Treatment Intensification With Biphasic Insulin Aspart 30 in Subjects With Type 2 Diabetes Inadequately Controlled on Sitagliptin and Metformin (SIT2MIX)

Novo Nordisk

Status and phase: Completed; Phase 4

Conditions: Diabetes; Diabetes Mellitus, Type 2

Treatments: Drug: biphasic insulin aspart 30; Drug: metformin; Drug: sitagliptin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01519674

BIASP-3963

2011-004930-33 (EudraCT Number)

U1111-1125-0850 (Other Identifier)

Details and patient eligibility

About

This trial is conducted in Asia, Europe, Oceania and South America. The aim of this clinical trial is to generate data demonstrating how to intensify diabetes treatment using BIAsp 30 (biphasic insulin aspart 30) by adding or substituting BIAsp 30 to sitagliptin in various regimens for type 2 patients inadequately controlled on sitagliptin and metformin (with or without other oral anti-diabetic drugs (OADs)).

The trial is conducted as a phase 4 trial in the majority of the participating countries. However, in some countries the trial is conducted as phase 3b.

Enrollment: 582 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosed with type 2 diabetes for a minimum of 6 months prior to screening (Visit 1)
• Stable treatment with a total daily dose of at least 1000 mg of metformin (with or without additional oral anti-diabetic drugs (OADs) treatment). The metformin dose must have been unchanged for at least 3 months prior to screening (Visit 1)
• Stable treatment with a total daily dose of at least 100 mg sitagliptin. The sitagliptin dose must have been unchanged for at least 3 months prior to screening (Visit 1)
• Subject is insulin-naïve (never previously treated with insulin). (However, short term insulin use due to intermittent illness of up to 14 days or insulin treatment for gestational diabetes is allowed)
• HbA1c (glycosylated haemoglobin) between 7.0 to 10.0 % (53-86 mmol/mol) (both inclusive) by central laboratory analysis demonstrating inadequate control on sitagliptin and metformin (with or without other OADs)
• Body Mass Index (BMI) below or equal to 40.0 kg/m^2
• Able and willing to eat at least 2 meals (breakfast and dinner) every day during the trial

Exclusion criteria

• Treatment with thiazolidinedione (TZD) or glucagon-like-peptide-1 (GLP-1) receptor agonist within the last 3 months prior to screening (Visit 1)
• Cardiac disease within the last 6 months prior to screening (Visit 1), defined as: decompensated heart failure New York Heart Association (NYHA) class III or IV; unstable angina pectoris; or myocardial infarction
• Severe hypertension, systolic blood pressure equal to or above 180 mm Hg or diastolic blood pressure equal to or above 100 mm Hg, after 5 minutes rest in the sitting position using mean value of 3 measurements at screening (Visit 1)
• Anticipated change of dose of any systemic treatment with products, which in the trial physician's opinion could interfere with glucose metabolism (e.g., systemic corticosteroids)
• Clinically significant diseases (except for conditions associated with type 2 diabetes) which, in the trial physician's opinion may confound the results of the trial or pose additional risk in administering trial product(s)
• Impaired hepatic function as indicated by aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) above 2.5 times the upper normal range, according to central laboratory reference ranges
• Impaired renal function as indicated by serum creatinine levels equal to or above 133 micromol/L (1.5 mg/dL) for males and equal to or above 124 micromol/L (1.4 mg/dL) for females or estimated creatinine clearance below 60 mL/min, based on the Cockroft & Gault formula and according to local practise for metformin use

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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582 participants in 3 patient groups

BIAsp 30 BID + sitagliptin + metformin

Active Comparator group

Treatment:

Drug: biphasic insulin aspart 30

Drug: sitagliptin

Drug: metformin

Drug: biphasic insulin aspart 30

BIAsp 30 BID + metformin

Active Comparator group

Treatment:

Drug: biphasic insulin aspart 30

Drug: metformin

Drug: biphasic insulin aspart 30

BIAsp 30 OD + sitagliptin + metformin

Active Comparator group

Treatment:

Drug: biphasic insulin aspart 30

Drug: sitagliptin

Drug: metformin

Drug: biphasic insulin aspart 30