Trial Outcomes & Findings for A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK2798745 in Participants With Diabetic Macular Edema (NCT NCT04292912)

NCT ID: NCT04292912

Last Updated: 2024-11-08

Results Overview

Ophthalmic examinations for Pupil motility and confrontation visual field examination, slit lamp evaluation of anterior ocular structures, intraocular pressure measurement and optical coherence tomography (OCT) was performed on left and right eye. Participants with data including abnormalities of potential clinical importance is listed here.

• Recruitment status: TERMINATED
• Study phase: PHASE1
• Target enrollment: 16 participants
• Primary outcome timeframe: Up to Day 28
• Results posted on: 2024-11-08

Participant Flow

All participants who passed screening and eligible for the study with intention to dose were enrolled in the study. A total of 16 participants were included who received at least one dose of study treatment for 28 days. Of which, 9 completed the study and 7 participants discontinued the study. The study was terminated early due to meeting the interim futility.

The analysis population included 16 participants who received at least 1 dose of study treatment. This included 6 participants from prematurely closed site due to protocol violations.

Participant milestones

Measure	GSK2798745 Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Overall Study STARTED	16
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Measure	GSK2798745 Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Overall Study Physician Decision	1
Overall Study Protocol Violation	6

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	GSK2798745 n=16 Participants Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	4 Participants n=5 Participants
Race/Ethnicity, Customized White	11 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Day 28

Population: Modified safety population comprised of all participants who received at least one dose of study treatment. Only those participants available at the time of assessment were analyzed.

Ophthalmic examinations for Pupil motility and confrontation visual field examination, slit lamp evaluation of anterior ocular structures, intraocular pressure measurement and optical coherence tomography (OCT) was performed on left and right eye. Participants with data including abnormalities of potential clinical importance is listed here.

Outcome measures

Measure	GSK2798745 n=10 Participants Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Number of Participants With Abnormal Ophthalmic Examination Findings Eyelids and Lashes	0 Participants
Number of Participants With Abnormal Ophthalmic Examination Findings Pupil motility	0 Participants
Number of Participants With Abnormal Ophthalmic Examination Findings Confrontation visual field examination	0 Participants
Number of Participants With Abnormal Ophthalmic Examination Findings Slit lamp evaluation of anterior ocular structures	0 Participants
Number of Participants With Abnormal Ophthalmic Examination Findings Intraocular pressure measurement, Left eye	1 Participants
Number of Participants With Abnormal Ophthalmic Examination Findings Intraocular pressure measurement, Right eye	1 Participants
Number of Participants With Abnormal Ophthalmic Examination Findings OCT center subfield, Left eye	0 Participants
Number of Participants With Abnormal Ophthalmic Examination Findings OCT center subfield, Right eye	1 Participants

PRIMARY outcome

Timeframe: Baseline and Day 28

Population: Pharmacodynamics (PD) analysis set included all participants from the modified Safety population who had at least 1 post-baseline non-missing PD assessment.

Best-correct visual acuity (BCVA) was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. The visual function of the study eye was assessed using the ETDRS protocol. ETDRS letters score can be calculated when 20 or more letters are read correctly at 4.0 meters (m); the visual acuity letter score is equal to the total number of letters read correctly at 4.0 m plus 30. If less than 20 letters are read correctly at 4.0 m, the visual acuity letter score is equal to the total number of letters read correctly at 4.0 m (number of letters recorded on line 1.0), plus the total number of letters read correctly at 1.0 m in the first six lines. The score ranges from 0-100 where a higher score represents better visual functioning. The change from baseline was calculated by subtracting baseline value from post-baseline value.

Outcome measures

Measure	GSK2798745 n=9 Participants Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Mean Change From Baseline to Day 28 in Visual Acuity	1.6 Letters Standard Deviation 4.67

PRIMARY outcome

Timeframe: Baseline and Day 28

Population: Modified safety population comprised of all participants who received at least one dose of study treatment. Only those participants available at the time of assessment were analyzed.

