Effect of Ivermectin Metabolites on Mosquito Survival

Inclusion Criteria for Ivermectin intervention group: 1. Healthy as judged by a responsible physician with no abnormality identified on a medical evaluation including medical history and physical examination. 2. Males and Females aged between 18 years to 60 years. 3. Males and Females weight between 36-75 kilograms. 4. 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 5. 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. 6. Provide a signed and dated written informed consent prior to study participation. 7. Willingness and ability to comply with the study protocol for the duration of the trial. 8. Able to tolerate direct mosquito feeding. 9. Blood hemoglobin in males \>13 g/dL and females \>12 g/dL. 10. Normal electrocardiogram (ECG) with QTc \<450 msec. Exclusion Criteria for Ivermectin intervention group: 1. Females who are pregnant, trying to get pregnant, or are lactating. 2. A positive hepatitis B surface antigen, positive hepatitis C antibody, or positive human immunodeficiency virus-1 (HIV-1) antibody result at screening. 3. 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. 4. 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 \[Cockcroft, 1976\]. 5. History of alcohol or substance abuse or dependence within 6 months of the study. 6. The subject has evidence of active substance abuse that may compromise safety, pharmacokinetics, or ability to adhere with protocol instructions 7. 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. 8. 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. 9. 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. 10. 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. 11. 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. 12. 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. 13. AST or ALT \>1.5 upper limit of normal (ULN) 14. Subjects with history of renal disease, hepatic disease, and/or cholecystectomy 15. History of IVM or other drug treatments known to be CYP3A4 inducers or inhibitors (e.g. piperaquine, ritonavir, rifampicin) within 3 months. 16. The subject is unwilling to abstain from the consumption of food containing vitamin C (e.g. fruits, juices, papaya salad) 12 hours before and after drug ingestion. 17. History of travel to West or Central Africa, unless it can be verified that subject does not have Loa loa infection. 18. History or suspected of hypersensitivity/anaphylaxis to mosquito bites and other insect bites/sting (e.g. history of cellulitis-like cutaneous inflammation, anaphylaxis, hives) Inclusion criteria for healthy blood donor: 1. Healthy as judged by a responsible physician with no abnormality identified on a medical evaluation including medical history and physical examination. 2. Males and Females aged between 18 years to 60 years. 3. Males and Females weight between 36-75 kilograms. 4. Provide a signed and dated written informed consent prior to study participation. 5. Willingness and ability to donate blood. Exclusion criteria for healthy blood donor: 1. Females who are pregnant, trying to get pregnant, or are lactating (determined by verbally asking and urine pregnancy test). 2. The subject has evidence of active substance abuse that may compromise safety or ability to adhere with protocol instructions. 3. A positive hepatitis B surface antigen, positive hepatitis C antibody, or positive human immunodeficiency virus-1 (HIV-1) antibody result at screening. 4. History of alcohol or substance abuse or dependence within 6 months of the study. 5. Any known blood disorders (e.g. thalassemia, sickle cell anemia) 6. 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 blood collection 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. 7. The subject has participated in a clinical trial and has received a drug (particularly IVM or any drug known to be a CYP3A4 inducer or inhibitor) or a new chemical entity within 90 days prior to blood collection. 8. The subject is unwilling to abstain from ingesting alcohol within 48 hours prior to blood collection. 9. The subject is unwilling to abstain from consumption of food containing vitamin C (e.g. fruits, juices, papaya salad within 12 hours prior to blood collection. 10. 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.