Clinical trial NCT03320174: Long-Term Safety Study of Tafenoquine
Official title: Single Site, Randomized, Double Blind, Placebo-Controlled Study to Assess the Long-Term Safety of Tafenoquine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Healthy Volunteers
Keywords: tafenoquine
australia
Lead sponsor: 60 Degrees Pharmaceuticals LLC
Sponsor class: INDUSTRY
First posted: 2017-10-25
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility 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

Primary outcomes:
measure: Proportion of Subjects with Spectral Domain Optical Coherence Tomography (SD-OCT) and Quantitative Fundus Auto Fluorescence (qFAF) with clinically significant changes compared with baseline.
timeFrame: After 12 months of exposure to study drug
Secondary outcomes:
measure: The incidence, severity and relationship to the investigational medicinal product of AEs
timeFrame: After 12 months of exposure to study drug
measure: 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
timeFrame: After 12 months of exposure to study drug
measure: Proportion of participants with ellipsoid or interdigitating zone disruption
timeFrame: After 12 months of exposure to study drug
measure: Mean change from baseline in Best Corrected Visual Acuity
timeFrame: After 12 months of exposure to study drug
measure: Proportion of participants with corneal deposits from slit lamp examination of the corneal epithelium
timeFrame: After 12 months of exposure to study drug
measure: Proportion of participants with new abnormalities compared with baseline observed with color retinal digital photography
timeFrame: After 12 months of exposure to study drug
measure: Proportion of participants with new abnormalities compared with baseline observed with multifocal electroretinography
timeFrame: After 12 months of exposure to study drug
measure: Proportion of participants with new abnormalities compared with baseline observed with microperimetry
timeFrame: After 12 months of exposure to study drug
measure: Proportion 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)
timeFrame: After 12 months of exposure to study drug
measure: Proportion of participants who develop a color deficiency using the Farnsworth-Munsell 100 (FM-100) hue test
timeFrame: After 12 months of exposure to study drug
measure: Proportion of participants who develop a loss of 0.12 or greater logarithm of contrast sensitivity (logCS) on the Mars letter contrast sensitivity test
timeFrame: After 12 months of exposure to study drug
measure: Proportion of participants with any new anomaly on the backlit ETDRS chart
timeFrame: After 12 months of exposure to study drug
measure: Proportion 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
timeFrame: After 12 months of exposure to study drug
measure: Proportion of participants with an AE of dizziness or vertigo and severity as assessed by the Dizziness Handicap Inventory
timeFrame: After 12 months of exposure to study drug
measure: Mean change from baseline visual analog scale score (1-100) in Getting to Sleep (GTS) as assessed by the Leeds Sleep Evaluation Questionnaire (LSEQ).
timeFrame: After 12 months of exposure to study drug
measure: Mean change from baseline visual analog scale score (1-100) Quality of Sleep (QOS) as assessed by the Leeds Sleep Evaluation Questionnaire (LSEQ).
timeFrame: After 12 months of exposure to study drug
measure: Mean change from baseline visual analog scale score (1-100) Awake Following Sleep (AFS) as assessed by the Leeds Sleep Evaluation Questionnaire (LSEQ).
timeFrame: After 12 months of exposure to study drug
measure: Mean change from baseline visual analog scale score (1-100) Behavior Following Wakening (BFW) as assessed by the Leeds Sleep Evaluation Questionnaire (LSEQ).
timeFrame: After 12 months of exposure to study drug
Other outcomes:
Locations:
city: Colorado Springs
country: United States
facility: Retina Consultants of Southern Colorado
state: Colorado
city: McAllen
country: United States
facility: Valley Retina Institute
state: Texas
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
Study officials:
References:
citation: Novitt-Moreno A, Martidis A, Gonzalez V, Ransom J, Scott CB, Dow G, Reid M, Smith B, Zottig VE, Read LT, Garver Baldwin LS, Chen FK. Long-term safety of the tafenoquine antimalarial chemoprophylaxis regimen: A 12-month, randomized, double-blind, placebo-controlled trial. Travel Med Infect Dis. 2022 Jan-Feb;45:102211. doi: 10.1016/j.tmaid.2021.102211. Epub 2021 Nov 18.