Clinical trial NCT02234570: Phase I Trial Evaluating the Safety and Pharmacokinetics of Oxfendazole
Official title: A Randomized, Double-Blind Placebo-Controlled Phase I Trial Evaluating the Safety and Pharmacokinetics of Oxfendazole
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neurocysticercosis
Keywords: neurocysticercosis
pork tapeworm
Taenia solium
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2014-09-09
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Males and females of non-childbearing potential between the ages of 18 and 45 years, inclusive.\* \*Surgically sterile via tubal ligation, bilateral oophorectomy or hysterectomy or who have been postmenopausal for \>/=1 year confirmed by LH and FSH levels. 2. In good health, as judged by the investigator and determined by vital signs\* Temperature \< 38 degrees Celsius, heart rate \</=100 bpm and \> 50 bpm, systolic blood pressure \</= 140 mmHg and \> 89 mmHg, diastolic blood pressure \</=90 mmHg and \>/= 60 mm Hg, medical history and a targeted physical examination. BMI \>/=18 and \</= 35. Athletically trained subjects with a pulse \>/= 45 may be enrolled at the discretion of the principal investigator or designated licensed clinical investigator. 3. Acceptable screening laboratories\* \*Hemoglobin, white blood cell (WBC) count, neutrophil, eosinophil and platelet counts within normal ranges. AST \< 44 and ALT \< 44 and total bilirubin, creatinine must be equal to or below the upper limit of normal (for eosinophil count, AST, ALT, creatinine, and total bilirubin values below the normal range are acceptable). Random blood glucose must be \<140. Urine dipstick testing must be negative for glucose and negative or trace for protein. The following serology tests must be negative: HIV 1/2 antibody, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibody. HIV and hepatitis C viral load PCR testing may be performed for individuals suspected of having indeterminate antibody testing. 4. Male participants must be willing to ensure use of condoms and spermicides for 4 months after study drug administration. 5. Provide written informed consent before initiation of any study procedures. 6. Willing to be available for all study-required procedures, and visits for the duration of the study. 7. Able to provide a home phone number, and the name, address, and/or email of a person willing to assist with making contact during the follow-up phase of the study.

Exclusion Criteria:

1. History of residing for 6 or more months in regions with endemic cysticercosis as determined by the principal investigator or a designated study physician. 2. Breastfeeding females. 3. Body temperature \>/=100.4 degrees Fahrenheit (\>/=38.0 degrees Celsius) or acute illness within 3 days before administration of study drug (subject may be rescheduled). 4. Chronic or acute medical disorder\* \*Disorders of the cardiac, pulmonary, liver, kidney, neurologic, gastrointestinal or other system, such that in the opinion of the investigator participation in the study creates additional risk to the subject, or to the validity of the study. 5. Use of chronic systemic medications\* \*Intermittent use of over the counter medications such as acetaminophen, ibuprofen, cold and sinus medications are permitted for enrollment (please see section 5.6 for instructions on medication use during the study).Topical medications, nasal steroids are permitted throughout the study. Use of the prescription medications used less than once per week on average are permitted for enrollment (see section 5.6 for instructions on medication use during the study). If the subject has taken a short term prescription medication within the past 30 days (e.g. an antibiotic), they should be postponed from enrollment until 30 days have elapsed since the last dose 6. Has history of sensitivity to related benzimidazole compounds (e.g., albendazole, mebendazole). 7. A diagnosis of schizophrenia, bipolar disease, or history of hospitalization for a psychiatric condition or previous suicide attempt. 8. A history of treatment for any other psychiatric disorder in the past 3 years.\* \*Past treatment for ADHD does not exclude participants from enrollment as long as the medications have been discontinued for a minimum of 3 months and symptoms are well controlled. 9. Received an experimental agent\* within 1 month before administration of study drug or expect to receive an experimental agent during the 15-day study period. \*Vaccine, drug, biologic, device, blood product, or medication. 10. Any condition that would, in the opinion of the investigator, place them at an unacceptable risk of injury, render them unable to meet the requirements of the protocol, or that may interfere with successful completion of the study. 11. A history of alcohol consumption\* or any illicit drug use†, or history of substance abuse#. Individuals must agree to abstain from drug or alcohol use for 48 hours prior to enrollment through day 15. \*Greater than 7 alcoholic drinks per week. †Other than occasional marijuana use (less than once per week for the past 60 days is acceptable). #Alcohol or illicit drugs within the past 3 years. 12. History of chronic tobacco use in the past 60 days.\* \*A history of occasional tobacco use (less than 1 pack per week on average) is acceptable. Individuals will be counseled to abstain from use of tobacco and marijuana from screening through day 15.

Primary outcomes:
measure: Number of Subjects Reporting Adverse Events Related to Oxfendazole Within 14 Days of Receipt of a Single Oral Dose.
timeFrame: Within 14 Days of first dose
Secondary outcomes:
measure: Area Under the Concentration Time-curve From Time Zero to Infinity (AUC(0-infinity)) for Oxfendazole
timeFrame: 0, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 336 hours post-dose
measure: Maximum Observed Concentration (Cmax) of Oxfendazole in Plasma
timeFrame: 0, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 336 hours post-dose
measure: Plasma Concentrations of Oxfendazole Fenbendazole
timeFrame: Day 1-Day15
measure: Plasma Concentrations of Oxfendazole Sulfone
timeFrame: Day 1-Day15
measure: Terminal Elimination Half-life (t1/2) of Oxfendazole
timeFrame: 0, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 336 hours post-dose
measure: Time of Maximum Observed Concentration (Tmax) of Oxfendazole
timeFrame: 0, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 336 hours post-dose
measure: Urine Concentrations of Oxfendazole Fenbendazole
timeFrame: Day 1-Day 15
measure: Urine Concentrations of Oxfendazole Sulfone
timeFrame: Day 1-Day 15
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa - Vaccine Research and Education Unit
state: Iowa
Study officials:
References:
citation: An G, Murry DJ, Gajurel K, Bach T, Deye G, Stebounova LV, Codd EE, Horton J, Gonzalez AE, Garcia HH, Ince D, Hodgson-Zingman D, Nomicos EYH, Conrad T, Kennedy J, Jones W, Gilman RH, Winokur P. Pharmacokinetics, Safety, and Tolerability of Oxfendazole in Healthy Volunteers: a Randomized, Placebo-Controlled First-in-Human Single-Dose Escalation Study. Antimicrob Agents Chemother. 2019 Mar 27;63(4):e02255-18. doi: 10.1128/AAC.02255-18. Print 2019 Apr.