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| Name | Class |
|---|---|
| Medicines for Malaria Venture | OTHER |
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The study aims to provide evidence of retinal safety to support the use of tafenoquine as a potential single dose radical cure treatment for patients with Plasmodium vivax (P. vivax) malaria (i.e., co-administration of a schizonticidal drug with TQ). The study will be conducted as a single masked, randomized, placebo-controlled, parallel group design. It will assess retinal changes from baseline using spectral domain optical coherence tomography (OCT) and fundus auto fluorescence (FAF) at Month 3 (90 days) post-dose in adult healthy volunteers (participants). A placebo control group will be used to compare the results in the TQ group. Interim analysis will be conducted after completing 100 out of 300 participants in TQ group and 50 out of 150 participants in matched placebo.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tafenoquine 300 milligram (mg) single dose | Experimental | Participants will receive single dose of TQ (2 tablets of 150mg) after standard meal. Participant will be randomized in a 2:1 ratio to 300mg TQ (n=300) or matched-placebo (n=150). |
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| Matched Placebo 300mg single dose | Placebo Comparator | Participants will receive single dose of matched placebo (2 tablets of 150mg) after standard meal. Participant will be randomized in a 2:1 ratio to 300mg TQ (n=300) or matched-placebo (n=150). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tafenoquine 150 mg | Drug | Tablet contains TQ as tafenoquine succinate. The 2 tablets (2 tablets of 150mg) of dark pink, capsule-shaped, film coated will be administered orally with 240ml of water. |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of participants in the TQ group having retinal changes from Baseline in Central subfield thickness and Central retinal lesion thickness | The change from baseline will be assessed as a binomial output as, Yes or No. Spectral domain OCT (SD-OCT) images/scan will be obtained. For Central subfield thickness and Central retinal lesion thickness, change from baseline of at least 40 microns (µ) will be consider 'Yes'. Central Retinal Lesion Thickness is defined as the distance between the inner limiting membrane of the retina and the inner border of the choriocapillaris measured in the central 1millimeter (mm) of the centre scan | Baseline and Day 90(follow-up) |
| Proportion of participants in the TQ group having retinal changes from Baseline in Total macular volume | The change from baseline will be assessed as a binomial output as, Yes or No. SD-OCT images/scan will be obtained. Total Macular Volume, change from baseline of 10% will be considered 'Yes' | Baseline and Day 90(follow-up) |
| Proportion of participants in the TQ group having retinal changes from Baseline in Ellipsoid zone disruption | The change from baseline will be assessed as a binomial output as, Yes or No. SD-OCT images/scan will be obtained. Ellipsoid zone disruption will be assessed by manual reading | Baseline and Day 90(follow-up) |
| Proportion of participants in the TQ group having retinal changes from Baseline in abnormal auto-fluorescence patterns | The change from baseline will be assessed as a binomial output as, Yes or No. SD-OCT images/scan will be obtained. Abnormal auto-fluorescence will be assessed by FAF by manual reading | Baseline and Day 90(follow-up) |
| Measure | Description | Time Frame |
|---|---|---|
| Mean change from baseline in OCT parameter like central retinal thickness as a safety measure | SD-OCT images/scan will be obtained. Central retinal thickness is the thickness at the centre point of the macula | Baseline and Day 90(follow-up) |
| Mean change from baseline in OCT parameter like central subfield thickness as a safety measure. |
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Inclusion Criteria:
Non-reproductive potential defined as Pre-menopausal females with one of the following: Documented tubal ligation or Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion or Hysterectomy or Documented Bilateral Oophorectomy or Postmenopausal defined as 12 months of spontaneous amenorrhea in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to site specific laboratory reference ranges for confirmatory levels). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from screening until completion of the Day 90 follow-up visit.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Glendale | California | 91206 | United States | ||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31187437 | Derived | Ackert J, Mohamed K, Slakter JS, El-Harazi S, Berni A, Gevorkyan H, Hardaker E, Hussaini A, Jones SW, Koh GCKW, Patel J, Rasmussen S, Kelly DS, Baranano DE, Thompson JT, Warren KA, Sergott RC, Tonkyn J, Wolstenholme A, Coleman H, Yuan A, Duparc S, Green JA. Randomized Placebo-Controlled Trial Evaluating the Ophthalmic Safety of Single-Dose Tafenoquine in Healthy Volunteers. Drug Saf. 2019 Sep;42(9):1103-1114. doi: 10.1007/s40264-019-00839-w. |
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| ID | Term |
|---|---|
| D016780 | Malaria, Vivax |
| D008288 | Malaria |
| ID | Term |
|---|---|
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000096724 | Mosquito-Borne Diseases |
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| ID | Term |
|---|---|
| C055852 | tafenoquine |
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| Matched placebo 150mg | Drug | It is the matched Placebo tablet. The 2 tablets (2 tablets of 150mg) of dark pink, capsule-shaped, film coated will be administered orally with 240ml of water. |
|
SD-OCT images/scan will be obtained. Central subfield thickness measures thickness from top of Internal limiting membrane (ILM) to bottom of Retinal pigment epithelium (RPE). |
| Baseline and Day 90(follow-up) |
| Mean change from baseline in OCT parameter like central retinal lesion thickness as a safety measure. | SD-OCT images/scan will be obtained. Central retinal lesion thickness measures a greatest linear thickness from ILM to inner border of choriocapillaris | Baseline and Day 90(follow-up) |
| Mean change from baseline in OCT parameters;. Total macular volume as a safety measure. | SD-OCT images/scan will be obtained. Total macular volume describes the overall thickness of retina from top of ILM to bottom of RPE as a volume measurement. | Baseline and Day 90(follow-up) |
| Mean change from baseline in OCT parameters ;. Ellipsoid zone disruption as a safety measure. | SD-OCT images/scan will be obtained. Ellipsoid zone disruption will measure zones of absent or irregular ellipsoid layer. | Baseline and Day 90(follow-up) |
| Changes from baseline in the status of the outer retina/photoreceptor complex as a safety measure. | SD-OCT images/scan will be obtained. | Baseline and Day 90(follow-up) |
| Proportion of participants with abnormal changes from baseline observed on FAF as a safety measure. | FAF images will be obtained. Qualitative assessment will be done to check for any abnormal patterns of auto-fluorescence in the macular region that may be indicative of disease of the retinal pigment epithelium. | Baseline and Day 90(follow-up) |
| Mean change from baseline in best corrected visual acuity (BCVA) as a safety measure of TQ in comparison to placebo. | BCVA will be measured by a trained examiner | Baseline and Day 90(follow-up) |
| Proportion of participants with vortex keratopathy from the slit lamp examination as a safety measure of TQ in comparison to placebo. | Vortex keratopathy (corneal deposits) will be confirmed by slit lamp examination. Anterior and posterior segment evaluation will be done. | Baseline and Day 90(follow-up) |
| Number of participants with of adverse events as a safety measure | An AE is any untoward medical occurrence in a participant or clinical investigation temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product | 90 days |
| Overland Park |
| Kansas |
| 66211 |
| United States |
| GSK Investigational Site | Baltimore | Maryland | 21225 | United States |
| D000079426 |
| Vector Borne Diseases |