This is a dose-ranging study that will evaluate the efficacy, safety and tolerability of a range of doses of investigational product and pioglitazone, compared to placebo, administered as monotherapy over 12 weeks in treatment naive patients with T2DM

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 70 YearsSexo: ALL

Criterios de inclusión

Subjects with a documented diagnosis of T2DM and have an HbA1c level at Visit 1 of ≥7.0% and ≤9.5% as measured by a central laboratory. Subjects with HbA1c \<7.5% must have a fasting fingerstick glucose ≥7 mmol/L (126 mg/dL) at Week 0 prior to randomization.
Subjects who are treatment-naïve and have not taken insulin, or any oral or injectable anti-diabetic medication in the past 3 months and have not taken a glucose lowering agent for ≥4 weeks at any time in the past, or Subjects who are newly diagnosed and treated with diet and exercise for a minimum of 6 weeks
Subjects who are 18 to 70 years of age inclusive at the time of Screening.
Females of non-childbearing and childbearing potential are eligible to participate as follows:
Women of childbearing potential must be willing to use one of the following contraception methods: intrauterine device, condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent for at least 30 days prior to the start of study medication, throughout the study and the follow-up visit. Note: use of oral contraceptives is not permitted.
Women of non-child bearing potential are defined as follows: females regardless of age, with functioning ovaries and who have a current documented tubal ligation \[Hatcher, 2004\] bilateral oophorectomy or total hysterectomy, or females who are post-menopausal).
(Post-menopausal is defined as after one year without menses with an appropriate clinical profile, e.g. age appropriate, \>45 years, in the absence of hormone replacement therapy. In addition to the above criteria, if the post-menopausal status is still questionable, a blood sample should be drawn for simultaneous measurement of follicle stimulating hormone and estradiol; values considered to confirm the post-menopausal state are respectively: FSH \>40 MIU/mL and estradiol \<40pg/mL (\<140 pmol/L)).
Informed Consent: a signed and dated written consent must be obtained from the subject before any procedures are performed.

