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

Diabetes Mellitus, Type 2 Clinical Trial

— 4T  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00184600
• Other study ID #: NN304-1613
• Secondary ID: 2004-000514-38
• Status: Completed
• Phase: Phase 3
• First received: September 13, 2005
• Last updated: May 23, 2012
• Start date: November 2004
• Est. completion date: August 2009

Study information

• Verified date: May 2012
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Health authority: Ireland: Irish Medicines BoardUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 708
• Est. completion date: August 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• biphasic insulin aspart
Treat-to-target (individually adjusted dose), subcutaneously (under the skin) injection, once or twice daily plus option for insulin aspart
• insulin detemir
Treat-to-target (individually adjusted dose), subcutaneously (under the skin) injection, once or twice daily plus option for insulin aspart
• insulin aspart
Treat-to-target (individually adjusted dose), subcutaneously (under the skin) injection, twice daily plus option for insulin detemir

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

Ireland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HbA1c (Glycosylated Haemoglobin) at Month 12	HbA1c values offer evidence of the efficacy and durability of the insulin regimens.	Baseline, Month 12	No
Primary	HbA1c (Glycosylated Haemoglobin) at Month 36	HbA1c values offer evidence of the efficacy and durability of the insulin regimens.	Baseline, Month 36	No
Secondary	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%	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.	Month 12	No
Secondary	Percentage of Participants Achieving a Month 36 Value in HbA1c Below or Equal to 6.5%	Percentage of participants who achieved the target (HbA1c below or equal to 6.5%) at Month 36	Month 36	No
Secondary	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%	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%.	Month 12	No
Secondary	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%	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%.	Month 36	No
Secondary	Percentage of Participants Who Required A Second Insulin Therapy by Month 12	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.	Month 12	No
Secondary	Percentage of Participants Who Required A Second Insulin Therapy by Month 36	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.	Month 36	No
Secondary	Change From Baseline in Body Weight at Month 12		Week 0 (baseline), month 12	No
Secondary	Change From Baseline in Body Weight at Month 36		Week 0 (baseline), month 36	No
Secondary	Change in Eight-point Capillary Plasma Glucose Profiles (Self-measured) at 12 Months	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.	Baseline, month 12	No
Secondary	Change in Eight-point Capillary Plasma Glucose Profiles (Self-measured) at 36 Months	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.	Baseline, month 36	No
Secondary	Quality of Life as Measured by the EuroQol Group 5-Dimension Self-Report Questionnaire Score (EQ5D) at 12 Months	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.	Month 12	No
Secondary	Quality of Life as Measured by the EuroQol Group 5-Dimension Self-Report Questionnaire Score (EQ5D) at 36 Months	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.	Month 36	No
Secondary	Number of Participants Having an 'Other' Adverse Event		Up to month 37 (36 months of treatment plus 1 month follow-up)	No

External Links

•   Clinical Trials at Novo Nordisk