Physical examination included the measuring of body weight and evaluated at indicated time points. The change from baseline was calculated by subtracting baseline value from post-baseline value.

Outcome measures

Measure	GSK2798745 n=9 Participants Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Mean Change From Baseline to Day 28 in Body Weight	-0.34 kilogram (kg) Standard Deviation 1.157

PRIMARY outcome

Timeframe: Baseline and Day 28

Population: Modified safety population comprised of all participants who received at least one dose of study treatment. Only those participants available at the time of assessment were analyzed.

Physical examination included the measuring of body temperature and evaluated at indicated time points. The change from Baseline was calculated by subtracting Baseline value from post-Baseline value.

Outcome measures

Measure	GSK2798745 n=9 Participants Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Mean Change From Baseline to Day 28 in Body Temperature	0.04 Degree Celsius (°C) Standard Deviation 0.416

PRIMARY outcome

Timeframe: Baseline and Day 28

Population: Modified safety population comprised of all participants who received at least one dose of study treatment. Only those participants available at the time of assessment were analyzed.

The change from baseline for Systolic Blood Pressure (SBP) and Diastolic blood Pressure (DBP) was calculated by subtracting baseline value from post-baseline value.

Outcome measures

Measure	GSK2798745 n=9 Participants Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Mean Change From Baseline to Day 28 in Vital Signs for Systolic Blood Pressure and Diastolic Blood Pressure SBP on Day 28	5.67 mmHg Standard Deviation 13.611
Mean Change From Baseline to Day 28 in Vital Signs for Systolic Blood Pressure and Diastolic Blood Pressure DBP on Day 28	1.44 mmHg Standard Deviation 9.167

PRIMARY outcome

Timeframe: Baseline and Day 28

Population: Modified safety population comprised of all participants who received at least one dose of study treatment. Only those participants available at the time of assessment were analyzed.

Pulse rate was measured at indicated time points. The change from baseline was calculated by subtracting baseline value from post-baseline value.

Outcome measures

Measure	GSK2798745 n=9 Participants Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Mean Change From Baseline to Day 28 in Pulse Rate	-1.33 Beats per Minute (beats/min) Standard Deviation 10.368

PRIMARY outcome

Timeframe: Baseline and Day 28

Population: The intensive pharmacokinetics (PK) analysis population included all participants from the modified Safety population who had intensive PK sampling on Day 7 and Day 28. However, since only one participant consented to intensive PK and this participant withdrew early, before Day 28, data for this endpoint were not collected.

The 12-lead ECGs was obtained at indicated timepoints during the study. The standard ECG criteria of potential clinical importance were 1) absolute QTc Interval, > 450 milliseconds (msec), 2) absolute PR Interval, <110 msec, 3) absolute QRS Interval, < 75 msec and 4) increase from baseline in QTc > 60 msec. The change from baseline was calculated by subtracting baseline value from post-baseline value.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Baseline and Day 28

Population: Modified safety population comprised of all participants who received at least one dose of study treatment. Only those participants available at the time of assessment were analyzed.

Summary of changes from baseline in laboratory parameters were assessed. The analysis included liver function tests for ALT, AP, AST, Creatine kinase and evaluated at indicated time points. The change from baseline was calculated by subtracting baseline value from post-baseline value.

Outcome measures

Measure	GSK2798745 n=9 Participants Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Mean Change From Baseline to Day 28 in Alanine Amino Transferase (ALT), Alkaline Phosphatase (AP), Aspartate Amino Transferase (AST), and Creatine Kinase Alanine Aminotransferase (ALT)	-0.01 Microkatal per Litre (ukat/L) Standard Deviation 0.087
Mean Change From Baseline to Day 28 in Alanine Amino Transferase (ALT), Alkaline Phosphatase (AP), Aspartate Amino Transferase (AST), and Creatine Kinase Alkaline Phosphatase	-0.11 Microkatal per Litre (ukat/L) Standard Deviation 0.179
Mean Change From Baseline to Day 28 in Alanine Amino Transferase (ALT), Alkaline Phosphatase (AP), Aspartate Amino Transferase (AST), and Creatine Kinase Aspartate Aminotransferase	-0.02 Microkatal per Litre (ukat/L) Standard Deviation 0.134
Mean Change From Baseline to Day 28 in Alanine Amino Transferase (ALT), Alkaline Phosphatase (AP), Aspartate Amino Transferase (AST), and Creatine Kinase Creatine Kinase	0.10 Microkatal per Litre (ukat/L) Standard Deviation 0.318