Criterios de exclusión

Metabolic Disease
Diagnosis of Type 1 diabetes mellitus.
History of ketoacidosis which has required hospitalization.
Thyroid disorder \[TSH below the lower limit of the reference range (LLRR) of 0.4mIU/L or above the upper limit of the reference range (ULRR) of \>5.5 mIU/L at Screening\]. Hypothyroidism treated with the same dose and regimen of thyroid hormone replacement for at least 3 months prior to Screening is allowed.
BMI of \<22 or \>43 kg/m2.
Significant weight gain or loss (as defined as \>5% of total body weight) in the 3 months prior to Screening.
Diabetic Medication
Has taken insulin or any oral or injectable anti-diabetic medication ≥4 weeks at any time prior to screening.
Has taken insulin or any oral or injectable anti-diabetic medication within 3 months of screening.
Cardiovascular Disease
Recent history or presence of clinically significant acute cardiovascular disease including:
Documented myocardial infarction in the 6 months prior to Screening.
Coronary revascularization including percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG) surgery either planned and/or occurred in the 6 months prior to Screening.
Unstable angina in the 6 months prior to Screening.
Clinically significant supraventricular arrhythmias requiring medical therapy, or history of nonsustained or sustained ventricular tachycardia. Symptomatic valvular heart disease or valvular heart disease requiring therapy other than endocarditis prophylaxis.
Congestive heart failure (CHF, New York Heart Association (NYHA) Class II to IV) requiring pharmacologic treatment. NYHA Class I may be included in accordance with the local prescribing information for pioglitazone.
Blood pressure (BP) \>150/100mmHg. If a subject is receiving permitted antihypertensive therapy, then they must be on stable dose(s) of therapy for at least 4 weeks prior to Screening.
Has a QTc interval (Bazett's) ≥450msec at Screening on a single ECG or an average value from 3 ECGs taken 5 minutes apart (on local reading of ECG).
Other clinically significant ECG abnormalities which, in the opinion of the investigator, may affect the interpretation of efficacy and safety data, or which otherwise contraindicates participation in a clinical trial with a new chemical entity.
Fasting triglycerides ≥400mg/dL (4.56mmol/L) at Screening. If a subject is receiving permitted lipid-lowering therapy, then they must be on a stable dose(s) of therapy for at least 6 weeks prior to Screening. Niacin and bile acid sequestrants are prohibited.
Hepatic Disease
Has a diagnosis of active hepatitis (hepatitis B surface antigen or hepatitis C antibody), or clinically significant hepatic enzyme elevation including:
Any one of the following enzymes greater than 2 times the upper limit of the reference range (ULRR) value at Screening.
alanine transaminase (ALT).
aspartate transaminase (AST).
alkaline phosphatase (AP). Has a total bilirubin level that is \>1.5 times the ULRR at Screening with the exception of suspected or confirmed Gilbert's disease.
Pancreatic Disease
Secondary causes of diabetes:
history of chronic or acute pancreatitis
Renal Disease
Significant renal disease at Screening as manifested by:
Glomerular filtration rate (GFR) \<60mL/min (as estimated from serum creatinine at Visit 1 and demographic data using the MDRD equation).For the MDRD equation, please refer to the study procedures manual.
Proteinuria of ≥1+ by urinary dipstick
Recurrent genitourinary tract infections defined as ≥2 episodes of complicated or uncomplicated cystitis or pyelonephritis in the 6 months prior to Screening
A positive qualitative urinary dipstick for leukocytes, red blood cells (RBC) or nitrites at Screening.
Concurrent Disease
Has any concurrent condition or any clinically significant abnormality identified on the screening physical examination, laboratory tests (including blood electrolytes), electrocardiogram, including pulmonary, neurological or inflammatory diseases, which, in the opinion of the investigator, may affect the interpretation of efficacy and safety data, or which otherwise contraindicates participation in a clinical trial with a new chemical entity
History of significant co-morbid diseases active in the 6 months prior to Screening (e.g., cholecystitis, acute pancreatitis, gastrointestinal disease, chronic diarrhea, etc.)
Has a history of malignancy within the past five years \[other than superficial squamous cell carcinoma which is non-invasive on pathology or basal cell carcinoma which is successfully treated with local excision\] and cervical cancer in situ treated definitively at least 6 months prior to Screening
Concurrent Medication
Is currently taking or has taken any of the following medications in the 8 weeks prior to Screening:
Digoxin
Warfarin and other oral anticoagulants (aspirin and non-steroidal anti-inflammatory drugs are permitted)
Bile acid sequestrants
Niacin (excluding routine vitamin supplementation)
Antiobesity agents (including fat absorption blocking agents)
Oral or injectable corticosteroids (inhaled and intranasal corticosteroids are permitted)
Loop diuretics
Monoamine oxidase inhibitors and tricyclic amines
Antiretroviral drugs
St John's Wort
Oral chromium
Pregnancy \& Breast Feeding
Is currently lactating or pregnant
Other
Current smoker who is unable to abstain from smoking while in the clinic at each visit
Has a history of alcohol or substance abuse within the past year at Screening or alcohol or substance abuse during treatment, as determined by the investigator:
Unwilling to refrain from the use of illicit drugs and adhere to other protocol-stated restrictions while participating in the study.
Has an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males) or an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to a half-pint of beer or 1 measure of spirits or 1 glass of wine
Has participated in any study with an investigational or marketed drug in the 3 months prior to Screening
In the opinion of the investigator has a risk of non-compliance with study procedures, or cannot read, understand, or complete study related materials, particularly the informed consent
Known allergy to any of the tablet excipients, or history of drug or other allergy, which, in the opinion of the responsible study physician

Ubicaciones

GSK Investigational Site

Buenos Aries, Buenos Aires, Argentina

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Córdoba, Córdoba Province, Argentina

GSK Investigational Site

Buenos Aires, Argentina

GSK Investigational Site

Córdoba, Argentina

GSK Investigational Site

Mendoza, Argentina

GSK Investigational Site

Quilmes, Argentina

GSK Investigational Site

San Miguel de Tucumán, Argentina

A Double-blind, Randomized 12-week Study to Evaluate the Safety and Efficacy of GSK189075 Tablets vs Pioglitazone in Treatment Naive Subjects With Type 2 Diabetes Mellitus

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

GSK189075

pioglitazone

Placebo

Ubicaciones

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

Patrocinadores