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PK, Safety and Tolerability of Single and Multiple Doses of Oxfendazole Tablets (HELP-OFZ)

Primary Purpose

Filariasis

Status
Completed
Phase
Phase 1
Locations
Tanzania
Study Type
Interventional
Intervention
Oxfendazole
Placebo
Sponsored by
Swiss Tropical & Public Health Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Filariasis focused on measuring Onchocerciasis, Parasitic Diseases, Neglected Disease, Phase I, Safety, Tolerability, Pharmacokinetics, Bioavailability, Volunteers

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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.
  • Relevant pathological abnormalities in the ECG such as a second or third-degree atrioventricular (AV) block, prolongation of the QRS complex over 120 msec or of the QTcF-interval over 450 msec (corrected interval according to Fridericia's formula).
  • Positive test for hepatitis B or C.
  • Positive test for HIV.
  • Positive pregnancy test (WOCBP).
  • Positive stool or urine test for helminth infestation by Kato-Katz, urine filtration or Baermann test.
  • Positive for malaria by thick blood smear.
  • Positive test for (neuro-) cysticercosis.
  • Positive test for echinococcosis.
  • Positive test for onchocerciasis.
  • Presence of abnormal physical findings, ECG, or laboratory values at the screening assessment that could interfere with the objectives of the trial or the safety of the subject.

Sites / Locations

  • Ifakara Health Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Single Dose of 100mg Oxfendazole versus Placebo

Single Dose of 400mg Oxfendazole versus Placebo

Multiple Doses of 400mg Oxfendazole versus Placebo

Arm Description

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

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

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.

Outcomes

Primary Outcome Measures

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
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
Maximum observed concentration (Cmax) of oxfendazole and its metabolites fenbendazole and fenbendazole sulfone
For single dose arms
Time to maximum observed concentration (Tmax) of oxfendazole and its metabolites fenbendazole and fenbendazole sulfone
For single dose arms
Elimination half-life (t1/2) of oxfendazole and its metabolites fenbendazole and fenbendazole sulfone
For single dose arms
Area under the plasma concentration curve over dosing interval (AUCtau) of oxfendazole and its metabolites fenbendazole
For multiple doses arm
Accumulation Ratio (Racc) of oxfendazole and its metabolites fenbendazole
For multiple doses arm
Maximum observed concentration (Cmax) of oxfendazole and its metabolites fenbendazole and fenbendazole sulfone
For multiple doses arm
Time to maximum observed concentration (Tmax) of oxfendazole and its metabolites fenbendazole and fenbendazole sulfone
For multiple doses arm
Elimination half-life (t1/2) of oxfendazole and its metabolites fenbendazole and fenbendazole sulfone
For multiple doses arm

Secondary Outcome Measures

Safety and tolerability of oxfendazole as measured by number of participants with treatment related adverse events and serious adverse events
Number of participants with treatment related adverse events and serious adverse events
Safety and tolerability of oxfendazole as measured by number of participants with physical examination findings
Number of participants with physical examination findings. Standard examination done on skin, lymph nodes, head, eyes, ears, nose, throat, respiratory, cardiovascular, abdomen, extremities, musculoskeletal, and neurological.
Safety and tolerability of oxfendazole as measured by number of participants with vital signs findings
Number of participants with vital signs findings (heart rate, blood pressure, axillar temperature, respiratory rate,)
Safety and tolerability of oxfendazole as measured by number of participants with clinical laboratory test findings
Number of participants with relevant abnormal clinical laboratory tests results (hematology (hemoglobin, white blood cells (differentiation of eosinophils and neutrophils) and platelets), coagulation (prothrombin time and activated partial thromboplastin time), biochemistry (Creatinine, Alanine aminotransferase, Aspartate aminotransferase, total bilirubin, sodium, potassium, chloride, bicarbonate, blood urea nitrogen), urinalysis (proteinuria and glucose))
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
Number of participants with 12-lead ECG findings (heart rate (HR), PR interval, QRS, QT, QTcB, QTcF, cardiac rhythm and T wave morphology)

Full Information

First Posted
May 28, 2021
Last Updated
December 19, 2022
Sponsor
Swiss Tropical & Public Health Institute
Collaborators
Ifakara Health Institute, Drugs for Neglected Diseases
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1. Study Identification

Unique Protocol Identification Number
NCT04920292
Brief Title
PK, Safety and Tolerability of Single and Multiple Doses of Oxfendazole Tablets
Acronym
HELP-OFZ
Official Title
A Phase 1, Bioavailability Study to Investigate the Pharmacokinetics, Safety and Tolerability of an Oxfendazole Tablet Formulation in a Randomized, Double-Blind, Placebo-Controlled Design After Single and Multiple Oral Dosing in Healthy Adult Volunteers
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
April 21, 2022 (Actual)
Primary Completion Date
November 7, 2022 (Actual)
Study Completion Date
November 14, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Swiss Tropical & Public Health Institute
Collaborators
Ifakara Health Institute, Drugs for Neglected Diseases

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
This is a randomized, placebo-controlled, double blinded, single center phase I bioavailability study with two Single Dose cohorts and one Multiple Doses cohort in a total of 30 healthy male and female healthy volunteers (10 per cohort).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Filariasis
Keywords
Onchocerciasis, Parasitic Diseases, Neglected Disease, Phase I, Safety, Tolerability, Pharmacokinetics, Bioavailability, Volunteers

