Healthy Volunteers
Conditions
Keywords
tafenoquine, australia
Brief summary
This randomized, double-blind, placebo controlled study will involve 600 healthy (Glucose-6-Phosphate Dehydrogenase \[G6PD\] normal) volunteers. Participants who meet the eligibility criteria will be randomized (ratio 1:1) to receive a loading dose of either tafenoquine 200 mg (2 x 100 mg tablets) or placebo daily for three consecutive days, followed by study treatment (tafenoquine 200 mg or placebo) once per week for 51 weeks, with safety follow-up visits at Weeks 4, 12, 24, and 52. All participants will return to the clinic at Week 64 for an end of study visit. If the participant has an ongoing AE at the Week 64 visit will continue to be assessed for up to 3 more times at approximately 12-week intervals or until resolution or stabilization of the AE whichever is earlier.
Interventions
DRUGTafenoquine
Tafenoquine 200mg
OTHERPlacebo
Placebo
Sponsors
60 Degrees Pharmaceuticals LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Identically matched placebo control.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Main Inclusion Criteria: 1. Completion of the written informed consent process (signed). 2. Male or female age 18 to 55 years inclusive, in good health as assessed by the Investigator. 3. Normal G6PD enzyme activity levels as defined by the parameters of the specific G6PD test employed at the local laboratory. 4. Negative HBsAg and HCV, HIV-1, HIV-2 antibody screen at the screening visit. 5. Negative serum pregnancy test. 6. Use acceptable method of birth control. 7. Hematology, biochemistry and urinalysis results at screening that are within the local laboratory reference range or, if outside the range, not clinically significant as judged by the Investigator in accordance with approved clinically acceptable laboratory ranges, documented prior to study start. 8. Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures. Main
Exclusion criteria
1. History of allergy or intolerance to tafenoquine, primaquine or any excipients. 2. History of thalassemia or current or past history of methemoglobinemia or methemoglobin \>2% at screening. 3. History of eye disease or surgery 4. Having previously received hydroxychloroquine for skin conditions or rheumatological diseases, chloroquine for malaria, tamoxifen, amiodarone or other drugs that may affect the optic nerve/retina/cornea within 30 days or 5 half-lives (whichever is longer) of study start. There are no travel restrictions, but the choice of concurrent anti-malarial must be atovaquone-proguanil if the participant chooses to take a registered antimalarial drug while travelling. 5. Any current diagnosis of Axis I psychiatric disorders
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serious Ophthalmic Safety Event | After 12 months of exposure to study drug | Number of Participants with One or More protocol-defined serious ophthalmic safety event (SOSE) assessed by retinal changes from baseline using SD-OCT and qFAF. SOSE is assessed by significant retinal changes from baseline using SD-OCT and qFAF. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Mean Change From Baseline in Key SD OCT Parameters | After 12 months of exposure to study drug | Mean change from baseline in key SD OCT parameters including central subfield thickness, total macular volume, and parafoveal (inner ring of Early Treatment Diabetic Retinopathy Study, and retinal thickness. Clinically significant change from baseline for central subfield thickness \[change from baseline of at least 40 µm (15% change)\]. Clinically significant change from baseline for total macular volume \[change of \> 10% (0.86 mm3) from baseline\]. Clinically significant change from baseline for parafoveal (inner ring) retinal thickness \[change from baseline of at least 10 µm\]. Clinically significant change from baseline for qFAF (change in mid-ring qFAF unit from baseline of at least 12% in both eyes at the same visit). |
| Number of Participants With Ellipsoid or Interdigitating Zone Disruption | After 12 months of exposure to study drug | Any ellipsoid or interdigitating zone disruption within the ETDRS grid |
| Number of Participants With Mean Change From Baseline in Best Corrected Visual Acuity | After 12 months of exposure to study drug | Mean change from baseline in BCVA score, the number of participants that have any clinically significant change in ETDRS BCVA (defined as ≥15 letter change \[≥ 3 lines\] of change in ETDRS BCVA at 4 meters). |
