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:
Novo Nordisk
Information provided by:
Novo Nordisk
ClinicalTrials.gov Identifier:
NCT00184600
First received: September 13, 2005
Last updated: May 23, 2012
Last verified: May 2012
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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:
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 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 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Insulin aspart |
Insulin Insulin, Long-Acting Insulin, NPH Hypoglycemic Agents Physiological Effects of Drugs Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 19, 2013