PRIMARY outcome

Timeframe: Baseline and Day 28

Population: Modified safety population comprised of all participants who received at least one dose of study treatment. Only those participants available at the time of assessment were analyzed.

Summary of changes from baseline in clinical chemistry parameters. The parameters included were calcium, glucose, potassium, sodium and urea nitrogen and evaluated at indicated time points. The change from baseline was calculated by subtracting baseline value from post-baseline value.

Outcome measures

Measure	GSK2798745 n=9 Participants Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Mean Change From Baseline to Day 28 in Calcium, Glucose, Potassium, Sodium, and Urea Nitrogen Calcium	0.0 Millimoles per Liter (mmol/L) Standard Deviation 0.107
Mean Change From Baseline to Day 28 in Calcium, Glucose, Potassium, Sodium, and Urea Nitrogen Glucose	2.15 Millimoles per Liter (mmol/L) Standard Deviation 3.485
Mean Change From Baseline to Day 28 in Calcium, Glucose, Potassium, Sodium, and Urea Nitrogen Potassium	0.04 Millimoles per Liter (mmol/L) Standard Deviation 0.354
Mean Change From Baseline to Day 28 in Calcium, Glucose, Potassium, Sodium, and Urea Nitrogen Sodium	1.33 Millimoles per Liter (mmol/L) Standard Deviation 2.550
Mean Change From Baseline to Day 28 in Calcium, Glucose, Potassium, Sodium, and Urea Nitrogen Urea Nitrogen	-0.46 Millimoles per Liter (mmol/L) Standard Deviation 2.606

PRIMARY outcome

Timeframe: Baseline and Day 28

Population: Modified safety population comprised of all participants who received at least one dose of study treatment. Only those participants available at the time of assessment were analyzed.

Summary of changes from baseline in clinical chemistry parameters. The parameters analyzed were creatinine, total bilirubin and direct bilirubin and evaluated at indicated timepoints. The change from baseline was calculated by subtracting baseline value from post-baseline value.

Outcome measures

Measure	GSK2798745 n=9 Participants Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Mean Change From Baseline to Day 28 in Creatinine, Total Bilirubin, and Direct Bilirubin Creatinine	1.18 Micromoles per Liter (umol/L) Standard Deviation 10.237
Mean Change From Baseline to Day 28 in Creatinine, Total Bilirubin, and Direct Bilirubin Total Bilirubin	0.92 Micromoles per Liter (umol/L) Standard Deviation 3.923
Mean Change From Baseline to Day 28 in Creatinine, Total Bilirubin, and Direct Bilirubin Direct Bilirubin	0.52 Micromoles per Liter (umol/L) Standard Deviation 0.995

PRIMARY outcome

Timeframe: Baseline and Day 28

Population: Modified safety population comprised of all participants who received at least one dose of study treatment. Only those participants available at the time of assessment were analyzed.

Summary of changes from baseline in clinical chemistry parameter, Protein. The change from baseline was calculated by subtracting baseline value from post-baseline value.

Outcome measures

Measure	GSK2798745 n=9 Participants Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Mean Change From Baseline to Day 28 in Clinical Chemistry Parameter Values of Protein	-0.89 Grams per Liter (g/L) Standard Deviation 4.014

PRIMARY outcome

Timeframe: Baseline and Day 28

Population: Modified safety population comprised of all participants who received at least one dose of study treatment. Only those participants available at the time of assessment were analyzed.

Summary of changes from baseline in clinical chemistry parameters for Cardiac troponin. The change from baseline was calculated by subtracting baseline value from post-baseline value.

