Effect of Ivermectin Metabolites on Mosquito Survival

NCT03690453 | Completed Phase 4

• 1 other identifier: MAL18006
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial will be designed to capture the full duration of mosquito-lethal effect of single dose Ivermectin to aid efforts to characterize metabolites with mosquito-lethal effect. Ivermectin and its metabolites likely have antiparasitic properties against asexual and sexual stage Plasmodium parasites that will be investigated with plasma samples from this study. This is an open-label pharmacokinetic study. Ten healthy participants will be admitted in the inpatient ward to receive a single oral dose of IVM (400 µg/kg). Another 10 healthy participants will be donate blood up to 42 ml each times for up to 3 times. There is no drug administration for these participants. The total duration for each volunteer's participation in the study is approximately 2 months.

Conditions

Healthy

Outcome Measures

Primary Outcomes (5)

• Area under the concentration-time curve for Ivermectin and its metabolites

  Pharmacokinetic parameters (area under the concentration-time curve \[(AUC∞ and AUCLAST\] for Ivermectin and its metabolites.

  41 days

• Maximum concentration for Ivermectin and its metabolites

  Pharmacokinetic parameters (maximum concentration \[CMAX\]) for Ivermectin and its metabolites.

  41 days

• Time to maximum concentration for Ivermectin and its metabolites

  Pharmacokinetic parameters (time to maximum concentration \[TMAX\]) for Ivermectin and its metabolites.

  41 days

• Terminal elimination half-life for Ivermectin and its metabolites

  Pharmacokinetic parameters (terminal elimination half-life \[t1/2\]) for Ivermectin and its metabolites.

  41 days

• Concentration associated with half maximum mosquito killing effect [LC50] for Ivermectin and its metabolites

  Pharmacodynamic parameters (concentration associated with half maximum mosquito killing effect \[LC50\]) for Ivermectin and its metabolites.

  41 days

Secondary Outcomes (9)

• Duration of mosquito survivorship

  14 days

• Compare Maximum Blood Concentrations (Cmax) for ivermectin components and metabolites measured between venous and capillary blood

  41 days

• Compare Area-Under-Curve (AUC) for ivermectin components and metabolites measured between venous and capillary blood

  41 days

• Compare mosquito (An. dirus) survival curves to day 14 between Direct Feeding Assay and Standard Membrane Feeding Assays

  14 days

• Compare mosquito (An. Minimus) survival curves to day 14 between Direct Feeding Assay and Standard Membrane Feeding Assays

  14 days

Study Arms (2)

Healthy volunteer for Clinical Trial

EXPERIMENTAL

Drug: Ivermectin

Healthy volunteer for blood donor

NO INTERVENTION

Interventions

Ivermectin DRUG

single dose of Ivermectin

Healthy volunteer for Clinical Trial

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy as judged by a responsible physician with no abnormality identified on a medical evaluation including medical history and physical examination.
• Males and Females aged between 18 years to 60 years.
• Males and Females weight between 36-75 kilograms.
• A female is eligible to enter and participate in this study if she is:
• of non-childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy or double oophorectomy
• or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone levels \>40 mIU/mL or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy
• or of childbearing potential, has a negative serum pregnancy test at screening and prior to start the study drug in each period, and abstain from sexual intercourse or agrees to using effective contraceptive methods (e.g., intrauterine device, hormonal contraceptive drug, tubal ligation or female barrier method with spermicide) during the study until completion of the follow-up procedures
• A male is eligible to enter and participate in this study if he: agrees to abstain from (or use a condom during) sexual intercourse with females of childbearing potential or lactating females; or is willing to use a condom/spermicide, during the study until completion of the follow-up procedures.
• Provide a signed and dated written informed consent prior to study participation.
• Willingness and ability to comply with the study protocol for the duration of the trial.
• Able to tolerate direct mosquito feeding.
• Blood hemoglobin in males \>13 g/dL and females \>12 g/dL.
• Normal electrocardiogram (ECG) with QTc \<450 msec.

You may not qualify if:

• Females who are pregnant, trying to get pregnant, or are lactating.
• A positive hepatitis B surface antigen, positive hepatitis C antibody, or positive human immunodeficiency virus-1 (HIV-1) antibody result at screening.
• Subjects with a personal history of cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for torsades de pointes (heart failure, hypokalemia) or with a family history of sudden cardiac death.
• A creatinine clearance \<70 mL/min as determined by Cockcroft-Gault equation:
• Clcr (mL/min) = (140 - age) \* Wt / (72 \* Scr) (multiply answer by 0.85 for females) Where age is in years, weight (wt) is in kg, and serum creatinine (Scr) is in units of mg/dL \[Cockcroft, 1976\].
• History of alcohol or substance abuse or dependence within 6 months of the study.
• The subject has evidence of active substance abuse that may compromise safety, pharmacokinetics, or ability to adhere with protocol instructions
• Use of prescription (especially CYP3A4 inhibitors or inducers) or non-prescription drugs except paracetamol at doses of up to 2 grams/day, including vitamins (especially vitamin C), herbal and dietary supplements (including St. John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 times the drug half-life (whichever is longer) prior to the first dose of study medication until the completion of the follow-up procedure, unless in the opinion of investigator, the medication will not interfere with the study procedures or compromise subject safety; the investigator will take advice from the manufacturer representative as necessary.
• The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of study medication.
• The subject is unwilling to abstain from ingesting alcohol within 48 hours prior to the first dose of study medication until collection of the final pharmacokinetic sample.
• Subjects who have donated blood to the extent that participation in the study would result in more than 300 mL blood donated within a 30-day period. Plasma donation during the study is not acceptable.
• Subjects who have a history of allergy to IVM, or a history of drug or other allergy that, in the opinion of the investigator, contraindicates participation in the trial. In addition, if heparin is used during pharmacokinetic sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.
• Lack of suitability for participation in this study, including but not limited to, unstable medical conditions, systemic disease manifested by tendency to granulocytopenia e.g. rheumatoid arthritis and lupus erythematosus that in the opinion of the investigator would compromise their participation in the trial.
• AST or ALT \>1.5 upper limit of normal (ULN)
• Subjects with history of renal disease, hepatic disease, and/or cholecystectomy

Sponsors & Collaborators

• University of Oxford: lead
• Bill and Melinda Gates Foundation: collaborator

Study Sites (1)

Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University

Bangkok, 10400, Thailand

Location

Related Publications (1)

• Kobylinski KC, Tipthara P, Wamaket N, Chainarin S, Kullasakboonsri R, Sriwichai P, Phasomkusolsil S, Hanboonkunupakarn B, Jittamala P, Gemmell R, Boyle J, Wrigley S, Steele J, White NJ, Tarning J. Author Correction: Ivermectin metabolites reduce Anopheles survival. Sci Rep. 2024 Oct 24;14(1):25243. doi: 10.1038/s41598-024-76902-z. No abstract available.

  PMID: 39448768 RESULT

MeSH Terms

Interventions

Ivermectin

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2018
• First Posted: October 1, 2018
• Study Start: February 4, 2019
• Primary Completion: April 5, 2022
• Study Completion: April 5, 2022
• Last Updated: November 26, 2024

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

TH (1)