Clinical pharmacology study of ipragliflozin in Japanese patients with type 1 diabetes mellitus : A phase 2, randomized, placebo-controlled trial
© 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd..
AIM: To evaluate the pharmacodynamics, pharmacokinetics, and safety of the novel oral sodium-glucose co-transporter-2 inhibitor, ipragliflozin, in Japanese patients with type 1 diabetes mellitus.
MATERIALS AND METHODS: We conducted a multicentre, double-blind, placebo-controlled, parallel-group study. Patients were randomized to receive 25, 50, or 100 mg/day ipragliflozin or placebo for 2 weeks. Key pharmacokinetic endpoints included area under the concentration-time curve 24 hours postdose (AUC24h ), maximum plasma concentration (Cmax ), and renal clearance. Key pharmacodynamic endpoints included 24-hour urinary glucose excretion, mean plasma glucose AUC0-24h , and mean renal glucose clearance. Changes in total, basal, and bolus insulin dosages were recorded. Adverse events (AEs) were monitored for safety.
RESULTS: Dose-dependent increases were observed in AUC24h and Cmax on days 1 and 14 for 25-, 50-, and 100-mg ipragliflozin. The mean plasma glucose AUC0-24h was lower than that of placebo and the mean renal glucose clearance increased in a dose-dependent manner from baseline, but remained unchanged in the placebo group. The mean (standard deviation) change from baseline in total daily insulin dose was greater in the ipragliflozin 25-, 50-, and 100-mg groups (-14.77 ± 14.04%, -18.40 ± 12.49% and -19.25 ± 16.77%, respectively), than placebo (-4.51 ± 16.28%). Most AEs were mild in severity; no patients discontinued the study because of treatment-emergent AEs.
CONCLUSIONS: The pharmacokinetic and pharmacodynamic properties of ipragliflozin in Japanese patients with type 1 diabetes mellitus were confirmed. Increases in urinary glucose excretion lead to dose-dependent decreases in plasma glucose. Concomitant insulin dose decreased with ipragliflozin treatment. No clinically relevant safety concerns were identified.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
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| Enthalten in: |
Diabetes, obesity & metabolism - 21(2019), 6 vom: 16. Juni, Seite 1445-1454 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kaku, Kohei [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 29.05.2020 Date Revised 09.01.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/dom.13679 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM294453962 |
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| 100 | 1 | |a Kaku, Kohei |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Clinical pharmacology study of ipragliflozin in Japanese patients with type 1 diabetes mellitus |b A phase 2, randomized, placebo-controlled trial |
| 264 | 1 | |c 2019 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 29.05.2020 | ||
| 500 | |a Date Revised 09.01.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. | ||
| 520 | |a AIM: To evaluate the pharmacodynamics, pharmacokinetics, and safety of the novel oral sodium-glucose co-transporter-2 inhibitor, ipragliflozin, in Japanese patients with type 1 diabetes mellitus | ||
| 520 | |a MATERIALS AND METHODS: We conducted a multicentre, double-blind, placebo-controlled, parallel-group study. Patients were randomized to receive 25, 50, or 100 mg/day ipragliflozin or placebo for 2 weeks. Key pharmacokinetic endpoints included area under the concentration-time curve 24 hours postdose (AUC24h ), maximum plasma concentration (Cmax ), and renal clearance. Key pharmacodynamic endpoints included 24-hour urinary glucose excretion, mean plasma glucose AUC0-24h , and mean renal glucose clearance. Changes in total, basal, and bolus insulin dosages were recorded. Adverse events (AEs) were monitored for safety | ||
| 520 | |a RESULTS: Dose-dependent increases were observed in AUC24h and Cmax on days 1 and 14 for 25-, 50-, and 100-mg ipragliflozin. The mean plasma glucose AUC0-24h was lower than that of placebo and the mean renal glucose clearance increased in a dose-dependent manner from baseline, but remained unchanged in the placebo group. The mean (standard deviation) change from baseline in total daily insulin dose was greater in the ipragliflozin 25-, 50-, and 100-mg groups (-14.77 ± 14.04%, -18.40 ± 12.49% and -19.25 ± 16.77%, respectively), than placebo (-4.51 ± 16.28%). Most AEs were mild in severity; no patients discontinued the study because of treatment-emergent AEs | ||
| 520 | |a CONCLUSIONS: The pharmacokinetic and pharmacodynamic properties of ipragliflozin in Japanese patients with type 1 diabetes mellitus were confirmed. Increases in urinary glucose excretion lead to dose-dependent decreases in plasma glucose. Concomitant insulin dose decreased with ipragliflozin treatment. No clinically relevant safety concerns were identified | ||
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a hyperglycaemia | |
| 650 | 4 | |a ipragliflozin | |
| 650 | 4 | |a plasma glucose | |
| 650 | 4 | |a sodium-glucose co-transporter | |
| 650 | 4 | |a type 1 diabetes mellitus | |
| 650 | 7 | |a Blood Glucose |2 NLM | |
| 650 | 7 | |a Glucosides |2 NLM | |
| 650 | 7 | |a Sodium-Glucose Transporter 2 Inhibitors |2 NLM | |
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| 650 | 7 | |a ipragliflozin |2 NLM | |
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| 700 | 1 | |a Isaka, Hiroyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Toyoshima, Junko |e verfasserin |4 aut | |
| 700 | 1 | |a Sakatani, Taishi |e verfasserin |4 aut | |
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