Clinical trial NCT00300768: Study Evaluating Orally Administered Moxidectin In Subjects With Onchocerca Volvulus Infection
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Onchocerciasis
Keywords: onchocerciasis
onchocerca volvulus
river blindness
ivermectin
moxidectin
Lead sponsor: Medicines Development for Global Health
Sponsor class: OTHER
Collaborators: name: World Health Organization
First posted: 2006-03-09
Enrollment: 172
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study was to determine the safety and tolerability of moxidectin in subjects infected with Onchocerca volvulus (a parasitic worm).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Written, signed (or thumb-printed), and dated informed consent
2. Aged 18 to 60 years, inclusive
3. Body weight ≥ 40 kg for women and ≥ 45 kg for men
4. Nonpregnant, nonbreastfeeding women. Women of child bearing potential must agree to use birth control during the first 150 days after treatment.
5. 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
6. Adequate hematologic, renal, and hepatic function
7. Skin microfilarial density within the required range for the cohort

Exclusion Criteria:

1. Participation in any studies other than purely observational ones, within 4 weeks before test article administration.
2. Any vaccination within 4 weeks before test article administration
3. Acute infection requiring therapy within the last 10 days before test article administration
4. 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
5. Clinically significant ECG abnormalities or history of cardiac abnormality
6. Past or current history of neurological or neuropsychiatric disease or epilepsy
7. Subjects with orthostatic hypotension at the screening evaluation
8. History of drug or alcohol abuse or regular use of ≥ 3 cigarettes per day
9. Use of alcohol or other drugs of abuse within 72 hours before test article administration
10. Any condition, in the investigator's opinion, that places the subject at undue risk
11. Subjects who have donated blood within 8 weeks before study entry
12. 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.
13. Subjects with hyperreactive onchodermatitis
14. Antifilarial therapy within the previous 5 years
15. Coincidental infection with Loa Loa
16. Female subjects of childbearing potential with a contraindication to DMPA if not on Norplant
17. Any other condition which the investigator feels would exclude the subject from the study

Primary outcomes:
measure: Incidence of clinical adverse events and clinically significant laboratory test results
timeFrame: Duration of follow up (18 months)
Secondary outcomes:
measure: Skin mf counts at day 8 and months 1, 2, 3, 6, 12 and 18
timeFrame: day 8 and months 1, 2, 3, 6, 12, 18
measure: Nodulectomy at 18 months
timeFrame: 18 months
measure: Pharmacokinetics (PKs) at days 1, 2, 4, 13, and 18 and months 1, 2, 3, 6 and 12
timeFrame: days 1, 2, 4, 13, and 18 and months 1, 2, 3, 6 and 12
Other outcomes:
Locations:
city: Hohoe
country: Ghana
facility: Onchocerciasis Chemotherapy Research Center
state: Volta Region
Study officials:
affiliation: Onchocerciasis Chemotherapy Research Center, Hohoe, Ghana
name: Nicholas Opoku, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Awadzi K, Opoku NO, Attah SK, Lazdins-Helds J, Kuesel AC. A randomized, single-ascending-dose, ivermectin-controlled, double-blind study of moxidectin in Onchocerca volvulus infection. PLoS Negl Trop Dis. 2014 Jun 26;8(6):e2953. doi: 10.1371/journal.pntd.0002953. eCollection 2014 Jun.