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Comparison of Insulin Detemir, Insulin Aspart and Biphasic Insulin Aspart 30 With OAD Treatment in Type 2 Diabetes (4T)

This study has been completed.
Sponsor:
Information provided by:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT00184600
First received: September 13, 2005
Last updated: May 23, 2012
Last verified: May 2012
  Purpose

This trial is conducted in Europe.

The aim of this research study is to compare the efficacy (reduction in HbA1c and in blood glucose levels) of insulin detemir, insulin aspart and biphasic insulin aspart 30, when added to current OAD (oral anti-diabetic drug) treatment in subjects with type 2 diabetes and to verify the safety of use (number and severity of episodes of hypoglycaemia, body weight and side effects).


Condition Intervention Phase
Diabetes
Diabetes Mellitus, Type 2
Drug: biphasic insulin aspart
Drug: insulin detemir
Drug: insulin aspart
Phase 3

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 36-month, Multi-centre, Open-label, Randomised, Parallel-group Trial Comparing the Safety, Efficacy and Durability of Adding a Basal Insulin Versus a Twice Daily Insulin Mixture Versus a Meal-time Rapid-Acting Insulin in Subjects With Type 2 Diabetes Inadequately Controlled on Therapy With Oral Agents, and Assessing the Requirement for More Complex Insulin Regimens to Achieve and Maintain Glycaemic Control, Their Efficacy and Durability

Resource links provided by NLM:


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

Primary Outcome Measures:
  • HbA1c (Glycosylated Haemoglobin) at Month 12 [ Time Frame: Baseline, Month 12 ] [ Designated as safety issue: No ]
    HbA1c values offer evidence of the efficacy and durability of the insulin regimens.

  • HbA1c (Glycosylated Haemoglobin) at Month 36 [ Time Frame: Baseline, Month 36 ] [ Designated as safety issue: No ]
    HbA1c values offer evidence of the efficacy and durability of the insulin regimens.


Secondary Outcome Measures:
  • Percentage of Participants (Total Participants and the Subset of Participants Who Did Not Have an Hypoglycaemic Episode) Achieving a Month 12 Value in HbA1c Below or Equal to 6.5% [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    Two participant counts are listed. The first is the percentage of total participants who achieved the target (HbA1c below or equal to 6.5%) at Month 12. The second is the percentage of subset of participants who achieved the target and did not have either minor or major hypoglycaemic episode within the four weeks prior to the month 12 exam. Minor hypoglycaemic episode is an episode in which the participant was able to treat her/himself and plasma glucose was below 3.1 mmol/L (56 mg/dL). Major hypoglycaemic episode is an episode in which the participant was unable to treat her/himself.

  • Percentage of Participants Achieving a Month 36 Value in HbA1c Below or Equal to 6.5% [ Time Frame: Month 36 ] [ Designated as safety issue: No ]
    Percentage of participants who achieved the target (HbA1c below or equal to 6.5%) at Month 36

  • Number of Hypoglycaemic Events Per Participant Per Year at Month 12 for All Participants and the Subset Who Achieved Target HbA1c Below or Equal to 6.5% [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    Rate of hypoglycaemic events was calculated as the median number of events per participant per year, defined as grade 1 (symptoms only), 2 (minor) and 3 (major). Symptoms only if self-measured plasma glucose level of 3.1 mmol/L (56 mg/dL) or more. Minor (grade 2) if able to treat her/himself and plasma glucose was below 3.1 mmol/L (56 mg/dL). Major (grade 3) if unable to treat her/himself. Rates are reported for all participants and for the subset of participants who achieved target HbA1c below or equal to 6.5%.

  • Number of Hypoglycaemic Events Per Participant Per Year at Month 36 for All Participants and the Subset Who Achieved Target HbA1c Below or Equal to 6.5% [ Time Frame: Month 36 ] [ Designated as safety issue: No ]
    Rate of hypoglycaemic events was calculated as the median number of events per participant per year, defined as grade 1 (symptoms only), 2 (minor) and 3 (major). Symptoms only if self-measured plasma glucose level of 3.1 mmol/L (56 mg/dL) or more. Minor (grade 2) if able to treat her/himself and plasma glucose was below 3.1 mmol/L (56 mg/dL). Major (grade 3) if unable to treat her/himself. Rates are reported for all participants and for the subset of participants who achieved target HbA1c below or equal to 6.5%.

  • Percentage of Participants Who Required A Second Insulin Therapy by Month 12 [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    Percentage of participants who required a second insulin formulation to be added to their treatment. This outcome offers evidence to the efficacy and durability of the insulin regimens.

  • Percentage of Participants Who Required A Second Insulin Therapy by Month 36 [ Time Frame: Month 36 ] [ Designated as safety issue: No ]
    Percentage of participants who required a second insulin formulation to be added to their treatment. This outcome offers evidence to the efficacy and durability of the insulin regimens.

