Malaria, Vivax
Conditions
Keywords
Healthy Volunteer, Malaria, Pharmacokinetics, Tafenoquine
Brief summary
This study will investigate the effect of Tafenoquine (TQ) 150 mg tablet ageing (dissolution profiles) on human exposure of TQ comparing the relative bioavailability of TQ from tablets exhibiting different dissolution profiles in healthy subjects. This is a single-centre, 2-arm, randomized open-label, parallel-group study in healthy subjects. All subjects will arrive in the unit approximately 24 hours prior to dosing and will be discharged after the 72-hour post-dose assessments are completed. Subjects will return for outpatient visits on Days 7, 14, 21, 28, and 56 after dosing. A total of 14 subjects (n=7 subjects in each arm) are planned to be enrolled. All subjects will receive a single dose of study medication (2x150 mg TQ tablets + 30 mg TQ SIL in solution) and participate through a 56-day post dose follow-up visit. To enable the application of peripheral microsampling in planned paediatric studies, a comparison of the measured pharmacokinetic (PK) exposure via peripheral blood collection (via microsampling) to venous collection will also be performed in this study.
Interventions
DRUGTafenoquine Control
It will be supplied as a dark pink, capsule-shaped, film-coated tablet plain on both sides containing 150 mg tafenoquine
DRUGTafenoquine dissolution profile X
It will be supplied as a dark pink, capsule-shaped, film-coated tablet plain on both sides containing 150 mg tafenoquine and will be intermediate aged TQ Product.
DRUGTafenoquine SIL
It will be compounded at site and will be administered as 0.3 mg/mL (100mL to be dosed, equivalent to 30 mg) aqueous Solution of SIL Tafenoquine.
Sponsors
Medicines for Malaria Venture
Parexel
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
A subject will be eligible for inclusion in this study only if all of the following criteria apply: * Between 18 and 55 years of age inclusive, at the time of signing the informed consent * Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. * A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
, outside the reference range for the population being studied may be included only if the investigator and the GlaxoSmithKline (GSK) Medical Monitor agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Subject values outside the normal range should always be excluded from enrolment. * Body weight between \>=35 kilogram (kg) and \<=100 kg. * Male subjects only. * Capable of giving signed informed consent as described in study protocol, which includes compliance with the requirements and restrictions listed in the consent form and in the study protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ratio of the geometric means for the area under plasma concentration-time curve (AUC) for Tafenoquine X | Samples will be collected at Pre-dose and 1, 2, 6, 9, 12, 15, 20, 24, 36, 48, 60, and 72 hours post dose on Day 1 and single sample on Day 7, 14, 21, 28, and 56 | Blood samples for PK analysis of TQ will be collected for evaluation of ratio of the geometric means (90% Confidence Interval \[CI\]) for the area under plasma concentration-time curve from 0 to time t (AUC \[0-t\]) and area under the concentration-time curve from 0 to infinity (AUC\[0-inf\]) for the treatment group dissolution profile X compared to Control. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety as assessed by clinical monitoring of pulse rate | Up to 12 hours | Pulse rate will be measured in semi-supine position after approximately 5 minutes rest. Pulse rate will be measured at pre-dose (at least 30 min. prior to dosing and at least 15 min. after waking) and at 12 hours post dose. |
| Safety as assessed by clinical monitoring of electrocardiogram (ECGs) | Day -1 | Single 12-lead ECGs will be obtained in the semi-supine position at screening using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT interval corrected for heart rate according to Fridericia's formula (QTcF) intervals |
| Safety as assessed by clinical monitoring of Haematology parameters | Up to Day 14 | Haematology parameters include Platelet Count, red blood cell (RBC) Indices, white blood cell (WBC) count with differential, RBC Count, mean cell volume (MCV), neutrophils, hemoglobin, mean corpuscular hemoglobin (MCH), lymphocytes, hematocrit, monocytes, methemoglobin %, eosinophils and basophils. It will be assessed on Day -1, Pre-dose and post-dose at Day 7 and Day 14. |
| Safety as assessed by clinical monitoring of Clinical Chemistry parameters | Up to Day 14 | Clinical chemistry parameters includes blood urea nitrogen, potassium, aspartate aminotransferase (SGOT), total and direct bilirubin, creatinine, sodium, alanine aminotransferase (SGPT), total protein, glucose, calcium, alkaline phosphatase and albumin. It will be assessed on Day -1, Pre-dose and post-dose at Day 7 and Day 14. |
| Safety as assessed by clinical monitoring of Urinalysis parameters | Up to Day 14 | Urinalysis parameters include specific gravity, pH, glucose, protein, blood and ketones. It will be assessed on Day -1, Pre-dose and post-dose at Day 7 and Day 14 |
| Safety as assessed by clinical monitoring of blood pressure | Up to 12 hours | Systolic and diastolic blood pressure will be measured in semi-supine position after approximately 5 minutes rest. Blood pressure will be measured at pre-dose (at least 30 min. prior to dosing and at least 15 min. after waking) and at 12 hours post dose. |
| Area under the plasma concentration-time curve from time 0 to last measurable concentration (AUC0-t) for Tafenoquine | Samples will be collected at Pre-dose and 1, 2, 6, 9, 12, 15, 20, 24, 36, 48, 60, and 72 hours post dose on Day 1 and single sample on Day 7, 14, 21, 28, and 56 | PK samples will be obtained from venous blood and peripheral blood collection (via microsampling) |
| Maximum plasma concentration (Cmax) for Tafenoquine | Samples will be collected at Pre-dose and 1, 2, 6, 9, 12, 15, 20, 24, 36, 48, 60, and 72 hours post dose on Day 1 and single sample on Day 7, 14, 21, 28, and 56 | PK samples will be obtained from venous blood and peripheral blood collection (via microsampling) |
| Time to Cmax (tmax) for Tafenoquine | Samples will be collected at Pre-dose and 1, 2, 6, 9, 12, 15, 20, 24, 36, 48, 60, and 72 hours post dose on Day 1 and single sample on Day 7, 14, 21, 28, and 56 | PK samples will be obtained from venous blood and peripheral blood collection (via microsampling) |
| Terminal half-life (t1/2) for Tafenoquine | Samples will be collected at Pre-dose and 1, 2, 6, 9, 12, 15, 20, 24, 36, 48, 60, and 72 hours post dose on Day 1 and single sample on Day 7, 14, 21, 28, and 56 | PK samples will be obtained from venous blood and peripheral blood collection (via microsampling) |
| Number of participants with adverse events (AE) | Up to Day 63 | An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal. |
Countries
United States
Outcome results
None listed