Assessment of Any Potential Retinal Effects of Tafenoquine (TQ)



Status:Completed
Conditions:Infectious Disease
Therapuetic Areas:Immunology / Infectious Diseases
Healthy:No
Age Range:18 - 45
Updated:4/17/2018
Start Date:February 2, 2016
End Date:September 14, 2017

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A Phase 1, Multi-center, Single-masked, Randomized, Placebo-controlled, Parallel-group Study to Investigate the Ophthalmologic Safety and Pharmacodynamics of 300mg Single Doses of Tafenoquine (SB 252263) in Adult Healthy Volunteers

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.


Inclusion Criteria:

- Between 18 and 45 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, brief physical examination, and
laboratory tests.

- Participant values for haematology and chemistry within the normal range. A
participant 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
documents that the finding is unlikely to introduce additional risk factors and will
not interfere with the study procedures.

- Body weight between >=35 kilogram (kg) and =<100kg

- Male OR Female. Female participant is eligible to participate if she is not pregnant
(as confirmed by a negative [serum or urine, according to site standard] human
chorionic gonadotrophin [hCG] test), not lactating, and at least one of the following
conditions applies:

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.

- Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the consent form and in this protocol.

Exclusion Criteria:

- Alanine Aminotransferase (ALT) and bilirubin >1.5 times Upper Limit of Normal (ULN)
(isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and
direct bilirubin <35%).

- Current or chronic history of liver disease, or known hepatic or biliary abnormalities
(with the exception of Gilbert's syndrome or asymptomatic gallstones).

- The QT interval corrected (QTc) for heart rate according to Fridericia's formula
(QTcF). QTcF > 450 milli second (msec). Other calculation methods (e.g. QT interval
corrected for heart rate according to Bazett's formula [QTcB], individually corrected
QT interval [QTcI]) machine-read or manually over-read are not acceptable.

- Use of prescription (except female contraception and acetaminophen at doses of =<2
grams(g)/day) or non-prescription drugs, including vitamins, herbal and dietary
supplements (including St John's Wort) within 7 days (or 14 days if the drug is a
potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first
dose of study medication, unless in the opinion of the Investigator and GSK Medical
Monitor the medication will not interfere with the study procedures or compromise
participant safety.

- History of regular alcohol consumption within 30 days of the study defined as: an
average weekly intake of >14 drinks for males or >7 drinks for females. One drink is
equivalent to 12 g of alcohol: 12 ounces (360 millilitre [mL]) of beer, 5 ounces (150
mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.

- Positive results for drugs of abuse

- Cotinine levels indicative of smoking or history or regular use of tobacco- or
nicotine-containing products within 30 days prior to screening.

- History of sensitivity to TQ, or components thereof or a history of drug or other
allergy that, in the opinion of the investigator or Medical Monitor, contraindicates
their participation.

- History of thalassaemia; or current or past history of methemoglobinemia or
methemoglobin percentage above the reference range at screening.

- Lactating females.

- Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test
result at screening or within 3 months prior to first dose of study treatment. A
positive pre-study drug/alcohol screen.

- A positive test for human immunodeficiency virus (HIV) antibody.

- Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within a 15 days of dosing with TQ or matched-placebo.

- The participant has participated in a clinical trial and has received an
investigational product within the following time period prior to the first dosing day
in the current study: 30 days, 5 half-lives or twice the duration of the biological
effect of the investigational product (whichever is longer).

- Exposure to more than four new chemical entities within 12 months prior to the first
dosing day

- Participants with a hemoglobin values outside the lower limit of normal range. A
single repeat is allowed for eligibility determination.

- Documented phenotypic Glucose-6-phosphate dehydrogenase (G6PD) deficiency, determined
by a quantitative assay of enzyme activity. Defined as <70% of locally defined median.

- A BCVA (bilateral) at screening of =<72 letters

- Eye disease that could compromise assessment of BCVA or imaging of the posterior pole
by fundus photography, or spectral domain OCT, FAF, or is likely to require
intervention during the 4 month (approximately) study participation (e.g. cataract,
glaucoma with documented visual field loss, ischemic optic neuropathy, retinitis
pigmentosa)

- History of retinal vascular disease, retinal detachment, inflammatory disease, central
serous chorioretinopathy, or other retinal disease that may affect posterior retinal
function or architecture.

- Vitreo-retinal interface disorders (e.g. epiretinal membrane, vitreo-macular traction)
that may affect posterior retinal function or architecture

- Intraocular surgery within 3 months of dosing

- Laser photocoagulation within 3 months of dosing

- High Myopia (defined as equal to, or worse than, -6.00 diopters)

- Anterior, intermediate or posterior uveitis (active or history of) or history of
significant intraocular infectious disease (e.g., conjunctivitis is not acceptable to
include) or another active inflammatory disease

- An OCT central subfield thickness <250 microns or >290 microns

- Presence of significant abnormal patterns on FAF or ocular abnormalities on fundus
photography at screening.

- Uncontrolled intraocular pressure >22millimetre of mercury (mmHg).
We found this trial at
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Baltimore, Maryland 21201
Phone: 877-379-3718
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Glendale, California 91204
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Overland Park, Kansas 66210
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