Dose-Ranging Study in Treatment Naive Type 2 Diabetes Mellitus(T2DM)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00500331
First received: January 24, 2007
Last updated: November 7, 2013
Last verified: November 2013
  Purpose

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


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: GSK189075
Drug: pioglitazone
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Dose-Ranging Study of GSK189075 Versus Placebo In The Treatment of Type 2 Diabetes Mellitus in Treatment Naïve Subjects.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Glycosylated haemoglobin A1c (HbA1c) at Week 12 [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • HbA1c at Weeks 4 and 8. HbA1c responders at Week 12, FPG, fructosamine, lipids at Weeks 4, 8 and 12 Body weight at each visit Waist circumference at Weeks 4, 8, 12 and Follow-up Adverse events over 12 weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • HbA1c [ Time Frame: at Weeks 4 and 8 ] [ Designated as safety issue: No ]
  • HbA1c responders [ Time Frame: at Week 12 ] [ Designated as safety issue: No ]
  • FPG, fructosamine, lipids [ Time Frame: at Weeks 4, 8 and 12 ] [ Designated as safety issue: No ]
  • Body weight [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Waist circumference [ Time Frame: at Weeks 4, 8, 12 and Follow-up ] [ Designated as safety issue: No ]
  • Adverse events [ Time Frame: over 12 weeks ] [ Designated as safety issue: No ]
  • Secondary efficacy endpoints include change from baseline in HbA1c over time; change from baseline in FPG, fructosamine, insulin, and lipids; proportion of HbA1c and FPG responders; [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
  • plasma glucose, insulin profiles and C-peptide during a glucose tolerance test (subgroup of subjects), change in body weight and waist circumference; population pharmacokinetic parameters of the investigational compound. [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
  • Safety endpoints include AEs, incidence of hypoglycemia, vital signs, ECGs and standard laboratory tests. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 336
Study Start Date: January 2007
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
GSK189075
Drug: GSK189075
Experimental Drug
Placebo Comparator: Arm 2
Placebo
Other: Placebo
Placebo Comparator
Arm 3
pioglitazone (active control)
Drug: pioglitazone
Active Control

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • 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.

Exclusion Criteria:

  • 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:

      1. Documented myocardial infarction in the 6 months prior to Screening.
      2. 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.
      3. Unstable angina in the 6 months prior to Screening.
      4. 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.
      5. 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.
      6. 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.
      7. 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).
      8. 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:

    1. Digoxin
    2. Warfarin and other oral anticoagulants (aspirin and non-steroidal anti-inflammatory drugs are permitted)
    3. Bile acid sequestrants
    4. Niacin (excluding routine vitamin supplementation)
    5. Antiobesity agents (including fat absorption blocking agents)
    6. Oral or injectable corticosteroids (inhaled and intranasal corticosteroids are permitted)
    7. Loop diuretics
    8. Monoamine oxidase inhibitors and tricyclic amines
    9. Antiretroviral drugs
    10. St John's Wort
    11. 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00500331

