Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
GW856553 · 11 trials · 12 indications
AE was any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE was any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
MACE was defined as all-cause death, adjudicated myocardial infarction, stroke/transient ischemic attack, heart failure or recurrent ischemia requiring urgent revascularization.
Pure MACE was defined as all-cause death, adjudicated myocardial infarction or stroke/transient ischemic attack.
Hematology parameters (PCI range): Eosinophils (\<0.045 or \>0.605 Giga cells per liter \[GI/L\]), Hematocrit (\<0.297 or \>0.506 ratio), Hemoglobin (\<85 or \>200 grams per liter \[g/L\]), Lymphocytes (\<0.765 or \>4.51GI/L), Mean Corpuscle Hemoglobin (MCH) (\<24.3 or \>38.5 picograms \[PG\]), Mean Corpuscle Hemoglobin Concentration (MCHC) (\<256 or \>432 g/L), Mean Corpuscle Volume (MCV) (\<70 or \>115 femtoliter \[FL\]), Monocytes (\<0.18 or \>1.21 GI/L), Platelet count (\<104 or \>480 GI/L), Red Cell Distribution Width (RDW) (\<7.2 or \>18%), Red Blood Cell (RBC) count (\<2.88 or \>6.12 trillion per liter \[TI/L\] for females and \<3.52 or \>6.96 TI/L for males) , Reticulocytes (\<22.5 or \>93.5 10\^9/L), Total Absolute Neutrophil Count (ANC) (\<1.62 or \>8.8 GI/L), White Blood Cell (WBC) count (\<3.04 or \>12 GI/L) were analyzed. The data was presented as High and low, at any visit post-Baseline. Only parameters with observed abnormal values were presented.
Clinical chemistry parameters (PCI range): Alanine Amino Transferase (ALT) (\>=3x upper limit normal \[ULN\] units per liter \[U/L\]), Albumin (\<25.6 or \>60 g/L), Alkaline Phosphatase (\>=2x ULN U/L), Aspartate Amino Transferase (AST) (\>=3x ULN U/L), Calcium (\<2.0776 or \>2.6112 millimoles per liter \[mmol/L\]), Carbon dioxide content/Bicarbonate (CO2/HCO3) (\<19.6 or \>32.64 mmol/L), Chloride (\<93.1 or \>110.16 mmol/L), Creatinine (\<39.6 or \>136.4 micromole per liter \[µmol/L\]) , Glucose (\<3.51 or \>6.05 mmol/L), Potassium (\<3.43 or \>5.406 mmol/L), Sodium (\<132.3 or \>148.92 mmol/L), Total Bilirubin (T. bilirubin) (\>=1.5xULN µmol/L) , Total Protein (\<50 or \>95 g/L), Urea/Blood urea nitrogen (BUN) (\<2.25 or \>11.55 mmol/L) and Uric acid (\<135 or \>495 µmol/L) were analyzed. The data was presented as High and low, at any visit post-Baseline. Only parameters with observed abnormal values were presented.
Liver function test parameters: Alanine aminotransferase (ALT), Total Bilirubin (T. Bilirubin), Aspartate aminotransferase (AST), Alkaline Phosphatase, Gamma glutamyl transferase (GGT) and Creatine Kinase were analyzed and presented as elevated test values at any time post-Baseline. The elevations were presented as \>=2xULN, \>=3xULN, \>=5xULN, \>=10xULN, and \>=20xULN. n= number of participants with at least one non-missing result of the particular lab test post-Baseline.
A single 12-lead ECG was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT corrected (QTc) intervals. ECG findings were presented as Normal, Abnormal - Not clinically significant and Abnormal - Clinically significant at any time post-Baseline.
Vital signs (PCI range): Systolic blood pressure (SBP) (\<75 and \>200 millimeter of mercury \[mmHg\]), Diastolic blood pressure (DBP) (\<40 and \>120 mmHg) and Heart rate (\<30 and \>200 beats per minute \[bpm\]) were analyzed and were presented at any visit post-Baseline. Participants with both Normal and Low values were counted once under their worst case (Low). Participants with both Normal and High values were counted once under their worst case (High). Participants with both High and Low values were counted under both categories. All heart rate values were within normal range, hence not presented.
Analysis of hsCRP included all participants who provided data at Baseline and at least one post-Baseline measure. Statistical analyses was performed to compare hsCRP levels between study drug and placebo. Log transformed ratio to Baseline hsCRP was analyzed using repeated measures analysis of covariance (ANCOVA) including a term for treatment, adjusting for Baseline hsCRP as a covariate, and accounting for other covariates as appropriate to the study design.
cTnI AUC was the average concentration of cTnI during hospital stay. Statistical analyses was performed to compare cTnI levels between study drug and placebo, via ANCOVA.
