Table 3 GPR119 clinical trial agonists
| Name | Condition or disease and ClinicalTrials.gov number | Sponsor | Interventions | Primary outcomes | Secondary outcomes |
|---|---|---|---|---|---|
| Oleoyl glycerol | Type 2 diabetes (NCT01043445) | Glostrup University Hospital, Copenhagen | 2-Oleyl glycerol, oleic acid, vehicle | The effect of this newly discovered GPR 119 agonist on gut hormone responses, in particular GLP-1 in response to the different meals administered to the subjects | Glucose homeostasis, gall bladder contraction in response of the different meals administered to the subjects |
| Type 2 diabetes (NCT02264951) | Glostrup University Hospital, Copenhagen | Tributyrin, C8-diet oil, olive oil, carrot | Plasma GLP-1 and GIP | Plasma insulin, PYY, glucose, neurotensin and cholecystokinin | |
| MBX-2982 | Type 2 diabetes (NCT01035879) | CymaBay Therapeutics, Inc | MBX-2982, sitagliptin, placebo | Absolute and percent change from baseline and placebo in mean weighted average of 14-point blood glucose levels associated with a standardized breakfast and lunch | Additional glycemic parameters |
| Type 1 diabetes (NCT04432090) | Translational Research Institute for Metabolism and Diabetes, Florida |
Placebo MBX-2982 No medication | Maximal glucagon concentration, total area under the curve (AUC) for glucagon and incremental AUC during hypoglycemia | ||
| GSK1292263 | Healthy volunteers (NCT00783549) | GlaxoSmithKline | An undetermined dose and ascending dose of GSK1292263 |
(1) Safety and tolerability parameters including adverse events, clinical laboratory, electrocardiogram, and vital signs assessments (2) Pharmacokinetic parameters, maximum observed plasma drug concentration, time to maximum observed concentration |
(1) Pharmacodynamic endpoints (2) Pharmacokinetic parameters following a dose, with and without food, and bioavailability (3) Relationships between drug exposures and pharmacodynamic parameters, safety, and tolerability, as appropriate |
| Healthy subjects (NCT01101568) | GlaxoSmithKline | Simvastatin, rosuvastatin, GSK1292263 |
(1) AUC(0-inf) and Cmax of rosuvastatin alone and in the presence of GSK1292263 (2) AUC(0-inf) and Cmax of simvastatin/simvastatin acid alone and in the presence of GSK1292263 |
(1) Adverse events, cardiovascular findings (blood pressure, heart rate, ECGs) and clinical laboratory values (2) PK parameters: time to maximum plasma concentration, apparent plasma terminal elimination half-life and area under the plasma concentration–time curve for rosuvastatin [AUC(0–72 h)] and simvastatin/simvastatin acid [AUC(0–24 h)] (3) PK parameter values: AUC(0–24 h), Cmax, tmax and t1/2 for GSK1292263 and assessment of steady-state | |
| Type 2 diabetes (NCT01128621) | GlaxoSmithKline | GSK1292263, GSK1292263 matching placebo, sitagliptin | Adverse events, serious adverse events, abnormal hematology values of potential clinical importance (PCI), abnormal clinical chemistry values of PCI, etc., 39 items in total | ||
| Type 2 diabetes (NCT01119846) | GlaxoSmithKline | GSK1292263,GSK1292263 matching placebo, sitagliptin | Adverse events, number of participants with abnormal hematology parameters of potential clinical importance (PCI) and abnormal clinical chemistry parameters of PCI, abnormal- clinically significant electrocardiogram (ECG) findings, Tmax and Cmax, etc. 31 items in total | Number of Participants With AEs and SAEs, Tmax,Tlag,Cmax, AUC(0-t) and AUC(0–24) etc. 13 items in total | |
