Effect of Ivermectin Metabolites on Mosquito Survival
- Registration Number
- NCT03690453
- Lead Sponsor
- University of Oxford
- 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.
- Detailed Description
HEALTHY PARTICIPANT FOR CLINICAL TRIAL
Study will enroll 10 Thai healthy participants, 5 male and 5 female, aged 18-60 years.
Participants will be admitted in the inpatient ward to receive a single oral dose of IVM (400 µg/kg).
After a volunteert has provided written informed consent, the investigator will determine if the volunteer is eligible for enrollment in the study. This will be done by reviewing the inclusion and exclusion criteria and completing all of the screening assessments. Screening assessments may be carried out over more than one day, provided that all required assessments are completed within the 14 days prior to admission for Ivermectin administration.
The blood collection for Standard Membrane Feeding Assay, Direct Feeding Assays, Pharmacokinetic analysis, Plasma for Plasmodium assays and mosquito IgG assays should be obtained at the scheduled times relative to when the participant was dosed.
The total duration for each volunteer's participation in the study is approximately 2 months.
HEALTHY PARTICIPANT FOR BLOOD DONOR
Study will enroll 10 healthy participants, aged 18-60 years. Each participant will donate blood up to 42 ml via venipuncture up to three blood donations. There will be at least 28 days between each blood donation from the same subject.
Blood will be maintained at 37°C in a warm water bath until mixed with ivermectin compounds or metabolites by Pharmacology staff and fed to mosquitoes by Armed Forces Research Institute of Medical Sciences (AFRIMS) staff. Any remaining blood after SMFAs will be discarded. No blood samples will be transferred to AFRIMS. Participants for blood donation should not be the same participants enrolled in the clinical trial above.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Healthy volunteer for Clinical Trial Ivermectin -
- Primary Outcome Measures
Name Time Method Terminal elimination half-life for Ivermectin and its metabolites 41 days Pharmacokinetic parameters (terminal elimination half-life \[t1/2\]) for Ivermectin and its metabolites.
Area under the concentration-time curve for Ivermectin and its metabolites 41 days Pharmacokinetic parameters (area under the concentration-time curve \[(AUC∞ and AUCLAST\] for Ivermectin and its metabolites.
Maximum concentration for Ivermectin and its metabolites 41 days Pharmacokinetic parameters (maximum concentration \[CMAX\]) for Ivermectin and its metabolites.
Time to maximum concentration for Ivermectin and its metabolites 41 days Pharmacokinetic parameters (time to maximum concentration \[TMAX\]) for Ivermectin and its metabolites.
Concentration associated with half maximum mosquito killing effect [LC50] for Ivermectin and its metabolites 41 days Pharmacodynamic parameters (concentration associated with half maximum mosquito killing effect \[LC50\]) for Ivermectin and its metabolites.
- Secondary Outcome Measures
Name Time Method Compare mosquito (An. dirus) survival curves to day 14 between Direct Feeding Assay and Standard Membrane Feeding Assays 14 days Mosquito survival curves to day 14 within a species will be compared between mosquitoes blood fed via Direct Feeding Assay and Standard Membrane Feeding Assays by Log-Rank survival curve analysis (Mantel-Cox method). This will assess if venous blood is more or less lethal to mosquitoes than blood ingested from subdermal capillaries.
The lethal concentration that kills 50% of mosquitoes (LC50) between two strains of An. dirus 14 days The lethal concentration that kills 50% of mosquitoes (LC50) between two strains of An. dirus will be evaluated. This will assess if one An. dirus strain is more or less susceptible to ivermectin.
Duration of mosquito survivorship 14 days Duration of mosquito survivorship following standard membrane feeding assay (SMFA) to determine duration of time post drug administration that IVM-treated volunteers are lethal to An. dirus and An. minimus.
Compare mosquito (An. Minimus) survival curves to day 14 between Direct Feeding Assay and Standard Membrane Feeding Assays 14 days Mosquito survival curves to day 14 within a species will be compared between mosquitoes blood fed via Direct Feeding Assay and Standard Membrane Feeding Assays by Log-Rank survival curve analysis (Mantel-Cox method). This will assess if venous blood is more or less lethal to mosquitoes than blood ingested from subdermal capillaries.
Mosquito survival curves to day 14 between two strains of An. dirus. 14 days Mosquito survival curves to day 14 between two strains of An. dirus will be evaluated. This will assess if one An. dirus strain is more or less susceptible to ivermectin.
Compare Maximum Blood Concentrations (Cmax) for ivermectin components and metabolites measured between venous and capillary blood 41 days Pharmacokinetic differences for Ivermectin and metabolites in venous and capillary blood.
The inhibitory concentration that kills 50% of parasites (IC50) for each P. falciparum strain. 48 hours The inhibitory concentration that kills 50% of parasites (IC50) will be evaluated for each P. falciparum strain to determine which strains are more or less susceptible to ivermectin.
Compare Area-Under-Curve (AUC) for ivermectin components and metabolites measured between venous and capillary blood 41 days Pharmacokinetic differences for Ivermectin and metabolites in venous and capillary blood.
The lethal concentration that kills 50% of mosquitoes (LC50) for each ivermectin component and synthesized metabolites 14 days The lethal concentration that kills 50% of mosquitoes (LC50) for each ivermectin component and synthesized metabolites. The LC50s and their corresponding 95% confidence intervals will be evaluated for each ivermectin component and synthesized metabolites. This will assess if any of the ivermectin components or metabolites are more or less lethal to An. dirus.
Trial Locations
- Locations (1)
Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University
🇹🇭Bangkok, Thailand