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

Macular Edema Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04292912
• Other study ID #: 212669
• Status: Completed
• Phase: Phase 1
• Start date: September 7, 2020
• Est. completion date: April 11, 2022

Study information

• Verified date: August 2022
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: April 11, 2022
• Est. primary completion date: April 11, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Edema
• Macular Edema

Intervention

Drug:
• GSK2798745
GSK2798745 will be administered.

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Adelaide	South Australia
Australia	GSK Investigational Site	Castle Hill	New South Wales
Australia	GSK Investigational Site	Melbourne	Victoria
Australia	GSK Investigational Site	Westmead	New South Wales
New Zealand	GSK Investigational Site	Christchurch
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Lake Worth	Florida
United States	GSK Investigational Site	McAllen	Texas
United States	GSK Investigational Site	Sacramento	California
United States	GSK Investigational Site	Shirley	New York
United States	GSK Investigational Site	Winter Haven	Florida

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with abnormal ophthalmic examination findings		Up to Day 28
Primary	Number of participants with abnormal refraction and visual acuity		Up to Day 28
Primary	Number of participants with abnormal physical examination findings		Up to Day 28
Primary	Number of participants with clinically significant changes in laboratory parameters, vital signs, and 12-lead electrocardiogram (ECG) findings		Up to Day 28
Primary	Number of participants with adverse events (AE) and serious adverse events (SAE)		Up to Day 28
Primary	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	Plasma concentrations of GSK2798745		At Day 28
Secondary	Plasma concentrations of major metabolite GSK3526876		At Day 28
Secondary	Absorption rate of GSK2798745		At Day 28
Secondary	Clearance of GSK2798745		At Day 28
Secondary	Volume of distribution of GSK2798745		At Day 28
Secondary	Maximum observed plasma concentration (Cmax) of GSK2798745		At Day 28
Secondary	Area under concentration-time curve (AUC) over dosing interval of GSK2798745		At Day 28