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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04292912




Registration number
NCT04292912
Ethics application status
Date submitted
28/02/2020
Date registered
3/03/2020
Date last updated
26/04/2021

Titles & IDs
Public title
Study 212669: A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2798745 in Participants With Diabetic Macular Edema
Scientific title
Phase I, Open-Label, Multi-Center Study to Evaluate Safety, Pharmacokinetics and Pharmacodynamics of GSK2798745 After 28 Day Repeat Oral Administration to Adults With Diabetic Macular Edema
Secondary ID [1] 0 0
212669
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Macular Edema 0 0
Condition category
Condition code
Eye 0 0 0 0
Diseases / disorders of the eye
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK2798745

Experimental: Participants receiving GSK2798745 -


Treatment: Drugs: GSK2798745
GSK2798745 will be administered.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with abnormal ophthalmic examination findings
Timepoint [1] 0 0
At Day 28
Primary outcome [2] 0 0
Number of participants with abnormal refraction and visual acuity
Timepoint [2] 0 0
At Day 28
Primary outcome [3] 0 0
Number of participants with abnormal physical examination findings
Timepoint [3] 0 0
At Day 28
Primary outcome [4] 0 0
Number of participants with clinically significant changes in laboratory parameters, vital signs, and 12-lead electrocardiogram (ECG) findings
Timepoint [4] 0 0
At Day 28
Primary outcome [5] 0 0
Number of participants with adverse events (AE) and serious adverse events (SAE)
Timepoint [5] 0 0
At Day 28
Primary outcome [6] 0 0
Mean change from Baseline in center subfield retinal thickness as measured by Spectral-Domain Optical Coherence Tomography (SD-OCT)
Timepoint [6] 0 0
Baseline and up to Day 28
Secondary outcome [1] 0 0
Plasma concentrations of GSK2798745
Timepoint [1] 0 0
Day 7 and Day 28
Secondary outcome [2] 0 0
Plasma concentrations of major metabolite GSK3526876
Timepoint [2] 0 0
Day 7 and Day 28

Eligibility
Key inclusion criteria
- At least 18 to 75 years of age inclusive, at the time of signing the informed consent.

- Diagnosis of diabetes mellitus (type 1 or type 2).

- Confirmation of DME with center involvement in at least one eye, including those with
focal or diffuse DME as determined by Investigator-determined fluorescein angiography.

- Retinal thickening (diabetic macular edema) involving the center of the fovea in the
study eye as defined by Investigator-determined SD-OCT central subfield thickness
greater than (>)340 microns for Heidelberg Spectralis or >320 for Zeiss Cirrus; if
both eyes are eligible, the eye with the greater OCT center subfield score is selected
as the study eye if all other criteria are met. SD-OCT assessments for individual
patients must be taken with the same machine throughout the duration of the study.

- Early Treatment Diabetic Retinopathy Study (ETDRS)-Best Corrected Visual Acuity (BCVA)
letter score of 80 letter or worse (Snellen equivalent: equivalent to 20/25) or worse
in the study eye. The non-study fellow eye should equivalent or better at Baseline,
pre-dose.

- Safe to withhold treatment of the study eye with laser photocoagulation, intravitreal
steroid injection, or intravitreal vascular endothelial growth factor (VEGF) inhibitor
for the duration of the study.

- Body weight greater than equal to (>=) 50 kilograms (kg) and Body mass index (BMI)
within the range 18 to 40kg per square meter (inclusive) at screening.

- Male participants will be eligible to participate if they agree to the following first
dose of study treatment until the follow-up visit: Refrain from donating sperm, plus
either be abstinent from heterosexual or homosexual intercourse as their preferred and
usual lifestyle (abstinent on a long term and persistent basis) and agree to remain
abstinent or Must agree to use contraception/barrier as detailed below: 1. Agree to
use a male condom and female partner to use an additional highly effective
contraceptive method with a failure rate of less than (<)1 percent (%) per year, 2.
Should also be advised of the benefit for a female partner to use a highly effective
method of contraception as a condom may break or leak when having sexual intercourse
with a woman of childbearing potential who is not currently pregnant.

- A female participant is eligible to participate if she is not of childbearing
potential.

- Contraceptive use by men or women should be consistent with local regulations
regarding the methods of contraception for those participating in clinical studies.

- Participant is willing and able to return for all study visits and to comply with all
protocol requirements and procedures.

- Participants capable of giving signed informed consent which includes compliance with
the requirements and restrictions listed in the consent form.
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Additional eye disease in the study eye that in the opinion of the Investigator could
compromise assessment of SD-OCT, BCVA or imaging of the posterior pole by Fundus
Photography (FP), fluorescein angiography, or is likely to require intervention during
the study ( for example [e.g.], cataract, glaucoma with documented visual field loss,
ischemic optic neuropathy, retinitis pigmentosa).

- History of choroidal neovascularization in the study eye, or current choroidal
neovascularization in the fellow eye requiring treatment.

