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MK-0431/ONO-5435 Phase III Clinical Trial -Rapid-acting Insulin Secretagogue Add-on Study in Patients with Type 2 Diabetes- (ONO-5435-17)

MK-0431/ONO-5435 Phase III Clinical Trial -Rapid-acting Insulin Secretagogue Add-on Study in Patients with Type 2 Diabetes- (ONO-5435-17)

155

Demographic, anthropometric, and disease characteristics were usually balanced between the two treatment groups except for body weight. Mean body weight was slightly higher in the sitagliptin group than in the placebo group, but no statistically significant differences between the groups were found for demographic, anthropometric, or disease characteristics.

Two hundred and one patients were screened, of whom 155 were randomized to treatment (75 to sitagliptin and 80 to placebo) . One hundred fifty patients completed the double-blind period and entered the open-label period; of those, 134 patients subsequently completed the open-label period.

Double-blind period (Weeks 0 through 12) In the double-blind period (Weeks 0-12), the frequency of overall clinical AE reported was 26.7 % (20/75) in the sitagliptin group and 33.8 % (27/80) in the placebo group. Drug-related clinical AE occurred for 5.3 % (4/75) in the sitagliptin group and 5.0 % (4/80) in the placebo group. There were no notable differences between treatment groups in the frequency of overall clinical or drug-related clinical AE at Week 12. In the double-blind period, the frequency of serious clinical AE was low and usually similar in both treatment groups (2.7 % (2/75) in the sitagliptin group and 1.3 % (1/80) in the placebo group). No serious drug-related clinical AE were reported for patients in either group. No patients discontinued because of a clinical AE. The proportion of patients with hypoglycemia AE, which was low for both groups, was numerically higher for sitagliptin than for placebo (4.0 vs. 1.3 %; 95 % CI -3.2, 10.1 %) for the between-group difference. All episodes of hypoglycemia were mild in intensity and none led to discontinuation of therapy. During the double-blind period, the frequencies of laboratory AE and drug-related laboratory AE were 1.3 % (1/75) and 1.3 % (1/80) in the sitagliptin and placebo groups, respectively. No specific laboratory AE occurred for two or more patients in either group. Open-label period (Weeks 12 through 52) Consistent with the longer period of observation for a patient population with T2DM, one or more clinical AE were reported for over half of the patients in both the S/S(Patients who received sitagliptin during the double-blind period continued to do so in the open-label period) and P/S (Patients who received placebo in the double-blind period started to receive sitagliptin on entry to the open-label period) groups during the open-label period (Weeks 12 to 52; 52.8 % (38/72) of patients in the S/S group and 67.9 % (53/78) of patients in the P/S group). Clinical AE reported with a frequency >=5 % in either the S/S or P/S group included nasopharyngitis, hypoglycemia, cystitis, diarrhea, and constipation. Drug-related clinical AE were reported by 4.2 % (3/72) and 10.3 % (8/78) of patients in the S/S and P/S groups, respectively. The nature of clinical AE through Weeks 12-52 in both the S/S and P/S groups was not notably different from that during Weeks 0-12 in the sitagliptin group. Serious clinical AE were reported for six patients in the S/S group and three patients in the P/S group. No serious clinical AE were believed by the investigator to be related to the study drug; one in the S/S group and none in the P/S group led to discontinuation because of clinical AE. No deaths were reported during the open-label period. In the open-label period, the frequency of hypoglycemia AE was 1.4 % (1/72) in the S/S group and 10.3 % (8/78) in the P/S group.All episodes of hypoglycemia in the open-label period were regarded as either mild or moderate in intensity, none required medical attention, and no patient was discontinued from the study because of hypoglycemia AE. In the open-label period, laboratory AE were reported by 5.6 % (4/72) patients in the S/S group and 3.8 % (3/78) patients in the P/S group, and drug-related laboratory AE were not reported in the S/S group and were reported by 1.3 % (1/78) patients in the P/S group; none was serious, and no patients discontinued because of a laboratory AE or a drug-related laboratory AE.

-In the double-blind period (Weeks 0-12), there were no notable differences between treatment groups in the frequency of overall clinical or drug-related clinical AE at Week 12. -In the double-blind period (Weeks 0-12), the proportion of patients with hypoglycemia AE, which was low for both groups, was numerically higher for sitagliptin than for placebo (4.0 vs. 1.3 %; 95%CI : -3.2, 10.1%) for the between-group difference. All episodes of hypoglycemia were mild in intensity and none led to discontinuation of therapy. -In the open-label period, the frequency of hypoglycemia AE was 1.4% (1/72) in the S/S group and 10.3% (8/78) in the P/S group. All episodes of hypoglycemia in the open-label period were regarded as either mild or moderate in intensity, none required medical attention, and no patient was discontinued from the study because of hypoglycemia AE. -Addition of sitagliptin to glinide monotherapy was generally well tolerated by Japanese patients with T2DM receiving glinide monotherapy during both the doubleblind (12-week) and open-label (52-week) periods.

HbA1c[Time Frame:12 weeks] A significant reduction from baseline of HbA1c in the sitagliptin group compared with the placebo group was observed at Week 12 (LS mean difference (95 % CI): -1.1 % (-1.3, -0.8), P<0.001). Fasting plasma glucose[Time Frame:12 weeks] A significant reduction of FPG from baseline was observed in the sitagliptin group compared with the placebo group at Week 12 (LS mean difference (95 % CI): -23.1 mg/dL (-32.2, -13.9), P<0.001). 2 hour post-meal glucose[Time Frame:12 weeks] A significant mean reduction of 2-h PMG from baseline was also observed in the sitagliptin group compared with the placebo group at Week 12 (LS mean difference (95 % CI): -51.2 mg/dL (-67.4, -35.0), P<0.001).

The safety, efficacy, and good tolerability of the addition of sitagliptin to glinides for up to 52 weeks of treatment have been confirmed in patients with T2DM who had inadequate glycemic control on diet/exercise therapy and monotherapy with glinides. The 52-week results indicate that sitagliptin is a drug that can be used in combination with glinides on a long-term basis.

Aug. 28, 2015

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6224996/

Yes

https://www.ono.co.jp/eng/rd/policy.html

ONO PHARMACEUTICAL CO.,LTD.

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ONO PHARMACEUTICAL CO.,LTD.

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completed

Oct. 29, 2011

Interventional

A multicenter, randomized, placebo-controlled, parallel-group, double-blind study and subsequent open-label, extension study.

treatment purpose

3

1. Patients with Type 2 Diabetes Mellitus.
2. Patients who have inadequate glycemic control on diet/exercise therapy and Rapid-acting Insulin Secretagogue monotherapy.

1. Patients with Type 1 Diabetes Mellitus

Both

Type 2 Diabetes Mellitus

investigational material(s)
Generic name etc : MK-0431/ONO-5435
INN of investigational material : -
Therapeutic category code : 396 Antidiabetic agents
Dosage and Administration for Investigational material : A tablet is orally administrated once daily.

control material(s)
Generic name etc : Placebo
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : A tablet is orally administrated once daily.

safety
other
Safety and Tolerability[Time Frame:12 weeks and 52 weeks]

efficacy
HbA1c[Time Frame:12 weeks],2 hour post-meal glucose[Time Frame:12 weeks],Fasting plasma glucose[Time Frame:12 weeks]

Oct. 04, 2011