| Dyslipidemia (NCT01218204) | GlaxoSmithKline | 10/80 mg atorvastatin, GSK1292263 placebo, 100/300/800 mg GSK1292263, 10 mg ezetimibe, washout | Adverse events, serious adverse events, abnormal- clinically significant electrocardiogram (ECG) findings, etc. 41 items in total | Trough concentration, AUC(0–24 h), Tmax and Cmax of atorvastatin metabolite (2-hydroxyatorvastatin) | |
| PSN821 | Type 2 diabetes (NCT01386099) | Prosidion Ltd | PSN821, placebo | Beta-cell function | HbA1c, fasting plasma glucose, body weight |
| JNJ-38431055 | Healthy male volunteers (NCT00910923) | Johnson & Johnson Pharmaceutical Research & Development, L.L.C | JNJ-38431055 | Safety and tolerability | Pharmacodynamic effects of JNJ-38431055 on plasma glucose and insulin, during a meal tolerance test (MTT) |
|
Healthy overweight or obese adult male volunteers (NCT01054118) | Johnson & Johnson Pharmaceutical Research & Development, L.L.C | JNJ-38431055, sitagliptin 100 mg, JNJ-38431055 + sitagliptin 100 mg, placebo | GLP-1 levels after a standard meal |
(1) Pharmacokinetics of JNJ-38431055 administered alone and in combination with sitagliptin (2) Appetite and satiety (3) Safety and tolerability of JNJ-38431055 administered alone and in combination with sitagliptin as measured by occurrence of adverse events, ECGs, vital signs, and safety laboratory measurements ⑷ Incremental glucose changes after MTT | |
| Type 2 diabetes (NCT00946972) | Johnson & Johnson Pharmaceutical Research & Development, L.L.C | JNJ-38431055, placebo | Adverse events, laboratory values, vital signs, ECGs |
24 h weighted mean glucose, fasting plasma glucose, glycosylated albumin, dose response, beta-cell function, incretin levels | |
| Type 2 diabetes (NCT00871507) | Johnson & Johnson Pharmaceutical Research & Development, L.L.C | JNJ-38431055 Dose 1/2, sitagliptin 100 mg, placebo | Incremental glucose AUC after an oral glucose tolerance test (OGTT) | Incremental glucose AUC after a MTT, beta-cell function, incretin levels, pharmacokinetics, safety and tolerability | |
| DS-8500a | Healthy subjects (NCT03699774) | Daiichi Sankyo, Inc | DS-8500a, rosuvastatin | Maximum observed plasma drug concentration (Cmax), time of maximum observed concentration (Tmax) and area under the plasma concentration time curve (AUC) from time 0 to the last quantifiable concentration (AUC last) for single dose rosuvastatin | Cmax, Tmax, AUC from time 0 to 24 h (AUC0-24 h), Metabolite to parent (M:P) AUC0-24 ratios, Minimum observed analyte concentration that was just prior to the beginning of the dosing interval (Ctrough), Cmax at steady state (Cmax,ss), AUC during the 24 h dosing interval (AUCtau), accumulation ratio (AccRatio), Tmax at steady state (Tmax,ss) |
| Healthy subjects (NCT02790684) | Daiichi Sankyo, Inc | DS-8500a | Total 14C radioactivity in urine and feces | Cmax, Tmax, AUC, number and severity of adverse events | |
| Healthy subjects (NCT02790671) | Daiichi Sankyo, Inc | Itraconazole, DS-8500a | Cmax, Tmax, AUC | Number and severity of adverse events, change in physical examination findings, 12-lead electrocardiogram, vital sign measurements and clinical laboratory test results | |
| Type 2 diabetes (NCT02685345) | Daiichi Sankyo Co., Ltd | DS-8500a 25/75 mg, placebo | Change in 24 h weighted mean glucose | Change in fasting plasma glucose, plasma glucose, glycoalbumin, serum insulin, proinsulin, C-peptide, pancreatic peptide YY3-36, GLP-1, total GIP, total glucagon, total cholesterol, HDL, LDL, TG, and derived (plasma glucose, serum insulin, C-peptide, pancreatic peptide YY3-36, GLP-1, total GIP, total glucagon) AUC, number and severity of adverse events | |