Outcome measures

Measure	GSK2798745 n=9 Participants Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Mean Change From Baseline to Day 28 in Clinical Chemistry Parameter Values of Cardiac Troponin	0.00 nanograms per milliliter (ng/mL) Standard Deviation 0.004

PRIMARY outcome

Timeframe: Baseline and Day 28

Population: Modified safety population comprised of all participants who received at least one dose of study treatment. Only those participants available at the time of assessment were analyzed.

Summary of changes from baseline in hematology. The parameters analyzed were Basophils, Eosinophils, Leukocytes, Monocytes, Lymphocytes, Neutrophils and Platelets at indicated time points. The change from baseline was calculated by subtracting baseline value from post-baseline value.

Outcome measures

Measure	GSK2798745 n=8 Participants Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Mean Change From Baseline to Day 28 in Basophils, Eosinophils, Leukocytes, Monocytes, Lymphocytes, Neutrophils, and Platelets Monocytes	-0.02 Giga (10^9) cells per liter Standard Deviation 0.106
Mean Change From Baseline to Day 28 in Basophils, Eosinophils, Leukocytes, Monocytes, Lymphocytes, Neutrophils, and Platelets Basophils	0.00 Giga (10^9) cells per liter Standard Deviation 0.014
Mean Change From Baseline to Day 28 in Basophils, Eosinophils, Leukocytes, Monocytes, Lymphocytes, Neutrophils, and Platelets Eosinophils	0.02 Giga (10^9) cells per liter Standard Deviation 0.092
Mean Change From Baseline to Day 28 in Basophils, Eosinophils, Leukocytes, Monocytes, Lymphocytes, Neutrophils, and Platelets Leukocytes	0.19 Giga (10^9) cells per liter Standard Deviation 1.860
Mean Change From Baseline to Day 28 in Basophils, Eosinophils, Leukocytes, Monocytes, Lymphocytes, Neutrophils, and Platelets Lymphocytes	-0.13 Giga (10^9) cells per liter Standard Deviation 0.506
Mean Change From Baseline to Day 28 in Basophils, Eosinophils, Leukocytes, Monocytes, Lymphocytes, Neutrophils, and Platelets Neutrophils	0.34 Giga (10^9) cells per liter Standard Deviation 1.450
Mean Change From Baseline to Day 28 in Basophils, Eosinophils, Leukocytes, Monocytes, Lymphocytes, Neutrophils, and Platelets Platelets	-0.50 Giga (10^9) cells per liter Standard Deviation 23.952

PRIMARY outcome

Timeframe: Baseline and Day 28

Population: Modified safety population comprised of all participants who received at least one dose of study treatment. Only those participants available at the time of assessment were analyzed.

Summary of changes from baseline in hematology. The parameters analyzed were MCHC and Hb at indicated time points. The change from baseline was calculated by subtracting baseline value from post-baseline value.

Outcome measures

Measure	GSK2798745 n=8 Participants Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Mean Change From Baseline to Day 28 in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) MCHC	-1.63 g/L Standard Deviation 9.709
Mean Change From Baseline to Day 28 in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) Hb	-0.88 g/L Standard Deviation 5.693

PRIMARY outcome

Timeframe: Baseline and Day 28

Population: Modified safety population comprised of all participants who received at least one dose of study treatment. Only those participants available at the time of assessment were analyzed.

Summary of changes from baseline in mean corpuscular hemoglobin at indicated time points. The change from baseline was calculated by subtracting baseline value from post-baseline value.

Outcome measures

Measure	GSK2798745 n=8 Participants Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Mean Change From Baseline to Day 28 in Mean Corpuscular Hemoglobin	-0.44 Picograms per cell (pg/cell) Standard Deviation 0.703

PRIMARY outcome

Timeframe: Baseline and Day 28

Population: Modified safety population comprised of all participants who received at least one dose of study treatment. Only those participants available at the time of assessment were analyzed.

Summary of changes from baseline in hematology MCV assessment. The change from baseline was calculated by subtracting baseline value from post-baseline value.

