Single Ascending Dose Safety Study of Oxfendazole

Study Overview
=================
Brief Summary
-----------------
This research is being done to learn about the safety in humans of a medicine that is already used in cows and pigs to treat worms. The medicine may be useful for people who have these or other worms. The medicine will be studied first in healthy people, who will be given a very small amount of the medicine once. If the smallest amount of medicine is found to be safe, a slightly higher amount will be given to a new group of volunteers. The highest amount that will be tested is similar to the amount given to animals. If the medicine can be given safely to healthy people in the planned amounts, a later study will be done in people who have worms to see if the medicine kills the worms.

Detailed Description
-----------------
The Phase I study proposed is a randomized, double-blind, placebo-controlled evaluation of the safety and pharmacokinetics of escalating single oral doses of oxfendazole (0.3 to 30 mg/kg) in healthy volunteers. The dose will be increased approximately three-fold (one-half log) at each increment, and each cohort will comprise ten volunteers (eight drug, two placebo). Subjects will be monitored for three weeks after dosing, including monitoring the pharmacokinetics and metabolism of oxfendazole in blood and urine. Each new cohort will be dosed only after the three week safety data for the preceding group have been analyzed. If a clinically significant adverse event is observed, and if this event is possibly drug-related, an additional (and final) cohort of volunteers will repeat the highest tolerated dose of oxfendazole. Up to 70 volunteers (56 drug, 14 placebo) will complete the study.

Official Title
-----------------
Phase I Study of Oxfendazole (Toward the Treatment of Neurocysticercosis)

Conditions
-----------------
Tenia Solium Infection

Intervention / Treatment
-----------------
* Drug: oxfendazole
* Drug: placebo
* Drug: oxfendazole
* Drug: oxfendazole
* Drug: oxfendazole
* Drug: oxfendazole
* Drug: oxfendazole


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Height and weight within 25% of means for his/her gender and age. Willing to use two acceptable methods of contraception (approved oral, injectable, or implantable drug, IUD, diaphragm or condom with spermicidal jelly or foam, or sexual abstinence) for a minimum of one week before, and three weeks after dosing with oxfendazole; or surgically sterile. Able to give written informed consent. Able to provide a home phone number, and the name, address, and phone number of a person willing to assist making contact during the follow-up phase of the study. Exclusion Criteria: Pregnant. Breast feeding. Chronic drug/alcohol user. Has clinically significant abnormalities in screening examinations Has history of sensitivity to related benzimidazole compounds (e.g. albendazole, mebendazole).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: oxfendazole 0.3<br>administration of a single oral 0.3mg/kg dose of oxfendazole | Drug: oxfendazole<br>* administration of a single oral 0.3 mg/kg dose of oxfendazole<br>|
| Placebo Comparator: placebo comparator<br>administration of a single oral dose of placebo | Drug: placebo<br>* single oral dose of placebo<br>|
| Experimental: oxfendazole 1.0<br>administration of a single oral 1.0 mg/kg dose of oxfendazole | Drug: oxfendazole<br>* administration of a single oral 1.0 mg/kg dose of oxfendazole<br>|
| Experimental: oxfendazole 3.0<br>administration of a single oral 3 mg/kg dose of oxfendazole | Drug: oxfendazole<br>* administration of a single oral 3.0 mg/kg dose of oxfendazole<br>|
| Experimental: oxfendazole 10<br>administration of a single oral 10 mg/kg dose of oxfendazole | Drug: oxfendazole<br>* administration of a single oral 10 mg/kg dose of oxfendazole<br>|
| Experimental: oxfendazole 20<br>administration of a single oral 20 mg/kg dose of oxfendazole | Drug: oxfendazole<br>* administration of a single oral 20 mg/kg dose of oxfendazole<br>|
| Experimental: oxfendazole 30<br>administration of a single oral 30 mg/kg dose of oxfendazole | Drug: oxfendazole<br>* administration of a single oral 30 mg/kg dose of oxfendazole<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serious adverse events | Proportion of patients who present with serious adverse events (SAEs) related to oxfendazole. | up to three weeks after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse events | proportion of subjects who present with adverse events (AEs) related to ocfendazole | up to three weeks after dosing | 
| Pharmacokinetic Profile | The following PK parameters will be analyzed: Maximum plasma concentration (Cmax), Time to Cmax (Tmax), Elimination rate constant (Iz), Elimination half-life (T½), Area under the curve to the final sample (AUC0-t), Area under the curve to infinity (AUC∞), Oral clearance (CL/F), Oral volume of distribution (Vz/F) | blood samples are drawn at 17 time points up to three weeks and urine is collected at 7 intervals up to 72 hours after dosing | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Taenia solium, neurocysticercosis, oxfendazole, clinical trial, phase 1, safety, pharmacokinetics