Safety of Anagliptin and MEtformin combination tablets evaluated by non-inferiority between pre- and post-serum Lactate levels In Japanese patients Of type 2 diabetes and moderate renal impairment

JRCT ID: jRCTs031200366

Registered date:18/02/2021

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Type 2 diabetes mellitus
• Date of first enrollment: 18/02/2021
• Target sample size: 38
• Study type: Interventional

Intervention(s)

If eGFRcreat at consenting is 45 ml/min/1.73m2 or higher and less than 60 ml/min/1.73m2, the study subjects are treated with anagliptin/metformin combination tablet LD for the first 4 weeks, and then treated with anagliptin/metformin combination tablet HD for the next 4 weeks.
If eGFRcreat at consenting is 30 ml/min/1.73m2 or higher and less than 45 ml/min/1.73m2, the study subjects are treated with anagliptin/metformin combination tablet LD throughout the study.
The day of the start of anagliptin/metformin combination tablet LD administration should be the day of the start of the observation period.
If the eGFRcreat at baseline is 30 ml/min/1.73m2 or higher and less than 45 ml/min/1.73m in the study subjects whose eGFRcreat at consenting was 45 ml/min/1.73m2 or higher and less than 60 ml/min/1.73m2, the study subjects are treated with anagliptin/metformin combination tablet LD throughout the study.

Outcome(s)

• Primary Outcome: noninferiority of serum latic acid at week 16 to that at baseline

Secondary Outcome

Measurements and change from baseline to week 16 in the following items:
1. serum lactic acid
2. biomarkers for glycemic control (HbA1c and postprandial plasma glucose)
3. biomarkers for renal function (eGFRcreat, serum creatinine, urinary ACR, urinary L-FABP, serum BUN, serum cystatin C, and eGFRcys)
4. biomarkers for hepatic function (AST, ALT, and gamma-GTP)
5. biomarkers for lipid metabolisim (LDL-chol (actual value), HDL-chol, TG (postprandial)
6. blood pressure
7. plasma trough concentration of metformin
8. body weight and BMI
9. proportion of subjects whose serum lactic acid becomes 2.5 mmol/L or higher, or proportion of subjects whose serum lactic acid becomes more than 5 mmol/L
10. proportion of subjects whose plasma trough concentration of metformin becomes 2.5 mcg/dL or higher, or proportion of subjects whose plasma trough concentration of metformin becomes more than 5 mcg/dL

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: < 75age old
• Gender: Both

Include criteria

Subjects who meet all of the following criteria are included in this study:
1. Outpatients with type 2 diabetes mellitus (without any plans of hospitalization).
2. Subjects who used DPP-4 inhibitors for 8 weeks before consenting without any change in the usage, dose, and type of the DPP-4 inhibitors.
3. Subjects whose latest HbA1c within 10 weeks before consenting is 7.0% or higher, and less than 10.0%.
4. Subjects whose latest eGFRcreat within 10 weeks before consenting is 30 mL/min/1.73m2 or higher, and less than 60 mL/min/1.73m2.
5. Subjects aged 20 years or older, and younger than 75 years.
6. Subjects who give their consent in a written form.

Exclude criteria

Subjects who fall into any of the following criteria are excluded from participating in the study:
1. Subjects who used biguanide within 8 weeks before consenting.
2. Subjects who used GLP-1 receptor agonist within 8 weeks before consenting.
3. Subjects who have history of hypersensitivity against anagliptin or biguanide.
4. Subjects who have history of lactic acidosis.
5. Subjects with severe renal dysfunction (eGFR is less than 30 ml/min/1.73m2) or subjects who are treated with dialysis.
6. Subjects with severe hepatic dysfunction.
7. Subjects have stroke, cerebral infarction, severe cardiovascular or pulmonary dysfunction (such as shock lung, heart failure, myocardial infarction, and pulmonary embolism), or subjects who are prone to hypoxemia.
8. Subjects with dehydration or subjects who are prone to dehydration (subjects with gastrointestinal dysfunction such as diarrhea or vomiting, subjects who have difficulty in ingestion).
9. Subjects with excess alcohol drinking.
10. Subjects with severe ketosis, diabetic coma, precoma, or type 1 diabetes mellitus.
11. Subjects with severe infection, during a perioperative period, or severe physical injury.
12. Subjects with malnutrition, starvation, debilitation, pituitary dysfunction, or adrenal dysfunction.
13. Subjects who are pregnant, breastfeeding, possibly pregnant, or planning to be pregnant.
14. Subjects with malignant tumor, or subjects who have history of malignant tumor. However, those who have completed treatment and/or show no redevelopment of malignant tumor, as well as manifest some degree of remission can be considered to be participants of this study.
15. Subjects who need legal representative for giving their consent.
16. Subjects who are considered to be unsuitable for participating in this study by investigators.

Related Information

• Primary Sponsor: Kajio Hiroshi
• Secondary Sponsor: Noda Mitsuhiko
• Source(s) of Monetary Support: Sanwa Kagaku Kenkyusho Co. Ltd.