Oral Combination of Glimepiride/Vildagliptin/Metformin in Patients With T2D and Dual Treatment Failure

Type 2 Diabetes Clinical Trial

Official title:

Efficacy and Safety of the Oral Combined Therapy Glimepiride / Vildagliptin / Metformin in Patients With Type 2 Diabetes With Dual Treatment Failure

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04841096
• Other study ID #: SIL-30013-III-20(1)
• Status: Recruiting
• Phase: Phase 3
• Start date: March 21, 2023
• Est. completion date: April 2024

Study information

• Verified date: October 2023
• Source: Laboratorios Silanes S.A. de C.V.
• Contact: Jorge A González, PhD
• Phone: 5254883785
• Email: jogonzalez[@]silanes.com.mx
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Phase IIIb, randomized, multicenter, double-blind, prospective study to evaluate the efficacy and safety of a daily fixed-dose combination of glimepiride / vildagliptin / metformin in patients with type 2 diabetes with a history of dual treatment failure and combined or individual oral antidiabetics with SGLT2 / Metformin, Biguanide / Sulfonylurea, Sulfonylurea / iDPP4 or Biguanide / iDPP4. To evaluate the changes in the percentage of HbA1c at 3 and 6 months with regard to their baseline measurement.

Description:

To achieve glycemic control goals, a combination of medications with complementary mechanisms of action, with fasting and postprandial effects, may be required to achieve and maintain clinically acceptable glycemic control in some patients. A fixed combination of two or more therapeutic agents with complementary mechanisms of action makes it possible to optimize compliance and adherence to treatment among patients with T2D because it is administered once a day with the same efficacy of the separate components, but with fewer gastrointestinal effects. This is reflected in a reduction in HA1c and a lower evolution to long-term complications of T2D. Phase IIIb, randomized, multicenter, double-blind, prospective study to evaluate the efficacy and safety of a daily fixed-dose combination of glimepiride / vildagliptin / metformin in patients with type 2 diabetes with a history of dual treatment failure and combined or individual oral antidiabetics with SGLT2 / Metformin, Biguanide / Sulfonylurea, Sulfonylurea / iDPP4 or Biguanide / iDPP4.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 172
• Est. completion date: April 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or Female.
• Age >18 years old at the beginning of the study.
• Diagnosis of type 2 diabetes prior to the start of the study.
• Therapeutic failure to a dual treatment with SGLT2 / Metformin, Biguanide / Sulfonylurea, Sulfonylurea / iDPP4, Biguanide / iDPP4.
• HbA1c = 7.5% and = 11% during screening tests.
• Women of childbearing potential using a contraceptive method (barrier, oral hormonal, injectable, subdermal) or naturally or surgically sterile in menopause.
• Subject agree to participate in the study and give informed consent in writing.

Exclusion Criteria:

• The drug is contraindicated for medical reasons.
• History of Type 1 Diabetes Mellitus.
• History of metabolic complications such as ketoacidosis or nonketotic hyperosmolar state.
• History of gastric bariatric surgery or gastric band in the last year.
• History of drug or alcohol abuse in the past year.
• Body Mass Index <20 kg/m2 and >40 kg/m2.
• Acute or severe renal dysfunction (glomerular filtration <30 ml / min / 1.72 m2).
• History of chronic liver disease or ALT and / or AST =3 times the normal upper limit and / or Total Bilirubin> 2.5 times the upper limit of normal, or GGT =3 times the upper limit of normal.
• Pregnant and / or lactating women.
• The patient is participating in another clinical study involving an investigational treatment or participated in one in the previous 4 weeks.
• At medical criteria, a disease that affects the prognosis and prevents outpatient management, for example, but not restricted to: end-stage cancer, kidney, heart, respiratory or liver failure, mental illness, with scheduled surgical or hospital procedures.
• Be a patient with a working relationship with the main researcher or the research center or deprived of liberty.

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• A1=Glimepiride / Vildagliptin / Metformin (1 mg/ 50 mg/ 500 mg)
Take one tablet of the prescribed dose of the investigational drug by mouth, preferably with food and in the morning. Initial dose for the first 45 days of intervention.
• B2=Glimepiride / Vildagliptin / Metformin (1 mg/ 50 mg/ 500 mg)
take one tablet of the prescribed dose of the investigational drug by mouth, preferably with food and in the morning. Initial dose for the first 45 days of intervention.
• (A2) Glimepiride/Vildagliptin/Metformin
Take one tablet of the prescribed dose of the investigational drug by mouth, preferably with food and in the morning. Escalation dose in cause the patient meets established criteria.
• (B2) Glimepiride/Vildagliptin/Metformin
Take one tablet of the prescribed dose of the investigational drug by mouth, preferably with food and in the morning. Escalation dose in cause the patient meets established criteria.

Locations

Country	Name	City	State
Mexico	Centro de Investigación Médica Aguascalientes	Aguascalientes
Mexico	Centro de Investigación y Avances Médicos Especializados	Cancún	Quintana Roo
Mexico	Mérida Investigación Clínica	Merida	Yucatan
Mexico	Oaxaca Site Management Organization SC.	Oaxaca
Mexico	Oncológico Potosino	San Luis Potosí

Sponsors (1)

Lead Sponsor	Collaborator
Laboratorios Silanes S.A. de C.V.

