A multi-center, double-blind, randomized, parallel group, placebo-controlled 12-week study to investigate glycemic parameters of efficacy, safety/ tolerability and pharmacokinetics of five dose levels of RO4998452 in patients with type 2 diabetes mellitus

• Conditions: Type 2 diabetes mellitus; MedDRA version: 9.1Level: LLTClassification code 10045242Term: Type II diabetes mellitus

• Registration Number: EUCTR2008-001249-24-DE
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-12-09
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 300

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

• 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 < 7
consecutive days)
• Patients currently or within 2 months prior to screening treated with any oral or
injectable anti-diabetic agent except stable dose of metformin
• Patients currently or within 6 months prior to screening treated with any PPAR?
agonist
• History of antidiabetic triple therapy
• Patients currently or within 3 months prior to screening treated with any
prescription weight-lowering medication or orlistat
• Patients treated with lipoprotein modifying therapy (e.g. niacin, statin) if dosage or
dosing regimen was changed within 4 weeks prior to screening. Dosage and
dosing regimen for fibrates need to be stable for 3 months prior to screening.
• Patients receiving antihypertensive medication, and/or thyroid hormones if the
dose(s) has (have) not been stable for at least 4 weeks prior to randomization
• Systemic, inhaled or topical corticosteroid therapy 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 (< 130 mM) or hypernatremia (> ULN with ULN=147 mM [age < 60
years] or ULN=145 mM [age greater than or equal to 60 years]) 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified