A Pharmacokinetic and Safety Study of Moxidectin to Identify an Optimal Dose for Treatment of Children 4 to 11 Years

Phase 1

Completed

• Conditions: Onchocerciasis
• Interventions: Drug: Moxidectin

• Registration Number: NCT03962062
• Lead Sponsor: Medicines Development for Global Health

Brief Summary

The primary purpose of this study is to determine a dose of moxidectin for children 4 to 11 years that is equivalent to an 8 mg dose administered for treatment of onchocerciasis in people 12 years and over. The secondary purpose is to evaluate the safety and pharmacokinetics of a single dose of moxidectin in children and adolescents aged 4 to 17 years.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-05-22
• Study First Submitted QC: 2019-05-22
• Study First Posted: 2019-05-23
• Study Start: 2021-03-29
• Primary Completion: 2022-05-30
• Study Completion: 2022-09-28
• Status Verified: 2022-12
• Last Update Submitted: 2022-12-13
• Last Update Posted: 2022-12-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

1. Aged 4 to 17 years, inclusive:

   1. Cohort I: 12 to 17 years;
   2. Cohort II: 8 to 11 years;
   3. Cohort III: 4 to 7 years;

2. Live in a region designated by the World Health Organization (WHO) as endemic for O. volvulus infection (World Health Organization, 2019). Specifically, participants will be recruited from the Kpassa sub-district of the Nkwanta North district.The specific communities will include Wii, Jagri-Do, and Azua where mass drug administration with ivermectin for onchocerciasis commenced in October 2017;

3. Willing and able to remain at the study clinic from Screening up to Day 7;

4. Provision of parental or guardian written informed consent and assent / lack of expression of 'deliberate objection' (as appropriate for age);

5. Females of childbearing potential must commit to using a reliable method of contraception as per local family planning guidelines from Baseline (pre-treatment on Day 0) until approximately 6 months after treatment with study drug.

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Exclusion Criteria

1. History of serious medical or psychiatric condition which, in the opinion of the investigator, would put the subject at increased risk by participating in the study or jeopardize study outcomes;

2. Known or suspected concurrent clinically significant renal, cardiac, pulmonary, vascular, metabolic (thyroid disorders, adrenal disease), immunological disorders or malignancy, congenital heart disease, chronic lung disease;

3. Has received an investigational product within 28 days or 5 half-lives of Baseline, whichever is longer;

4. Has received ivermectin or any other anti-helminthic treatments within 28 days of Baseline;

5. Has received a vaccination within 7 days of Baseline;

6. Known or suspected hypersensitivity to macrocyclic lactones or excipients used in the formulation of moxidectin;

7. Poor venous access;

8. Unable to swallow tablets (flat oval, 8.0 millimeters (mm) x 4.5 mm x 3.0 mm);

9. Weight:

   1. Cohort I (12 to 17 years): < 30 kg;
   2. Cohort II (8 to 11 years): < 18 kg;
   3. Cohort III (4 to 7 years): < 12 kg;

10. Clinically relevant laboratory abnormalities at Screening, including:

    1. Hemoglobin < 9.5 grams per deciliter (g/dL);
    2. Neutrophil (granulocyte) count < 1.5 x 109/L;
    3. Platelet count < 110 x 109/L;
    4. Alanine aminotransferase (ALT) > 1.5 times the upper limit of normal range (ULN);
    5. Total bilirubin > 1.5 times ULN;

11. Hepatitis B, Hepatitis C, or human immunodeficiency virus (HIV) positive;

12. Known or suspected malaria or other ongoing viral, bacterial, or plasmodium infection at Screening and/or Baseline;

13. Loa loa co-infection;

14. Unwilling, unlikely or unable to comply with all protocol specified assessments;

15. For females of child bearing potential, pregnant or breastfeeding, or planning to become pregnant;

16. Previous enrolment in this study;

17. Is a sibling of another child already enrolled in this study.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 3: 4-7 years	Moxidectin	Moxidectin single dose, determined by population pharmacokinetic modelling including data from Cohorts 1 and 2
Cohort 2: 8-11 years	Moxidectin	Moxidectin 8mg (or lower dose) per oral, single dose
Cohort 1: 12-17 years	Moxidectin	Moxidectin 8mg per oral, single dose

Primary Outcome Measures

Name	Time	Method
Area under the plasma concentration versus time curve of moxidectin	Pre-dose to Day 28	Moxidectin concentration in plasma collected at pre-specified intervals after dosing with oral moxidectin determined using a validated liquid chromatography-mass spectrometry(MS)/MS method.

Secondary Outcome Measures

Name	Time	Method
Area under the concentration versus time curve (zero to infinity) of moxidectin	Pre-dose to Week 12	Moxidectin concentration in plasma collected at pre-specified intervals after dosing with oral moxidectin determined using a validated liquid chromatography-mass spectrometry(MS)/MS method.
Maximum observed plasma concentrations (Cmax) of moxidectin	Hour 0 to Hour 8	Moxidectin concentration in plasma collected at pre-specified intervals after dosing with oral moxidectin determined using a validated liquid chromatography-mass spectrometry(MS)/MS method.
Incidence and severity of adverse events	Day 0 to Week 24	Incidence and severity of adverse events, assessed by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Paediatric Adverse Events, Version 2.1.

Trial Locations

Locations (1)

University of Health and Allied Services School of Public Health; 🇬🇭 Hohoe, Volta Region, Ghana