Type 2 diabetes mellitus MedDRA version: 9.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus
Conditions
Interventions
Product Name: SGLT2 co-transporter inhibitor
Product Code: RO4998452
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: SGLT2 co-transporter inhibitor
CAS Number: 461432-26-8
Current Sponsor cod
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients with type 2 diabetes, diagnosed for at least 3 months at screening examination, based on WHO criteria • Patients who are either (1) treated with diet and exercise and a stable dose of metformin (daily dose 1.5 g to 3.0 g but not higher than recommended in the locally approved label) for at least 3 months or (2) treated with diet and exercise • HbA1c equal to or greater than 7.0 % and equal to or less than 10.0 % at screening and at the visit preceding randomization • Age 18 to 75 years (inclusive) at the time of screening • BMI > 22 kg/m2 and equal to or less than 45 kg/m2 at screening • Able and willing to give written informed consent and able to comply independently to all study requirements Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Type 1 diabetes mellitus patients • History of ketoacidosis or lactic acidosis • Fasting serum C-peptide equal to or less than 1 ng/ml at screening for patients with a BMI equal to or less than 25 kg/m2 • Fasting plasma glucose > 240 mg/dl (13.3 mmol/l) • Any contraindication to metformin as indicated in the label such as congestive heart failure (NYHA class III or IV or requiring pharmacological treatment) or respiratory failure • History of body weight changes within 3 months prior to screening > 10% of body weight measured at screening • Patients currently or within 12 months prior screening treated with insulin (with the exception of emergency situations in which insulin was given for 14 treatment days within 3 months prior to screening • Impaired liver function (as suggested by ALT, AST, total bilirubin or alkaline phosphatase > 2.5x ULN) at screening • Hyponatremia ( 150 mM) at screening or within 3 months prior to screening • Renal disease or renal dysfunction (as suggested by serum creatinine levels equal to or greater than 1.5 mg/dl (133 µmol/l) [males], equal to or greater than 1.4 mg/dl (124 µmol/l) [females]) at screening • Personal or family history of renal glucosuria (= glucosuria in the absence of diabetes mellitus) • History of bariatric surgery or small bowel resection • History of uncontrolled hypertension (SBP > 150 mmHg and/or DBP > 95 mmHg, despite treatment) < 3 months prior to screening • Myocardial infarction or stroke within 6 months prior to screening • Evidence of significant pre-diagnosed diabetic complication requiring medical treatment (e.g., medically treated gastroparesis, diagnosed proliferative diabetic retinopathy) • Any known serious illness (such as cancer, major active infection, severe psychiatric disorders, clinical significant gastrointestinal disorder, active autoimmune disease, chronic inflammatory condition, chronic anemia, all hemoglobino¬pathies) at screening which could interfere with the conduct of the study • Any new conditions diagnosed at screening requiring treatment longer than 10 days or chronic therapies that can not be stabilized during the screening period • Any abnormalities in clinical laboratory tests or ECG (e.g., clinically relevant QTc prolongation, family history of long QT syndrome, concomitant use of class I antiarrythmic drugs such as disopyramide, quinidine, procainamide, mexiletine, flecainide, propafenone) which precludes safe involvement in the study a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To determine the absolute change in HbA1c concentration from baseline to the end of the treatment period compared to placebo;Secondary Objective: To determine additional efficacy parameters, safety and tolerability following RO4998452 administration compared to placebo, including • the absolute change in fasting plasma glucose from baseline to the end of the treatment period • the glycemic response with additional parameters of glycemic control (such as mean daily blood glucose obtained from 7-point plasma glucose profile, fructosamine, Meal Tolerance Test) • the tolerability and safety profile • the effects on body weight • the pharmacokinetics and the exposure-response relationship of RO4998452 including the influence of covariates (by a population analysis approach) Exploratory objectives: • to determine the effects on feeling of hunger and thirst • to determine the dose-response curve of RO4998452 on 24-h urinary glucose excretion ;Primary end point(s): • Absolute change in HbA1c from baseline to the end of the treatment period | — |
Countries
Germany, Latvia, Spain
Outcome results
None listed