Effect of Different Insulin Administrations, All in Combination With Metformin, on Glycaemic Control in Subjects With Type 2 Diabetes Inadequately Controlled by Oral Anti-diabetic Drugs

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Effect of 50-week Treatment With Stepwise Insulin Intensification of Basal-bolus Insulin Analogues (Insulin Detemir and Aspart) or Biphasic Insulin Aspart 30 (NovoMix 30) All in Combination With Fixed Dose of Metformin on Glycaemic Control (Measured as HbA1c) in Subjects With Type 2 Diabetes. Open Labelled, Randomized, Two-arm, Parallel Group, Multi-centre, Multi-national Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01068652
• Other study ID #: INS-3782
• Secondary ID: U1111-1112-6407
• Status: Completed
• Phase: Phase 4
• First received: February 12, 2010
• Last updated: November 15, 2013
• Start date: March 2010
• Est. completion date: May 2012

Study information

• Verified date: November 2013
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Africa: Medicines Control CouncilAlgeria: Ministry of HealthEgypt: Ministry of Health and PopulationTunisia: Ministry of Public Health
• Study type: Interventional

Clinical Trial Summary

This trial is conducted in Africa. The aim of this clinical trial is to investigate the effect of 50 weeks of treatment with different intensified insulin administrations (all in combination with a fixed dose of metformin) on blood sugar control in subjects with type 2 diabetes inadequately controlled by oral anti-diabetic drugs (OADs).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 403
• Est. completion date: May 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject)

• Diagnosed type 2 diabetes (WHO 1999 criteria)

• Currently treated with suboptimal daily dose of OADs (mono or combination therapy) for at least 6 months

• Male or female age at least 18 years old

• HbA1c at least 7.0 % and maximum 11.0% for subjects treated with metformin mono-therapy, or maximum 10% for subjects treated with OAD combination therapy

• BMI maximum 40 kg/m^2

• Able and willing to perform self-monitoring of plasma glucose according to the protocol and to keep a diary

• Able and willing to be treated with up to 4 insulin injections per day

Exclusion Criteria:

• Known or suspected allergy to trial product(s) or related products

• Previous participation in this trial. Participation is defined as randomisation

• Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (adequate contraceptive measures as required by local law or practice)

• Participated in another clinical trial and received an investigational drug within the last weeks prior to the present trial

• Impaired hepatic function defined as alanine aminotransferase (ALT) or alkaline phosphatase (ALP) at least 2.5 times upper referenced limit

• Impaired renal function defined as serum-creatinine at least 1.3 mg/dL (at least 115 mmol/L) for males and at least 1.2 mg/dL (at least 106 mmol/L) for females

• Subject has a clinically significant, active (or over the past 12 months) cardiovascular history (including a history of myocardial infarction (MI), arrhythmias or conduction delays on ECG, unstable angina, or decompensated heart failure (New York Heart Association class III and IV)

• Severe uncontrolled treated or untreated hypertension (sitting systolic blood pressure at least 180 mmHg or sitting diastolic blood pressure at least 100 mmHg)

• Proliferative retinopathy or macular oedema requiring acute treatment

• Metformin contraindications according to the package insert

• Current treatment with systemic corticosteroids

• Subject has a history of any illness that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering study drug to the subject

• Current addiction to alcohol or other addictive substances as determined by the Investigator

• Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation in the study or use of the glucose monitor

• History of hypoglycaemic unawareness and/or two or more severe hypoglycaemic episodes in the past year as judged by the Investigator

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:
• insulin detemir
Initial dose of 0.1 U/kg once daily, injected s.c. (under the skin).
• insulin aspart
Pending evaluation of HbA1c every 3 months, insulin aspart was added to the insulin detemir treatment (up to three does daily, injected s.c. (under the skin)
• biphasic insulin aspart 30
Initial dose of 0.1 U/kg once daily, injected s.c. (under the skin). Pending evaluation of HbA1c every 3 months, the dose will intensified up to 3 doses daily
• metformin
1000-2000 mg/day in combination with insulin treatment

