PK, Safety and Tolerability of Single and Multiple Doses of Oxfendazole Tablets

NCT04920292 | Completed Phase 1 DMC

• 1 other identifier: P1773-20A
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The study evaluates the pharmacokinetics (PK), safety and tolerability of oxfendazole, after administration as a tablet formulation in healthy male and female participants.

Conditions

Filariasis

Keywords

Onchocerciasis; Parasitic Diseases; Neglected Disease; Phase I; Safety; Tolerability; Pharmacokinetics; Bioavailability; Volunteers

Outcome Measures

Primary Outcomes (10)

• Area under the plasma concentration curve from time zero to the last quantifiable concentration at time t (AUC0-t) of oxfendazole and its metabolites fenbendazole and fenbendazole sulfone

  For single dose arms

  At different time points from pre-dose up to 48 hours after single dose administration

• Area under the plasma concentration curve (AUC) from time zero extrapolated to infinity (AUC0-∞) of oxfendazole and its metabolites fenbendazole and fenbendazole sulfone

  For single dose arms

  At different time points from pre-dose up to 48 hours after single dose administration

• Maximum observed concentration (Cmax) of oxfendazole and its metabolites fenbendazole and fenbendazole sulfone

  For single dose arms

  At different time points from pre-dose up to 48 hours after single dose administration

• Time to maximum observed concentration (Tmax) of oxfendazole and its metabolites fenbendazole and fenbendazole sulfone

  For single dose arms

  At different time points from pre-dose up to 48 hours after single dose administration

• Elimination half-life (t1/2) of oxfendazole and its metabolites fenbendazole and fenbendazole sulfone

  For single dose arms

  At different time points from pre-dose up to 48 hours after single dose administration

• Area under the plasma concentration curve over dosing interval (AUCtau) of oxfendazole and its metabolites fenbendazole

  For multiple doses arm

  At different time points from pre-dose up to 72 hours after last dose administration

• Accumulation Ratio (Racc) of oxfendazole and its metabolites fenbendazole

  For multiple doses arm

  At different time points from pre-dose up to 72 hours after last dose administration

• Maximum observed concentration (Cmax) of oxfendazole and its metabolites fenbendazole and fenbendazole sulfone

  For multiple doses arm

  At different time points from pre-dose up to 72 hours after last dose administration

• Time to maximum observed concentration (Tmax) of oxfendazole and its metabolites fenbendazole and fenbendazole sulfone

  For multiple doses arm

  At different time points from pre-dose up to 72 hours after last dose administration

• Elimination half-life (t1/2) of oxfendazole and its metabolites fenbendazole and fenbendazole sulfone

  For multiple doses arm

  At different time points from pre-dose up to 72 hours after last dose administration

Secondary Outcomes (5)

• Safety and tolerability of oxfendazole as measured by number of participants with treatment related adverse events and serious adverse events

  From Day 1 to Day 14.

• Safety and tolerability of oxfendazole as measured by number of participants with physical examination findings

  At different time points from baseline to Day 14

• Safety and tolerability of oxfendazole as measured by number of participants with vital signs findings

  At different time points from baseline to Day 14

• Safety and tolerability of oxfendazole as measured by number of participants with clinical laboratory test findings

  At different time points from baseline to Day 14

• Safety and tolerability of oxfendazole as measured by number of participants with 12-lead ECG findings Safety and tolerability of oxfendazole as measured by the change in ECG parameters

  Pre-dose, 1 and 2 hours after single dose administration on Day 1; Pre-dose, 1 and 2 hours after dose administration on Day 1 and pre-dose, 1 and 2 hours after dose administration on Day 5 (last dose) for multiple doses administration arm.

Study Arms (3)

Single Dose of 100mg Oxfendazole versus Placebo

EXPERIMENTAL

8 participants will receive a single oral dose of 100mg of oxfendazole. 2 participants will receive a single oral dose of placebo.

Drug: Oxfendazole; Drug: Placebo

Single Dose of 400mg Oxfendazole versus Placebo

EXPERIMENTAL

8 participants will receive a single oral dose of 400mg of oxfendazole. 2 participants will receive a single oral dose of placebo.

Drug: Oxfendazole; Drug: Placebo

Multiple Doses of 400mg Oxfendazole versus Placebo

EXPERIMENTAL

8 participants will receive multiple oral doses of 400mg of oxfendazole on 5 consecutive days. 2 participants will receive multiple oral doses of placebo on 5 consecutive days.