  • Change From Baseline in Body Weight at Month 12 [ Time Frame: Week 0 (baseline), month 12 ] [ Designated as safety issue: No ]
  • Change From Baseline in Body Weight at Month 36 [ Time Frame: Week 0 (baseline), month 36 ] [ Designated as safety issue: No ]
  • Change in Eight-point Capillary Plasma Glucose Profiles (Self-measured) at 12 Months [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: No ]
    For each visit and telephone contact, participants were asked to perform in advance three capillary glucose profiles (using blood glucose metre provided for the trial) obtained before breakfast and before the evening meal for participants in the biphasic and basal groups and before meals and two hours after meals and at bedtime in the prandial group.

  • Change in Eight-point Capillary Plasma Glucose Profiles (Self-measured) at 36 Months [ Time Frame: Baseline, month 36 ] [ Designated as safety issue: No ]
    For each visit and telephone contact, participants were asked to perform in advance three capillary glucose profiles (using blood glucose metre provided for the trial) obtained before breakfast and before the evening meal for participants in the biphasic and basal groups and before meals and two hours after meals and at bedtime in the prandial group.

  • Quality of Life as Measured by the EuroQol Group 5-Dimension Self-Report Questionnaire Score (EQ5D) at 12 Months [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    The EuroQol Group 5-Dimension Self-Report Questionnaire score (EQ5D) is a standardised instrument for use as a measure of health outcome in medical research. Responses can be used to generate a single numerical value associated with a given health state. The scale of values is graded from -0.59 to 1.00, with lower scores indicating a poorer health status. A score of 0 represents no quality of life and scores less than 0 represent states perceived by the respondent to be worse than death.

  • Quality of Life as Measured by the EuroQol Group 5-Dimension Self-Report Questionnaire Score (EQ5D) at 36 Months [ Time Frame: Month 36 ] [ Designated as safety issue: No ]
    The EuroQol Group 5-Dimension Self-Report Questionnaire score (EQ5D) is a standardised instrument for use as a measure of health outcome in medical research. Responses can be used to generate a single numerical value associated with a given health state. The scale of values is graded from -0.59 to 1.00, with lower scores indicating a poorer health status. A score of 0 represents no quality of life and scores less than 0 represent states perceived by the respondent to be worse than death.

  • Number of Participants Having an 'Other' Adverse Event [ Time Frame: Up to month 37 (36 months of treatment plus 1 month follow-up) ] [ Designated as safety issue: No ]

Enrollment: 708
Study Start Date: November 2004
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Insulin detemir (basal insulin)
Individually adjusted insulin detemir injected subcutaneously once daily before bed and administered in combination with current OAD treatment. Subjects had the option to add a second pre-breakfast basal insulin analogue injection if pre-breakfast but not pre-dinner meal plasma glucose targets were met. In the second and third years, a second insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin detemir once (or twice) daily were asked to add insulin aspart three times daily with meals i.e. a basal-bolus insulin analogue regimen.
Drug: insulin detemir
Treat-to-target (individually adjusted dose), subcutaneously (under the skin) injection, once or twice daily plus option for insulin aspart
Active Comparator: Insulin aspart (prandial insulin)
Individually adjusted insulin aspart injected subcutaneously at meal-times (breakfast, lunch and dinner) and administered in combination with current OAD treatment. In the second and third years, a second insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin aspart three times a day with meals were asked to add insulin detemir once or twice daily i.e. a basal-bolus insulin analogue regimen.
Drug: biphasic insulin aspart
Treat-to-target (individually adjusted dose), subcutaneously (under the skin) injection, once or twice daily plus option for insulin aspart
Active Comparator: Biphasic insulin aspart 30 (biphasic insulin)
Individually adjusted biphasic insulin aspart 30 injected subcutaneously twice daily with meals (breakfast and dinner) and administered in combination with current OAD treatment. In the second and third years, a second insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to biphasic insulin aspart twice daily were asked to add insulin aspart at lunchtime (midday) i.e. an augmented pre-mixed insulin analogue regimen.
Drug: insulin aspart
Treat-to-target (individually adjusted dose), subcutaneously (under the skin) injection, twice daily plus option for insulin detemir

  Eligibility

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

Inclusion Criteria:

  • Type 2 diabetes
  • Insulin naive
  • On OAD treatment for at least 4 months with metformin, a sulphonylurea or a combination
  • Body Mass Index (BMI) below or equal to 40.0 kg/m2
  • HbA1c (glycosylated haemoglobin): 7.0%-10% (both inclusive)

Exclusion Criteria:

  • Proliferative retinopathy
  • Recurrent major hypoglycaemia
  • Cardial problems
  • Uncontrolled hypertension
  • Impaired hepatic or renal function
  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: NCT00184600

Locations
Ireland
Dublin, Ireland
United Kingdom
Oxford, United Kingdom
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
Study Director: Jens Larsen, MD Novo Nordisk A/S
  More Information

Additional Information:
No publications provided

Responsible Party: Public Access to Clinical Trials, Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT00184600     History of Changes
Other Study ID Numbers: NN304-1613, 2004-000514-38
Study First Received: September 13, 2005
Results First Received: May 10, 2011
Last Updated: May 23, 2012
Health Authority: Ireland: Irish Medicines Board
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Biphasic Insulins
Insulin
Insulin Aspart
Insulin aspart, insulin aspart protamine drug combination 30:70
Insulin, Globin Zinc
Insulin, Isophane
Insulin, Long-Acting
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 24, 2014