A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK2798745 in Participants With Diabetic Macular Edema

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

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).

Study Overview

• Status: Completed
• Conditions: Macular Edema
• Intervention / Treatment: Drug: GSK2798745

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Castle Hill, New South Wales, Australia, 2154
      • GSK Investigational Site
    • Westmead, New South Wales, Australia, 2145
      • GSK Investigational Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • GSK Investigational Site
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • GSK Investigational Site
• New Zealand
  • Christchurch, New Zealand, 8011
    • GSK Investigational Site
• United States
  • California
    • Sacramento, California, United States, 95841
      • GSK Investigational Site
  • Florida
    • Lake Worth, Florida, United States, 33467
      • GSK Investigational Site
    • Winter Haven, Florida, United States, 33880
      • GSK Investigational Site
  • New York
    • Shirley, New York, United States, 11967
      • GSK Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45202
      • GSK Investigational Site
  • Texas
    • McAllen, Texas, United States, 78503
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 by fluorescein angiography.
• Confirmation of retinal thickening (diabetic macular edema) involving the center of the fovea in the study by Investigator.
• Best Corrected Visual Acuity (BCVA) letter score of 80 letter or worse (Snellen equivalent: equivalent to 20/25) or worse in the study eye.
• 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 43 kg per square meter (inclusive) at screening.
• Male participants must agree to 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 acceptable contraception/barrier to use acceptable contraceptive methods if their partner is of childbearing potential. This criterion must be followed from the first dose of study treatment until the follow-up visit.
• A female participant is eligible to participate if she is not of childbearing potential.

Exclusion Criteria:

• Additional eye disease in the study eye that in the opinion of the Investigator could compromise assessment.
• 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.
• Intraocular surgery or laser photocoagulation in the study eye within 90 day.
• Use of intravitreal ranibizumab,or bevacizumab within 42 days (6 weeks), or aflibercept within 56 days (8 weeks) of dosing in the study eye.
• Use of intraocular steroids in the study eye within 180 days of dosing.
• Use of or expected need for intravitreal or intraocular treatment in the study eye during course of the study.
• Use of any systemically administered anti-angiogenic agent within 6 months of dosing.
• Evidence of vitreomacular traction as determined by the Investigator.
• Uncontrolled intraocular pressure 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
• Uncontrolled diabetes as indicated by glycated hemoglobin (HbA1c) >12% at Screening.
• Active ulcer disease or gastrointestinal bleeding by history within 6 months of screening or by exam at the time of screening.
• Certain type of liver disease.
• Participant who, in the Investigator's opinion, poses a significant suicide risk.
• History or current evidence of any serious or clinically significant cardiac, gastrointestinal, renal, endocrine, neurologic, hematologic, infectious or other condition that is uncontrolled.
• Corrected (QTc) interval >450 milliseconds (msec) or QTc >480 msec in participants with bundle branch block.
• Use of certain medications that may interfere with the study medication or eye assessments (these will be identified by the study doctor).
• Current enrollment, or recent participation in a study of investigational intervention or medical research.
• 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.
• Any other reason the investigator deems the participant should not participate in the study.
• Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants receiving GSK2798745	Drug: GSK2798745; GSK2798745 will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with abnormal ophthalmic examination findings	Up to Day 28
Number of participants with abnormal refraction and visual acuity	Up to Day 28
Number of participants with abnormal physical examination findings	Up to Day 28
Number of participants with clinically significant changes in laboratory parameters, vital signs, and 12-lead electrocardiogram (ECG) findings	Up to Day 28
Number of participants with adverse events (AE) and serious adverse events (SAE)	Up to Day 28
Mean change from Baseline in center subfield retinal thickness as measured by Spectral-Domain Optical Coherence Tomography (SD-OCT)	Baseline and at Day 28

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma concentrations of GSK2798745	At Day 28
Plasma concentrations of major metabolite GSK3526876	At Day 28
Absorption rate of GSK2798745	At Day 28
Clearance of GSK2798745	At Day 28
Volume of distribution of GSK2798745	At Day 28
Maximum observed plasma concentration (Cmax) of GSK2798745	At Day 28
Area under concentration-time curve (AUC) over dosing interval of GSK2798745	At Day 28

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2020
• Primary Completion (Actual): April 11, 2022
• Study Completion (Actual): April 11, 2022

Study Registration Dates

• First Submitted: February 28, 2020
• First Submitted That Met QC Criteria: February 28, 2020
• First Posted (Actual): March 3, 2020

Study Record Updates

• Last Update Posted (Actual): August 25, 2022
• Last Update Submitted That Met QC Criteria: August 24, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Diabetic macular edema; Refraction; GSK2798745; Visual acuity.
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema
• Other Study ID Numbers: 212669

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No