Efficacy of Ipragliflozin Compared With Sitagliptin in Uncontrolled Type 2 Diabetes With Sulfonylurea and Metformin

NCT03076112 | Completed Phase 3 DMC

• 1 other identifier: B-1612/375-004
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 1

Brief Summary

The objectives of this study are 1) to compare the effect of ipragliflozin 50 mg on glucose-lowering effect with sitagliptin 100 mg in patients with type 2 diabetes mellitus, whose HbA1c level is ≥ 7.5% with sulfonylurea and metformin, 2) to investigate changes of other metabolic and cardiovascular risk factors such as triglyceride, HDL-cholesterol, uric acid, blood pressure, and inflammatory markers, 3) to examine changes of body composition including fat and muscle mass with volume status.

Conditions

Type 2 Diabetes Mellitus

Keywords

Ipragliflozin; Sitagliptin

Outcome Measures

Primary Outcomes (1)

• Glycated hemoglobin

  Change of HbA1c after 24 weeks' treatment

  Baseline, week 12, week 24

Secondary Outcomes (10)

• Glycemic target goal achievement

  Baseline, week 12, week 24

• Body weight

  Baseline, week 12, week 24

• Body fat mass

  Baseline, week 24

• Fasting plasma glucose level

  Baseline, week 12, week 24

• Postprandial 2hr glucose level

  Baseline, week 12, week 24

Study Arms (2)

Ipragliflozin

EXPERIMENTAL

Ipragliflozin 50 mg in addition to their preexisting sulfonylurea and metformin \*\* Metformin and sulfonylurea's dosages * Metformin 500 mg - 2550 mg * Sulfonylurea: Glimepiride 1 mg - 8 mg or Gliclazide MR 30 mg - 120 mg

Drug: Ipragliflozin

Sitagliptin

ACTIVE COMPARATOR

Sitagliptin 100 mg in addition to their preexisting sulfonylurea and metformin \*\* Metformin and sulfonylurea's dosages * Metformin 500 mg - 2550 mg * Sulfonylurea: Glimepiride 1 mg - 8 mg or Gliclazide MR 30 mg - 120 mg

Drug: Sitagliptin

Interventions

Ipragliflozin DRUG

Ipragliflozin as add-on to Metformin and Sulfonylurea in patients with poorly controlled type 2 diabetes

Also known as: Suglat

Ipragliflozin

Sitagliptin DRUG

Sitagliptin as add-on to Metformin and Sulfonylurea in patients with poorly controlled type 2 diabetes

Also known as: Januvia

Sitagliptin

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 2 diabetes with HbA1c 7.5% - 9.0% at screening visit
• Male or female between 20 and 75 years of age
• Patients taking sulfonylurea (glimepiride 1\~8mg or gliclazide 30\~120 mg or equivalent dose) and metformin (≥ 1000 mg or maximum tolerated dose) for more than 3 months
• BMI ≥23 kg/m²
• Estimated GFR ≥ 60 ml/min/1.73m²
• Women of child bearing potential must take precautions to avoid pregnancy throughout the study and for 4 weeks after intake of the last dose and must have a negative urinary pregnancy test.

You may not qualify if:

• Type 1 diabetes, gestational diabetes, or diabetes with secondary cause
• Patients with acute coronary syndrome within 3 months prior to screening visit
• Patients with acute coronary syndrome within 3 months prior to screening visit
• Pregnant or breastfeeding women or reproductive-age women who refuse contraception
• Chronic hepatitis B or C (except healthy carrier of HBV), liver disease (AST/ALT \> 3-fold the upper limit of normal)
• Cancer within 5 years (except squamous cell cancer, cervical cancer, thyroid cancer with appropriate treatment) except thyroid cancer or carcinoma in situ
• Other clinical trials within 30 days
• Alcohol abuse
• Contraindication to SGLT2 inhibitors or Dipeptidyl-peptidase 4 inhibitors
• Taking insulin, oral hypoglycemic agents other than metformin, sulfonylurea, and the study drugs.