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Locations
United States, Arizona
GSK Investigational Site
Mesa, Arizona, United States, 85206
United States, Florida
GSK Investigational Site
Hollywood, Florida, United States, 33023
GSK Investigational Site
Miami, Florida, United States, 33156
GSK Investigational Site
St. Cloud, Florida, United States, 34769
United States, Louisiana
GSK Investigational Site
Sunset, Louisiana, United States, 70584
United States, Maryland
GSK Investigational Site
Oxon Hill, Maryland, United States, 20745
United States, Nevada
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Las Vegas, Nevada, United States, 89106
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Las Vegas, Nevada, United States, 89016
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Las Vegas, Nevada, United States, 89128
United States, New Mexico
GSK Investigational Site
Albuquerque, New Mexico, United States, 87102
United States, Ohio
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Canal Fulton, Ohio, United States, 44614
United States, South Carolina
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Simpsonville, South Carolina, United States, 29681
United States, Texas
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San Antonio, Texas, United States, 78229
United States, Virginia
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Burke, Virginia, United States, 22015
Argentina
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Buenos Aries, Buenos Aires, Argentina, C1425AWC
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Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1012AAR
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Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1117ABH
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Cordoba, Córdova, Argentina, 5000
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Buenos Aires, Argentina, 1425
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Cordoba, Argentina, X5002AOQ
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Mendoza, Argentina, M5500CCG
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Quilmes, Argentina, 1878
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Tucuman, Argentina, 4000
Bulgaria
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Pleven, Bulgaria, 5800
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Plovdiv, Bulgaria, 4000
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Sofia, Bulgaria, 1606
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Sofia, Bulgaria, 1233
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Varna, Bulgaria, 9010
Chile
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Santiago, Región Metro De Santiago, Chile, 7510605
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Santiago, Región Metro De Santiago, Chile, 7500010
Costa Rica
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San José, Costa Rica
Czech Republic
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Brno, Czech Republic, 662 50
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Brno, Czech Republic, 625 00
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Brno, Czech Republic, 624 00
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Ceske Budejovice, Czech Republic, 370 87
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Cheb, Czech Republic, 350 02
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Havirov - Soumbrak, Czech Republic, 736 01
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Olomouc, Czech Republic, 779 00
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Prague, Czech Republic, 181 00
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Praha 5, Czech Republic, 15030
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Praha 5, Czech Republic, 158 00
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Praha 5, Czech Republic, 155 00
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Praha 5, Czech Republic, 158 00
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Semily, Czech Republic, 513 01
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Sumperk, Czech Republic, 78752
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Usti nad Labem, Czech Republic, 40001
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Znojmo, Czech Republic, 67035
Germany
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Bammental, Baden-Wuerttemberg, Germany, 69245
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Kippenheim, Baden-Wuerttemberg, Germany, 77971
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Mannheim, Baden-Wuerttemberg, Germany, 68161
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Weinheim, Baden-Wuerttemberg, Germany, 69469
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Haag, Bayern, Germany, 83527
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Hoehenkirchen-Siegertsbrunn, Bayern, Germany, 85635
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Lampertheim, Hessen, Germany, 68623
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Damme, Niedersachsen, Germany, 49401
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Hannover, Niedersachsen, Germany, 30161
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Hildesheim, Niedersachsen, Germany, 31139
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Bergkamen, Nordrhein-Westfalen, Germany, 59192
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Mainz, Rheinland-Pfalz, Germany, 55116
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Rhaunen, Rheinland-Pfalz, Germany, 55624
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Speyer, Rheinland-Pfalz, Germany, 67346
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Berlin, Germany, 10787
Hungary
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Budapest, Hungary, 1088
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Budapest, Hungary, 1036.
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Budapest, Hungary, 1021
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Budapest, Hungary, 1076
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Debrecen, Hungary, 4043
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Erd, Hungary, 2030
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Győr, Hungary, 9023
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Miskolc, Hungary, 3501
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Miskolc, Hungary, 3530
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Mosonmagyaróvár, Hungary, 9200
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Nyirtegyhaza, Hungary, 4400
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Pécs, Hungary, 7623
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Szentes, Hungary, 6600
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Szigetvar, Hungary, 7900
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Szombathely, Hungary, 9700
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Veszprem, Hungary, 8200
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Zalaegerszeg, Hungary, 8900
India
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Bangalore, India, 560017
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Bangalore, India, 560 054
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Bangalore, India, 560034
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Kochi, India, 682026
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Mumbai, India, 400007
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New Delhi, India, 110065
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Pune, India, 411004
Latvia
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Jelgava, Latvia, LV 3001
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Limbazi, Latvia, LV 4001
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Riga, Latvia, LV 1011
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Riga, Latvia, LV 1002
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Riga, Latvia, LV1058
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Riga, Latvia, LV 1012
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Riga, Latvia, LV1002
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Talsi, Latvia, LV 3201
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Tukums, Latvia, LV 3100
Lithuania
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Kaunas, Lithuania, LT-50009
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Kaunas, Lithuania, LT-51270
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Kaunas, Lithuania, LT-49335
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Vilnius, Lithuania, LT-07156
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Vilnius, Lithuania, LT-08661
Mexico
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Tijuana, Baja California Norte, Mexico, 22320
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Mexico City, Estado de México, Mexico, 14000
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Monterrey, Nuevo León, Mexico, 64460
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Durango, Mexico, 34079
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Mexico, Mexico, 14080
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Mexico, Mexico, 03100
New Zealand
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Auckland, New Zealand, 1701
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Auckland, New Zealand, 1311
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Hamilton, New Zealand, 2001
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Rotorua, New Zealand, 3201
Peru
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Lima, Peru, Lima 1
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Lima, Peru, Lima 29
Poland
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Bydgoszcz, Poland, 85-021
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Grudziadz, Poland, 86-300
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Lodz, Poland, 90-153
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Porabka, Poland, 43-353
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Siemianowice Slaskie, Poland, 41-103
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Wroclaw, Poland, 50-349
Puerto Rico
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Ponce, Puerto Rico, 00717
Romania
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Brasov, Romania, 500334
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Bucharest, Romania, 020045
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Deva, Romania, 330084
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Iasi, Romania, 700514
Russian Federation
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Moscow, Russian Federation, 115446
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Moscow, Russian Federation, 127411
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Moscow, Russian Federation, 125367
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Moscow, Russian Federation, 117 036
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St. Petersburg, Russian Federation, 197110
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St.-Petersburg, Russian Federation, 194354
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Tomsk, Russian Federation, 634009
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Tumen, Russian Federation, 625023
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Ufa, Russian Federation, 450083
South Africa
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Bellville, South Africa, 7530
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Gauteng, South Africa, 1459
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Orangegrove, Linksfield West, South Africa, 2192
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Parow, South Africa, 7505
GSK Investigational Site
Roodepoort, South Africa, 1709
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00500331     History of Changes
Other Study ID Numbers: KG2105255
Study First Received: January 24, 2007
Last Updated: November 7, 2013
Health Authority: Latvia: State Agency of Medicines
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Pioglitazone
HbA1c
Diabetes mellitus

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 31, 2014