HAMD-17 has 17 questions. The HAMD-17 Total Score was calculated by summing the individual response scores over the 17 individual components of the interview. The highest possible score was 52, which represented the most severe measure of depression; the lowest possible score was 0, which represented an absence of depression. There were 9 five point questions and 8 three point questions. The responses to the individual questions had values of 0-2 (three points response) or 0-4 (five points response). The BECH scale was extracted from the HAMD-17 and comprises of 6 items out of which 5 are 5 point questions and 1 is 3 point question. The Bech Total Score was calculated by summing the individual response scores and ranged from 0 to 22, with higher scores indicating more severe depression. Week 0 values were considered as Baseline.The change from randomization was analysed using suitable Bayesian mixed-effects model repeated measures (BMMRM) assuming missing at random (MAR).
The PI-NRS is an eleven point scale with 0=no pain and 10=worst pain imaginable. Participants rated the pain intensity for the neuropathic pain associated with the nerve injury and not pain from other concomitant causes. Change from baseline was calculated as endpoint value minus the baseline value.
Induced sputum samples were collected at Baseline (Week 0), Week 4 and at Week 12 to evaluate the effects of 12 weeks of treatment with GW856553 7.5 mg twice daily. Baseline was defined at Week 0. Change from Baseline in neutrophil count was calculated as the Week 12 value minus the Baseline value (percentage of neutrophil of total cells in induced sputum at Week 12 minus the Baseline value). Data for adjusted mean was presented for least square mean.
The urinary and fecal cumulative excretion will be analyzed.
| Arm | Type | Description |
|---|---|---|
| Treatment A | EXPERIMENTAL | 7.5 mg GW856553 starting dose, followed 12 hours later by 7.5mg twice daily for 12 weeks |
| Treatment B | EXPERIMENTAL | 15 mg GW856553 starting dose, followed 12 hours later by 7.5mg twice daily for 12 weeks |
| Treatment C | PLACEBO_COMPARATOR | Placebo twice daily for 12 weeks |
| GW856553 | EXPERIMENTAL | GW856553 7.5 mg BID |
| Placebo | PLACEBO_COMPARATOR | Matching Placebo BID |
| Active | EXPERIMENTAL | Eligible participant with at least moderate intensity of pain (an average daily pain score of ≥ 4 on the 11 point PI-NRS at baseline) will receive 7.5 mg twice daily (bid) GW856553 for 28 days. |
| Seretide | ACTIVE_COMPARATOR | - |
| Healthy male volunteers | EXPERIMENTAL | Six healthy male volunteers aged between 30-60 years old will be recruited for this study, |
| Name | Type | Description |
|---|---|---|
| GW856553 | DRUG | 7.5 mg GW856553 starting dose, followed 12 hours later by 7.5mg BID |
| Placebo | DRUG | Placebo |
| Seretide | DRUG | Active comparator inhaler |
Inclusion Criteria: * Subjects with a NSTEMI, defined as: symptoms (e.g. chest pain, dyspnea) consistent with acute coronary syndrome, lasting at least 10 minutes, with most recent symptoms occurring within the 24 hours prior to presentation, without persistent ST-segment elevation on admission 12-...
GW856553 is an investigational small molecule drug developed by GSK plc (ticker GSK). It has been studied in Phase 2 clinical trials across several conditions, including major depressive disorder, neuropathic pain, acute coronary syndrome, and chronic obstructive pulmonary disease. It is not described as approved and remains an investigational agent.
GW856553 has been evaluated in clinical studies for major depressive disorder, neuropathic pain, acute coronary syndrome, and chronic obstructive pulmonary disease. The listed development indications also include rheumatoid arthritis, atherosclerosis, dyslipidaemias, and other pain conditions. All of these were Phase 2 investigations rather than approved uses.
GW856553 is developed by GSK plc, which trades under the ticker GSK. GSK sponsored the Phase 2 clinical program studying the compound in major depressive disorder, neuropathic pain, acute coronary syndrome, and chronic obstructive pulmonary disease.
GW856553 is in Phase 2 development. Four Phase 2 trials have been completed, and none are currently active. The studies were randomized, double-blind, and placebo-controlled, with a combined enrollment of 526 participants across the reported program.
Four completed Phase 2 trials have studied GW856553: NCT00976560 in major depressive disorder, NCT00969059 in neuropathic pain with peripheral nerve injury, NCT00910962 in acute coronary syndrome, and NCT00642148 in chronic obstructive pulmonary disease. All four trials are listed as completed, and no active trials are ongoing.
Yes. The Phase 2 trial NCT00910962 evaluated 12 weeks of dosing with GW856553 in patients with myocardial infarction without ST-segment elevation, a form of acute coronary syndrome. That randomized, double-blind, placebo-controlled study enrolled 526 participants across the United States, Australia, Canada, Germany, India, Netherlands, Poland, Spain, and the United Kingdom.