Outcome measures

Measure	GSK2798745 n=8 Participants Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Mean Change From Baseline to Day 28 in Mean Corpuscular Volume (MCV)	-1.10 Femtoliter Standard Deviation 2.943

PRIMARY outcome

Timeframe: Baseline and Day 28

Population: Modified safety population comprised of all participants who received at least one dose of study treatment. Only those participants available at the time of assessment were analyzed.

Summary of changes from baseline in erythrocytes at indicated time points. The change from baseline was calculated by subtracting baseline value from post-baseline value.

Outcome measures

Measure	GSK2798745 n=8 Participants Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Mean Change From Baseline to Day 28 in Erythrocytes	0.04 10^12 cells per Liter Standard Deviation 0.213

PRIMARY outcome

Timeframe: Baseline and Day 28

Population: Modified safety population comprised of all participants who received at least one dose of study treatment. Only those participants available at the time of assessment were analyzed.

Summary of changes from baseline in hematocrit parameter at indicated time points. The change from baseline was calculated by subtracting baseline value from post-baseline value.

Outcome measures

Measure	GSK2798745 n=8 Participants Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Mean Change From Baseline to Day 28 in Hematocrit	0.0 Proportion of red blood cells in blood Standard Deviation 0.018

PRIMARY outcome

Timeframe: Until follow-up (Up to Day 56)

Population: Modified safety population comprised of all participants who received at least one dose of study treatment. Only those participants available at the time of assessment were analyzed.

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury. Data has been presented for number of participants with ocular and non-ocular AEs and SAEs.

Outcome measures

Measure	GSK2798745 n=16 Participants Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Ocular and Non-ocular AEs and SAEs AEs	4 Participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Ocular and Non-ocular AEs and SAEs SAEs	0 Participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Ocular and Non-ocular AEs and SAEs Ocular AEs	2 Participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Ocular and Non-ocular AEs and SAEs Ocular SAEs	0 Participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Ocular and Non-ocular AEs and SAEs Non-ocular AEs	3 Participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Ocular and Non-ocular AEs and SAEs Non-ocular SAEs	0 Participants

PRIMARY outcome

Timeframe: Baseline and Day 28

Population: Modified safety population comprised of all participants who received at least one dose of study treatment. Only those participants available at the time of assessment were analyzed.

The SD-OCT effect is a pharmacodynamics (PD) measure of daily repeated dosing of GSK2798745. The mean change from baseline in macular thickness was measured by SD-OCT in the study eye after 28 days of dosing. Measurements was obtained by an appropriately trained photographer/technician using SD-OCT equipment that has been approved by a central reader. The change from baseline was calculated by subtracting baseline value from post-baseline value.

Outcome measures

Measure	GSK2798745 n=9 Participants Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Mean Change From Baseline to Day 28 in Center Subfield Retinal Thickness as Measured by Spectral-Domain Optical Coherence Tomography (SD-OCT)	-3.6 Micrometer (um) Standard Deviation 35.05

SECONDARY outcome

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)

Population: The pharmacokinetic population included all participants from the modified safety population who received at least one dose of study treatment for whom PK sample was obtained and analyzed. Only those participants with evaluable PK data at the specified time points were used for analysis. Overall number of participants analyzed=number of participants contributed to the analysis.

Blood samples were collected at indicated time points for plasma concentrations of GSK2798745.

Outcome measures

Measure	GSK2798745 n=5 Participants Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Plasma Concentrations of GSK2798745 Day 7	6.24 nanograms per milliliter Geometric Coefficient of Variation 70.4
Plasma Concentrations of GSK2798745 Day 28	8.61 nanograms per milliliter Geometric Coefficient of Variation 125.1

SECONDARY outcome

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)

Population: The pharmacokinetic population included all participants from the modified safety population who received at least one dose of study treatment for whom PK sample was obtained and analyzed. Only those participants with evaluable PK data at the specified time points were used for analysis. Overall number of participants analyzed=number of participants contributed to the analysis.

Blood samples were collected at indicated time points for PK analysis of major metabolite of GSK2798745.

