NCT02568098

Pharmacokinetic and Mosquito-Lethal Effects of Ivermectin (IVM), Primaquine (PQ), Dihydroartemisinin-Piperaquine (DHA-PQP) and Albendazole (ABZ) in Healthy Subjects

Open-Label Study to Evaluate Safety, Tolerability, Potential Pharmacokinetic Interactions and Mosquito-Lethal Effects of Orally Administered Ivermectin, Primaquine, Dihydroartemisinin-Piperaquine, and Albendazole in Healthy Adult Subjects

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (actual)
• Sponsor: University of Oxford · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Accepted

Summary

Primary Objective * To evaluate the safety and tolerability of co-administered single dose Dihydroartemisinin-Piperaquine (DHA-PQP), Ivermectin (IVM), Primaquine (PQ), and Albendazole (ABZ) in healthy subjects. Secondary Objectives * To characterize the potential pharmacokinetic interactions between DHA-PQP, IVM, PQ, and ABZ in healthy adult subjects. * To characterize the pharmacokinetic properties of PQ (and its major metabolite), DHA-PQP, IVM, and ABZ (and its major metabolite) when given alone and in combination. * To investigate pharmacogenetic polymorphisms affecting drug levels of PQ, DHA-PQP, IVM, ABZ and their metabolites. * To determine mosquito lethal efficacy of IVM, PQ, ABZ, and DHA-PQP combinations against Anopheles dirus and Anopheles minimus. * To determine if IVM concentrations in venous blood differs from capillary blood.

Detailed description

This is an open-label, sequential pharmacokinetic study in 16 healthy glucose-6-phosphate dehydrogenase (G6PD) normal Thai subjects. These 16 subjects have previously participated in either study: 1. Open-Label Study to Evaluate Potential Pharmacokinetic Interaction of Orally Administered Primaquine (PQ) and Dihydroartemisinin-Piperaquine (DHA-PQP) in Healthy Adult Subjects (TMEC 12-004 (OxTREC ref. 58-11)) or study 2. Comparison of the electrocardiographic effects in relation to Pharmacokinetic profile of chloroquine (CQ) and piperaquine (PQ) in healthy Thai subjects (TMEC 14-022 (OxTREC ref. 39-14)) or 3. subjects who not previously participated in study "TMEC 12-004 (OxTREC ref. 58-11)" and study "TMEC 14-022 (OxTREC ref. 39-14)". The study team will use the results of DHA-PQP regimen of the subjects from the above mentioned studies to compare with combination regimens in this study. This is to avoid unnecessary exposure of Subjects from (TMEC 12-004 (OxTREC ref. 58-11)) and (TMEC 14-022 (OxTREC ref. 39-14)) to the subjects. In addition, subjects have previously been tested for G6PD deficiency during screening process from the above mentioned study with result showed as normal. Therefore, a G6PD deficiency test is not needed. A G6PD deficiency test is needed for subjects who not previously participated in study subjects who not previously participated in study "TMEC 12-004 (OxTREC ref. 58-11)" and study "TMEC 14-022 (OxTREC ref. 39-14)" for this study. Subjects will be admitted in the inpatient ward to receive single dose of 6 regimens (regimens 1-4 and 8-9) described below. Every subject will have at least 6 admissions in the hospital. 1: IVM (400 μg/kg) via 6 mg tabs, w-o\*\* \>4wks; 2: IVM (400 μg/kg)+PQ (15 mg): 2 tabs), w-o \>4wks; 3: IVM (400 μg/kg)+DHA-PQP (40mg/320 mg): 3 tabs), w-o \>8wks; 4: IVM (400 μg/kg)+DHA-PQP+PQ, w-o \>8wks; 5\*#: PQ (15 mg): 2 tabs, w-o \> 2wks; 6#: DHA-PQP (40mg/320 mg): 3 tabs, w-o \>8wks; 7\*#: DHA-PQP (40mg/320 mg): 3 tabs +PQ (15 mg): 2 tabs, w-o \>8wks; 8: ABZ (200 mg) 2 tabs, w-o \>2wks; 9: IVM (400 μg/kg)+DHA-PQP (40mg/320 mg): 3 tabs+PQ (15 mg): 2 tabs +ABZ (400 mg): 1 tab, w-o \>8wks \* The subjects from TMEC-14-022 (OxTREC ref. 39-14) will have two additional admissions to receive two additional regimen PQ, and DHA-PQP with PQ \# Subjects who not previously participated in study "TMEC 12-004 (OxTREC ref. 58-11)" and study "TMEC 14-022 (OxTREC ref. 39-14)" will have three additional admissions to receive three additional regimens PQ, DHA-PQP, and DHA-PQP with PQ. \*\*w-o = washout period

Conditions

• Drug Combination
• Pharmacokinetics
• Healthy

Interventions

Type	Name	Description
DRUG	IVM, IVM and PQ, IVM and DHA-PQP, IVM and DHA-PQP and PQ	Regimen 1: IVM; Regimen 2: IVM and PQ; Regimen 3: IVM and DHA-PQP; Regimen 4: IVM and DHA-PQP and PQ;
DRUG	PQ and DHA-PQP and PQ	Regimen 5: PQ; Regimen 7: DHA-PQP and PQ
DRUG	DHA-PQP	Regimen 6: DHA-PQP

Timeline

• Start date: 2015-10-01
• Primary completion: 2016-12-01
• Completion: 2016-12-01
• First posted: 2015-10-05
• Last updated: 2017-05-31

Locations

1 site across 1 country: Thailand