Sponsors & Collaborators

• Seoul National University Bundang Hospital: lead
• Astellas Pharma Korea, Inc.: collaborator

Study Sites (1)

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 463-707, South Korea

Location

Related Publications (9)

• Hedrington MS, Davis SN. Ipragliflozin , a sodium-glucose cotransporter 2 inhibitor, in the treatment of type 2 diabetes. Expert Opin Drug Metab Toxicol. 2015 Apr;11(4):613-23. doi: 10.1517/17425255.2015.1009893. Epub 2015 Feb 2.

  PMID: 25643044 BACKGROUND

• Kadokura T, Zhang W, Krauwinkel W, Leeflang S, Keirns J, Taniuchi Y, Nakajo I, Smulders R. Clinical pharmacokinetics and pharmacodynamics of the novel SGLT2 inhibitor ipragliflozin. Clin Pharmacokinet. 2014 Nov;53(11):975-88. doi: 10.1007/s40262-014-0180-z.

  PMID: 25316572 BACKGROUND

• Veltkamp SA, van Dijk J, Collins C, van Bruijnsvoort M, Kadokura T, Smulders RA. Combination treatment with ipragliflozin and metformin: a randomized, double-blind, placebo-controlled study in patients with type 2 diabetes mellitus. Clin Ther. 2012 Aug;34(8):1761-71. doi: 10.1016/j.clinthera.2012.06.027. Epub 2012 Jul 15.

  PMID: 22795925 BACKGROUND

• Takasu T, Hayashizaki Y, Tahara A, Kurosaki E, Takakura S. Antihyperglycemic effect of ipragliflozin, a sodium-glucose co-transporter 2 inhibitor, in combination with oral antidiabetic drugs in mice. Clin Exp Pharmacol Physiol. 2015 Jan;42(1):87-93. doi: 10.1111/1440-1681.12317.

  PMID: 25311502 BACKGROUND

• Smulders RA, Zhang W, Veltkamp SA, van Dijk J, Krauwinkel WJ, Keirns J, Kadokura T. No pharmacokinetic interaction between ipragliflozin and sitagliptin, pioglitazone, or glimepiride in healthy subjects. Diabetes Obes Metab. 2012 Oct;14(10):937-43. doi: 10.1111/j.1463-1326.2012.01624.x. Epub 2012 Jun 7.

  PMID: 22587345 BACKGROUND

• Macdonald FR, Peel JE, Jones HB, Mayers RM, Westgate L, Whaley JM, Poucher SM. The novel sodium glucose transporter 2 inhibitor dapagliflozin sustains pancreatic function and preserves islet morphology in obese, diabetic rats. Diabetes Obes Metab. 2010 Nov;12(11):1004-12. doi: 10.1111/j.1463-1326.2010.01291.x.

  PMID: 20880347 BACKGROUND

• Bolinder J, Ljunggren O, Johansson L, Wilding J, Langkilde AM, Sjostrom CD, Sugg J, Parikh S. Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab. 2014 Feb;16(2):159-69. doi: 10.1111/dom.12189. Epub 2013 Aug 29.

  PMID: 23906445 BACKGROUND

• Matthaei S, Bowering K, Rohwedder K, Grohl A, Parikh S; Study 05 Group. Dapagliflozin improves glycemic control and reduces body weight as add-on therapy to metformin plus sulfonylurea: a 24-week randomized, double-blind clinical trial. Diabetes Care. 2015 Mar;38(3):365-72. doi: 10.2337/dc14-0666. Epub 2015 Jan 15.

  PMID: 25592197 BACKGROUND

• Hermansen K, Kipnes M, Luo E, Fanurik D, Khatami H, Stein P; Sitagliptin Study 035 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin. Diabetes Obes Metab. 2007 Sep;9(5):733-45. doi: 10.1111/j.1463-1326.2007.00744.x. Epub 2007 Jun 26.

  PMID: 17593236 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

ipragliflozin; Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Study Officials

• Soo Lim

  Seoul National University Bundang Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 6, 2017
• First Posted: March 9, 2017
• Study Start: April 25, 2017
• Primary Completion: June 30, 2022
• Study Completion: August 31, 2022
• Last Updated: October 4, 2022

Record last verified: 2022-10

Locations

KR (1)