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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
45
Oxantel Pamoate tablet, 250mg
Placebo tablet
Ifakara Health Institute
Bagamoyo, Tanzania
General safety (number, frequency, severity, seriousness and duration of adverse events)
Summarized statistics on adverse events will be reported under categories such as total adverse events, serious adverse events, treatment emerging adverse events
Time frame: After first dosage on day 0 to day 14
Heart rate from baseline
Change of pulse rate from baseline
Time frame: After first dosage on day 0 to day 14
Blood pressure from baseline
Change of blood pressure from baseline. Systolic and diastolic blood pressure will be assessed
Time frame: After first dosage on day 0 to day 14
Temperature from baseline
Change of axillary temperature from baseline
Time frame: After first dosage on day 0 to day 14
Respiratory rate from baseline
Change of respiratory rate from baseline
Time frame: After first dosage on day 0 to day 14
Creatinine value from baseline
Change of creatinine value from baseline
Time frame: After first dosage on day 0 to day 14
Alanine aminotransferase value from baseline
Change of alanine aminotransferase value from baseline
Time frame: After first dosage on day 0 to day 14
Aspartate aminotransferase value from baseline
Change of aspartate aminotransferase value from baseline
Time frame: After first dosage on day 0 to day 14
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Total bilirubin value from baseline
Change of total bilirubin value from baseline
Time frame: After first dosage on day 0 to day 14
Sodium value from baseline
Change of sodium value from baseline
Time frame: After first dosage on day 0 to day 14
Potassium value from baseline
Change of potassium value from baseline
Time frame: After first dosage on day 0 to day 14
Blood urea nitrogen value from baseline
Change of blood urea nitrogen value from baseline
Time frame: After first dosage on day 0 to day 14
Haemoglobin value from baseline
Change of haemoglobin value from baseline
Time frame: After first dosage on day 0 to day 14
Red blood cell count from baseline
Change of red blood cell count from baseline
Time frame: After first dosage on day 0 to day 14
Mean corpuscular volume from baseline
Change of mean corpuscular volume from baseline
Time frame: After first dosage on day 0 to day 14
Mean corpuscular haemoglobin value from baseline
Change of mean corpuscular haemoglobin value from baseline
Time frame: After first dosage on day 0 to day 14
Mean corpuscular haemoglobin concentration from baseline
Change of mean corpuscular haemoglobin concentration from baseline
Time frame: After first dosage on day 0 to day 14
Platelets value from baseline
Change of platelets value from baseline
Time frame: After first dosage on day 0 to day 14
White blood cell count from baseline
Change of white blood cell count from baseline
Time frame: After first dosage on day 0 to day 14
Neutrophils value from baseline
Change of neutrophils value from baseline
Time frame: After first dosage on day 0 to day 14
Lymphocytes value from baseline
Change of lymphocytes value from baseline
Time frame: After first dosage on day 0 to day 14
Monocytes value from baseline
Change of monocytes value from baseline
Time frame: After first dosage on day 0 to day 14
Eosinophils value from baseline
Change of eosinophils value from baseline
Time frame: After first dosage on day 0 to day 14
Basophils value from baseline
Change of basophils value from baseline
Time frame: After first dosage on day 0 to day 14
Prothrombin time from baseline
Change of prothrombin time value from baseline
Time frame: After first dosage on day 0 to day 14
Activated partial thromboplastin time from baseline
Change of activated partial thromboplastin time value from baseline
Time frame: After first dosage on day 0 to day 14
Protein in urine from baseline
Change of proteine in urine from baseline
Time frame: After first dosage on day 0 to day 14
Blood in urine from baseline
Change of blood in urine from baseline
Time frame: After first dosage on day 0 to day 14
Cmax of oxantel pamoate
Peak Plasma Concentration (Cmax) of oxantel pamoate, if detectable
Time frame: 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
Tmax of oxantel pamoate
Time to reach Cmax (Tmax), in case of plasma concentration determined.
Time frame: 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
AUC of oxantel pamoate
Area under the curve (AUC) of the plasma concentration determined.
Time frame: 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
AUC (0-t) of oxantel pamoate
Concentration from time zero to the last quantifiable concentration at time t, in case plasma concentration can be determined.
Time frame: 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
T1/2 of oxantel pamoate
The plasma elimination half-life, In case plasma concentration can be determined.
Time frame: 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
AUC (tau) of oxantel pamoate
The area under the plasma concentration curve over dosing interval, in case plasma concentration can be determined.
Time frame: 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
AUC (0-∞) of oxantel pamoate
The AUC of the plasma concentration from time zero to infinity with extrapolation of the terminal phase, In case plasma concentration can be determined.
Time frame: 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