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
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
250
Mean Change From Baseline in Hemoglobin A1c (Glycosylated Hemoglobin) (HbA1c) at Week 12
The blood samples were collected at Baseline, Week 4, Week 8 and at Week 12 (or early withdrawal). Baseline was defined as the period immediately preceding treatment with study medication (Week 0). For participants with missing Baseline assessment, the last pre-therapy value prior to the Baseline visit was used as the Baseline value. Change from Baseline was the value at Week 12 minus Baseline value. The primary analysis was performed on the Intent-to-Treat (ITT) Population with Last observation carried forward (LOCF). Adjusted mean is presented as least square (LS) mean.
Time frame: Baseline (Week 0) and at Week 12
Mean Change From Baseline in HbA1c at Weeks 4 and 8
The blood samples were collected at Baseline, Week 4, Week 8 and at Week 12 (or early withdrawal). Baseline was defined as the period immediately preceding treatment with study medication (Week 0). For participants with missing Baseline assessment, the last pre-therapy value prior to the Baseline visit was used as the Baseline value. Change from Baseline was the value at Week 4 and 8 minus Baseline value. The primary analysis was performed on the ITT Population with LOCF.
Time frame: Baseline (Week 0) and at Week 4 nad 8
Mean Change From Baseline to Week 12 in Fasting Plasma Glucose (FPG)
The samples were collected at Baseline, Week 2, Week 4, Week 8, Week 12 and Week 14 (follow up). Participants were asked to be on fast for at least 8 hours prior to each study visits and collection of lab samples. Baseline was defined as the period immediately preceding treatment with study medication (Week 0). For participants with missing Baseline assessment, the last pre-therapy value prior to the Baseline visit was used as the Baseline value. Change from Baseline was the value at Week 12 minus Baseline value. The primary analysis was performed on the ITT Population with LOCF. Adjusted mean is presented as LS mean.
Time frame: Baseline (Week 0) and at Week 12
Mean Change From Baseline to Week 12 in Fructosamine (Corrected)
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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
...and 147 more locations
The blood samples were collected at Baseline, Week 2, Week 4, Week 8, Week 12 and Week 14 (follow up). Participants were asked to be on fast for at least 8 hours prior to each study visits and collection of lab samples. Baseline was defined as the period immediately preceding treatment with study medication (Week 0). For participants with missing Baseline assessment, the last pre-therapy value prior to the Baseline visit was used as the Baseline value. Change from Baseline was the value at Week 12 minus Baseline value. The primary analysis was performed on the ITT Population with LOCF. Adjusted mean is presented as LS mean.
Time frame: Baseline (Week 0) and at Week 12
Number of Participants Who Were HbA1c Responders at Week 12
Differences between treatment groups in the proportion of participants who achieved HbA1c targets of \<=6.5% and \<7% at Week 12 in the ITT population with LOCF were assessed based on a logistic regression model with terms included for treatment and Baseline HbA1c. Differences between treatment groups in the proportion of participants who achieved a clinically meaningful decreases from Baseline in HbA1c (\>=0.7%) at Week 12 were assessed in the same manner.
Time frame: Week 12
Number of Participants Who Were Fasting Plasma Glucose (FPG) Responders at Week 12
Differences between treatment groups in the proportion of participants who achieved FPG targets of \<7.0 millimoles per liter (mmol/L) (126 milligrams per deciliter \[mg/dL\]) and \<7.8 mmol/L (140 mg/dL) at Week 12 in the ITT population with LOCF were assessed based on a logistic regression model with terms included for treatment and Baseline FPG. The proportion of participants who achieved the target of \<5.5 mmol/L (100 mg/dL) at Week 12 within each treatment group were summarized only. Differences between treatment groups in the proportion of participants who achieved a clinically meaningful decreases from Baseline in FPG (1.7 mmol/L \[\>=30 mg/dL\]) at Week 12 were assessed in the same manner.
Time frame: Week 12
Mean Change From Baseline to Week 12 in Triglycerides
Samples were collected at Baseline and at Week 12 (or early withdrawal). Baseline was defined as the period immediately preceding treatment with study medication (Week 0). For participants with missing Baseline assessment, the last pre-therapy value prior to the Baseline visit was used as the Baseline value. Change from Baseline was the value at Week 12 minus Baseline value. Adjusted mean is presented as LS mean.
Time frame: Baseline (Week 0) and at Week 12
Mean Change From Baseline to Week 12 in Total Cholesterol
Samples were collected at Baseline and at Week 12 (or early withdrawal). Baseline was defined as the period immediately preceding treatment with study medication (Week 0). For participants with missing Baseline assessment, the last pre-therapy value prior to the Baseline visit was used as the Baseline value. Change from Baseline was the value at Week 12 minus Baseline value. Adjusted mean is presented as LS mean.
Time frame: Baseline (Week 0) and at Week 12
Mean Change From Baseline to Week 12 in Low Density Lipoprotein Cholesterol (LDL-c)
Blood samples were collected at Baseline and at Week 12 (or early withdrawal). Baseline was defined as the period immediately preceding treatment with study medication (Week 0). For participants with missing Baseline assessment, the last pre-therapy value prior to the Baseline visit was used as the Baseline value. Change from Baseline was the value at Week 12 minus Baseline value. Adjusted mean is presented as LS mean.
Time frame: Baseline (Week 0) and Week 12
Mean Change From Baseline to Week 12 in High Density Lipoprotein Cholesterol (HDL-c)
Blood samples were collected at Baseline and at Week 12 (or early withdrawal). Baseline was defined as the period immediately preceding treatment with study medication (Week 0). For participants with missing Baseline assessment, the last pre-therapy value prior to the Baseline visit was used as the Baseline value. Change from Baseline was the value at Week 12 minus Baseline value. Adjusted mean is presented as LS mean.
Time frame: Baseline (Week 0) and Week 12
Mean Change From Baseline to Week 12 in LDL-c/HDL-c Ratio
Blood samples were collected at Baseline and at Week 12 (or early withdrawal). Baseline was defined as the period immediately preceding treatment with study medication (Week 0). For participants with missing Baseline assessment, the last pre-therapy value prior to the Baseline visit was used as the Baseline value. Change from Baseline was the value at Week 12 minus Baseline value. Adjusted mean is presented as LS mean.
Time frame: Baseline (Week 0) and Week 12
Mean Change From Baseline to Week 12 in Total Cholesterol/HDL-c Ratio
Blood samples were collected at Baseline and at Week 12 (or early withdrawal). Baseline was defined as the period immediately preceding treatment with study medication (Week 0). For participants with missing Baseline assessment, the last pre-therapy value prior to the Baseline visit was used as the Baseline value. Change from Baseline was the value at Week 12 minus Baseline value. Adjusted mean is presented as LS mean.
Time frame: Baseline (Week 0) and Week 12
Mean Change From Baseline to Week 12 in Body Weight
Body weight measurement was taken at Baseline, Week 2, Week 4, Week 8, Week 12 and at Week 14 (follow up). Baseline was defined as the period immediately preceding treatment with study medication (Week 0). For participants with missing Baseline assessment, the last pre-therapy value prior to the Baseline visit was used as the Baseline value. Change from Baseline was the value at Week 12 minus Baseline value. Adjusted mean is presented as LS mean.
Time frame: Baseline (Week 0) and Week 12
Number of Participants With Any On-therapy Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE was defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE was defined as any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
Time frame: Up to Week 12
Number of Participants With On-therapy Hypoglycemia
Participants were provided with a Daily Glucose Monitoring Log to record glucose meter readings and to record symptoms of hypoglycemia. A separate electronic case report form (eCRF) page was provided to capture events of hypoglycemia.
Time frame: Up to Week 12
Number of Participants With Vital Signs of Potential Clinical Importance (PCI) at Any Time on Therapy
Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) were measured pre-dose in duplicate, after the participant has been lying quietly for 5 minutes, and then in duplicate 3 minutes after standing up. Participants were asked to refrain from smoking for at least 30 minutes prior to vital sign measurements.
Time frame: Up to Week 12
Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Any Time Post-Baseline
Full 12-lead ECGs were recorded at Randomization (Week 0), Week 4, and Week 12 or early withdrawal. If the QTc was \>500 milliseconds on the locally read ECG recording, an additional 2 ECG recordings at 10 minute intervals were made at that visit. If the average QTc for the 3 recordings was \>500 milliseconds, the participant was withdrawn from the study.
Time frame: Up to Week 12
Number of Participants With Abnormal Chemistry Value of PCI at Any Time on Therapy
Chemistry parameters: Albumin, Alkaline phosphatase, Alanine animotransferase, Aspartate aminotransferase, Total billirubin, Calcium, Carbon dioxide/Bicarbonate, Glucose, Potassium, Sodium, Phosphorus and Total protein were assessed for abnormal PCI values. Participants were instructed to fast for at least 8 hours prior to all study visits for the collection of laboratory samples. Samples were collected at Baseline, Week 2, Week 4, Week 8, Week 12 and at Week 14 (follow up).
Time frame: Up to Week 12
Number of Participants With Abnormal Hematology Value of PCI at Any Time on Therapy
Hematology parameters: Hemoglobin, Hematocrit, Platelet count and White blood cells were assessed for abnormal PCI values. Participants were instructed to fast for at least 8 hours prior to all study visits for the collection of laboratory samples. Samples were collected at Baseline, Week 2, Week 4, Week 8, Week 12 and at Week 14 (follow up).
Time frame: Up to Week 12