Table 1.
Summary of studies included in the population pharmacokinetic analysis
| Study no | Dose regimen | N | Study description | PK sampling design | References |
|---|---|---|---|---|---|
| HMM0102 (NCT02077452) |
25 mg BID 50 mg BID 100 mg BID 150 mg BID 200 mg BID |
53 | A randomized, double-blinded, placebo-controlled study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple ascending doses of dorzagliatin in adult patients with type 2 diabetes mellitus | Day 1 and 8: pre-dose, 0.25 h, 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 8 h, 12 h, 16 h, 24 h, 36 h, and 48 h post-dose; Day 3 and 7: pre-dose, 0.25 h, 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 8 h, and 12 h post-dose | |
| HMM0103 (NCT02386982) |
75 mg BID 75 mg QD |
24 | A single-center, randomized, open-label, 2-arm, 4-week treatment study to investigate the beta cell function and related pharmacodynamics in type 2 diabetes mellitus (T2DM) patients | Day 7, 14 and 21: pre-dose; Day 28: pre-dose, 0.5 h, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 12.5 h, 13 h, 13.5 h, 14 h, 16 h, 18 h, 24 h, 36 h, 48 h, 72 h, and 96 h post-dose | [6] |
| HMM0201 (NCT02561338) |
50 mg BID 75 mg BID 75 mg QD 100 mg QD |
258 | A multi-center, randomized, double-blind, placebo-controlled, 12-week phase II study to evaluate the safety, tolerability, efficacy and population PK of dorzagliatin in type 2 diabetic adult subjects |
V4, 5, 6, and 7: pre-dose V8: pre-dose, 0.5 h, 1 h, and 2 h post-dose |
[4] |
| HMM0301 (NCT03173391) | 75 mg BID | 463 | A 24-week multi-center, randomized, double-blind, placebo-controlled, phase III study to evaluate the efficacy and safety of dorzagliatin with additional 28-week open-label treatment to evaluate the safety of dorzagliatin alone in T2DM subjects |
V5: pre-dose V7, V10, V15: pre-dose, 2 h post-dose |
[5] |
| HMM0302 (NCT03141073) | 75 mg BID | 767 | A 24-week multi-center, randomized, double-blind, placebo-controlled, phase III study to evaluate the efficacy and safety of dorzagliatin add-on to metformin with additional 28-week open-label treatment to evaluate the safety in T2DM subjects |
V5: pre-dose V7, V10, V15: pre-dose, 2 h post-dose |
[3] |
| HMM0110 (NCT04324424) | 25 mg | 16 | An open-label, paralleled study of the pharmacokinetics of dorzagliatin following a single oral dose in renal impaired subjects and matched healthy volunteers | Plasma was collected at pre-dose, 0.25 h, 0.5 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, and 72 h post-dose | [7] |
BID twice daily, PK pharmacokinetics, QD once daily, T2DM type 2 diabetes mellitus