A Randomized, Single-Ascending Dose, Ivermectin-Controlled, Double-Blind, Safety, Tolerability, Pharmacokinetic, and Efficacy Study Of Orally Administered Moxidectin In Subjects With Onchocerca Volvulus Infection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 172
- 试验地点
- 1
- 主要终点
- Incidence of clinical adverse events and clinically significant laboratory test results
研究概览
简要总结
The primary purpose of this study was to determine the safety and tolerability of moxidectin in subjects infected with Onchocerca volvulus (a parasitic worm).
详细描述
This was a phase 2, randomized, ivermectin-controlled, double-blind, single-ascending-dose, parallel design, inpatient/outpatient study of moxidectin administered to subjects of both sexes with different degrees of severity of O. volvulus infection. The study was conducted at a single site in Ghana.
Secondary objects are to determine the pharmacokinetics of moxidectin, to obtain initial indication of the efficacy in terms of long term effect on skin microfilaria levels and an indication of the effect on the macrofilaria that may underlie the effect on skin microfilaria levels.
Subjects were enrolled in consecutive cohorts to receive a single oral dose of 2 mg, 4 mg or 8 mg or moxidectin or ivermectin 150 µg/kg by severity of infection, based on the mean of the skin microfilariae densities at each of 4 body locations, both iliac crests and calves.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written, signed (or thumb-printed), and dated informed consent
- •Aged 18 to 60 years, inclusive
- •Body weight ≥ 40 kg for women and ≥ 45 kg for men
- •Nonpregnant, nonbreastfeeding women. Women of child bearing potential must agree to use birth control during the first 150 days after treatment.
- •Healthy, as determined by a physician on the basis of a physical examination, ECG, and a thorough review of the medical history and clinical laboratory results
- •Adequate hematologic, renal, and hepatic function
- •Skin microfilarial density within the required range for the cohort
排除标准
- •Participation in any studies other than purely observational ones, within 4 weeks before test article administration.
- •Any vaccination within 4 weeks before test article administration
- •Acute infection requiring therapy within the last 10 days before test article administration
- •Administration of any medication (with the exception of medication required to treat any reactions during the screening fluorescein angiography (chlorpheniramine) or paracetamol) or herbal preparation within 10 days prior to test article administration or any condition currently requiring regular medication
- •Clinically significant ECG abnormalities or history of cardiac abnormality
- •Past or current history of neurological or neuropsychiatric disease or epilepsy
- •Subjects with orthostatic hypotension at the screening evaluation
- •History of drug or alcohol abuse or regular use of ≥ 3 cigarettes per day
- •Use of alcohol or other drugs of abuse within 72 hours before test article administration
- •Any condition, in the investigator's opinion, that places the subject at undue risk
- •Subjects who have donated blood within 8 weeks before study entry
- •Subjects with ocular onchocerciasis in cohorts intended to enroll subjects with mild infection. Ocular onchocerciasis is defined by the presence of live or dead microfilariae, onchocercal punctate opacities, onchocercal lesions of the posterior segment or lesions that mimic those seen in onchocerciasis.
- •Subjects with hyperreactive onchodermatitis
- •Antifilarial therapy within the previous 5 years
- •Coincidental infection with Loa Loa
- •Female subjects of childbearing potential with a contraindication to DMPA if not on Norplant
- •Any other condition which the investigator feels would exclude the subject from the study
研究组 & 干预措施
2 mg moxidectin
2 mg moxidectin (Dose-escalation 1st step)
干预措施: 2 mg moxidectin (Drug)
Ivermectin 150 mcg/kg
Active comparator arm (ivermectin 150 mcg/kg).
干预措施: ivermectin 150 mcg/kg (Drug)
4 mg moxidectin
4 mg moxidectin (dose escalation second step)
干预措施: 4 mg moxidectin (Drug)
8 mg moxidectin
8 mg moxidectin (dose escalation third step)
干预措施: 8 mg moxidectin (Drug)
结局指标
主要结局
Incidence of clinical adverse events and clinically significant laboratory test results
时间窗: Duration of follow up (18 months)
次要结局
- Pharmacokinetics (PKs) at days 1, 2, 4, 13, and 18 and months 1, 2, 3, 6 and 12(days 1, 2, 4, 13, and 18 and months 1, 2, 3, 6 and 12)
- Skin mf counts at day 8 and months 1, 2, 3, 6, 12 and 18(day 8 and months 1, 2, 3, 6, 12, 18)
- Nodulectomy at 18 months(18 months)