Dose-Ranging Study In Subjects With Type 2 Diabetes Mellitus Who Are Treatment-Naive

NCT ID: NCT00495469

Last Updated: 2017-10-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-08-17
• Study Completion Date: 2008-06-05

Brief Summary

This is a dose-ranging study to evaluate the efficacy, safety and tolerability of a range of doses of GSK189075 (an SGLT2 inhibitor) compared to placebo, administered over 12 weeks in treatment-naive subjects with type 2 diabetes mellitus

Conditions

Diabetes Mellitus, Type 2

Keywords

Diabetes mellitus HbA1c

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

GSK189075

Participants will receive GSK189075 for 12 weeks

Group Type: EXPERIMENTAL

GSK189075

Intervention Type: DRUG

GSK189075 is available as a white, capsule-shaped tablet dosage form containing 50mg, 125mg, 250mg or 500mg of GSK189075 per tablet

Placebo

Participants will receive GSK189075 matching Placebo for 12 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Available as Placebo matching tablet to GSK189075

Interventions

GSK189075

GSK189075 is available as a white, capsule-shaped tablet dosage form containing 50mg, 125mg, 250mg or 500mg of GSK189075 per tablet

Intervention Type: DRUG

Placebo

Available as Placebo matching tablet to GSK189075

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subjects with a documented diagnosis of T2DM and HbA1c ≥7.0% and ≤9.5% measured by the central laboratory at Visit 1.

• Note: Subjects with HbA1c <7.5% must have a fasting fingerstick glucose ≥7 mmol/L (126 mg/dL) at Week 0, prior to randomization.
• Note: The proportion of subjects who are randomized with an HbA1c <7.5% will be limited to be no more than 20% (approximately 51 subjects)
• 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 childbearing and non-childbearing and 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 who have a current documented tubal ligation, or who are surgically sterile (i.e. documented total hysterectomy or bilateral oophorectomy), or females who are post-menopausal.

All females must have a negative urine pregnancy test on the day of, and prior to randomization.

• 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 <0.4 MIU/L (<0.4 MCIU/mL) or >5.5 mIU/L (>5.5 MCIU/mL) at Screening
• BMI of <22 kg/m2 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 within 3 months of screening
• Has taken insulin or any oral or injectable anti-diabetic medication ≥4 weeks at any time in the past
• 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 or the NYHA Class criteria 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.
• Based on local readings, the subject has an initial QTc interval (Bazett's)≥450msec at Screening, and after two additional ECGs taken 5 minutes apart, the average of the QTC interval from the three ECGs is ≥450msec.
• Other clinically significant ECG abnormalities which, in the opinion of the Investigator, may affect the interpretation of efficacy or 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 aminotransferase (ALT)
• aspartate aminotransferase (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 calculated by Quest at Visit using the Modification of Diet in Renal Disease (MDRD) equation

•≥1+ protein on urine dipstick

• Trace or ≥1+ leukocyte esterase on urine dipstick
• Trace or ≥1+ blood on urine dipstick
• Positive nitrite on urine dipstick
• Recurrent genitourinary tract infections defined as ≥2 episodes of complicated or uncomplicated cystitis or pyelonephritis in the 6 months prior to Screening.

• Concurrent Disease
• Has any concurrent condition or any clinically significant abnormality identified on the screening physical examination, laboratory tests (including blood electrolytes), ECG, 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.).
• History of malignancy within the past 5 years other than superficial squamous cell carcinoma (non-invasive on pathology) or basal cell carcinoma (successfully treated with local excision).
• History of 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, topical and intranasal corticosteroids are permitted)
• Loop diuretics
• Monoamine oxidase inhibitors and tricyclic amines
• Antiretroviral drugs
• St John's Wort
• Oral chromium 9.Breast Feeding 10.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 alcohol of >21 units or an average daily intake of >3 units (males) or an average weekly intake of >14 units or an average daily intake of >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 or capsule excipients, or history of drug or other allergy, which, in the opinion of the responsible study physician, contraindicates participation.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Mesa, Arizona, United States