| Type 2 diabetes (NCT02669732) | Daiichi Sankyo Co., Ltd | DS-8500a, placebo | First-phase and second-phase secretion insulin and C-peptide | M value, M/I value, disposition index, number and severity of adverse events, plasma concentration of DS-8500a | |
| Type 2 diabetes (NCT02222350) | Daiichi Sankyo Co., Ltd | 10/75 mg DS-8500a tablet, placebo | Change in 24-h weighted mean blood glucose | Change in 24-h weighted mean blood glucose, blood fasting plasma glucose level, blood plasma glucose level, blood insulin level, blood C-peptide level, blood active GLP-1 level, blood PYY level, blood HbA1c level, blood glycoalbumin level and postprandial plasma glucose level, number and severity of adverse events, pharmacokinetic profile of DS-8500a | |
| Type 2 diabetes (NCT02628392) | Daiichi Sankyo Co., Ltd | DS-8500a, placebo, sitagliptin | Change in HbA1c |
Change in HbA1c, plasma glucose, AUC derived from plasma glucose, serum insulin, AUC 0–3 h serum insulin, AUC 0–3 h proinsulin, AUC 0–3 h C-peptide, AUC 0–3 h PYY, PYY, GLP-1, AUC 0–3 h total GIP, total GIP, AUC 0–3 h glucagon, glucagon, AUC 0–3 h 1,5 AG, 1,5 AG, total cholesterol, HDL cholesterol, LDL cholesterol and TG Proportion of subjects with HbA1c < 7.0 | |
| Type 2 diabetes (NCT02647320) | Daiichi Sankyo, Inc | Sitagliptin 100 mg, DS-8500a 25 mg, placebo tablet, placebo capsule | Change from baseline in glycated hemoglobin (HbA1c) |
Change from baseline in total cholesterol (TC), LDL-C, HDL-C, non-HDL-C, triglycerides, area under the curve 0–3 h (AUC 0–3 h) of plasma glucose (PG), AUC 0–3 h of PG, Cmax, Cmax of PG and fasting plasma glucose (FPG) Count of participants with HbA1c less than 7.0% | |
| LEZ763 | Normal healthy volunteers and patients with type 2 diabetes (NCT01619332) | Novartis Pharmaceuticals | Placebo, sitagliptin, LEZ763, | Adverse events, serious adverse events, death, pharmacokinetics of LEZ763 | Area under the GLP-1 curve (AUC0-24 h), 2-h value of post-prandial glucose, change from baseline in fasting C-peptide, fasting insulin, fasting plasma glucose, peak glucose level following meal test, peptide YY and GIP. Peak effect (Emax) on postprandial GLP-1 |
| ZYG-19 | CTRI/2011/12/003013 (Clinical Trials Registry—India) | ||||
| BMS-903452 | Normal healthy volunteers and patients with type 2 diabetes (NCT01240980) | Bristol-Myers Squibb | BMS-903452, placebo | Safety and tolerability | Pharmacodynamic activity of the investigational drug on glucose and hormones regulating glucose metabolism, ECG parameters, percent urinary recovery (% UR), renal clearance (CLR) from plasma, Cmax, Tmax, pharmacokinetics parameter |
| APD668 | Discontinued | Arena | |||
| "NN" | Discontinued | Novartis | |||
| DA-1241 | Type 2 diabetes (NCT03061981) | Dong-A ST Co., Ltd | placebo, metformin, DA-1241 | Safety and tolerability | Cmax, Tmax, AUC, apparent terminal elimination half-life (t½), apparent total systemic clearance after oral administration (CL/F), apparent volume of distribution (Vz/F), amount of DA-1241 excreted unchanged in the urine in each collection interval (Ae), renal clearance (CLR), cumulative percentage fraction of DA-1241 excreted unchanged in the urine (Cum Fe) |
| Type 2 diabetes (NCT03646721) | Dong-A ST Co., Ltd | placebo, sitagliptin, DA-1241 | 12-lead ECGs, blood pressure, heart rate, body temperature, respiratory rate, physical examination, clinical laboratory testing, adverse events | Cmax, Tmax, AUC, apparent terminal elimination half-life (t½), apparent total systemic clearance after oral administration (CL/F), apparent volume of distribution (Vz/F), HbA1c, fasting insulin, glycated albumin, incremental WMG (iWMG), weighted mean glucose (WMG) etc. 21 items in total |