Clinical trial NCT00405418: Lantus Versus Levemir Treat-To-Target
Official title: Target Glycemic Control and the Incidence of Documented Symptomatic Hypoglycemia in Insulin naïve Subjects With Type 2 Diabetes Failing on Oral Hypoglycemic Agent(s) and Treated With Insulin Glargine or Insulin Detemir.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2006-11-30
Enrollment: 973
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary objective:

To demonstrate the non-inferiority of insulin glargine in comparison to insulin detemir in term of percentage of patients who reach the target of HbA1c \< 7% at the end of the treatment period and do not experience symptomatic hypoglycemia, confirmed by plasma glucose (PG) ≤ 56 mg/dL (3.1 mmol/L)

Secondary objectives:

* To compare between the 2 treatment groups, the percentage of patients who reach the target of HbA1c \< 7% and \< 6.5% at the end of the treatment period
* To compare the changes in HbA1c and fasting plasma glucose (FPG)
* To compare the evolution of blood glucose profiles
* To compare the day to day FPG variability, the insulin doses
* To determine in each treatment group the biochemical and patient-related determinants of failure to reach HbA1c targets
* To compare the overall incidence and rate of symptomatic hypoglycemia and nocturnal symptomatic hypoglycemia confirmed by PG ≤ 56 mg/dL (3.1 mmol/L)
* To compare over the treatment period, the overall incidence and rate of symptomatic hypoglycemia and symptomatic nocturnal hypoglycemia (with PG ≤ 70 mg/dL \[3.9 mmol/L\]), of symptomatic day-time hypoglycemia (with PG ≤ 70 mg/dL and with PG ≤ 56 mg/dL), of severe hypoglycemia, of asymptomatic hypoglycemia with PG ≤ 56 mg/dL
* To compare the overall safety: incidence of adverse events (including serious hypoglycemia and local tolerance at injection site), change in body weight, in waist circumference and in waist / hip ratio
* To assess the quality of life and treatment satisfaction


Eligibility criteria: Inclusion Criteria:

* Type 2 diabetes for at least 1 year
* Insulin naïve
* Treated with stable doses of oral antidiabetics for at least 3 months prior to study start, including at least metformin (at least 1g/day)
* 7% ≤ HbA1c ≤ 10.5 %
* Body mass index (BMI) \< 40 kg/m²
* Ability and willingness to perform blood glucose monitoring using a blood glucose meter and to use a patient diary

Exclusion Criteria:

* Type 1 diabetes
* Current or previous use of insulin (except for previous treatment of gestational diabetes or brief treatment with insulin for less than 1 week)
* Treatment with glucagon-like peptide (GLP)-1 receptor agonists or with dipeptidyl peptidase (DPP)-IV inhibitors
* Active proliferative diabetic retinopathy, as defined by the application of photocoagulation or surgery, in the 6 months before study entry or any other unstable (rapidly progressing) retinopathy that may require photocoagulation or surgery during the study (an optic fundus examination should have been performed in the 2 years prior to study entry)
* Pregnancy (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraceptive method)
* Breast-feeding
* History of hypersensitivity to the study drugs or to drugs with a similar chemical structure
* Treatment with systemic corticosteroids in the 3 months prior to study entry
* Treatment with any investigational product in the 2 months prior to study entry
* Likelihood of requiring treatment during the study period with drugs not permitted by the clinical study protocol
* Clinically relevant cardiovascular, hepatic, neurological, endocrine, or other major disease making implementation of the protocol or interpretation of the study results difficult
* Impaired hepatic function as shown by Alamine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) greater than three times the upper limit of normal range at study entry
* Impaired renal function as shown by serum creatinine ≥ 1.5 mg/dL (≥ 133 μmol/L) in men and ≥ 1.4 mg/dL (124 μmol/L) in women at study entry
* History of drug or alcohol abuse in the last year

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: HbA1c recorded
timeFrame: At baseline, week 12 and week 24
measure: Self-monitored fasting BG in both treatment arms and pre-dinner BG in detemir arm
timeFrame: On the 4 consecutive days before each visit
measure: Self-monitored BG values from 8-point 24-hour profile recorded on 2 consecutive days
timeFrame: Within the week prior to baseline, week 12 and week 24
measure: Episodes of hypoglycemia (symptomatic, total and categorized as day-time/nocturnal, severe or asymptomatic)
timeFrame: All across the study
measure: Self-monitored BG values whenever patient experiences symptoms possibly related to hypoglycemia.
timeFrame: All across the study
Secondary outcomes:
measure: Doses of insulin glargine or insulin detemir
timeFrame: Daily
measure: Laboratory fasting plasma glucose
timeFrame: At baseline, week 12 and week 24
measure: Insulinemia and fasting C-peptide level
timeFrame: At baseline
measure: Lipid profile
timeFrame: at baseline and week 24
measure: Patient reported outcomes (quality of life and treatment satisfaction)
timeFrame: at baseline, week 4, week 12 and at the last visit
measure: Safety data: occurrence of adverse events and weight
timeFrame: assessed at each visit
measure: Waist and hip circumferences
timeFrame: measured at baseline, week 12 and week 24
measure: Systolic and diastolic blood pressure
timeFrame: measured at study entry, baseline, week 12 and week 24
measure: Physical examination
timeFrame: performed at study entry and at last visit.
Other outcomes:
Locations:
city: North Ryde
country: Australia
facility: Sanofi-Aventis
city: Sao Paolo
country: Brazil
facility: Sanofi-Aventis
city: Laval
country: Canada
facility: Sanofi-Aventis
city: Hoersholm
country: Denmark
facility: Sanofi-Aventis
city: Helsinki
country: Finland
facility: Sanofi-Aventis
city: Berlin
country: Germany
facility: Sanofi-Aventis
city: Mumbai
country: India
facility: Sanofi-Aventis
city: Dublin
country: Ireland
facility: Sanofi-Aventis
city: Seoul
country: Korea, Republic of
facility: Sanofi-Aventis
city: Gouda
country: Netherlands
facility: Sanofi-Aventis
city: Porto Salvo
country: Portugal
facility: Sanofi-Aventis
city: Bucharest
country: Romania
facility: Sanofi-Aventis
city: Moscow
country: Russian Federation
facility: Sanofi-Aventis
city: Belgrade
country: Serbia
facility: Sanofi-Aventis
city: Barcelona
country: Spain
facility: Sanofi-Aventis
city: Stockholm
country: Sweden
facility: Sanofi-Aventis
city: Meyrin
country: Switzerland
facility: Sanofi-Aventis
city: Taipe
country: Taiwan
facility: Sanofi-Aventis
city: Istanbul
country: Turkey
facility: Sanofi-Aventis
city: Guildford
country: United Kingdom
facility: Sanofi-Aventis
Study officials:
affiliation: Sanofi
name: Valérie Pilorget
role: STUDY_DIRECTOR
References:
citation: Swinnen SG, Dain MP, Aronson R, Davies M, Gerstein HC, Pfeiffer AF, Snoek FJ, Devries JH, Hoekstra JB, Holleman F. A 24-week, randomized, treat-to-target trial comparing initiation of insulin glargine once-daily with insulin detemir twice-daily in patients with type 2 diabetes inadequately controlled on oral glucose-lowering drugs. Diabetes Care. 2010 Jun;33(6):1176-8. doi: 10.2337/dc09-2294. Epub 2010 Mar 3.