GSK Investigational Site

Artesia, California, United States

GSK Investigational Site

Buena Park, California, United States

GSK Investigational Site

Fresno, California, United States

GSK Investigational Site

Greenbrae, California, United States

GSK Investigational Site

La Jolla, California, United States

GSK Investigational Site

Norwalk, California, United States

GSK Investigational Site

Petaluma, California, United States

GSK Investigational Site

Sacramento, California, United States

GSK Investigational Site

San Mateo, California, United States

GSK Investigational Site

Santa Ana, California, United States

GSK Investigational Site

Tarzana, California, United States

GSK Investigational Site

Torrance, California, United States

GSK Investigational Site

Deland/Florida, Florida, United States

GSK Investigational Site

Hollywood, Florida, United States

GSK Investigational Site

Jacksonville/Florida, Florida, United States

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

Ocoee/Florida, Florida, United States

GSK Investigational Site

Saint Cloud, Florida, United States

GSK Investigational Site

Atlanta, Georgia, United States

GSK Investigational Site

Atlanta, Georgia, United States

GSK Investigational Site

Bloomingdale, Illinois, United States

GSK Investigational Site

Chicago, Illinois, United States

GSK Investigational Site

Oak Brook, Illinois, United States

GSK Investigational Site

South Bend, Indiana, United States

GSK Investigational Site

Lafayette, Louisiana, United States

GSK Investigational Site

Lake Charles, Louisiana, United States

GSK Investigational Site

Oxon Hill, Maryland, United States

GSK Investigational Site

Boston, Massachusetts, United States

GSK Investigational Site

Gulfport, Mississippi, United States

GSK Investigational Site

Jackson, Mississippi, United States

GSK Investigational Site

Kosciusko, Mississippi, United States

GSK Investigational Site

Rolling Fork, Mississippi, United States

GSK Investigational Site

Chesterfield, Missouri, United States

GSK Investigational Site

Saint Louis/Missouri, Missouri, United States

GSK Investigational Site

Henderson, Nevada, United States

GSK Investigational Site

Las Vegas, Nevada, United States

GSK Investigational Site

Las Vegas, Nevada, United States

GSK Investigational Site

Las Vegas, Nevada, United States

GSK Investigational Site

Las Vegas, Nevada, United States

GSK Investigational Site

Clifton, New Jersey, United States

GSK Investigational Site

Albuquerque, New Mexico, United States

GSK Investigational Site

Commack, New York, United States

GSK Investigational Site

Ithaca, New York, United States

GSK Investigational Site

New York, New York, United States

GSK Investigational Site

Asheboro/North Carolina, North Carolina, United States

GSK Investigational Site

Canal Fulton, Ohio, United States

GSK Investigational Site

Bensalem/Pennsylvania, Pennsylvania, United States

GSK Investigational Site

West Chester, Pennsylvania, United States

GSK Investigational Site

Manning, South Carolina, United States

GSK Investigational Site

Simpsonville, South Carolina, United States

GSK Investigational Site

Athens/Tennessee, Tennessee, United States

GSK Investigational Site

Corpus Christi, Texas, United States

GSK Investigational Site

Dallas, Texas, United States

GSK Investigational Site

Dallas, Texas, United States

GSK Investigational Site

Harlingen/Texas, Texas, United States

GSK Investigational Site

Houston, Texas, United States

GSK Investigational Site

Houston, Texas, United States

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Houston, Texas, United States

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Midland, Texas, United States

GSK Investigational Site

San Anonio, Texas, United States

GSK Investigational Site

San Antonio, Texas, United States

GSK Investigational Site

Burke, Virginia, United States

GSK Investigational Site

Bellevue, Washington, United States

GSK Investigational Site

Langley, British Columbia, Canada

GSK Investigational Site

Bathurst, New Brunswick, Canada

GSK Investigational Site

Bay Roberts, Newfoundland and Labrador, Canada

GSK Investigational Site

Brampton, Ontario, Canada

GSK Investigational Site

Mississauga, Ontario, Canada

GSK Investigational Site

Oakville, Ontario, Canada

GSK Investigational Site

Ottawa, Ontario, Canada

GSK Investigational Site

Thornhill, Ontario, Canada

GSK Investigational Site

Toronto, Ontario, Canada

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Toronto, Ontario, Canada

GSK Investigational Site

L'Ancienne-Lorette, Quebec, Canada

GSK Investigational Site

Québec, , Canada

GSK Investigational Site

Brno, , Czechia

GSK Investigational Site

Brno, , Czechia

GSK Investigational Site

Prague, , Czechia

GSK Investigational Site

Prague, , Czechia

GSK Investigational Site

Pärnu, , Estonia

GSK Investigational Site

Tallinn, , Estonia

GSK Investigational Site

Tallinn, , Estonia

GSK Investigational Site

Tartu, , Estonia

GSK Investigational Site

Allmendingen, Baden-Wurttemberg, Germany

GSK Investigational Site

Wangen, Baden-Wurttemberg, Germany

GSK Investigational Site

Großheirath, Bavaria, Germany

GSK Investigational Site

Hohenau, Bavaria, Germany

GSK Investigational Site

Künzing, Bavaria, Germany

GSK Investigational Site

Munich, Bavaria, Germany

GSK Investigational Site

Munich, Bavaria, Germany

GSK Investigational Site

Parsberg, Bavaria, Germany

GSK Investigational Site

Ruhmannsfelden, Bavaria, Germany

GSK Investigational Site

Sulzbach-Rosenberg, Bavaria, Germany

GSK Investigational Site

Falkensee, Brandenburg, Germany

GSK Investigational Site

Brinkum/Stuhr, Lower Saxony, Germany

GSK Investigational Site

Einbeck, Lower Saxony, Germany

GSK Investigational Site

Hanover, Lower Saxony, Germany

GSK Investigational Site

Lüneburg, Lower Saxony, Germany

GSK Investigational Site

Tostedt, Lower Saxony, Germany

GSK Investigational Site

Haßloch, Rhineland-Palatinate, Germany

GSK Investigational Site

Ingelheim, Rhineland-Palatinate, Germany

GSK Investigational Site

Dresden, Saxony, Germany

GSK Investigational Site

Freital, Saxony, Germany

GSK Investigational Site

Schmiedeberg, Saxony, Germany

GSK Investigational Site

Wolmirstedt, Saxony-Anhalt, Germany

GSK Investigational Site

Lübeck, Schleswig-Holstein, Germany

GSK Investigational Site

Berlin, , Germany

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Berlin, , Germany

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Berlin, , Germany

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Berlin, , Germany

GSK Investigational Site

Athens, , Greece

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Athens, , Greece

GSK Investigational Site

Thessaloniki, , Greece

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Thessaloniki, , Greece

GSK Investigational Site

Bangalore, , India

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Bangalore, , India

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Chennai, , India

GSK Investigational Site

Mumbai, , India

GSK Investigational Site

Pune, , India

GSK Investigational Site

Kaunas, , Lithuania

GSK Investigational Site

Kaunas, , Lithuania

GSK Investigational Site

Kaunas, , Lithuania

GSK Investigational Site

Vilnius, , Lithuania

GSK Investigational Site

Guadalajara, Jalisco, Mexico

GSK Investigational Site

Cuernavaca, Morelos, Mexico

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Mérida, Yucatán, Mexico

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Durango, , Mexico

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Rotorua, , New Zealand

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Bydgoszcz, , Poland

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Porąbka, , Poland

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Siemianowice Śląskie, , Poland

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Wroclaw, , Poland

GSK Investigational Site

Aibonito/Puerto Rico, Puerto Rico, Puerto Rico

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Trujillo Alto/Puerto Rico, Puerto Rico, Puerto Rico

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Caguas, , Puerto Rico

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Carolina, , Puerto Rico

GSK Investigational Site

Ponce, , Puerto Rico

GSK Investigational Site

Rio Piedras, , Puerto Rico

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Arad, , Romania

GSK Investigational Site

Brasov, , Romania

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Sfântu Gheorghe, , Romania

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Timișoara, , Romania

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint-Peterburgh, , Russia

GSK Investigational Site

Tomsk, , Russia

GSK Investigational Site

Tyumen, , Russia

GSK Investigational Site

Lenasia South, Gauteng, South Africa

GSK Investigational Site

Bellville, , South Africa

GSK Investigational Site

Gauteng, , South Africa

GSK Investigational Site

Parow, , South Africa

GSK Investigational Site

Roodepoort, , South Africa

GSK Investigational Site

Dnipropetrovsk, , Ukraine

GSK Investigational Site

Kyiv, , Ukraine

GSK Investigational Site

Vinnitsa, , Ukraine

Countries

Costa Rica; Hungary; Peru; United States; Canada; Czechia; Estonia; Germany; Greece; India; Lithuania; Mexico; New Zealand; Poland; Puerto Rico; Romania; Russia; South Africa; Ukraine

References

Sykes AP, Kemp GL, Dobbins R, O'Connor-Semmes R, Almond SR, Wilkison WO, Walker S, Kler L. Randomized efficacy and safety trial of once-daily remogliflozin etabonate for the treatment of type 2 diabetes. Diabetes Obes Metab. 2015 Jan;17(1):98-101. doi: 10.1111/dom.12393. Epub 2014 Nov 3.

Reference Type: DERIVED

PMID: 25238025 (View on PubMed)

Other Identifiers

KG2110375

Identifier Type: -

Identifier Source: org_study_id