understand verbal and/or written Arabic, English, or French (languages in which certified translations of the informed consent were available).
- •The subject presented with an immuno-compromising condition, including recidivant leishmaniasis (during the past 2 years), or diabetes.
- •The subject had a history of known or suspected idiosyncratic reactions or hypersensitivity to aminoglycosides.
排除标准
- 未提供
研究组 & 干预措施
WR 279,396 Topical Treament
WR 279,396 topical cream (15% paromomycin + 0.5% gentamicin topical cream)
干预措施: WR 279,396 topical cream (Drug)
Paromomycin Alone Topical treatment
Paromomycin Alone topical cream (15% paromomycin topical cream)
干预措施: Paromomycin Alone topical cream (Drug)
Vehicle Placebo Cream
The cream base without the addition of paromomycin or gentamicin
干预措施: Vehicle placebo cream (Drug)
结局指标
主要结局
Final Clinical Cure Rate
时间窗: Day 42, 98, and 168
Final clinical cure was defined as an index lesion that met the criteria for initial clinical cure without relapse. Definitions for index lesion outcomes were as follows: * Initial Clinical Improvement: At least 50% to 99% reduction in the size of the measured lesion from the baseline measurement by the Day 42 evaluation. * Initial Clinical Cure: 100% re-epithelialization (ie, a 0 x 0 length x width measurement) of the lesion at the nominal Day 42 evaluation, or initial clinical improvement followed by 100% re-epithelialization by Day 98. * Relapse: Initial clinical cure followed by re-ulceration by Day 168, or initial clinical improvement followed by lesion enlargement by Day 168. * Final Clinical Cure: Initial clinical cure without relapse through study Day 168.Clinical Failure: Lack of at least initial clinical improvement by Day 42, or relapse.
次要结局
- Estimated Percentage Subjects With Re-epithelialization of the Index Lesion Without Relapse(Day 42)
- Estimated Percentage of All Treated Ulcerated Lesions Without Relapse at Day 42(Days 42)
- Estimated Percentage of All Treated Ulcerated Lesions Without Relapse at Day 49(Days 49)
- Final Clinical Cure Rate (Per Protocol Dataset)(Day 42, 98, and 168)
- Estimated Percentage of Subjects With Re-epithelialization of the Index Lesion Without Relapse at Various Times of Follow-up(Days 42, 49, and 98)
- Number of Subjects Achieving Re-epithelialization of the Index Lesion Without Relapse(Day 168)
- Estimated Percentage of All Treated Ulcerated Lesions Without Relapse at Day 98(Days 98)
- Number of Subjects Achieving Initial Clinical Improvement of the Index Lesion(Day 42)
- Number of Subjects Achieving Re-epithelialization of All Treated Ulcerated Lesions Without Subsequent Relapse(Day 168)
- Number of All Ulcerated Lesions Achieving 100% Re-epithelialization by Day 42(Day 42)
- Number of Subjects With a Relapse on or After Day 42(Day 168)