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

Algeria,  Egypt,  South Africa,  Tunisia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glycosylated Haemoglobin (HbA1c)	Estimated mean difference in HbA1c after 50 weeks of treatment	Week 50	No
Secondary	Change in Glycosylated Haemoglobin (HbA1c) After 14 Weeks of Treatment	Observed mean change from baseline in HbA1c at Week 14 (visit 11)	Week 0, Week 14	No
Secondary	Change in Glycosylated Haemoglobin (HbA1c) After 26 Weeks of Treatment	Observed mean change in from baseline in HbA1c at Week 26 (visit 18)	Week 0, Week 26	No
Secondary	Change in Glycosylated Haemoglobin (HbA1c) After 38 Weeks of Treatment	Observed mean change from baseline in HbA1c at Week 38 (visit 25)	Week 0, Week 38	No
Secondary	Change in Glycosylated Haemoglobin (HbA1c) at Week 50	Observed mean change from baseline in HbA1c at Week 50 (visit 32)	Week 0, Week 50	No
Secondary	Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 14 Weeks of Treatment	Number of subjects achieving HbA1c below 7.0% after 14 weeks of treatment (visit 11)	Week 14	No
Secondary	Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 26 Weeks of Treatment	Number of subjects achieving HbA1c below 7.0% after 26 weeks of treatment (visit 18)	Week 26	No
Secondary	Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 38 Weeks of Treatment	Number of subjects achieving HbA1c below 7.0% after 38 weeks of treatment (visit 25)	Week 38	No
Secondary	Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 50 Weeks of Treatment	Number of subjects achieving HbA1c below 7.0% after 50 weeks of treatment (visit 32)	Week 50	No
Secondary	Mean of Prandial Plasma Glucose (PG) Increment After 14 Weeks of Treatment	Observed overall mean of PG increment after 14 weeks of treatment (Visit 11). Mean PG Increment was calculated using the average of difference between the Post Prandial and Pre Prandial Glucose values {ie .average of (Post Breakfast - Pre Breakfast), (Post Lunch - Pre Lunch) and (Post Dinner - Pre Dinner)}	Week 14	No
Secondary	Mean of Prandial Plasma Glucose (PG) Increment After 26 Weeks of Treatment	Observed overall mean of PG increment after 26 weeks of treatment (visit 18). Mean PG Increment was calculated using the average of difference between the Post Prandial and Pre Prandial Glucose values {ie .average of (Post Breakfast - Pre Breakfast), (Post Lunch - Pre Lunch) and (Post Dinner - Pre Dinner)}	Week 26	No
Secondary	Mean of Prandial Plasma Glucose (PG) Increment After 38 Weeks of Treatment	Observed overall mean of PG increment after 38 weeks of treatment (visit 25). Mean PG Increment was calculated using the average of difference between the Post Prandial and Pre Prandial Glucose values {ie .average of (Post Breakfast - Pre Breakfast), (Post Lunch - Pre Lunch) and (Post Dinner - Pre Dinner)}.	Week 38	No
Secondary	Mean of Prandial Plasma Glucose (PG) Increment After 50 Weeks of Treatment	Observed overall mean of PG increment after 50 weeks of treatment (visit 32). Mean PG Increment was calculated using the average of difference between the Post Prandial and Pre Prandial Glucose values {ie .average of (Post Breakfast - Pre Breakfast), (Post Lunch - Pre Lunch) and (Post Dinner - Pre Dinner)}.	Week 50	No
Secondary	Mean of 8-point Plasma Glucose (PG) Profile After 14 Weeks of Treatment	Observed overall mean of 8-point PG profile after 14 weeks of treatment (visit 11)	Week 14	No
Secondary	Mean of 8-point Plasma Glucose (PG) Profile After 26 Weeks of Treatment	Observed overall mean of 8-point PG profile after 26 weeks of treatment (visit 18)	Week 26	No
Secondary	Mean of 8-point Plasma Glucose (PG) Profile After 38 Weeks of Treatment	Observed overall mean of 8-point PG profile after 38 weeks of treatment (visit 25)	Week 38	No
Secondary	Mean of 8-point Plasma Glucose (PG) Profile After 50 Weeks of Treatment	Observed overall mean of 8-point PG profile after 50 weeks of treatment (visit 32)	Week 50	No

External Links

•   Clinical Trials at Novo Nordisk