Single Ascending Dose Safety Study of Oxfendazole (OXFEND-02)

Phase I Study of Oxfendazole (Toward the Treatment of Neurocysticercosis)

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.

Study Overview

• Status: Withdrawn
• Conditions: Tenia Solium Infection
• Intervention / Treatment: Drug: oxfendazole; Drug: oxfendazole; Drug: oxfendazole; Drug: oxfendazole; Drug: oxfendazole; Drug: oxfendazole; Drug: placebo

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.

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: oxfendazole 0.3; administration of a single oral 0.3mg/kg dose of oxfendazole	Drug: oxfendazole; administration of a single oral 1.0 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 3.0 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 0.3 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 10 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 20 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 30 mg/kg dose of oxfendazole
PLACEBO_COMPARATOR: placebo comparator; administration of a single oral dose of placebo	Drug: placebo; single oral dose of placebo
EXPERIMENTAL: oxfendazole 1.0; administration of a single oral 1.0 mg/kg dose of oxfendazole	Drug: oxfendazole; administration of a single oral 1.0 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 3.0 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 0.3 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 10 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 20 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 30 mg/kg dose of oxfendazole
EXPERIMENTAL: oxfendazole 3.0; administration of a single oral 3 mg/kg dose of oxfendazole	Drug: oxfendazole; administration of a single oral 1.0 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 3.0 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 0.3 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 10 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 20 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 30 mg/kg dose of oxfendazole
EXPERIMENTAL: oxfendazole 10; administration of a single oral 10 mg/kg dose of oxfendazole	Drug: oxfendazole; administration of a single oral 1.0 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 3.0 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 0.3 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 10 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 20 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 30 mg/kg dose of oxfendazole
EXPERIMENTAL: oxfendazole 20; administration of a single oral 20 mg/kg dose of oxfendazole	Drug: oxfendazole; administration of a single oral 1.0 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 3.0 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 0.3 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 10 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 20 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 30 mg/kg dose of oxfendazole
EXPERIMENTAL: oxfendazole 30; administration of a single oral 30 mg/kg dose of oxfendazole	Drug: oxfendazole; administration of a single oral 1.0 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 3.0 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 0.3 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 10 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 20 mg/kg dose of oxfendazole; Drug: oxfendazole; administration of a single oral 30 mg/kg dose of oxfendazole

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

Collaborators and Investigators

• Sponsor: Johns Hopkins Bloomberg School of Public Health
• Collaborators: Universidad Peruana Cayetano Heredia; School of Veterinary Medicine, Universidad Nacional Mayor de San Marcos
• Investigators: Principal Investigator: Robert H Gilman, MD, Johns Hopkins University

Publications and helpful links

General Publications

• Gonzalez AE, Falcon N, Gavidia C, Garcia HH, Tsang VC, Bernal T, Romero M, Gilman RH. Treatment of porcine cysticercosis with oxfendazole: a dose-response trial. Vet Rec. 1997 Oct 18;141(16):420-2. doi: 10.1136/vr.141.16.420.
• Gonzales AE, Garcia HH, Gilman RH, Gavidia CM, Tsang VC, Bernal T, Falcon N, Romero M, Lopez-Urbina MT. Effective, single-dose treatment or porcine cysticercosis with oxfendazole. Am J Trop Med Hyg. 1996 Apr;54(4):391-4. doi: 10.4269/ajtmh.1996.54.391.
• Gonzalez AE, Falcon N, Gavidia C, Garcia HH, Tsang VC, Bernal T, Romero M, Gilman RH. Time-response curve of oxfendazole in the treatment of swine cysticercosis. Am J Trop Med Hyg. 1998 Nov;59(5):832-6. doi: 10.4269/ajtmh.1998.59.832.

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (ACTUAL): August 1, 2016
• Study Completion (ACTUAL): August 1, 2016

Study Registration Dates

• First Submitted: April 18, 2012
• First Submitted That Met QC Criteria: April 24, 2012
• First Posted (ESTIMATE): April 25, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): August 30, 2016
• Last Update Submitted That Met QC Criteria: August 29, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: safety; pharmacokinetics; neurocysticercosis; Taenia solium; clinical trial, phase 1; oxfendazole
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Central Nervous System Infections; Parasitic Diseases; Helminthiasis; Cestode Infections; Central Nervous System Helminthiasis; Central Nervous System Parasitic Infections; Cysticercosis; Taeniasis; Neurocysticercosis; Anti-Infective Agents; Antiparasitic Agents; Antinematodal Agents; Anthelmintics; Oxfendazole
• Other Study ID Numbers: OXFEND-02, IND 113,628; IND 113,628 (OTHER: FDA)