Insulin Glargine "All to Target" Trial - Full Text View

Sponsor:	Sanofi-Aventis
Information provided by:	Sanofi-Aventis
ClinicalTrials.gov Identifier:	NCT00384085

Purpose

The primary objectives were:

To demonstrate the superiority of Lantus plus stepwise addition of mealtime Apidra® (Lantus/Apidra-3) versus twice-daily Premixed insulin based on the proportion of patients achieving target glycemic control (as measured by hemoglobin A1c [HbA1c] <7.0%) at Week 60
To demonstrate the noninferiority of Lantus plus addition of 1 mealtime Apidra injection (Lantus/Apidra-1) versus twice-daily Premixed insulin based on the reduction from Baseline to Week 60 in HbA1c

Condition	Intervention	Phase
Diabetes Mellitus, Type 2	Drug: Insulin Glulisine Drug: Insulin Glargine Drug: Premixed Insulin	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	All to Target Trial Lantus® (Insulin Glargine) With Stepwise Addition of APIDRA® (Insulin Glulisine) or Lantus With One Injection of Apidra vs a Twice-Daily Premixed Insulin Regimen (Novolog® Mix 70/30) in Adult Subjects With Type 2 Diabetes Failing Dual or Triple Therapy With Oral Agents: a 64-week, Multi-center, Randomized, Parallel, Open-label Clinical Study.

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Diabetes Medicines Diabetes Type 2

Drug Information available for: Insulin Insulin beef Insulin aspart Insulin glargine Insulin glulisine

U.S. FDA Resources

Further study details as provided by Sanofi-Aventis:

Primary Outcome Measures:

Percentage of Patients Achieving Glycosylated Hemoglobin A1c (HbA1c) < 7.0% at Week 60 (Lantus/Apidra-3 Versus Novolog Mix 70/30 - Intent To Treat (ITT) Population Without Good Clinical Practices (GCP) Noncompliant Sites) [ Time Frame: At week 60 ] [ Designated as safety issue: No ]
Responders defined as patients who achieved an HbA1c value <7.0% versus nonresponders. Patients who did not achieve an HbA1c value <7.0% and patients with a missing HbA1c value at Week 60 were considered to be nonresponders.
Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Week 60 (Lantus/Apidra-1 Versus Novolog Mix 70/30)Per Protocol Population [ Time Frame: At week 60 ] [ Designated as safety issue: No ]
Absolute Change in HbA1c from Baseline to Week 60. If the Week 60 HbA1c evaluation was missing, the patient was counted as having not completed per protocol.
Percentage of Patients Achieving Glycosylated Hemoglobin A1c (HbA1c) < 7.0% at Week 60 (Lantus/Apidra-3 Versus Novolog Mix 70/30 - ITT Population With All Sites) (Sensitivity Analysis) [ Time Frame: At week 60 ] [ Designated as safety issue: No ]
Responders defined as patients who achieved an HbA1c value <7.0% versus nonresponders. Patients who did not achieve an HbA1c value <7.0% and patients with a missing HbA1c value at Week 60 were considered to be nonresponders.

Secondary Outcome Measures:

Absolute Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Week 60 (Lantus/Apidra-3 Versus Novolog Mix 70/30) [ Time Frame: From baseline to week 60 ] [ Designated as safety issue: No ]
Absolute Change in HbA1c from Baseline to Week 60.
Percentage of Patients Achieving Glycosylated Hemoglobin A1c (HbA1c) <7.0% at Week 60 (Lantus/Apidra-1 Versus Novolog Mix 70/30) [ Time Frame: At week 60 ] [ Designated as safety issue: No ]
Patients who achieved an HbA1c value <7.0% were defined as responders. Patients who did not achieve HbA1c values <7.0% and patients with missing HbA1c values were considered nonresponders.
Percentage of Patients Achieving Glycosylated Hemoglobin A1c (HbA1c) <7.0% at Week 60 Without a Severe Hypoglycemic Event or a Symptomatic Hypoglycemic Event With an Self Monitoring Blood Glucose (SMBG) <50 mg/dl [ Time Frame: At week 60 ] [ Designated as safety issue: No ]
Severe hypoglycemia was defined as an event with clinical symptoms that are considered to result from hypoglycemia in which the patient required assistance of another person and one of the following: the event was associated with a measured blood glucose level below 36 mg/dL or the event was associated with prompt recovery after oral carbohydrate, iv glucose, or glucagon administration.