Country where clinical trial is conducted

Mexico, 

References & Publications (14)

American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020 Jan;43(Suppl 1):S14-S31. doi: 10.2337/dc20-S002. — View Citation

Benford M, Milligan G, Pike J, Anderson P, Piercy J, Fermer S. Fixed-dose combination antidiabetic therapy: real-world factors associated with prescribing choices and relationship with patient satisfaction and compliance. Adv Ther. 2012 Jan;29(1):26-40. doi: 10.1007/s12325-011-0096-z. Epub 2012 Jan 12. — View Citation

Bianchi C, Daniele G, Dardano A, Miccoli R, Del Prato S. Early Combination Therapy with Oral Glucose-Lowering Agents in Type 2 Diabetes. Drugs. 2017 Mar;77(3):247-264. doi: 10.1007/s40265-017-0694-4. — View Citation

Cahn A, Raz I, Kleinman Y, Balicer R, Hoshen M, Lieberman N, Brenig N, Del Prato S, Cefalu WT. Clinical Assessment of Individualized Glycemic Goals in Patients With Type 2 Diabetes: Formulation of an Algorithm Based on a Survey Among Leading Worldwide Diabetologists. Diabetes Care. 2015 Dec;38(12):2293-300. doi: 10.2337/dc15-0187. Epub 2015 Oct 30. — View Citation

Cramer JA. A systematic review of adherence with medications for diabetes. Diabetes Care. 2004 May;27(5):1218-24. doi: 10.2337/diacare.27.5.1218. — View Citation

Dennis JM, Henley WE, Weedon MN, Lonergan M, Rodgers LR, Jones AG, Hamilton WT, Sattar N, Janmohamed S, Holman RR, Pearson ER, Shields BM, Hattersley AT; MASTERMIND Consortium. Sex and BMI Alter the Benefits and Risks of Sulfonylureas and Thiazolidinediones in Type 2 Diabetes: A Framework for Evaluating Stratification Using Routine Clinical and Individual Trial Data. Diabetes Care. 2018 Sep;41(9):1844-1853. doi: 10.2337/dc18-0344. Epub 2018 Aug 2. — View Citation

Garber AJ, Handelsman Y, Grunberger G, Einhorn D, Abrahamson MJ, Barzilay JI, Blonde L, Bush MA, DeFronzo RA, Garber JR, Garvey WT, Hirsch IB, Jellinger PS, McGill JB, Mechanick JI, Perreault L, Rosenblit PD, Samson S, Umpierrez GE. CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM - 2020 EXECUTIVE SUMMARY. Endocr Pract. 2020 Jan;26(1):107-139. doi: 10.4158/CS-2019-0472. No abstract available. — View Citation

Khunti K, Kosiborod M, Ray KK. Legacy benefits of blood glucose, blood pressure and lipid control in individuals with diabetes and cardiovascular disease: Time to overcome multifactorial therapeutic inertia? Diabetes Obes Metab. 2018 Jun;20(6):1337-1341. doi: 10.1111/dom.13243. Epub 2018 Mar 11. — View Citation

Levy J, Atkinson AB, Bell PM, McCance DR, Hadden DR. Beta-cell deterioration determines the onset and rate of progression of secondary dietary failure in type 2 diabetes mellitus: the 10-year follow-up of the Belfast Diet Study. Diabet Med. 1998 Apr;15(4):290-6. doi: 10.1002/(SICI)1096-9136(199804)15:43.0.CO;2-M. — View Citation

Lukashevich V, Del Prato S, Araga M, Kothny W. Efficacy and safety of vildagliptin in patients with type 2 diabetes mellitus inadequately controlled with dual combination of metformin and sulphonylurea. Diabetes Obes Metab. 2014 May;16(5):403-9. doi: 10.1111/dom.12229. Epub 2013 Dec 2. — View Citation

Maruthur NM, Tseng E, Hutfless S, Wilson LM, Suarez-Cuervo C, Berger Z, Chu Y, Iyoha E, Segal JB, Bolen S. Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis. Ann Intern Med. 2016 Jun 7;164(11):740-51. doi: 10.7326/M15-2650. Epub 2016 Apr 19. — View Citation

Orozco-Beltran D, Mata-Cases M, Artola S, Conthe P, Mediavilla J, Miranda C. [Adherence of Type 2 Diabetes Mellitus approach: Current situation and possible solutions]. Aten Primaria. 2016 Jun-Jul;48(6):406-20. doi: 10.1016/j.aprim.2015.09.001. Epub 2016 Jan 13. Spanish. — View Citation

Rubin RR. Adherence to pharmacologic therapy in patients with type 2 diabetes mellitus. Am J Med. 2005 May;118 Suppl 5A:27S-34S. doi: 10.1016/j.amjmed.2005.04.012. — View Citation

U.K. prospective diabetes study 16. Overview of 6 years' therapy of type II diabetes: a progressive disease. U.K. Prospective Diabetes Study Group. Diabetes. 1995 Nov;44(11):1249-58. Erratum In: Diabetes 1996 Nov;45(11):1655. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compare changes in HbA1	Mean change in HbA1c	baseline, 3 and 6 months of treatment
Primary	Proportion of patients who change their HbA1c concentration	Proportion of patients who change their HbA1c by at least 1 percent	baseline, 3 and 6 months of treatment
Primary	Mean difference change between groups in HbA1c concentration	Difference greater than 0.3 between group A and B HbA1c concentration	baseline, 3 and 6 months of treatment
Secondary	Mean glucose change	Compare changes in glucose between baseline, 3 and 6 months of treatment	baseline, 3 and 6 months of treatment
Secondary	Incidence of adverse events and reactions	Description of al the adverse events and reactions presented during the study	baseline, 3 and 6 months of treatment