A Study to Evaluate Efficacy and Safety of GSK3858279 in Diabetic Peripheral Neuropathic Pain

Adverse events, SAEs, and AESIs were collected. An AE is any untoward medical occurrence in participant, temporally associated with use of study intervention, whether or not considered related to medicinal product. Any untoward event resulting in death, life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, medically important were categorized as SAE. AESIs of the study drug includes serious and opportunistic infections, tuberculosis (TB), serious hypersensitivity reactions and Injection site reactions.

The laboratory measurements included hematology and clinical chemistry. The parameters evaluated were Eosinophils, Hemoglobin, White blood cell, Lymphocyte count, Neutrophil count and Platelet count, Alanine aminotransferase, Alkaline phosphatase, Aspartate aminotransferase, Blood bilirubin, Hypercalcemia, Hypocalcemia, Cholesterol, Creatine Phosphokinase, Creatinine, Gamma Glutamyl Transferase (GGT), Hypoglycemia, Hyperkalemia, Hypernatremia and Hypertriglyceridemia. Worst case grade (G) increase from baseline grade was evaluated for all the laboratory tests that were gradable by National Cancer Institute Common Terminology Criteria (NCI CTCAE). Data is presented for only those parameters for which participants had worst case >= Grade 3 increase from Baseline.

Blood samples were collected for the determination of serum concentrations of GSK3858279 from which pharmacokinetic (PK) parameters were determined. Cmax was predicted from the population PK model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis.

Blood samples were collected for the determination of serum concentrations of GSK3858279 from which PK parameters were determined. Tmax was predicted from the population PK model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis.

Blood samples were collected for the determination of serum concentrations of GSK3858279 from which PK parameters were determined. Ctau is defined as the lowest concentration reached by a drug before the next dose is administered. Ctau was predicted from the population PK model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis.

Blood samples were collected for the determination of serum concentrations of GSK3858279 from which PK parameters were determined. Cavg is the average concentration over the dosing interval (weekly). Cavg was predicted from the population PK model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis.

Blood samples were collected for the determination of serum concentrations of GSK3858279 from which PK parameters were determined. AUC(0-tau) was predicted from the population model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis.

The McGill pain questionnaire Short Form 2 is a 22-item questionnaire total score, which evaluated multi-dimensional pain over time. The questionnaire consists of 22 different descriptors of pain, and each item is rated based on a 0-10 pain intensity scale with 0 indicating no pain and 10 as worst possible pain. The total score was calculated as the mean of all item ratings. Higher scores indicate more severe pain. Baseline is defined as the last assessment prior to the first dose with a non-missing value, including those from unscheduled visits. Posterior mean change from baseline, 95 percent (%) credible interval (CI) was derived using Bayesian mixed model repeated measures. The data presented as 'Mean' refers to 'posterior mean' and '95% confidence interval' refers to '95% credible intervals'.

The change from baseline (CFB) in the weekly average of the average daily pain score at indicated time points was assessed using NRS. Participants recorded their average daily pain response daily using a Brief Pain Inventory Item 5. It is a single item designed for self-reporting average pain score for past 24 hours. Participants were asked to mark their average pain intensity daily, using the NRS, on an 11-point scale (0 = no pain, 10 = worst pain imaginable). The weekly average was computed as weekly average of the average daily scores (range: 0-10), where higher scores indicate more severe pain. A negative CFB indicates pain improvement. Baseline was defined as the average score over the 7 days before dosing (Day - 7 to -1). Posterior mean CFB and the 95% credible interval were derived using a Bayesian mixed model repeated measures analysis. The data presented as 'Mean' refers to the 'posterior mean' and '95% confidence interval' to the '95% credible interval'.

The proportion of participants who achieved >=30 percentage reduction from Baseline (responders) in the weekly average of the average daily pain score at Week 12 as measured by NRS is reported. Participants were instructed to assess their average daily pain daily, and to record the response in a Brief Pain Inventory item 5. It is a single item designed to capture information on the self- reported average pain score over the past 24 hours. Participants were asked to mark their pain- intensity daily, using the NRS, on an 11- point scale (0-10), with 0 = no pain, and 10 = worst pain imaginable. The weekly average was computed as weekly average of the average daily scores (range: 0-10), where higher scores indicate more severe pain. The data is presented for proportion of responders where 'Mean' refers to 'posterior mean proportion' and '95% confidence interval' refers to '95% credible interval'.

The proportion of participants who achieved >=50 percentage reduction from Baseline (responders) in the weekly average of the average daily pain score at Week 12 as measured by NRS is reported. Participants were instructed to assess their average daily pain daily, and to record the response in a Brief Pain Inventory item 5. It is a single item designed to capture information on the self- reported average pain score over the past 24 hours. Participants were asked to mark their pain- intensity daily, using the NRS, on an 11- point scale (0-10), with 0 = no pain, and 10 = worst pain imaginable. The weekly average was computed as weekly average of the average daily scores (range: 0-10), where higher scores indicate more severe pain. The data is presented for proportion of responders where 'Mean' refers to 'posterior mean proportion' and '95% confidence interval' refers to '95% credible interval'.