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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT01068652
First received: February 12, 2010
Last updated: November 15, 2013
Last verified: November 2013
  Purpose

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).


Condition Intervention Phase
Diabetes
Diabetes Mellitus, Type 2
Drug: insulin detemir
Drug: insulin aspart
Drug: biphasic insulin aspart 30
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: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Glycosylated Haemoglobin (HbA1c) [ Time Frame: Week 50 ] [ Designated as safety issue: No ]
    Estimated mean difference in HbA1c after 50 weeks of treatment


Secondary Outcome Measures:
  • Change in Glycosylated Haemoglobin (HbA1c) After 14 Weeks of Treatment [ Time Frame: Week 0, Week 14 ] [ Designated as safety issue: No ]
    Observed mean change from baseline in HbA1c at Week 14 (visit 11)

  • Change in Glycosylated Haemoglobin (HbA1c) After 26 Weeks of Treatment [ Time Frame: Week 0, Week 26 ] [ Designated as safety issue: No ]
    Observed mean change in from baseline in HbA1c at Week 26 (visit 18)

  • Change in Glycosylated Haemoglobin (HbA1c) After 38 Weeks of Treatment [ Time Frame: Week 0, Week 38 ] [ Designated as safety issue: No ]
    Observed mean change from baseline in HbA1c at Week 38 (visit 25)

  • Change in Glycosylated Haemoglobin (HbA1c) at Week 50 [ Time Frame: Week 0, Week 50 ] [ Designated as safety issue: No ]
    Observed mean change from baseline in HbA1c at Week 50 (visit 32)

  • Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 14 Weeks of Treatment [ Time Frame: Week 14 ] [ Designated as safety issue: No ]
    Number of subjects achieving HbA1c below 7.0% after 14 weeks of treatment (visit 11)

  • Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 26 Weeks of Treatment [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    Number of subjects achieving HbA1c below 7.0% after 26 weeks of treatment (visit 18)

  • Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 38 Weeks of Treatment [ Time Frame: Week 38 ] [ Designated as safety issue: No ]
    Number of subjects achieving HbA1c below 7.0% after 38 weeks of treatment (visit 25)

  • Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 50 Weeks of Treatment [ Time Frame: Week 50 ] [ Designated as safety issue: No ]
    Number of subjects achieving HbA1c below 7.0% after 50 weeks of treatment (visit 32)

  • Mean of Prandial Plasma Glucose (PG) Increment After 14 Weeks of Treatment [ Time Frame: Week 14 ] [ Designated as safety issue: No ]
    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)}

  • Mean of Prandial Plasma Glucose (PG) Increment After 26 Weeks of Treatment [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    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)}

  • Mean of Prandial Plasma Glucose (PG) Increment After 38 Weeks of Treatment [ Time Frame: Week 38 ] [ Designated as safety issue: No ]
    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)}.

  • Mean of Prandial Plasma Glucose (PG) Increment After 50 Weeks of Treatment [ Time Frame: Week 50 ] [ Designated as safety issue: No ]
    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)}.

  • Mean of 8-point Plasma Glucose (PG) Profile After 14 Weeks of Treatment [ Time Frame: Week 14 ] [ Designated as safety issue: No ]
    Observed overall mean of 8-point PG profile after 14 weeks of treatment (visit 11)

  • Mean of 8-point Plasma Glucose (PG) Profile After 26 Weeks of Treatment [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    Observed overall mean of 8-point PG profile after 26 weeks of treatment (visit 18)

  • Mean of 8-point Plasma Glucose (PG) Profile After 38 Weeks of Treatment [ Time Frame: Week 38 ] [ Designated as safety issue: No ]
    Observed overall mean of 8-point PG profile after 38 weeks of treatment (visit 25)

  • Mean of 8-point Plasma Glucose (PG) Profile After 50 Weeks of Treatment [ Time Frame: Week 50 ] [ Designated as safety issue: No ]
    Observed overall mean of 8-point PG profile after 50 weeks of treatment (visit 32)


Enrollment: 403
Study Start Date: March 2010
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Detemir + Met
Individually adjusted insulin detemir (Detemir) was given subcutaneoulsy (s.c.) at bedtime in the thigh at an initial dose of 0.1 U/kg once daily for 50 weeks in combination with 1000-2000 mg/day metformin (Met). Pending evaluation of HbA1c every 3 months, individually adjusted insulin aspart was added to the insulin detemir treatment (up to three doses daily for maximum 36 weeks, injected s.c. [under the skin]) if treatment target of HbA1c below 7.0% was not reached.
Drug: insulin detemir
Initial dose of 0.1 U/kg once daily, injected s.c. (under the skin).
Drug: 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)
Drug: metformin
1000-2000 mg/day in combination with insulin treatment
Active Comparator: BIAsp 30 + Met
Individually adjusted biphasic insulin aspart 30 (BIAsp 30) was given subcutaneously (s.c.) in the abdomen at dinner at an initial dose of 0.1 U/kg once daily for 50 weeks in combination with 1000-2000 mg/day metformin (Met). Pending evaluation of HbA1c every 3 months, the dose was intensified up to 3 doses daily, injected s.c. (under the skin) if treatment target of HbA1c below 7.0% was not reached.
Drug: 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
Drug: metformin
1000-2000 mg/day in combination with insulin treatment

  Eligibility

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

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
  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: NCT01068652

Locations
Algeria
Setif, Algeria, 19000
Egypt
Alexandria, Egypt, 21599
South Africa
Port Elizabeth, Eastern Cape, South Africa, 6014
Tunisia
Tunisia, Tunisia, 1053
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
Study Director: Timothy Kedijang, MD Novo Nordisk Pty. Ltd.
  More Information

Additional Information:
No publications provided

Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT01068652     History of Changes
Other Study ID Numbers: INS-3782, U1111-1112-6407
Study First Received: February 12, 2010
Results First Received: February 26, 2013
Last Updated: November 15, 2013
Health Authority: South Africa: Medicines Control Council
Algeria: Ministry of Health
Egypt: Ministry of Health and Population
Tunisia: Ministry of Public Health

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

ClinicalTrials.gov processed this record on September 22, 2014