The objectives of the Phase I study are to evaluate the safety and tolerance of increasing single oral doses of oxfendazole in healthy volunteers.The secondary objectives assess the pharmacokinetic profile of oxfendazole and assess the metabolism of oxfendazole. The description of agent used is single oral dose of an aqueous suspension of oxfendazole, a benzimidazole carbamate antiparasitic drug. Each new cohort will be dosed only after the two week safety data for the preceding group have been reviewed. If a clinically significant AE is observed, and if this event is drug-related the safety monitoring committee will be convened to determine whether the study should continue.
This Phase I study is a randomized, double-blind, placebo-controlled evaluation of the safety and pharmacokinetics of escalating single oral doses of oxfendazole (0.5 to 60 mg/kg) in healthy volunteers. Up to 70 healthy males and females (non-chldbearing potential), ages 18-45 volunteers recruited from one site will participate in this study. The study duration is approximately 18 months with subject participation of 2 weeks. The primary objective assess the safety and tolerability of oxfendazole in healthy adults. The secondary objectives assess the pharmacokinetic profile of oxfendazole and assess the metabolism of oxfendazole. Two sentinel subjects will receive the study product (1 drug/1 placebo) in each group and be monitored 48 hours for adverse events prior to completing enrollment of the remaining 8 subjects in the group.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
70
A benzimidazole carbamate antiparasitic drug. Oral Dose levels of 0.5,1, 3, 7.5, 15, 30, and 60 mg/kg will be evaluated sequentially, the dose increasing with each new cohort Group 1 to Group 7.
Normal Saline administered with an oral dosing syringe. Group 1- Group 6
University of Iowa - Vaccine Research and Education Unit
Iowa City, Iowa, United States
Number of Subjects Reporting Adverse Events Related to Oxfendazole Within 14 Days of Receipt of a Single Oral Dose.
All adverse events, defined as any untoward medical occurrence regardless of its causal relationship to the study treatment, were collected for 14 days after dosing. The PI then determined relatedness to the study drug. Related was defined as "there is a reasonable possibility that the study product caused the adverse event. Reasonable possibility means that there is evidence to suggest a causal relationship between the study product and the adverse event."
Time frame: Within 14 Days of first dose
Area Under the Concentration Time-curve From Time Zero to Infinity (AUC(0-infinity)) for Oxfendazole
AUC(0-infinity) was defined as the total area under the concentration-time curve from dosing (time 0) taken to the limit as the end time becomes arbitrarily large. AUC(0-infinity) and was calculated by adding AUC(0-last) to an extrapolated value equal to the last measured concentration greater than the lower limit of quantification of the bioanalytical assay divided by the terminal phase elimination rate constant (Ke) computed from concentrations that were measured using a validated HPLCMS/MS method
Time frame: 0, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 336 hours post-dose
Maximum Observed Concentration (Cmax) of Oxfendazole in Plasma
Cmax is defined as the maximum observed drug concentration observed in plasma over all PK sample concentrations computed from concentrations that were measured using a validated HPLC-MS/MS method.
Time frame: 0, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 336 hours post-dose
Plasma Concentrations of Oxfendazole Fenbendazole
Concentrations of oxfendazole fenbendazole in plasma were measured using a validated HPLCMS/MS method. Concentrations \<LLOQ (2 ng/mL) set to LLOQ/2 if after 1st =LLOQ concentration or 0 otherwise for calculating summary statistics.
Time frame: Day 1-Day15
Plasma Concentrations of Oxfendazole Sulfone
Concentrations of oxfendazole sulfone in plasma were measured using a validated HPLCMS/MS method. Concentrations \<LLOQ (2 ng/mL) set to LLOQ/2 if after 1st =LLOQ concentration or 0 otherwise for calculating summary statistics.
Time frame: Day 1-Day15
Terminal Elimination Half-life (t1/2) of Oxfendazole
The apparent terminal elimination half-life (t1/2) was defined as the time required for the drug concentration to decrease by a factor of one-half in the terminal phase computed from concentrations that were measured using a validated HPLCMS/MS method.
Time frame: 0, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 336 hours post-dose
Time of Maximum Observed Concentration (Tmax) of Oxfendazole
Tmax was defined as the time at which the maximum concentration (Cmax) occurs in plasma computed from concentrations that were measured using a validated HPLCMS/MS method.
Time frame: 0, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 336 hours post-dose
Urine Concentrations of Oxfendazole Fenbendazole
Concentrations of oxfendazole fenbendazole in urine were measured using a validated HPLCMS/MS method. Concentrations \<LLOQ (2 ng/mL) set to LLOQ/2 if after 1st =LLOQ concentration or 0 otherwise for calculating summary statistics.
Time frame: Day 1-Day 15
Urine Concentrations of Oxfendazole Sulfone
Concentrations of oxfendazole sulfone in urine were measured using a validated HPLCMS/MS method. Concentrations \<LLOQ (2 ng/mL) set to LLOQ/2 if after 1st =LLOQ concentration or 0 otherwise for calculating summary statistics.
Time frame: Day 1-Day 15
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