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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00495469
Recruitment Status : Completed
First Posted : July 3, 2007
Results First Posted : October 30, 2017
Last Update Posted : October 30, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 2
Interventions Drug: GSK189075
Drug: Placebo
Enrollment 250

Recruitment Details The study was conducted at 130 centers in 14 countries (9 European, 3 International countries, Canada, and the United States) during the period from 17 August 2007 to 5 June 2008.
Pre-assignment Details A total of 822 participants with Type 2 Diabetes Mellitus who were treatment naïve, entered the 2-week screening period. Of these, 570 were screen failures. The primary reason for screening failure was the participant not meeting eligibility criteria. Out of 252 randomized participants, 250 participants received study drug.
Arm/Group Title Placebo GSK189075 100 mg QD GSK189075 250 mg QD GSK189075 500 mg QD GSK189075 1000 mg QD GSK189075 250 mg BID Pioglitazone 30 mg QD
Hide Arm/Group Description Participants received 2 placebo tablets matching for GSK189075 twice daily (BID) before breakfast and dinner and 1 placebo capsule matching for Pioglitazone once daily (QD) before breakfast for 12 weeks Participants received 2 tablets of GSK189075 50 milligrams (mg) each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks. Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks. Participants received 2 tablets of GSK189075 250 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks. Participants received 2 tablets of GSK189075 500 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks. Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 tablets of GSK189075 125 mg each before dinner daily for 12 weeks. Participants received 2 placebo tablets matching GSK189075, 1 capsule of Pioglitazone 30 mg before breakfast and 2 placebo tablets matching GSK189075 before dinner daily for 12 weeks.
Period Title: Overall Study
Started 36 37 34 36 36 36 35
Completed 30 30 27 32 31 31 30
Not Completed 6 7 7 4 5 5 5
Reason Not Completed
Adverse Event             0             1             3             0             1             1             1
Lost to Follow-up             1             1             3             1             0             0             0
Protocol Violation             0             0             0             0             1             2             0
Withdrawal by Subject             5             3             1             3             3             2             3
Lack of Efficacy             0             0             0             0             0             0             1
Liver function test abnormality             0             1             0             0             0             0             0
ST depression at randomisation in ECG             0             1             0             0             0             0             0
Arm/Group Title Placebo GSK189075 100 mg QD GSK189075 250 mg QD GSK189075 500 mg QD GSK189075 1000 mg QD GSK189075 250 mg BID Pioglitazone 30 mg QD Total
Hide Arm/Group Description Participants received 2 placebo tablets matching for GSK189075 BID before breakfast and dinner and 1 placebo capsule matching for Pioglitazone QD before breakfast for 12 weeks Participants received 2 tablets of GSK189075 50 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks. Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks. Participants received 2 tablets of GSK189075 250 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks. Participants received 2 tablets of GSK189075 500 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks. Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 tablets of GSK189075 125 mg each before dinner daily for 12 weeks. Participants received 2 placebo tablets matching GSK189075, 1 capsule of Pioglitazone 30 mg before breakfast and 2 placebo tablets matching GSK189075 before dinner daily for 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 36 37 34 36 36 36 35 250
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 36 participants 37 participants 34 participants 36 participants 36 participants 36 participants 35 participants 250 participants
50.6  (10.60) 53.5  (9.35) 54.4  (9.57) 52.6  (10.91) 54.5  (10.19) 50.0  (10.21) 53.2  (10.35) 52.7  (10.19)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 37 participants 34 participants 36 participants 36 participants 36 participants 35 participants 250 participants
Female
20
  55.6%
19
  51.4%
14
  41.2%
23
  63.9%
13
  36.1%
21