Outcome measures

Measure	GSK2798745 n=5 Participants Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Plasma Concentrations of Major Metabolite M1 Day 7	9.32 nanograms per milliliter Geometric Coefficient of Variation 49.9
Plasma Concentrations of Major Metabolite M1 Day 28	9.83 nanograms per milliliter Geometric Coefficient of Variation 64.8

SECONDARY outcome

Timeframe: Day 28

Population: The intensive PK analysis population included all participants from the modified Safety population who had intensive PK sampling on Day 7 and Day 28. However, since only one participant consented to intensive PK and this participant withdrew early, before Day 28, data for this endpoint were not collected.

Blood samples were collected at indicated time points for PK analysis of GSK2798745 absorption rate.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Day 28

Population: The intensive PK analysis population included all participants from the modified Safety population who had intensive PK sampling on Day 7 and Day 28. However, since only one participant consented to intensive PK and this participant withdrew early, before Day 28, data for this endpoint were not collected.

Blood samples were collected at indicated time points for PK parameters including clearance of GSK2798745.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Day 28

Population: The intensive PK analysis population included all participants from the modified Safety population who had intensive PK sampling on Day 7 and Day 28. However, since only one participant consented to intensive PK and this participant withdrew early, before Day 28, data for this endpoint were not collected.

Blood samples were collected at indicated time points for PK parameters including volume of distribution of GSK2798745.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Day 28

Population: The intensive PK analysis population included all participants from the modified Safety population who had intensive PK sampling on Day 7 and Day 28. However, since only one participant consented to intensive PK and this participant withdrew early, before Day 28, data for this endpoint were not collected.

Blood samples were collected at indicated time points for PK parameters including Cmax of GSK2798745.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Day 28

Population: The intensive PK analysis population included all participants from the modified Safety population who had intensive PK sampling on Day 7 and Day 28. However, since only one participant consented to intensive PK and this participant withdrew early, before Day 28, data for this endpoint were not collected.

Blood samples were collected at indicated time points for PK parameters including AUC of GSK2798745.

Outcome measures

Outcome data not reported

Adverse Events

GSK2798745

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	GSK2798745 n=16 participants at risk Eligible participants received single dose of GSK2798745 for 28 days. Participants were instructed to have GSK2798745 about the same time each day.
Eye disorders Diabetic retinal oedema	6.2% 1/16 • Number of events 1 • On treatment AEs, SAEs and non-SAEs were collected from the start of the study treatment until the follow-up (up to Day 56, Week 8). The results are based on the safety analysis population, which comprised the participants who received at least one dose of study treatment.
Gastrointestinal disorders Diarrhoea	6.2% 1/16 • Number of events 1 • On treatment AEs, SAEs and non-SAEs were collected from the start of the study treatment until the follow-up (up to Day 56, Week 8). The results are based on the safety analysis population, which comprised the participants who received at least one dose of study treatment.
General disorders Feeling abnormal	6.2% 1/16 • Number of events 1 • On treatment AEs, SAEs and non-SAEs were collected from the start of the study treatment until the follow-up (up to Day 56, Week 8). The results are based on the safety analysis population, which comprised the participants who received at least one dose of study treatment.
Eye disorders Vision blurred	6.2% 1/16 • Number of events 1 • On treatment AEs, SAEs and non-SAEs were collected from the start of the study treatment until the follow-up (up to Day 56, Week 8). The results are based on the safety analysis population, which comprised the participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Diabetes mellitus	6.2% 1/16 • Number of events 1 • On treatment AEs, SAEs and non-SAEs were collected from the start of the study treatment until the follow-up (up to Day 56, Week 8). The results are based on the safety analysis population, which comprised the participants who received at least one dose of study treatment.
Eye disorders Vitreous floaters	6.2% 1/16 • Number of events 1 • On treatment AEs, SAEs and non-SAEs were collected from the start of the study treatment until the follow-up (up to Day 56, Week 8). The results are based on the safety analysis population, which comprised the participants who received at least one dose of study treatment.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: GSKClinicalSupportHD@gsk.com

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER