Clinical trial NCT04292912: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK2798745 in Participants With Diabetic Macular Edema
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Macular Edema
Keywords: Diabetic macular edema
GSK2798745
Refraction
Visual acuity.
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2020-03-03
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a multi-center, open-label, single arm study.
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Abnormal Ophthalmic Examination Findings
timeFrame: Up to Day 28
measure: Mean Change From Baseline to Day 28 in Visual Acuity
timeFrame: Baseline and Day 28
measure: Mean Change From Baseline to Day 28 in Body Weight
timeFrame: Baseline and Day 28
measure: Mean Change From Baseline to Day 28 in Body Temperature
timeFrame: Baseline and Day 28
measure: Mean Change From Baseline to Day 28 in Vital Signs for Systolic Blood Pressure and Diastolic Blood Pressure
timeFrame: Baseline and Day 28
measure: Mean Change From Baseline to Day 28 in Pulse Rate
timeFrame: Baseline and Day 28
measure: Mean Change From Baseline to Day 28 in 12-lead Electrocardiogram (ECG) Findings
timeFrame: Baseline and Day 28
measure: Mean Change From Baseline to Day 28 in Alanine Amino Transferase (ALT), Alkaline Phosphatase (AP), Aspartate Amino Transferase (AST), and Creatine Kinase
timeFrame: Baseline and Day 28
measure: Mean Change From Baseline to Day 28 in Calcium, Glucose, Potassium, Sodium, and Urea Nitrogen
timeFrame: Baseline and Day 28
measure: Mean Change From Baseline to Day 28 in Creatinine, Total Bilirubin, and Direct Bilirubin
timeFrame: Baseline and Day 28
measure: Mean Change From Baseline to Day 28 in Clinical Chemistry Parameter Values of Protein
timeFrame: Baseline and Day 28
measure: Mean Change From Baseline to Day 28 in Clinical Chemistry Parameter Values of Cardiac Troponin
timeFrame: Baseline and Day 28
measure: Mean Change From Baseline to Day 28 in Basophils, Eosinophils, Leukocytes, Monocytes, Lymphocytes, Neutrophils, and Platelets
timeFrame: Baseline and Day 28
measure: Mean Change From Baseline to Day 28 in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb)
timeFrame: Baseline and Day 28
measure: Mean Change From Baseline to Day 28 in Mean Corpuscular Hemoglobin
timeFrame: Baseline and Day 28
measure: Mean Change From Baseline to Day 28 in Mean Corpuscular Volume (MCV)
timeFrame: Baseline and Day 28
measure: Mean Change From Baseline to Day 28 in Erythrocytes
timeFrame: Baseline and Day 28
measure: Mean Change From Baseline to Day 28 in Hematocrit
timeFrame: Baseline and Day 28
measure: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Ocular and Non-ocular AEs and SAEs
timeFrame: Until follow-up (Up to Day 56)
measure: Mean Change From Baseline to Day 28 in Center Subfield Retinal Thickness as Measured by Spectral-Domain Optical Coherence Tomography (SD-OCT)
timeFrame: Baseline and Day 28
Secondary outcomes:
measure: Plasma Concentrations of GSK2798745
timeFrame: Day 7 (Pre-dose, 0.5 hour [h], 1h, 2h, 3h, 4h, 6h, 8h) and Day 28 (Pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h)
measure: Plasma Concentrations of Major Metabolite M1
timeFrame: Day 7 (Pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h) and Day 28 (Pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h)
measure: Absorption Rate of GSK2798745
timeFrame: Day 28
measure: Clearance of GSK2798745
timeFrame: At Day 28
measure: Volume of Distribution of GSK2798745
timeFrame: At Day 28
measure: Maximum Observed Plasma Concentration (Cmax) of GSK2798745
timeFrame: At Day 28
measure: Area Under Concentration-Time Curve (AUC) Over Dosing Interval of GSK2798745
timeFrame: At Day 28
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: GSK Investigational Site
state: California
city: Lake Worth
country: United States
facility: GSK Investigational Site
state: Florida
city: Winter Haven
country: United States
facility: GSK Investigational Site
state: Florida
city: Shirley
country: United States
facility: GSK Investigational Site
state: New York
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: McAllen
country: United States
facility: GSK Investigational Site
state: Texas
city: Castle Hill
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Westmead
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Adelaide
country: Australia
facility: GSK Investigational Site
state: South Australia
city: Melbourne
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Christchurch
country: New Zealand
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: