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

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

Purpose

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.

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

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Insulin Glargine With Step-Wise Addition of Insulin Glulisine or With One Injection of Insulin Glulisine vs a Twice-Daily Premixed Insulin Regimen (Insulin Aspart Mix 70/30) in Adult Subjects With Type-2 Diabetes Failing Dual or Triple Therapy With Oral Agents.

Resource links provided by NLM:

MedlinePlus related topics: Diabetes

Drug Information available for: Insulin Insulin glargine Insulin glulisine

U.S. FDA Resources

Further study details as provided by Sanofi-Aventis:

Primary Outcome Measures:

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 subjects achieving target glycemic control [ Time Frame: 60 weeks ] [ Designated as safety issue: No ]
To demonstrate the non-inferiority of Lantus plus addition of one mealtime Apidra injection (Lantus/Apidra-1) versus twice-daily premixed insulin [ Time Frame: 60 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Reduction from baseline in wk 60 A1c w/twice-daily premixed insulin vs morning insulin glargine plus addition of mealtime insulin glulisine injection (insulin glargine/insulin glulisine-3) [ Time Frame: 60 weeks ] [ Designated as safety issue: No ]
Proportion of subjects achieving target glycemic control at week 60 of study with twice-daily premixed insulin vs morning insulin glargine plus addition of one mealtime insulin glulisine injection (insulin glargine/insulin glulisine-1) [ Time Frame: 60 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	600
Study Start Date:	June 2006
Estimated Study Completion Date:	March 2010
Estimated Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental PREMIXED REGIMEN ARM Subjects randomized to this arm will discontinue glimepiride (if taking), continue metformin and/or TZD, and start with 10 units (5 units + 5 units) of premixed insulin (Novolog® Mix 70/30). Premixed insulin (Novolog® Mix 70/30) will be administered two times per day (within 15 min of meal initiation) 5 units before breakfast and 5 units before dinner.	Drug: Insulin Glulisine PREMIXED REGIMEN ARM Subjects randomized to this arm will discontinue glimepiride (if taking), continue metformin and/or TZD, and start with 10 units (5 units + 5 units) of premixed insulin (Novolog® Mix 70/30). Premixed insulin (Novolog® Mix 70/30) will be administered two times per day (within 15 min of meal initiation) 5 units before breakfast and 5 units before dinner
2: Experimental LANTUS/APIDRA-1 REGIMEN ARM Subjects randomized to this arm will receive basal insulin (Lantus), and if required, one injection of prandial insulin (Apidra).	Drug: Insulin Glulisine LANTUS/APIDRA-1 REGIMEN ARM Subjects randomized to this arm will receive basal insulin (Lantus), and if required, one injection of prandial insulin (Apidra).
3: Experimental LANTUS/APIDRA-3 REGIMEN ARM Subjects randomized to this arm will receive basal insulin (Lantus), and if required prandial insulin (Apidra) using a stepwise approach.	Drug: Insulin Glulisine LANTUS/APIDRA-3 REGIMEN ARM Subjects randomized to this arm will receive basal insulin (Lantus), and if required prandial insulin (Apidra) using a stepwise approach.

Eligibility

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

Criteria

The following information on clinical trials is provided for information purposes only to allow patients and physicians to have an initial discussion about the trial. This information is not intended to be complete information about the trial, to contain all considerations that may be relevant to potential participation in the trial, or to replace the advice of a personal physician or health professional.

INCLUSION CRITERIA:

Diagnosis of Type 2 Diabetes Mellitus for at least 2 years
Male or Female subjects 30-80 years of age
A1C >7.5 % at screening, and A1c >7.0% at randomization
BMI <45 kg/m2
On stable dual or triple oral therapy for at least 3 months (any combination of secretagogue (sulfonylurea or repaglinide), metformin, and Actos (pioglitazone). The oral agents must be in 2 or 3 of the following 3 different classes: a.Sulfonylurea or repaglinide: dosage greater than or equal to one-half the maximum daily recommended dosage; i.e., glimepiride > 4 mg; glipizide, including GITS >10 mg; glyburide > 10 mg; Glynase® > 3 mg; or repaglinide (Prandin®) > 2 mg with each meal. The dosage must have been stable for at least 3 months prior to screening. b. Biguanide: metformin dosage > 1000 mg daily including Glucophage XR®.