A symptomatic hypoglycemic event was defined as a hypoglycemic episode with an associated SMBG value of <50 mg/dL with reported symptoms.
Adjusted Incidence Rate of Hypoglycemia [ Time Frame: Week 60 ] [ Designated as safety issue: Yes ]
Adjusted incidence rate of hypoglycemia: estimated percent of patients having at least 1 event of a given type of hypoglycemia.

A severe Hypoglycemic Event (HE) is one where patient requires assistance. It is confirmed either by a prompt response to certain countermeasures or by a blood Glucose (BG) <36 mg/dL during or soon after the event.

A serious HE is one where the patient has loss of consciousness, coma, seizure, or convulsion.

Nocturnal = events occurring between 00:00 & 06:00 based on a 24-hour clock.

An event is included if the HE start date is within the treatment period.
Adjusted Hypoglycemic Event Rates (Event/Patient-year) [ Time Frame: Week 60 ] [ Designated as safety issue: Yes ]
Adjusted Hypoglycemic event rate: Total # of events for a given type of hypoglycemia divided by the total exposure to study drug (patient-years). Rates are estimated from a general linear model adjusted for baseline BMI and oral agent combination of antidiabetic medications on which the patient entered the study.

An event is included if the hypoglycemic event start date is within the treatment period (i.e., from the Randomization date to & including 1 day after the date of last dose of study drug).

Enrollment:	588
Study Start Date:	May 2006
Study Completion Date:	March 2010
Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Lantus/Apidra-3 Insulin glargine (Lantus) plus up to 3 injections of insulin glulisine (Apidra) added to oral agents.	Drug: Insulin Glargine Subcutaneous injection once-a-day Other Name: Lantus Drug: Insulin Glulisine Subcutaneous injection up to 3 injections per day. Other Name: Apidra
Experimental: Lantus/Apidra-1 Insulin glargine (Lantus) plus up to 1 injection of insulin glulisine (Apidra) added to oral agents.	Drug: Insulin Glulisine Subcutaneous injection up to 1 injection per day Other Name: Apidra Drug: Insulin Glargine Subcutaneous injection once-a-day Other Name: Lantus
Experimental: Novolog Mix 70/30 Premixed insulin (Novolog® Mix 70/30) added to oral agents.	Drug: Premixed Insulin Subcutaneous injection twice-a-day. Other Name: Novolog Mix 70/30

Eligibility

Ages Eligible for Study:	30 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Male or female patients
30 to 80 years of age
Body Mass Index <45 kg/m2
With Type 2 diabetes mellitus for at least 2 years
With an HbA1c level at screening of >7.5% and >7.0% at randomization
On stable dual or triple oral therapy for at least 3 months
Oral agents in 2 or 3 of the following classes: SU or repaglinide, biguanide, or TZD, willing and able to perform self-monitoring of BG
Females of child-bearing potentially were required to be willing and able to use adequate contraception

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00384085

Locations

United States, New Jersey
Sanofi-Aventis Administrative Office
Bridgewater, New Jersey, United States

Sponsors and Collaborators

Sanofi-Aventis

Investigators

Study Director:

Medical Affairs

Sanofi-Aventis

More Information

No publications provided

Responsible Party:	Study Director, sanofi-aventis
ClinicalTrials.gov Identifier:	NCT00384085 History of Changes
Other Study ID Numbers:	HMR1964A_3515
Study First Received:	October 3, 2006
Results First Received:	March 31, 2011
Last Updated:	May 4, 2011
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin aspart
Glargine

Insulin glulisine
Insulin
Insulin, Long-Acting
Insulin, NPH
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012