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| Name | Class |
|---|---|
| Medicines for Malaria Venture | OTHER |
| Parexel | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TQ Control+ TQ SIL | Experimental | Subjects received TQ Control product (2 tablets) and 30 mg TQ SIL solution orally with water after a meal. |
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| TQ X + TQ SIL | Experimental | Subjects received 2 tablets of Tafenoquine dissolution profile X and 30 mg TQ SIL solution orally with water after a meal. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tafenoquine Control | Drug | It will be supplied as a dark pink, capsule-shaped, film-coated tablet plain on both sides containing 150 mg tafenoquine |
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| Measure | Description | Time Frame |
|---|---|---|
| Ratio of the geometric means for the area under plasma concentration-time curve (AUC) for Tafenoquine X | 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. | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Safety as assessed by clinical monitoring of blood pressure | 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. | Up to 12 hours |
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Inclusion Criteria:
A subject will be eligible for inclusion in this study only if all of the following criteria apply:
Exclusion Criteria:
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Baltimore | Maryland | 21225 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29869298 | Derived | Goyal N, Mohamed K, Rolfe K, Sahota S, Ernest T, Duparc S, Taylor M, Casillas L, Koh GCKW. Application of the Stable Isotope Label Approach in Clinical Development-Supporting Dissolution Specifications for a Commercial Tablet Product with Tafenoquine, a Long Half-life Compound. AAPS J. 2018 Jun 4;20(4):74. doi: 10.1208/s12248-018-0234-5. |
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| Tafenoquine dissolution profile X | Drug | 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". |
|
| Tafenoquine SIL | Drug | 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. |
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| Safety as assessed by clinical monitoring of pulse rate |
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. |
| Up to 12 hours |
| Safety as assessed by clinical monitoring of electrocardiogram (ECGs) | 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 | Day -1 |
| Safety as assessed by clinical monitoring of Haematology parameters | 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. | Up to Day 14 |
| Safety as assessed by clinical monitoring of Clinical Chemistry parameters | 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. | Up to Day 14 |
| Safety as assessed by clinical monitoring of Urinalysis parameters | 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 | Up to Day 14 |
| Number of participants with adverse events (AE) | 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. | Up to Day 63 |
| Area under the plasma concentration-time curve from time 0 to last measurable concentration (AUC0-t) for Tafenoquine | PK samples will be obtained from venous blood and peripheral blood collection (via microsampling) | 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 |
| Maximum plasma concentration (Cmax) for Tafenoquine | PK samples will be obtained from venous blood and peripheral blood collection (via microsampling) | 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 |
| Time to Cmax (tmax) for Tafenoquine | PK samples will be obtained from venous blood and peripheral blood collection (via microsampling) | 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 |
| Terminal half-life (t1/2) for Tafenoquine | PK samples will be obtained from venous blood and peripheral blood collection (via microsampling) | 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 |
| ID | Term |
|---|---|
| D016780 | Malaria, Vivax |
| D008288 | Malaria |
| ID | Term |
|---|---|
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000096724 | Mosquito-Borne Diseases |
| D000079426 | Vector Borne Diseases |
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