Last updated: 08/26/2024 17:50:10
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK2798745 in Participants with Diabetic Macular Edema
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Other
Other
Trial overview
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
Trial description: 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).
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Not applicable
Primary outcomes:
Number of participants with abnormal ophthalmic examination findings
Timeframe: Up to Day 28
Mean Change From Baseline to Day 28 in Visual Acuity
Timeframe: Baseline and Day 28
Mean Change from Baseline to Day 28 in Body Weight
Timeframe: Baseline and Day 28
Mean Change from Baseline to Day 28 in Body Temperature
Timeframe: Baseline and Day 28
Mean Change from Baseline to Day 28 in Vital Signs for Systolic Blood Pressure and Diastolic Blood Pressure
Timeframe: Baseline and Day 28
Mean Change From Baseline to Day 28 in Pulse Rate
Timeframe: Baseline and Day 28
Mean Change from Baseline to Day 28 in 12-lead Electrocardiogram (ECG) Findings
Timeframe: Baseline and Day 28
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
Mean Change From Baseline to Day 28 in Calcium, Glucose, Potassium, Sodium, and Urea Nitrogen
Timeframe: Baseline and Day 28
Mean Change From Baseline to Day 28 in Creatinine, Total Bilirubin, and Direct Bilirubin
Timeframe: Baseline and Day 28
Mean Change From Baseline to Day 28 in Clinical Chemistry Parameter Values of Protein
Timeframe: Baseline and Day 28
Mean Change From Baseline to Day 28 in Clinical Chemistry Parameter Values of Cardiac Troponin
Timeframe: Baseline and Day 28
Mean Change From Baseline to Day 28 in Basophils, Eosinophils, Leukocytes, Monocytes, Lymphocytes, Neutrophils, and Platelets
Timeframe: Baseline and Day 28
Mean Change From Baseline to Day 28 in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb)
Timeframe: Baseline and Day 28
Mean Change From Baseline to Day 28 in Mean Corpuscular Hemoglobin
Timeframe: Baseline and Day 28
Mean Change From Baseline to Day 28 in Mean Corpuscular Volume (MCV)
Timeframe: Baseline and Day 28
Mean Change From Baseline to Day 28 in Erythrocytes
Timeframe: Baseline and Day 28
Mean Change From Baseline to Day 28 in Hematocrit
Timeframe: Baseline and Day 28
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)
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:
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)
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)
Absorption Rate of GSK2798745
Timeframe: Day 28
Clearance of GSK2798745
Timeframe: At Day 28
Volume of Distribution of GSK2798745
Timeframe: At Day 28
Maximum Observed Plasma Concentration (Cmax) of GSK2798745
Timeframe: At Day 28
Area Under Concentration-Time Curve (AUC) Over Dosing Interval of GSK2798745
Timeframe: At Day 28
Interventions:
Enrollment:
16
Primary completion date:
2022-11-04
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Macular Edema
Product
GSK2798745
Collaborators
Not applicable
Study date(s)
September 2020 to April 2022
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18 - 75 Years
Accepts healthy volunteers
No
- 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).
- 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.
Inclusion and exclusion 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.
Trial location(s)
Location
GSK Investigational Site
Adelaide, South Australia, Australia, 5000
Status
Study Complete
Location
GSK Investigational Site
Castle Hill, New South Wales, Australia, 2154
Status
Study Complete
Location
GSK Investigational Site
Westmead, New South Wales, Australia, 2145
Status
Study Complete
Location
GSK Investigational Site
Cincinnati, Ohio, United States, 45202
Status
Study Complete
Location
GSK Investigational Site
Lake Worth, Florida, United States, 33467
Status
Study Complete
Showing 1 - 6 of 11 Results
Study documents
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Other
Actual primary completion date
2022-11-04
Actual study completion date
2022-11-04
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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