- Active Proliferative diabetic retinopathy (PDR) in the study eye or untreated active
PDR in the fellow eye.

- Ischemic maculopathy on fluorescein angiography defined as a total area of capillary
loss greater that 2-disc areas (>5millimeter square [mm^2]) within the ETDRA macular
grid or a foveal avascular zone greatest linear diameter of >1000 microns.

- Intraocular surgery or laser photocoagulation in the study eye within 90 day of dosing
which might compromise assessment of SD-OCT, BCVA or imaging of the posterior pole by
FP, fluorescein angiography. Allowed in fellow eye.

- Use of intravitreal ranibizumab,or bevacizumab within 42 days (6 weeks), or
aflibercept within 56 days (8 weeks) of dosing in the study eye. Allowed in fellow
eye.

- Use of intraocular steroids in the study eye within 180 days of dosing. Allowed in
fellow eye.

- Use of or expected need for intravitreal or intraocular treatment in the study eye
during course of the study. Allowed in fellow eye.

- Use of any systemically administered anti-angiogenic agent (e.g., bevacizumab,
sunitinib, cetuximab, sorafenib, pazopanib), approved or investigational, within 6
months of dosing.

- Evidence of vitreomacular traction as determined by the Investigator.

- Uncontrolled intraocular pressure >22 millimeters of mercury in the study eye despite
treatment with glaucoma medication.

- Within 6 months prior to the Screening Visit, use of medications known to be toxic to
the retina, lens or optic nerve (e.g., desferoximine, chloroquine/hydrochloroquine,
chlorpromazine, phenothiazines, tamoxifen, interferons and ethambutol) or are
implicated in the development of macular edema (e.g. thiazolidinesdiones, fingolimod).

- Uncontrolled diabetes as indicated by glycated hemoglobin (HbA1c) >10% at Screening.

- Active ulcer disease or gastrointestinal bleeding at the time of Screening (positive
Fecal Occult Blood Test (FOBT) at screening).

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

- History of stroke or seizure disorder within 1 year of Screening.

- Participant who, in the Investigator's opinion, poses a significant suicide risk.
Evidence of serious suicide risk may include any history of suicidal behavior and/or
any evidence of suicidal ideation on any questionnaires e.g., Type 4 or 5 on the
Columbia Suicidality Severity Rating Scale (CSSRS) in the last 6 months (assessed at
Screening).

- History or current evidence of any serious or clinically significant cardiac,
gastrointestinal, renal, endocrine, neurologic, hematologic, infectious or other
condition that is uncontrolled on permitted therapies or that would, in the opinion of
the Investigator or the Medical Monitor, make the participant unsuitable for inclusion
in this study.

- Alanine aminotransferase (ALT) >1.5 times upper limit of normal (ULN).

- Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin
is fractionated and direct bilirubin <35%).

- Evidence of abnormal clinical laboratory finding prior to enrollment that, in the
opinion of the Investigator, makes the participant unsuitable for the study.

- Corrected (QTc) interval >450 milliseconds (msec) or QTc >480 msec in participants
with bundle branch block.

- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary
supplements 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 drug, unless in the
opinion of the Investigator and GlaxoSmithKline (GSK) Medical Monitor the medication
will not interfere with the study procedures or compromise participant safety.

- Use of a listed precluded medication, including strong inhibitors or inducers of
cytochrome P450 (CYP) 3A or p-glycoprotein, within the restricted timeframe relative
to the first dose of the study treatment.

- Participation in the study would result in loss of blood or blood products in excess
of 500 milliliter within 3 months from screening.

- Exposure to more than 4 new chemical entities within 12 months prior to the first
dosing day.

- Current enrollment, or past participation within the last 60 days, of any clinical
study involving an investigational study intervention, or any other type of medical
research, before signing of consent for this study.

- Positive human immunodeficiency virus (HIV) antibody test.

- Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior
to first dose of study intervention.

- Positive Hepatitis C antibody test result at screening or within 3 months prior to
starting study intervention.

- Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3
months prior to first dose of study intervention.

- Cardiac troponin at screening > ULN for the assay.

- Sensitivity to any of the study interventions, or components thereof, or drug or other
allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates
participation in the study.

- Regular substance abuse including drug and/or alcohol consumption within 6 months
prior to the study. Alcohol consumption is defined as: An average weekly intake of >
14 units. One unit is equivalent to 8 gram of alcohol: a half-pint (equivalent to 240
milliliters[mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
GSK Investigational Site - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a multi-center, open-label, single arm, 28-day treatment in participants with DME.
The study will be composed of 3 periods for all participants: Screening, 28-day Treatment
period, and Follow-up visit (approximately 28 days after the final dose).
Trial website
https://clinicaltrials.gov/show/NCT04292912
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
US GSK Clinical Trials Call Center
Address 0 0
Country 0 0
Phone 0 0
877-379-3718
Fax 0 0
Email 0 0
GSKClinicalSupportHD@gsk.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04292912