Drug: Oxfendazole; Drug: Placebo

Interventions

Oxfendazole DRUG

Oxfendazole is a benzimidazole anthelminthic drug.

Multiple Doses of 400mg Oxfendazole versus Placebo; Single Dose of 100mg Oxfendazole versus Placebo; Single Dose of 400mg Oxfendazole versus Placebo

Placebo DRUG

The placebo tablet is made using the same non-active ingredients and matches the investigational tablet.

Multiple Doses of 400mg Oxfendazole versus Placebo; Single Dose of 100mg Oxfendazole versus Placebo; Single Dose of 400mg Oxfendazole versus Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult male and non-pregnant (confirmed by pregnancy test) and non-breastfeeding female participants (18 to 45 years of age at the time of consent).
• Willingness to give written consent to participate in the trial, after reading the participant information and consent form and after having had the opportunity to discuss the trial with the Investigator or any delegate.
• Ability to read and write and to understand the participant information sheet and the nature of the trial and any hazards from participating in it. Ability to communicate satisfactorily with the Investigator and to participate in, and comply with the requirements of, the entire trial.
• Women of childbearing potential (WOCBP) must agree to use a highly effective form of contraception in combination with a barrier method from at least 28 days prior to first dosage to 30 days after last dosage.
• Male participants must be willing to ensure the use of condoms from the first dosage to 90 days after last dosage.
• Normal body weight range (body mass index (BMI) between 18 and 29.9 kg/ m2)

You may not qualify if:

• Participation in another clinical trial within 3 months prior to the study, or within 5-times the half-life of the drug tested in the previous clinical trial, whichever is longer. (Time calculated relative to the last dose in the previous clinical trial).
• Regular daily consumption of more than one liter of xanthine-containing beverages (e.g. chocolates, tea, coffee or cola drinks).
• Regular daily consumption of more than 5 cigarettes daily.
• Use of a prescription medicine during the 28 days before the first dose of trial medication or use of an over-the-counter medicine, during the 7 days before the first dose of trial medication.
• Use of dietary supplements or herbal remedies (such as St John's Wort) known to interfere with the CYP3A4 and/or P-gp metabolic pathway during the 28 days before the first dose of trial medication.
• Therapies which may impact on the interpretation of study results in the opinion of the Investigator.
• Medical, social condition, psychiatric disorder or occupational reasons that, in the judgment of the Investigator, is a contraindication to protocol participation, may impair the volunteer's ability to give informed consent or effectively participate in the study, may significantly increase the risk to the volunteer because of participation in the study or may impair interpretation of the study data.
• Blood pressure and heart rate in supine position at the screening examination outside one (or more) of the ranges 105-136 mm Hg systolic, 58-84 mm Hg diastolic; heart rate 56- 96 beats/min.
• Febrile illness within 1 week before the start of study treatment.
• History of relevant diseases of vital organs, of the central nervous system or other organs.
• Participants with a history of allergies, non-allergic drug reactions, adverse reaction to any drug, or multiple drug allergies.
• Participants with a hypersensitivity to the investigational drug, related benzimidazole compounds or the control agent and/ or to inactive constituents.
• Presence or history of drug or alcohol abuse in the last 10 years.
• Surgery (e.g. stomach bypass) or medical condition that might affect absorption of study drug taken orally.
• Clinically relevant abnormal medical history, concurrent medical condition, acute or chronic illness or history of chronic illness sufficient to invalidate the subject's participation in the trial or make it unnecessarily hazardous.

Sponsors & Collaborators

• Swiss Tropical & Public Health Institute: lead
• Ifakara Health Institute: collaborator
• Drugs for Neglected Diseases: collaborator

Study Sites (1)

Ifakara Health Institute

Bagamoyo, Tanzania

Location

MeSH Terms

Conditions

Filariasis; Onchocerciasis; Parasitic Diseases; Neglected Diseases

Interventions

oxfendazole

Condition Hierarchy (Ancestors)

Spirurida Infections; Secernentea Infections; Nematode Infections; Helminthiasis; Infections; Skin Diseases, Parasitic; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Daniel Paris

  Swiss TPH

  STUDY DIRECTOR

• Said Jongo

  Ifakara Health Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2021
• First Posted: June 9, 2021
• Study Start: April 21, 2022
• Primary Completion: November 7, 2022
• Study Completion: November 14, 2022
• Last Updated: December 20, 2022

Record last verified: 2022-12

Locations

TA (1)