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Single Dose of 100mg Oxfendazole versus Placebo
Arm Type
Experimental
Arm Description
8 participants will receive a single oral dose of 100mg of oxfendazole. 2 participants will receive a single oral dose of placebo.
Arm Title
Single Dose of 400mg Oxfendazole versus Placebo
Arm Type
Experimental
Arm Description
8 participants will receive a single oral dose of 400mg of oxfendazole. 2 participants will receive a single oral dose of placebo.
Arm Title
Multiple Doses of 400mg Oxfendazole versus Placebo
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Oxfendazole
Intervention Description
Oxfendazole is a benzimidazole anthelminthic drug.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
The placebo tablet is made using the same non-active ingredients and matches the investigational tablet.
Primary Outcome Measure Information:
Title
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
Description
For single dose arms
Time Frame
At different time points from pre-dose up to 48 hours after single dose administration
Title
Area under the plasma concentration curve (AUC) from time zero extrapolated to infinity (AUC0-∞) of oxfendazole and its metabolites fenbendazole and fenbendazole sulfone
Description
For single dose arms
Time Frame
At different time points from pre-dose up to 48 hours after single dose administration
Title
Maximum observed concentration (Cmax) of oxfendazole and its metabolites fenbendazole and fenbendazole sulfone
Description
For single dose arms
Time Frame
At different time points from pre-dose up to 48 hours after single dose administration
Title
Time to maximum observed concentration (Tmax) of oxfendazole and its metabolites fenbendazole and fenbendazole sulfone
Description
For single dose arms
Time Frame
At different time points from pre-dose up to 48 hours after single dose administration
Title
Elimination half-life (t1/2) of oxfendazole and its metabolites fenbendazole and fenbendazole sulfone
Description
For single dose arms
Time Frame
At different time points from pre-dose up to 48 hours after single dose administration
Title
Area under the plasma concentration curve over dosing interval (AUCtau) of oxfendazole and its metabolites fenbendazole
Description
For multiple doses arm
Time Frame
At different time points from pre-dose up to 72 hours after last dose administration
Title
Accumulation Ratio (Racc) of oxfendazole and its metabolites fenbendazole
Description
For multiple doses arm
Time Frame
At different time points from pre-dose up to 72 hours after last dose administration
Title
Maximum observed concentration (Cmax) of oxfendazole and its metabolites fenbendazole and fenbendazole sulfone
Description
For multiple doses arm
Time Frame
At different time points from pre-dose up to 72 hours after last dose administration
Title
Time to maximum observed concentration (Tmax) of oxfendazole and its metabolites fenbendazole and fenbendazole sulfone
Description
For multiple doses arm
Time Frame
At different time points from pre-dose up to 72 hours after last dose administration
Title
Elimination half-life (t1/2) of oxfendazole and its metabolites fenbendazole and fenbendazole sulfone
Description
For multiple doses arm
Time Frame
At different time points from pre-dose up to 72 hours after last dose administration
Secondary Outcome Measure Information:
Title
Safety and tolerability of oxfendazole as measured by number of participants with treatment related adverse events and serious adverse events
Description
Number of participants with treatment related adverse events and serious adverse events
Time Frame
From Day 1 to Day 14.
Title
Safety and tolerability of oxfendazole as measured by number of participants with physical examination findings
Description
Number of participants with physical examination findings. Standard examination done on skin, lymph nodes, head, eyes, ears, nose, throat, respiratory, cardiovascular, abdomen, extremities, musculoskeletal, and neurological.
Time Frame
At different time points from baseline to Day 14
Title
Safety and tolerability of oxfendazole as measured by number of participants with vital signs findings
Description
Number of participants with vital signs findings (heart rate, blood pressure, axillar temperature, respiratory rate,)
Time Frame
At different time points from baseline to Day 14
Title
Safety and tolerability of oxfendazole as measured by number of participants with clinical laboratory test findings
Description
Number of participants with relevant abnormal clinical laboratory tests results (hematology (hemoglobin, white blood cells (differentiation of eosinophils and neutrophils) and platelets), coagulation (prothrombin time and activated partial thromboplastin time), biochemistry (Creatinine, Alanine aminotransferase, Aspartate aminotransferase, total bilirubin, sodium, potassium, chloride, bicarbonate, blood urea nitrogen), urinalysis (proteinuria and glucose))
Time Frame
At different time points from baseline to Day 14
Title
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
Description
Number of participants with 12-lead ECG findings (heart rate (HR), PR interval, QRS, QT, QTcB, QTcF, cardiac rhythm and T wave morphology)
Time Frame
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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) Exclusion Criteria: 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. Relevant pathological abnormalities in the ECG such as a second or third-degree atrioventricular (AV) block, prolongation of the QRS complex over 120 msec or of the QTcF-interval over 450 msec (corrected interval according to Fridericia's formula). Positive test for hepatitis B or C. Positive test for HIV. Positive pregnancy test (WOCBP). Positive stool or urine test for helminth infestation by Kato-Katz, urine filtration or Baermann test. Positive for malaria by thick blood smear. Positive test for (neuro-) cysticercosis. Positive test for echinococcosis. Positive test for onchocerciasis. Presence of abnormal physical findings, ECG, or laboratory values at the screening assessment that could interfere with the objectives of the trial or the safety of the subject.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel Paris
Organizational Affiliation
Swiss TPH
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Said Jongo
Organizational Affiliation
Ifakara Health Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ifakara Health Institute
City
Bagamoyo
Country
Tanzania

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
It is intended that Summary results will be shared once Clinical Study Report will be available.

Learn more about this trial

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

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