Study Evaluating Orally Administered Moxidectin In Subjects With Onchocerca Volvulus Infection

Sponsor

Medicines Development for Global Health (Other)

Overall Status

Completed

CT.gov ID

NCT00300768

Collaborator

World Health Organization (Other)

172

Enrollment

Location

Arms

Duration (Months)

4.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary purpose of this study is to determine the safety and tolerability of moxidectin in subjects infected with O. volvulus with special emphasis on Mazzotti reactions to determine whether it is safe enough to expose a number of subjects sufficient for obtaining statistically significant data on the safety and efficacy of moxidectin relative to ivermectin.

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.

Condition or Disease	Intervention/Treatment	Phase
Onchocerciasis	Drug: 2 mg moxidectin Drug: ivermectin 150 mcg/kg Drug: 4 mg moxidectin Drug: 8 mg moxidectin	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

172 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2006

Actual Primary Completion Date :

Nov 1, 2009

Actual Study Completion Date :

Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 2 mg moxidectin 2 mg moxidectin (Dose-escalation 1st step)	Drug: 2 mg moxidectin Single-dose, tablet encapsulated for blinding
Active Comparator: Ivermectin 150 mcg/kg Active comparator arm (ivermectin 150 mcg/kg).	Drug: ivermectin 150 mcg/kg Single-dose, tablets encapsulated for blinding
Experimental: 4 mg moxidectin 4 mg moxidectin (dose escalation second step)	Drug: 4 mg moxidectin Single dose, tablets encapsulated for blinding
Experimental: 8 mg moxidectin 8 mg moxidectin (dose escalation third step)	Drug: 8 mg moxidectin single dose, tablets encapsulated for blinding

Outcome Measures

Primary Outcome Measures

Incidence of clinical adverse events and clinically significant laboratory test results [Duration of follow up (18 months)]

Secondary Outcome Measures

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]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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