Clinical trial NCT06606860: Safety, Tolerability and PK of Single and Multiple Doses of Oxantel Pamoate Tablets
Official title: A Placebo Controlled, Double-Blind, 3-Arm Phase I Study to Investigate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Doses of 20 mg/kg Oxantel Pamoate in Healthy Adult Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Soil transmitted helminths
Phase I
Safety
Tolerability
Pharmacokinetics
Trichuriasis
Whipworm
Parasitic Diseases
Neglected Diseases
Lead sponsor: Swiss Tropical & Public Health Institute
Sponsor class: OTHER
Collaborators: name: Ifakara Health Institute
name: Drugs for Neglected Diseases initiative
First posted: 2024-09-23
Enrollment: 45
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 goal of this clinical trial is to evaluate the safety, tolerability and pharmacokinetics of oxantel pamoate tablet after administration of a single and multiple dose in healthy male and female adult volunteers.

The main questions aim to answer if oxantel pamoate is safe and well tolerated in healthy volunteers and if is it absorbed by the human body.

A single dose and a multiple dose of oxantel pamoate will be compared to placebo to see if there are any different effects.

Detailed description: Objectives:

Primary objective:

To investigate the safety and tolerability of oxantel pamoate after single and multiple oral administration of a chewable tablet formulation.

Secondary objective:

To investigate the pharmacokinetics (PK) of oxantel pamoate after single and multiple oral administration of a chewable tablet formulation.

Study Design:

This is a randomized, placebo controlled, double blind, 3-arm Phase I single centre study in a total of 45 healthy adults. The participants will be randomized into one of the following three study arms:

* Study arm 1, 20 participants: Treatment with single dose of 20 mg/kg oxantel pamoate on day 1 followed by administration of two daily doses placebo
* Study arm 2, 20 participants: Treatment with three daily dose of 20 mg/kg oxantel pamoate
* Study arm 3, 5 participants: Treatment with three daily dose of placebo PK sampling will be performed at 13 defined time points (baseline included).

The participants will be admitted to the ward one day prior to commencement of the study treatment (day -1) and will stay until one day after the last dose has been administered. They will have a final follow-up visit on day 14. The safety and tolerability will be assessed as of the first dosage up to the last follow-up visit. Biochemistry, haematology, coagulation and urinalysis will be checked at baseline, day 3 and at the final follow-up visit.

Eligibility criteria: Inclusion Criteria:

* Healthy adult male or non-pregnant (confirmed by a negative serum pregnancy test) and non-breastfeeding female participants, aged between 18 to 45 years at the time of consent.
* Written informed consent (IC) obtained before any study procedure.
* 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 (following a test with a maximum of two attempts). 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 from at least 28 days prior to first dosage to 30 days after discharge from the ward.
* Normal body weight range (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. tea, coffee, cola or chocolate 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\&#39;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 the protocol, 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 (BP) and heart rate (HR) in supine position at the screening examination outside the ranges (systolic BP range: 105-136 mm Hg systolic, diastolic BP range: 58-84 mm Hg diastolic; HR range: 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.
* Known renal or hepatic impairment
* Participants with a history of allergies, non-allergic drug reactions, adverse reaction to any drug, or multiple drug allergies.
* 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 volunteer\&#39;s participation in the trial or make it unnecessarily hazardous.
* Relevant pathological abnormalities in the electrocardiogram (ECG) such as a second or third-degree 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 human immunodeficiency virus (HIV), hepatitis B or C.
* Positive stool or urine test for helminth infestation by Kato-Katz, urine filtration or Baermann test.
* Positive for malaria by thick blood smear (TBS).
* Presence of abnormal physical findings, or laboratory values at the screening assessment that could interfere with the objectives of the trial or the safety of the volunteer.

Primary outcomes:
measure: General safety (number, frequency, severity, seriousness and duration of adverse events)
timeFrame: After first dosage on day 0 to day 14
measure: Heart rate from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Blood pressure from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Temperature from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Respiratory rate from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Creatinine value from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Alanine aminotransferase value from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Aspartate aminotransferase value from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Total bilirubin value from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Sodium value from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Potassium value from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Blood urea nitrogen value from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Haemoglobin value from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Red blood cell count from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Mean corpuscular volume from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Mean corpuscular haemoglobin value from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Mean corpuscular haemoglobin concentration from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Platelets value from baseline
timeFrame: After first dosage on day 0 to day 14
measure: White blood cell count from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Neutrophils value from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Lymphocytes value from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Monocytes value from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Eosinophils value from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Basophils value from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Prothrombin time from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Activated partial thromboplastin time from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Protein in urine from baseline
timeFrame: After first dosage on day 0 to day 14
measure: Blood in urine from baseline
timeFrame: After first dosage on day 0 to day 14
Secondary outcomes:
measure: Cmax of oxantel pamoate
timeFrame: Plasma samples taken pre-dose -0.5 hours prior first dose, then 1 hour, 3 hours, 5 hours, 8 hours, 12 hours, 24 hours after first dose and 1 hour, 3 hours, 5 hours, 8 hours, 12 hours, 24 hours after third dose
measure: Tmax of oxantel pamoate
timeFrame: Plasma samples taken pre-dose -0.5 hours prior first dose, then 1 hour, 3 hours, 5 hours, 8 hours, 12 hours, 24 hours after first dose and 1 hour, 3 hours, 5 hours, 8 hours, 12 hours, 24 hours after third dose
measure: AUC of oxantel pamoate
timeFrame: Plasma samples taken pre-dose -0.5 hours, then 1 hour, 3 hours, 5 hours, 8 hours, 12 hours, 24 hours after first dose and 1 hour, 3 hours, 5 hours, 8 hours, 12 hours, 24 hours after third dose
measure: AUC (0-t) of oxantel pamoate
timeFrame: Plasma samples taken pre-dose -0.5 hours prior first dose, then 1 hour, 3 hours, 5 hours, 8 hours, 12 hours, 24 hours after first dose and 1 hour, 3 hours, 5 hours, 8 hours, 12 hours, 24 hours after third dose
measure: T1/2 of oxantel pamoate
timeFrame: Plasma samples taken pre-dose -0.5 hours prior first dose, then 1 hour, 3 hours, 5 hours, 8 hours, 12 hours, 24 hours after first dose and 1 hour, 3 hours, 5 hours, 8 hours, 12 hours, 24 hours after third dose
measure: AUC (tau) of oxantel pamoate
timeFrame: Plasma samples taken pre-dose -0.5 hours prior first dose, then 1 hour, 3 hours, 5 hours, 8 hours, 12 hours, 24 hours after first dose and 1 hour, 3 hours, 5 hours, 8 hours, 12 hours, 24 hours after third dose
measure: AUC (0-∞) of oxantel pamoate
timeFrame: Plasma samples taken pre-dose -0.5 hours prior first dose, then 1 hour, 3 hours, 5 hours, 8 hours, 12 hours, 24 hours after first dose and 1 hour, 3 hours, 5 hours, 8 hours, 12 hours, 24 hours after third dose
Other outcomes:
Locations:
city: Bagamoyo
country: Tanzania
facility: Ifakara Health Institute
Study officials:
affiliation: Swiss Tropical & Public Health Institute
name: Daniel Paris, MD, PhD
role: STUDY_DIRECTOR
affiliation: Swiss Tropical & Public Health Institute
name: Jennifer Keiser, PhD
role: STUDY_CHAIR
affiliation: Ifakara Health Insitute, Tanzania
name: Hussein Mbarak, MD
role: PRINCIPAL_INVESTIGATOR
References: