臨床研究等提出・公開システム

Comparison of canagliflozin vs. tenegliptin against basic metabolic risks in patients with type 2 diabetes mellitus (CANTABILE study)

CANTABILE study (CANTABILE study)

162

Baseline characteristics in efficacy analysis set [N=70 in teneligliptin group (Group A), N=75 in canagliflozin group (Group B)] were summarized as follows. Sex (Male/Female) [n (%)] Group A: 47 (67.1%)/23 (32.9%), Group B: 51 (68.0%)/24 (32.0%) Age (Mean+-SD) Group A: 55.2+-11.4 years, Group B: 57.2+-11.5 years Height (Mean+-SD) Group A (N=69): 165.5+-9.5 cm, Group B: 165.5+-9.2 cm Weight (Mean+-SD) Group A: 79.2+-16.7 kg, Group B: 79.0+-15.2 kg BMI (Mean+-SD) Group A: 28.8+-4.8 kg/m2, Group B: 28.7+-4.7 kg/m2 Abdominal circumference (Mean+-SD) Group A: 98.0+-14.4 cm, Group B: 97.6+-9.7 cm Duration of diabetes mellitus (Mean+-SD) Group A (N=67): 6.7+-6.3 years, Group B (N=69): 5.9+-4.9 years HbA1c (Mean+-SD) Group A (N=69): 7.84+-0.75%, Group B: 7.69+-0.61% HDL-C (Mean+-SD) Group A: 53.6+-11.4 mg/dL, Group B: 52.1+-12.1 mg/dL Fasting TG (Mean+-SD) Group A (N=69): 169.7+-115.5 mg/dL, Group B (N=73): 202.1+-195.0 mg/dL Systolic blood pressure/Diastolic blood pressure (Mean+-SD) Group A: 137.8+-14.7/82.7+-9.9 mmHg, Group B: 140.7+-19.0/83.4+-10.5 mmHg Concomitant use of metformine [n (%)] Group A: 44 (62.9%), Group B: 44 (58.7%)

29 Sep 2017: Start of patients registration 19 Feb 2018: Initial treatment for the first patient 11 Apr 2019: Initial treatment for the last patient 27 Sep 2019: Last study visit of the last patient

Adverse events were collected after initial treatment. In safety analysis set (Group A: N=80, Group B: N=82), the incidence rate of adverse events (AE) was 33.8% (n=27) in Group A and 53.7% (n=44) in Group B. The incidence rate of AE of which causal relationship to study drug cannot be ruled out was 8.8% (n=7) in Group A and 31.7% (n=26) in Group B. AEs occurred in more than one subject in each treatment group are summarized as follows. There were no serious AEs in each treatment group. Group A: Hypoglycaemia (n=2, 2.5%) Group B: Glucose urine (n=6, 7.3%), Pollakiuria (n=5, 6.1%), Thirst (n=4, 4.9%), Diabetic ketosis, Constipation, Polyuria and Blood ketone body increased (n=2 each, 2.4%)

Primary endpoint The proportion of subjects who met one or more of the composite endpoints [(a), (b) or (c)] was 31.3% (n=21) in Group A and 62.2% (n=46) in Group B. The treatment difference (Group A - Group B) was statistically significant (-30.8%, p=0.0004, Fisher's exact test). Secondary endpoint As the statistical methods for each endpoint, Fisher's exact test was used for treatment group comparison on achievement rate or proportion, and analysis of covariance (ANCOVA) was used for treatment group comparison on changes from baseline. 1) Proportion of study subjects to whom each of the primary endpoints [(a), (b) and (c)] apply The proportion of subject who met (a) was 10.5% (n=6) in Group A and 55.9% (n=33) in Group B, and the treatment difference (Group A - Group B) was statistically significant (-45.4%, p<0.0001). The proportion of subject who met (b) was 32.0% (n=16) in Group A and 32.7% (n=18) in Group B, and the treatment difference (Group A - Group B) was not statistically significant. The proportion of subject who met (c) was 9.7% (n=3) in Group A and 20.6% (n=7) in Group B, and the treatment difference was not statistically significant. 2) Amount of change in HbA1c HbA1c in each treatment group decreased from baseline from treatment period week 6 and these decreases were sustained up to Week 24. The change from baseline at treatment period Week 24 (Mean+-SD) was -0.68+-0.69% in Group A and -0.64+-0.45% in Group B. The treatment difference was not statistically significant at each timepoint. 3) Amount of change in fasting blood glucose Fasting blood glucose in each treatment group decreased from baseline from treatment period Week 6 and these decreases were sustained up to Week 24. The change from baseline at treatment period Week 24 (Mean+-SD) was -14.8+-31.7 mg/dL in Group A and -20.2+-38.5 mg/dL in Group B. The treatment difference (Group A - Group B, LS Mean) was statistically significant at Week 12 (-13.5 mg/dL, p<0.0001) and Week 18 (-16.9 mg/dL, p<0.0001). 4) Achievement rate of HbA1c below 6.0% and achievement rate of HbA1c below 7.0% Achievement rate of HbA1c below 6.0% The achievement rate of HbA1c below 6.0% in Group A was 0.0% (n=0) at Week 6 and Week 12, 1.4% (n=1) at Week18 and Week 24, and that in Group B was 0.0% (n=0) at Week 6, Week 12 and Week 18, and 2.7% (n=2) at Week 24. The treatment difference was not statistically significant at each timepoint. Achievement rate of HbA1c below 7.0% The achievement rate of HbA1c below 7.0% in Group A was 34.4% (n=22) at Week 6, 42.9% (n=30) at Week 12, 44.3% (n=31) at Week 18 and 44.3% (n=31) at Week 24, and that in Group B was 27.5% (n=19) at Week 6, 49.3% (n=36) at Week 12, 50.7% (n=38) at Week 18 and 46.7% (n=35) at Week 24. The treatment difference was not statistically significant at each timepoint. 5) Achievement rate of a decrease of 3% or greater in body weight, achievement rate of a decrease of 5% or greater in body weight Achievement rate of a decrease of 3% or greater in body weight The achievement rate of a decrease of 3% or greater in body weight at treatment period Week 24 was 10.5% (n=6) in Group A and 55.9% (n=33) in Group B, and the treatment difference was statistically significant (p<0.0001). Achievement rate of a decrease of 5% or greater in body weight The achievement rate of a decrease of 5% or greater in body weight at treatment period Week 24 was 1.8% (n=1) in Group A and 22.0% (n=13) in Group B, and the treatment difference was statistically significant (p=0.0010). 6) Amount of change in abdominal circumference, BMI, and body weight Abdominal circumference Abdominal circumference in Group A didn't decrease from baseline at each timepoint, while that in Group B decreased from treatment period Week 6 and this decrease was sustained up to Week 24. The change from baseline at treatment period Week 24 (Mean+-SD) was 0.23+-6.19 cm in Group A and -2.35+-3.78 cm in Group B. The treatment difference (Group A - Group B, LS Mean) was statistically significant at all timepoints (Week 6: -2.16 cm [p=0.0064], Week 12: -2.63 cm [p=0.0011], Week 18: -2.81 cm [p=0.0002], Week 24: -2.66 cm [p=0.0006]). BMI BMI in Group A didn't decrease from baseline at each timepoint, while that in Group B decreased from treatment period Week 6 and this decrease was sustained up to Week 24. The change from baseline at treatment period Week 24 (Mean+-SD) was 0.14+-0.78 kg/m2 in Group A and -0.94+-0.90 kg/m2 in Group B. The treatment difference (Group A - Group B, LS Mean) was statistically significant at all timepoints (Week 6: -0.71 kg/m2 [p<0.0001], Week 12: -0.87 kg/m2 [p<0.0001], Week 18: -1.03 kg/m2 [p<0.0001], Week 24: -1.08 kg/m2 [p<0.0001]). Body weight Body weight in Group A didn't decrease from baseline at each timepoint, while that in Group B decreased from treatment period Week 6 and this decrease was sustained up to Week 24. The change from baseline at treatment period Week 24 (Mean+-SD) was 0.34+-2.14 kg in Group A and -2.55+-2.51 kg in Group B. The treatment difference (Group A - Group B, LS Mean) was statistically significant at all timepoints (Week 6: -1.90 kg [p<0.0001], Week 12: -2.34 kg [p<0.0001], Week 18: -2.81 kg [p<0.0001], Week 24: -2.90 kg [p<0.0001]). 7) Amount of change in HDL-C and fasting TG Amount of change in HDL-C HDL-C in Group A didn't increase from baseline at each timepoint while that in Group B increased from treatment period Week 6 and this increase was sustained up to Week 24. The change from baseline at treatment period Week 24 (Mean+-SD) was -0.8+-6.1 mg/dL in Group A and 4.8+-6.8 mg/dL in Group B. The treatment difference (Group A - Group B, LS Mean) was statistically significant at Week 12 (2.9 mg/dL, p=0.0039), Week 18 (2.9 mg/dL, p=0.0035) and Week 24 (5.6 mg/dL, p<0.0001). Amount of change in fasting TG Fasting TG in each treatment group decreased from baseline from treatment period Week 6 and these decreases were sustained up to Week 24. The change from baseline at treatment period Week 24 (Mean+-SD) was -8.6+-72.8 mg/dL in Group A and -35.9+-134.8 mg/dL in Group B. The treatment difference was not statistically significant at each timepoint. 8) Amount of change in blood pressure (systolic blood pressure, diastolic blood pressure) Amount of change in systolic blood pressure Systolic blood pressure in each treatment group decreased from baseline from treatment period Week 6 and these decreases were sustained up to Week 24. The change from baseline at treatment period Week 24 (Mean+-SD) was -5.2+-13.4 mmHg in Group A and -8.6+-15.1 mmHg in Group B. The treatment difference was not statistically significant at each timepoint. Amount of change in diastolic blood pressure Diastolic blood pressure in each treatment group decreased from baseline from treatment period Week 6 and these decreases were sustained up to Week 24. The change from baseline at treatment period Week 24 (Mean+-SD) was -2.4+-8.5 mmHg in Group A and -4.4+-9.4 mmHg in Group B. The treatment difference was not statistically significant at each timepoint.

The proportion of subjects who met one or more of the composite endpoints [(a),(b),(c)] was 31.3%(n=21,95%CI:20.6%-43.8%) in Group A, and 62.2%(n=46,95%CI: 50.1%-73.2%) in Group B. The ratio of achievement of>-3% body weight loss was higher in the Canagliflozin group than Teneligliptin group(55.9% vs.10.5%,P<0.0001), with larger reduction of abdominal circumference(-2.4+-0.5cm vs.0.3+-0.5cm). The rates of improvement of blood pressure and dyslipidemia were not significantly different between two groups.

Sept. 30, 2021

http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1463-1326

Undecided

Undecided

https://jrct.mhlw.go.jp/latest-detail/jRCTs051180112

Hosoda Kiminori

National Cerebral and Cardiovascular Center

6-1 Kishibe Shinmachi, Suita, Osaka 564-8565, Japan.

kiminorihosoda@ncvc.go.jp

Son Cheol

National Cerebral and Cardiovascular Center

6-1 Kishibe Shinmachi, Suita, Osaka

+81-6-6170-1070

son@ncvc.go.jp

Complete

Oct. 01, 2017

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

1. Written informed consent by the patient
2. 20 years old or older, less than 85 years old
3. HbA1c of 7.0% or higher and less than 10.0%
4. Fulfill one or more of the following criteria on the date of consent;
- BMI 25 kg/m2 or higher
- Systolic blood pressure of 130 mmHg or higer, or diastolic blood pressure of 85 mmHg or higher
-Fasting triglyceride of 150 mg/dL or higher, or HDL-C of less than 40 mg/dL
5. No anti-diabetic medication during the preceding 8 weeks, or have been receiving fixed dose metformin hydrochloride monotherapy during the preceding 8 weeks
6. Undertaking dietary and exercise therapy of the same intensity/content during the preceding 8 weeks. Exercise is not mandatory If exercise is not recommended due to complications.

1. Type 1 diabetes mellitus
2. BMI of 22 kg/m2 or less
3. Hypersensitivity to contents of TENELIA or CANAGLU
4. Require insulin therapy (Severe ketosis, diabetic coma or precoma, severe infection, perioperative, severe trauma etc.)
5. Congestive heart failure of NYHA III or IV
6. Pregnancy, possible pregnancy, or lactating
7. Malignancy or suspected malignancy
8. Taking unallowed medications or undertaking unallowed therapy defined in the study protocol during the preceding 8 weeks
9. Changes in dosage of concomitantly administered drugs or therapy contents during the preceding 8 weeks
10. Other subjects deemed unsuitable by the doctor in charge of the research

Both

T2DM patients with basic metabolic risks

Group A: Teneligliptin group: Orally given one tablet of TENELIA 20mg daily from the next day of the 0 week clinic visit until the 24 week of treatment. If the doctor in charge finds it suitable during the treatment with 20mg, dose escalation up to 40mg (2 tablets) once daily is allowed.
Group B: Canagliflozin group: Orally given one tablet of CANAGLU 100mg daily either before or after breakfast from the next day of the 0 week clinic visit until the 24 week of treatment.

Rate of subjects who meet one or more of the below criteria : Composite endpoints (a) BMI 25 kg/m2 or more at 0 week of treatment and show 3% or more weight loss at 24 week of treatment. (b) Systolic blood pressure of 130 mmHg or more or diastolic blood pressure of 85 mmHg or more at 0 week and show systolic blood pressure of less than 130 mmHg and diastolic blood pressure of less than 85 mmHg at 24 week of treatment. (c) Fasting triglyceride of 150 mg/dL or more or HDL-C of less than 40 mg/dL at 0 week and fasting triglycreride of less than 150 mg/dL and HDL-C of 40 mg/dL or more at 24 week of treatment.

1) Proportion of study subjects to whom each of the primary endpoints ((a), (b), and (c)) apply
2) Amount of change in HbA1c
3) Amount of change in fasting blood glucose
4) Achievement rate of HbA1c below 6.0% and achievement rate of HbA1c below 7.0%
5) Achievement rate of a decrease of 3% or greater in body weight, achievement rate of a decrease of 5% or greater in body weight (of the study subjects for whom BMI was at 25 kg/m2 or above at treatment period week 0, proportions who had lost at least 3% or at least 5% of body weight at treatment period week 24)
6) Amount of change in abdominal circumference, BMI, and body weight
7) Amount of change in HDL-C and fasting TG
8) Amount of change in blood pressure (systolic blood pressure, diastolic blood pressure)

+81-744-29-8835

Jan. 04, 2019

none