Table 1.
Summary of demographics and laboratory variables for healthy and T2DM patients
| Study | Study A | Study B and C | Study D, E, F, and G† | |
|---|---|---|---|---|
| Phase I | Clinical pharmacology | Phase II, III | ||
| Subjects | Healthy volunteers | T2DM patients | T2DM | Total in T2DM |
| Number (active/placebo) | n = 84 (60/24) | n = 53 (43/10) | n = 834 (652/182) | n = 887 (695/192) |
| PK/PD variables | AUC24h, UGE24h, FPG | AUC24h, UGE24h, FPG | Ctrough, FPG, HbA1c | |
| Sex n (%) | ||||
| Male | 84 (100.0%) | 37 (69.8%) | 569 (68.2%) | 606 (68.3%) |
| Female | 0 (0.0%) | 16 (30.2%) | 265 (31.8%) | 281 (31.7%) |
| Age category n (%) | ||||
| <65 y | 84 (100.0%) | 34 (64.2%) | 563 (67.5%) | 597 (67.3%) |
| ≥65 y | 0 (0.0%) | 19 (35.8%) | 271 (32.5%) | 290 (32.7%) |
| Renal function n (%)† | ||||
| Normal (eGFR≥90 mL/min/1.73 m2) | 58 (69.0%) | 22 (41.5%) | 296 (35.5%) | 318 (35.9%) |
| Mild (eGFR 60 to <90 mL/min/1.73 m2) | 26 (31.0%) | 21 (39.6%) | 445 (53.4%) | 466 (52.5%) |
| Moderate (eGFR 30 to <60 mL/min/1.73 m2) | 0 (0.0%) | 10 (18.9%) | 93 (11.2%) | 103 (11.6%) |
| Severe (eGFR<30 mL/min/1.73 m2) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Age (y) | ||||
| Mean (SD) | 25.4 (5.2) | 59.3 (10.4) | 58.7 (10.1) | 58.7 (10.1) |
| Range | (20–41) | (34–75) | (26–86) | (26–86) |
| Body weight (kg) | ||||
| Mean (SD) | 64.08 (5.26) | 69.06 (11.89) | 68.14 (12.13) | 68.19 (12.11) |
| Range | (51.4–80.1) | (45.6–100.8) | (41.5–128.0) | (41.5–128.0) |
| BMI (kg/m 2 ) | ||||
| Mean (SD) | 21.59 (1.55) | 25.78 (3.14) | 25.60 (3.62) | 25.62 (3.59) |
| Range | (18.5–25.8) | (20.0–33.9) | (19.1–40.6) | (19.1–40.6) |
| BSA (m 2 ) | ||||
| Mean (SD) | 1.758 (0.086) | 1.744 (0.183) | 1.731 (0.178) | 1.732 (0.178) |
| Range | (1.56–2.03) | (1.35–2.14) | (1.28–2.47) | (1.28–2.47) |
| GFR (mL/min) †, ‡ | ||||
| Mean (SD) | 101.28 (15.68) | 84.28 (29.29) | 84.50 (23.49) | 84.46 (23.91) |
| Range | (72.2–153.0) | (29.8–169.8) | (24.1–175.4) | (24.1–181.5) |
| Total protein (g/dL) | ||||
| Mean (SD) | 6.73 (0.31) | 7.19 (0.47) | 7.28 (0.40) | 7.27 (0.40) |
| Range | (5.8–7.5) | (6.1–8.3) | (5.8–9.1) | (5.8–9.1) |
| Total bilirubin (mg/dL) | ||||
| Mean (SD) | 0.76 (0.23) | 0.81 (0.33) | 0.81 (0.31) | 0.81 (0.31) |
| Range | (0.4–1.3) | (0.4–2.7) | (0.2–3.6) | (0.2–3.6) |
| FPG (mg/dL) | ||||
| Mean (SD) | 92.6 (5.1) | 156.0 (40.2) | 169.1 (37.7) | 168.3 (37.9) |
| Range | (83–110) | (84–255) | (73–342) | (73–342) |
| HbA1c (NGSP) (%) | ||||
| Mean (SD) | 5.11 (0.19) | 8.05 (1.45) | 8.08 (0.82) | 8.08 (0.87) |
| Range | (4.8–5.6) | (5.8–14.0) | (6.3–11.4) | (5.8–14.0) |
†
In study G, eGFR during placebo run‐in period were summarized as the baseline values
‡
eGFR corrected by individual BSA were summarized
AUC24h, area under the concentration–time curve from time of dosing to 24 h after administration; BMI, body mass index; BSA, body surface area; Ctrough, plasma trough concentration; eGFR, estimated glomerular filtration rate; FPG, fasting plasma glucose; HbA1c, glycosylated haemoglobin; PK/PD, pharmacokinetic/pharmacodynamic; SD, standard deviation; T2DM, type 2 diabetes mellitus; UGE24h, change in urinary glucose excretion for 24 hours