  58.3%
16
  45.7%
126
  50.4%
Male
16
  44.4%
18
  48.6%
20
  58.8%
13
  36.1%
23
  63.9%
15
  41.7%
19
  54.3%
124
  49.6%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 36 participants 37 participants 34 participants 36 participants 36 participants 36 participants 35 participants 250 participants
African American/African Heritage 2 3 3 4 2 4 1 19
American Indian or Alaska Native 0 0 0 0 0 1 2 3
Asian - Central/South Asian Heritage 5 7 3 2 5 5 2 29
Asian - East Asian Heritage 1 0 0 0 0 0 0 1
Asian - South East Asian Heritage 0 1 1 0 0 1 0 3
White - Arabic/North African Heritage 2 1 0 0 3 1 1 8
White - White/Caucasian/European Heritage 25 19 24 24 22 23 23 160
Mixed Race 1 6 3 6 4 1 6 27
1.Primary Outcome
Title Mean Change From Baseline in Hemoglobin A1c (Glycosylated Hemoglobin) (HbA1c) at Week 12
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population consisted of all randomized participants who received at least one dose of study medication, had a Baseline assessment, and had at least one corresponding on-therapy efficacy assessment. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK189075 100 mg QD GSK189075 250 mg QD GSK189075 500 mg QD GSK189075 1000 mg QD GSK189075 250 mg BID Pioglitazone 30 mg QD
Hide Arm/Group Description:
Participants received 2 placebo tablets matching for GSK189075 BID before breakfast and dinner and 1 placebo capsule matching for Pioglitazone QD before breakfast for 12 weeks
Participants received 2 tablets of 50 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of 250 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of 500 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 tablets of GSK189075 125 mg each before dinner daily for 12 weeks.
Participants received 2 placebo tablets matching GSK189075, 1 capsule of 30 mg before breakfast and 2 placebo tablets matching GSK189075 before dinner daily for 12 weeks.
Overall Number of Participants Analyzed 33 36 32 34 35 35 34
Least Squares Mean (Standard Error)
Unit of Measure: Percentage
-0.19  (0.141) -0.53  (0.135) -0.75  (0.143) -0.53  (0.139) -0.85  (0.137) -0.78  (0.137) -0.38  (0.139)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 100 mg QD, GSK189075 250 mg QD, GSK189075 500 mg QD, GSK189075 1000 mg QD
Comments [Not Specified]
Type of Statistical Test Other
Comments Tukey’s trend test for dose response
Statistical Test of Hypothesis P-Value 0.003
Comments Tukey’s trend test adjusts for multiplicity with statistical significance based on p-value <0.05
Method ANCOVA
Comments Change=Baseline+Treatment
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 100 mg QD, GSK189075 250 mg QD, GSK189075 500 mg QD
Comments [Not Specified]
Type of Statistical Test Other
Comments Tukey’s trend test for dose response
Statistical Test of Hypothesis P-Value 0.047
Comments Tukey’s trend test adjusts for multiplicity with statistical significance based on p-value <0.05.
Method ANCOVA
Comments Change=Baseline+Treatment
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 100 mg QD, GSK189075 250 mg QD
Comments [Not Specified]
Type of Statistical Test Other
Comments Tukey’s trend test for dose response
Statistical Test of Hypothesis P-Value 0.006
Comments Tukey’s trend test adjusts for multiplicity with statistical significance based on p-value <0.05.
Method ANCOVA
Comments Change=Baseline+Treatment
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 100 mg QD
Comments [Not Specified]
Type of Statistical Test Other
Comments Tukey’s trend test for dose response
Statistical Test of Hypothesis P-Value 0.085
Comments Tukey’s trend test adjusts for multiplicity with statistical significance based on p-value <0.05.
Method ANCOVA
Comments Change=Baseline+Treatment
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 100 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.085
Comments Pairwise comparison included for informational purposes and not controlled for multiplicity.
Method ANCOVA
Comments Change=Baseline+Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.34
Confidence Interval (2-Sided) 95%
-0.73 to 0.05
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments Pairwise comparison included for informational purposes and not controlled for multiplicity
Method ANCOVA
Comments Change=Baseline+Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.56
Confidence Interval (2-Sided) 95%
-0.95 to -0.16
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 500 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.084
Comments Pairwise comparison included for informational purposes and not controlled for multiplicity.
