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

NCT00500331 | Completed Phase 2 Results

• 1 other identifier: KG2105255
• Study Type: interventional
• Target: 334
• Locations: 19 countries
• Sites: 136

Brief Summary

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

Conditions

Diabetes Mellitus, Type 2

Keywords

Pioglitazone; HbA1c; Diabetes mellitus

Outcome Measures

Primary Outcomes (1)

• Change From Baseline (Week 0) in Glycosylated Hemoglobin (HbA1c) (%) at Week 12

  Fasted blood samples for HbA1c were collected at Baseline and Week 12. Participants were required to fast for at least 8 hours prior to laboratory samples and were told not to take the morning dose of study medication on these visit days and to refrain from eating until instructed to do so by study personnel in the clinic. When the participant had not fasted, the participant was rescheduled to return to the clinic to have a fasted sample taken. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Only those participants with a value at Baseline and at Week 12 (after Last Observation Carried Forward \[LOCF\]) were used for this analysis. Adjusted mean is presented as least square mean.

  Baseline (Week 0) and Week 12

Secondary Outcomes (17)

• Change From Baseline in HbA1c (%) at Weeks 4 and 8

  Baseline (Week 0) and Week 4 and Week 8

• Change From Baseline to Week 12 in Fasting Plasma Glucose (FPG) at Weeks 4, 8 and 12

  Baseline (Week 0) and Week 4, Week 8 and Week 12

• Change From Baseline to Week 12 in Fructosamine

  Baseline (Week 0) to Week 12

• Change From Baseline to Week 12 in Fasting Insulin

  Baseline (Week 0) to Week 12

• Number of Participants at Week 12 With: HbA1c <= 6.5%, HbA1c <7.0%; FPG <7 Mmo/L, FPG <7.8 mmol/L; FPG <5.5 mmol/L; a Decrease From Baseline of HbA1c >= 0.7%; a Decrease From Baseline of FPG ≥1.7 mmol/L

  Week 12

Study Arms (3)

Arm 1

EXPERIMENTAL

GSK189075

Drug: GSK189075

Arm 2

PLACEBO COMPARATOR

Placebo

Other: Placebo

Arm 3

OTHER

pioglitazone (active control)

Drug: pioglitazone

Interventions

GSK189075 DRUG

Experimental Drug

Arm 1

pioglitazone DRUG

Active Control

Arm 3

Placebo OTHER

Placebo Comparator

Arm 2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (136)

GSK Investigational Site

Mesa, Arizona, 85206, United States

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GSK Investigational Site

Hollywood, Florida, 33023, United States

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GSK Investigational Site

Miami, Florida, 33156, United States

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GSK Investigational Site

Saint Cloud, Florida, 34769, United States

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Sunset, Louisiana, 70584, United States

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GSK Investigational Site

Oxon Hill, Maryland, 20745, United States

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Las Vegas, Nevada, 89016, United States

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GSK Investigational Site

Las Vegas, Nevada, 89106, United States

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GSK Investigational Site

Las Vegas, Nevada, 89128, United States

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GSK Investigational Site

Albuquerque, New Mexico, 87102, United States

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GSK Investigational Site

Canal Fulton, Ohio, 44614, United States

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GSK Investigational Site

Simpsonville, South Carolina, 29681, United States

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GSK Investigational Site

San Antonio, Texas, 78229, United States

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Burke, Virginia, 22015, United States

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GSK Investigational Site

Buenos Aries, Buenos Aires, C1425AWC, Argentina

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GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1012AAR, Argentina

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Ciudad Autónoma de Buenos Aires, Buenos Aires, C1117ABH, Argentina

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GSK Investigational Site

Córdoba, Córdoba Province, 5000, Argentina

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Buenos Aires, 1425, Argentina

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Córdoba, X5002AOQ, Argentina

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Mendoza, M5500CCG, Argentina

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Quilmes, 1878, Argentina

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GSK Investigational Site

San Miguel de Tucumán, 4000, Argentina

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Pleven, 5800, Bulgaria

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Plovdiv, 4000, Bulgaria

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Sofia, 1233, Bulgaria

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Sofia, 1606, Bulgaria

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Varna, 9010, Bulgaria

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GSK Investigational Site

Santiago, Región Metro de Santiago, 7500010, Chile

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Santiago, Región Metro de Santiago, 7510605, Chile

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San José, Costa Rica

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Brno, 624 00, Czechia

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Brno, 625 00, Czechia

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Brno, 662 50, Czechia

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GSK Investigational Site

Cheb, 350 02, Czechia

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České Budějovice, 370 87, Czechia

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GSK Investigational Site

Havirov - Soumbrak, 736 01, Czechia

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Olomouc, 779 00, Czechia

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Prague, 15030, Czechia

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Prague, 155 00, Czechia

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Prague, 158 00, Czechia

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GSK Investigational Site

Prague, 181 00, Czechia

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GSK Investigational Site

Semily, 513 01, Czechia

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Šumperk, 78752, Czechia

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Ústí nad Labem, 40001, Czechia

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GSK Investigational Site

Znojmo, 67035, Czechia

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Bammental, Baden-Wurttemberg, 69245, Germany

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Kippenheim, Baden-Wurttemberg, 77971, Germany

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Mannheim, Baden-Wurttemberg, 68161, Germany

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Weinheim, Baden-Wurttemberg, 69469, Germany

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GSK Investigational Site

Haag, Bavaria, 83527, Germany

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GSK Investigational Site

Höhenkirchen-Siegertsbrunn, Bavaria, 85635, Germany

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Lampertheim, Hesse, 68623, Germany

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Damme, Lower Saxony, 49401, Germany

