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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT01519674
First received: January 24, 2012
Last updated: October 22, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Diabetes
Diabetes Mellitus, Type 2
Drug: biphasic insulin aspart 30
Drug: sitagliptin
Drug: metformin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A 24 Week Randomised, Open Label, 3 Parallel-group Comparison of Once and Twice Daily Biphasic Insulin Aspart (BIAsp) 30 Plus Sitagliptin and Twice Daily BIAsp 30, All in Combination With Metformin in Insulin naïve Type 2 Diabetic Subjects Inadequately Controlled on Sitagliptin and Metformin

Resource links provided by NLM:


Further study details as provided by Novo Nordisk A/S:

Primary Outcome Measures:
  • Change from baseline in HbA1c (glycosylated haemoglobin) [ Time Frame: Week 0, week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Responder for HbA1c, proportion of subjects achieving pre-defined HbA1c targets [ Time Frame: After 24 weeks of treatment ] [ Designated as safety issue: No ]
  • Change from baseline in fasting plasma glucose (FPG) [ Time Frame: Week 0, week 24 ] [ Designated as safety issue: No ]
  • Prandial plasma glucose (PPG) increments at each meal (breakfast, lunch and dinner) and overall mean increment [ Time Frame: After 24 weeks of treatment ] [ Designated as safety issue: No ]
  • Adverse Events (AEs) [ Time Frame: Weeks 0-24 ] [ Designated as safety issue: No ]
  • Number of treatment emergent hypoglycaemic episodes (nocturnal and day-time) classified both according to the American Diabetes Association (ADA) definition and to an additional definition for minor episodes [ Time Frame: Weeks 0-24 ] [ Designated as safety issue: No ]
  • Change from baseline in Patient Reported Outcome by use of the Treatment Related Impact Measure - Diabetes [ Time Frame: Week 0, week 24 ] [ Designated as safety issue: No ]

Enrollment: 582
Study Start Date: June 2012
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: BIAsp 30 twice daily + sitagliptin + metformin Drug: biphasic insulin aspart 30
BIAsp 30 will be injected subcutaneously (under the skin) twice daily. Individually adjusted dose.
Drug: sitagliptin
Subjects will continue on their pre-trial sitagliptin treatment.
Drug: metformin
Subjects will continue on their pre-trial metformin treatment.
Active Comparator: BIAsp 30 twice daily + metformin Drug: biphasic insulin aspart 30
BIAsp 30 will be injected subcutaneously (under the skin) twice daily. Individually adjusted dose.
Drug: metformin
Subjects will continue on their pre-trial metformin treatment.
Active Comparator: BIAsp 30 once daily + sitagliptin + metformin Drug: biphasic insulin aspart 30
BIAsp 30 will be injected subcutaneously (under the skin) once daily. Individually adjusted dose.
Drug: sitagliptin
Subjects will continue on their pre-trial sitagliptin treatment.
Drug: metformin
Subjects will continue on their pre-trial metformin treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01519674

Locations
Argentina
Buenos Aires, Argentina, B1704ETD
Australia, New South Wales
Broadmeadow, New South Wales, Australia, 2292
Brazil
Porto Alegre, Brazil, 90035-170
Greece
Athens, Greece, 17562
India
Bangalore, Karnataka, India, 560043
Korea, Republic of
Seoul, Korea, Republic of, 110-744
Malaysia
Penang, Malaysia, 10459
Portugal
Lisboa, Portugal, 1649-035
Thailand
Bangkok, Thailand, 10400
Turkey
Istanbul, Turkey, 34360
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
Study Director: Global Clinical Registry (GCR, 1452) Novo Nordisk A/S
  More Information

Additional Information:
No publications provided

Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT01519674     History of Changes
Other Study ID Numbers: BIASP-3963, U1111-1125-0850, 2011-004930-33
Study First Received: January 24, 2012
Last Updated: October 22, 2013
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia
Australia: Department of Health and Ageing Therapeutic Goods Administration
Brazil: National Health Surveillance Agency
India: Ministry of Health
Greece: Ministry of Health
South Korea: Korea Food and Drug Administration (KFDA)
Malaysia: Ministry of Health
Portugal: INFARMED
Thailand: Thai FDA
Turkey: Ministry of Health

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Sitagliptin
Insulin aspart, insulin aspart protamine drug combination 30:70
Insulin
Metformin
Insulin Aspart
Biphasic Insulins
Insulin, Isophane
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2014