Clinical trial NCT02836704: Comparison of Standard vs Higher Starting Dose of Insulin Glargine in Chinese Patients With Type 2 Diabetes (Glargine Starting Dose)
Official title: Comparison of Efficacy and Safety of Standard vs Higher Starting Dose of Insulin Glargine in Overweight and Obese Chinese Patients With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2016-07-19
Enrollment: 892
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

-To test the hypothesis that higher initial dose of basal insulin (0.3 U/kg) is non inferior to standard initial dose (0.2 U/kg) based on the percentage of patients with at least one episode of hypoglycemia (≤3.9 mmol/L or severe) during the 16 weeks of treatment in overweight and obese type 2 diabetic patients uncontrolled with oral anti-diabetes drugs (OADs).

Secondary Objective:

* To evaluate the percentage of patients achieving glycated hemoglobin (HbA1c) \<7%.
* To evaluate the percentage and accumulated percentage of patients achieving fasting plasma glucose (FPG) target (\<5.6, \<6.1, and \<7.0 mmol/L).
* To assess the changes in HbA1c, FPG, and postprandial glucose (PPG).
* To evaluate the insulin doses change.
* To evaluate the weight change.
* To evaluate overall hypoglycemia, nocturnal hypoglycemia and severe hypoglycemia occurrence.
* To descriptively evaluate the safety profile.
* To assess patient and physician satisfaction and adherence (drop-out rate and the percentage of patients who can follow the treatment and insulin titration).
* Subgroup analysis on efficacy (control rate, control rate without confirmed hypoglycemia, and changes in HbA1c, FPG and PPG) and safety data according to:
* Age
* Duration of diabetes
* Baseline treatment (OAD)
* Baseline HbA1c, FPG and PP

Detailed description: The duration of study for each patient is approximately 20 weeks from screening visit to end-of-study follow-up phone call.

Eligibility criteria: Inclusion criteria :

* Age ≥ 18 and ≤ 70 years.
* Type 2 diabetes patients with diabetes diagnosis at least 2 years.
* Continuous treatment with stable doses of 2-3 OADs, for more than three months prior to randomization, among which metformin ≥1.5 g/day or at maximum tolerated dose
* HbA1c \>7.5% and ≤11%.
* FPG \>9 mmol/L.
* BMI ≥25 and ≤40 kg/m\^2.
* Ability and willingness to perform self-monitoring of blood glucose using the Sponsor-provided glucose meter and to complete the patient diary.
* Willingness and ability to comply with the study protocol.
* Signed informed consent obtained prior any study procedure.

Exclusion criteria:

* Known hypersensitivity/intolerance to insulin glargine or any of its excipients.
* History of hypoglycemia unawareness.
* Unexplained hypoglycemia in the past 6 months.
* Pregnancy or planned pregnancy or current lactation (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraception method).
* Acute diabetic complications (diabetic ketoacidosis, lactic acidosis, hyperosmolar nonketotic diabetic coma).
* History of stroke, myocardial infarction, angina pectoris, coronary artery bypass graft, or percutaneous transluminal coronary angioplasty within the previous 12 months.
* Active proliferative retinopathy, as defined by a photocoagulation or vitrectomy occurrence in the 6 months prior to study entry, or any other unstable (rapidly progressing) retinopathy that may require photocoagulation or surgical treatment during the study, documented by retina examination or disease history record, in the 2 years prior to study entry.
* Impaired renal function defined as, but not limited to, serum creatinine levels ≥1.5 mg/dL (132 μmol/L) for males and ≥1.4 mg/dL (123 μmol/L) for females or presence of macroproteinuria (\>2 g/day).
* Active liver disease (alanine transaminase \[ALT\] greater than two times the upper limit of the reference range, as defined by the local laboratory).

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

Primary outcomes:
measure: Percentage of patients with at least one episode of hypoglycemia
timeFrame: 16 weeks
Secondary outcomes:
measure: Percentage of patients achieving HbA1c <7%
timeFrame: 16 weeks
measure: Percentage of patients achieving Fasting Plasma Glucose target (<5.6, <6.1, and <7.0 mmol/L)
timeFrame: 16 weeks
measure: Accumulated percentage of patients achieving Fasting Plasma Glucose target (<5.6, <6.1, and <7.0 mmol/L)
timeFrame: 16 weeks
measure: Change from baseline in HbA1c
timeFrame: Baseline, 16 weeks
measure: Change from baseline in Fasting Plasma Glucose
timeFrame: Baseline, 16 weeks
measure: Change from baseline in Post Prandial Glucose
timeFrame: Baseline, 16 weeks
measure: Change in body weight
timeFrame: Baseline, 16 weeks
measure: - Change in insulin dose
timeFrame: Baseline, 16 weeks
measure: Number of overall hypoglycemic events (with severe or confirmed hypoglycemia [≤3.9 mmol/L])
timeFrame: Baseline, 16 weeks
measure: Number of nocturnal hypoglycemic events
timeFrame: Baseline, 16 weeks
measure: Number of severe hypoglycemic events
timeFrame: Baseline, 16 weeks
Other outcomes:
Locations:
city: China
country: China
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Wan H, Wen B, Wang X, Wang J, Zhang Y, Ning T, Duan B, Li Y, Feng W, Zhang X, Cui N, Ji L. Effect of Baseline Characteristics on Hypoglycaemia Risk with Insulin Glargine 100 U/mL: Post Hoc Analysis of the BEYOND 7 Study. Diabetes Ther. 2021 Sep;12(9):2359-2369. doi: 10.1007/s13300-021-01112-z. Epub 2021 Jul 21.
citation: Ji L, Gao Z, Shi B, Bian R, Yin F, Pang W, Gao H, Cui N. Safety and Efficacy of High Versus Standard Starting Doses of Insulin Glargine in Overweight and Obese Chinese Individuals with Type 2 Diabetes Mellitus Inadequately Controlled on Oral Antidiabetic Medications (Beyond VII): Study Protocol for a Randomized Controlled Trial. Adv Ther. 2018 Jun;35(6):864-874. doi: 10.1007/s12325-018-0717-x. Epub 2018 Jun 5.