The dosage must have been stable for at least 3 months prior to screening c. Thiazolidinedione: Actos pioglitazone) greater than or = to 15 mg only. The subject must have been using Actos for at least 6 months, and the dosage must have been stable for at least 3 months, prior to screening. Subjects using Avandia (rosiglitazone) will not be allowed to enroll into the study.

Ability and willing to perform SMBG up to four times a day, and at least 8 times daily during the 8-point BG profile measurement days
Able and willing to adhere to and be compliant with the study protocol
Able to read English or Spanish at the sixth- grade level in order to complete the subject reported outcomes component of the study
Signed informed consent and study specific HIPAA documents

EXCLUSION CRITERIA:

Subjects on any other anti-diabetic drug treatments other than the one required by the protocol within the last 3 months before the study entry. Subjects discontinuing Januvia due to nontolerance may be allowed in the study after a 2-week wash out period.
Clinically significant peripheral edema, if on a TZD
Planned pregnancy, pregnant or lactating females
History of hypoglycemia unawareness
Acute or chronic or history of metabolic acidosis, including diabetic ketoacidosis
Impaired renal function, as shown by but not limited to, serum creatinine greater than or = to 3.0 mg/dL.

For subjects treated with metformin - serum creatinine greater than or = to 1.5 mg/dL (133 μmol/L) for males or greater than or = to 1.4 mg/dL (124 μmoL) for females

Subjects receiving glucocorticoids, nonselective B-blockers, or weight-control agents
Insulin use >1 week within prior year
Acute infection
Any clinically significant renal disease (other than proteinuria) or hepatic disease
A serum SGPT level greater than 2.5 X the upper limit of normal
Any malignancy within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma, or adequately treated cervical carcinoma in situ
Diagnosis of dementia or mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study
Diagnosis of impaired dexterity or vision rendering the subject unable to administer MDI injections
History of or current congestive heart failure (cardiac status NYHA II-IV) requiring pharmacological treatment; history of stroke, myocardial infarction coronary artery bypass graft, percutaneous transluminal coronary angioplasty, or angina pectoris within the last 12 months
Known hypersensitivity to insulin glargine, insulin glulisine, NovoLog Mix® (70/30) or any components of Lantus®, Apidra® or NovoLog Mix® (70/30).
Any disease or condition (including abuse of illicit drugs, prescription medicines or alcohol)within last 2 years, that in the opinion of the investigator or sponsor may interfere with the completion of the study
Unlikely to comply with protocol, e. g., uncooperative attitude, inability to return for followup visits, and/or unlikely to complete the study
Subject is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff, or relative thereof directly involved in the conduct of the protocol

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:

Lisa Jean-Louis

Sanofi-Aventis

More Information

No publications provided

Responsible Party:	sanofi-aventis ( Study Director )
Study ID Numbers:	HMR1964A_3515
Study First Received:	October 3, 2006
Last Updated:	September 1, 2009
ClinicalTrials.gov Identifier:	NCT00384085 History of Changes
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Metabolic Diseases
Insulin glulisine
Metformin
Diabetes Mellitus
Endocrine System Diseases
Insulin
Glimepiride

Hypoglycemic Agents
Diabetes Mellitus, Type 2
Glargine
Insulin, Asp(B28)-
Endocrinopathy
Glucose Metabolism Disorders
Metabolic Disorder

Additional relevant MeSH terms:

Hypoglycemic Agents
Insulin glulisine
Metabolic Diseases
Physiological Effects of Drugs
Diabetes Mellitus, Type 2
Glargine

Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Pharmacologic Actions
Insulin

ClinicalTrials.gov processed this record on September 03, 2009