A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK2798745 in Participants With Diabetic Macular Edema
Study Details
Study Description
Brief 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).
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Participants receiving GSK2798745
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Drug: GSK2798745
GSK2798745 will be administered.
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Outcome Measures
Primary Outcome Measures
- 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
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria:
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At least 18 to 75 years of age inclusive, at the time of signing the informed consent.
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Diagnosis of diabetes mellitus (type 1 or type 2).
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Confirmation of DME with center involvement in at least one eye by fluorescein angiography.
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Confirmation of retinal thickening (diabetic macular edema) involving the center of the fovea in the study by Investigator.
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Best Corrected Visual Acuity (BCVA) letter score of 80 letter or worse (Snellen equivalent: equivalent to 20/25) or worse in the study eye.
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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.
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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.
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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.
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A female participant is eligible to participate if she is not of childbearing potential.
Exclusion Criteria:
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Additional eye disease in the study eye that in the opinion of the Investigator could compromise assessment.
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History of choroidal neovascularization in the study eye, or current choroidal neovascularization in the fellow eye requiring treatment.
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Active Proliferative diabetic retinopathy (PDR) in the study eye or untreated active PDR in the fellow eye.
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Ischemic maculopathy on fluorescein angiography.
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Intraocular surgery or laser photocoagulation in the study eye within 90 day.
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Use of intravitreal ranibizumab,or bevacizumab within 42 days (6 weeks), or aflibercept within 56 days (8 weeks) of dosing in the study eye.
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Use of intraocular steroids in the study eye within 180 days of dosing.
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Use of or expected need for intravitreal or intraocular treatment in the study eye during course of the study.
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Use of any systemically administered anti-angiogenic agent within 6 months of dosing.
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Evidence of vitreomacular traction as determined by the Investigator.
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Uncontrolled intraocular pressure in the study eye despite treatment with glaucoma medication.
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Within 6 months prior to the Screening Visit, use of medications known to be toxic to the retina, lens or optic nerve
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Uncontrolled diabetes as indicated by glycated hemoglobin (HbA1c) >12% at Screening.
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Active ulcer disease or gastrointestinal bleeding by history within 6 months of screening or by exam at the time of screening.
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Certain type of liver disease.
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Participant who, in the Investigator's opinion, poses a significant suicide risk.
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History or current evidence of any serious or clinically significant cardiac, gastrointestinal, renal, endocrine, neurologic, hematologic, infectious or other condition that is uncontrolled.
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Corrected (QTc) interval >450 milliseconds (msec) or QTc >480 msec in participants with bundle branch block.
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Use of certain medications that may interfere with the study medication or eye assessments (these will be identified by the study doctor).
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Current enrollment, or recent participation in a study of investigational intervention or medical research.
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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.
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Any other reason the investigator deems the participant should not participate in the study.
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Other protocol-defined inclusion/exclusion criteria may apply.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | GSK Investigational Site | Sacramento | California | United States | 95841 |
2 | GSK Investigational Site | Lake Worth | Florida | United States | 33467 |
3 | GSK Investigational Site | Winter Haven | Florida | United States | 33880 |
4 | GSK Investigational Site | Shirley | New York | United States | 11967 |
5 | GSK Investigational Site | Cincinnati | Ohio | United States | 45202 |
6 | GSK Investigational Site | McAllen | Texas | United States | 78503 |
7 | GSK Investigational Site | Castle Hill | New South Wales | Australia | 2154 |
8 | GSK Investigational Site | Westmead | New South Wales | Australia | 2145 |
9 | GSK Investigational Site | Adelaide | South Australia | Australia | 5000 |
10 | GSK Investigational Site | Melbourne | Victoria | Australia | 3004 |
11 | GSK Investigational Site | Christchurch | New Zealand | 8011 |
Sponsors and Collaborators
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 212669