| Number of Participants With Corneal Deposits From Slit Lamp Examination of the Corneal Epithelium | After 12 months of exposure to study drug | Slit lamp examination was use to detect and grade corneal deposits (also known as vortex keratopathy or cornea verticillata) and retinal abnormalities arising from drug-induced phospholipidosis. |
| Number of Participants With New Abnormalities Compared With Baseline Observed With Color Retinal Digital Photography | After 12 months of exposure to study drug | Corneal deposits as determined by digital corneal photographs that are indicative of cornea verticillata also known as vortex keratopathy |
| Number of Participants With New Abnormalities Compared With Baseline Observed With Microperimetry | After 12 months of exposure to study drug | Microperimetry can be a useful tool for objective evaluation of macular function and progression of disease. Macular disease causes impairment of central vision, metamorphopsia, macropsia, micropsia and color vision defect. Microperimetry measures fixation stability which is associated with visual acuity. |
| Number of Participants With Any Clinically Significant Change in ETDRS BCVA (Defined as >15 Letter Change [≥ 3 Lines] of Change in ETDRS BCVA at 4 Meters) | After 12 months of exposure to study drug | Visual acuity was measured in a consistent way in order to detect any changes in vision as described in the Ophthalmic Reference Manual using a set of Early Treatment Diabetic Retinopathy Study (ETDRS) charts and a retro-illuminated box providing standardized illumination. Subjects are seated 4 meters from the letter chart and asked to read the letters. Letters read correctly count towards the total score. In addition, there are 5 letters in each of the 14 lines. The lines are of equal difficulty and follow a logarithmic progression of diminishing letter size related to the minimum angle of resolution. The endpoints include mean change from baseline in BCVA score, the proportion of participants that have any clinically significant change in ETDRS BCVA (defined as ≥15 letter change \[≥ 3 lines\] of change in ETDRS BCVA at 4 meters). |
| Proportion of Participants Who Develop a Color Deficiency Using the Farnsworth-Munsell 100 (FM-100) Hue Test | After 12 months of exposure to study drug | Color deficiency was assessed using the Farnsworth-Munsell 100 (FM-100) hue test |
| Number of Participants Who Develop a Loss of 0.12 or Greater Logarithm of Contrast Sensitivity (logCS) on the Mars Letter Contrast Sensitivity Test | After 12 months of exposure to study drug | The Mars letter contrast sensitivity test is a set of charts for testing peak visual contrast sensitivity. Subjects are asked to read to letters from left to right across the chart. The logarithm of contrast sensitivity (logCS) score is given by the log contrast sensitivity value at the lowest contrast letter just prior to two incorrectly identified letters, minus a scoring correction. |
| Number of Participants Who Develop a Psychiatric Disorder in Accordance With DSM-5 as Assessed With the Mini International Neuropsychiatric Interview (M.I.N.I.) 7.0.2 Assessment Questionnaire | After 12 months of exposure to study drug | Psychiatric disorders were reported as adverse events |
| Number of Participants With an AE of Dizziness or Vertigo and Severity as Assessed by the Dizziness Handicap Inventory | After 12 months of exposure to study drug | The period of observation for collection of AEs extended from the time of dosing (Day 1, Week 1 \[Visit 2\]) through the Week 64 follow-up visit. Proportion of participants with an AE of dizziness or vertigo are reported here. |
Countries
Australia, United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 600 Participants |
| Age, Continuous | 31.3 years |
| Best Corrected Visual Accuity | 60.2 letters STANDARD_DEVIATION 3.55 |
| Central Subfield Thickness | 268.82 um STANDARD_DEVIATION 19.3 |
| Parafoveal (inner ring) retinal thickness | 343.40 um STANDARD_DEVIATION 14.35 |
| Parafoveal (outer ring) retinal thickness | 301.87 um STANDARD_DEVIATION 12.75 |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants |
| Race (NIH/OMB) Asian | 31 Participants |
| Race (NIH/OMB) Black or African American | 17 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 256 Participants |
| Region of Enrollment Australia | 246 participants |
| Region of Enrollment United States | 56 participants |
| Sex: Female, Male Female | 372 Participants |
| Sex: Female, Male Male | 116 Participants |
| Total Macular Volume | 8.78 mm STANDARD_DEVIATION 0.36 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 301 | 0 / 299 |
| other Total, other adverse events | 274 / 301 | 268 / 299 |
| serious Total, serious adverse events | 23 / 301 | 17 / 299 |
Outcome results
None listed