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Hanover, Lower Saxony, 30161, Germany

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Hildesheim, Lower Saxony, 31139, Germany

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Bergkamen, North Rhine-Westphalia, 59192, Germany

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GSK Investigational Site

Mainz, Rhineland-Palatinate, 55116, Germany

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Rhaunen, Rhineland-Palatinate, 55624, Germany

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Speyer, Rhineland-Palatinate, 67346, Germany

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Berlin, 10787, Germany

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Budapest, 1021, Hungary

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Budapest, 1036., Hungary

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Budapest, 1076, Hungary

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Budapest, 1088, Hungary

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Debrecen, 4043, Hungary

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GSK Investigational Site

Érd, 2030, Hungary

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Győr, 9023, Hungary

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Miskolc, 3501, Hungary

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GSK Investigational Site

Miskolc, 3530, Hungary

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GSK Investigational Site

Mosonmagyaróvár, 9200, Hungary

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GSK Investigational Site

Nyirtegyhaza, 4400, Hungary

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GSK Investigational Site

Pécs, 7623, Hungary

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Szentes, 6600, Hungary

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GSK Investigational Site

Szigetvár, 7900, Hungary

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GSK Investigational Site

Szombathely, 9700, Hungary

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GSK Investigational Site

Veszprém, 8200, Hungary

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GSK Investigational Site

Zalaegerszeg, 8900, Hungary

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GSK Investigational Site

Bangalore, 560 054, India

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GSK Investigational Site

Bangalore, 560017, India

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GSK Investigational Site

Bangalore, 560034, India

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GSK Investigational Site

Kochi, 682026, India

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GSK Investigational Site

Mumbai, 400007, India

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GSK Investigational Site

New Delhi, 110065, India

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Pune, 411004, India

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GSK Investigational Site

Jelgava, LV 3001, Latvia

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Limbaži, LV 4001, Latvia

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Riga, LV 1002, Latvia

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Riga, LV 1011, Latvia

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Riga, LV 1012, Latvia

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Riga, LV1002, Latvia

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Riga, LV1058, Latvia

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Talsi, LV 3201, Latvia

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Tukums, LV 3100, Latvia

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Kaunas, LT-49335, Lithuania

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Kaunas, LT-50009, Lithuania

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Kaunas, LT-51270, Lithuania

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Vilnius, LT-07156, Lithuania

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GSK Investigational Site

Vilnius, LT-08661, Lithuania

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GSK Investigational Site

Tijuana, Baja California Norte, 22320, Mexico

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Monterrey, Nuevo León, 64460, Mexico

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GSK Investigational Site

México, State of Mexico, 14000, Mexico

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GSK Investigational Site

Durango, 34079, Mexico

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GSK Investigational Site

México, 03100, Mexico

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GSK Investigational Site

México, 14080, Mexico

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GSK Investigational Site

Auckland, 1311, New Zealand

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GSK Investigational Site

Auckland, 1701, New Zealand

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GSK Investigational Site

Hamilton, 2001, New Zealand

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GSK Investigational Site

Rotorua, 3201, New Zealand

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Lima, Lima 1, Peru

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Lima, Lima 29, Peru

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Bydgoszcz, 85-021, Poland

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Grudziądz, 86-300, Poland

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Lodz, 90-153, Poland

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Porąbka, 43-353, Poland

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GSK Investigational Site

Siemianowice Śląskie, 41-103, Poland

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Wroclaw, 50-349, Poland

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GSK Investigational Site

Ponce, 00717, Puerto Rico

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GSK Investigational Site

Brasov, 500334, Romania

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GSK Investigational Site

Bucharest, 020045, Romania

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GSK Investigational Site

Deva, 330084, Romania

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GSK Investigational Site

Iași, 700514, Romania

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GSK Investigational Site

Moscow, 115446, Russia

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GSK Investigational Site

Moscow, 117 036, Russia

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GSK Investigational Site

Moscow, 125367, Russia

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GSK Investigational Site

Moscow, 127411, Russia

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GSK Investigational Site

Saint Petersburg, 194354, Russia

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GSK Investigational Site

Saint Petersburg, 197110, Russia

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GSK Investigational Site

Tomsk, 634009, Russia

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GSK Investigational Site

Tyumen, 625023, Russia

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GSK Investigational Site

Ufa, 450083, Russia

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GSK Investigational Site

Bellville, 7530, South Africa

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GSK Investigational Site

Gauteng, 1459, South Africa

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GSK Investigational Site

Orangegrove, Linksfield West, 2192, South Africa

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GSK Investigational Site

Parow, 7505, South Africa

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GSK Investigational Site

Roodepoort, 1709, South Africa

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Related Publications (1)

• Sykes AP, O'Connor-Semmes R, Dobbins R, Dorey DJ, Lorimer JD, Walker S, Wilkison WO, Kler L. Randomized trial showing efficacy and safety of twice-daily remogliflozin etabonate for the treatment of type 2 diabetes. Diabetes Obes Metab. 2015 Jan;17(1):94-7. doi: 10.1111/dom.12391. Epub 2014 Nov 3.

  PMID: 25223369 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2007
• First Posted: July 12, 2007
• Study Start: January 23, 2007
• Primary Completion: February 14, 2008
• Study Completion: February 14, 2008
• Last Updated: December 6, 2017
• Results First Posted: December 6, 2017

Record last verified: 2017-09

Locations

HU (17); CO (1); PR (1); IN (7); LA (9); CL (2); LI (5); NZ (4); RU (9); BU (5); ME (6); US (14); DE (15); PE (2); AR (9); CZ (15); RO (4); ZA (5); PL (6)