Method ANCOVA
Comments Change=Baseline+Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.34
Confidence Interval (2-Sided) 95%
-0.73 to 0.05
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 1000 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments Pairwise comparison included for informational purposes and not controlled for multiplicity.
Method ANCOVA
Comments Change=Baseline+Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.66
Confidence Interval (2-Sided) 95%
-1.05 to -0.28
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments Pairwise comparison included for informational purposes and not controlled for multiplicity.
Method ANCOVA
Comments Change=Baseline+Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.59
Confidence Interval (2-Sided) 95%
-0.97 to -0.20
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, Pioglitazone 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.337
Comments Pairwise comparison included for informational purposes and not controlled for multiplicity.
Method ANCOVA
Comments Change=Baseline+Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-0.58 to 0.20
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Mean Change From Baseline in HbA1c at Weeks 4 and 8
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo GSK189075 100 mg QD GSK189075 250 mg QD GSK189075 500 mg QD GSK189075 1000 mg QD GSK189075 250 mg BID Pioglitazone 30 mg QD
Hide Arm/Group Description:
Participants received 2 placebo tablets matching for GSK189075 BID before breakfast and dinner and 1 placebo capsule matching for Pioglitazone QD before breakfast for 12 weeks
Participants received 2 tablets of 50 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of 250 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of 500 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 tablets of GSK189075 125 mg each before dinner daily for 12 weeks.
Participants received 2 placebo tablets matching GSK189075, 1 capsule of 30 mg before breakfast and 2 placebo tablets matching GSK189075 before dinner daily for 12 weeks.
Overall Number of Participants Analyzed 33 37 33 34 35 35 34
Mean (Standard Deviation)
Unit of Measure: Percentage
Week 4 Number Analyzed 30 participants 32 participants 31 participants 30 participants 33 participants 32 participants 30 participants
-0.18  (0.523) -0.37  (0.437) -0.57  (0.639) -0.40  (0.528) -0.45  (0.601) -0.31  (0.541) -0.07  (0.579)
Week 8 Number Analyzed 33 participants 36 participants 32 participants 34 participants 35 participants 35 participants 34 participants
-0.08  (0.943) -0.42  (0.720) -0.76  (0.671) -0.60  (0.827) -0.77  (0.660) -0.67  (0.646) -0.25  (0.819)
3.Secondary Outcome
Title Mean Change From Baseline to Week 12 in Fasting Plasma Glucose (FPG)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK189075 100 mg QD GSK189075 250 mg QD GSK189075 500 mg QD GSK189075 1000 mg QD GSK189075 250 mg BID Pioglitazone 30 mg QD
Hide Arm/Group Description:
Participants received 2 placebo tablets matching for GSK189075 BID before breakfast and dinner and 1 placebo capsule matching for Pioglitazone QD before breakfast for 12 weeks.
Participants received 2 tablets of GSK189075 50 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 250 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 500 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 tablets of GSK189075 125 mg each before dinner daily for 12 weeks.
Participants received 2 placebo tablets matching GSK189075, 1 capsule of Pioglitazone 30 mg before breakfast and 2 placebo tablets matching GSK189075 before dinner daily for 12 weeks.
Overall Number of Participants Analyzed 33 36 33 34 35 35 34
Least Squares Mean (Standard Error)
Unit of Measure: millimoles per liter (mmol/L)
-0.50  (0.298) -1.35  (0.286) -1.56  (0.298) -1.13  (0.294) -1.45  (0.289) -1.63  (0.289) -1.01  (0.295)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 100 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.039
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change=Baseline+Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.85
Confidence Interval (2-Sided) 95%
-1.67 to -0.04
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.013
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change=Baseline+Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.06
Confidence Interval (2-Sided) 95%
-1.89 to -0.23
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 500 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.131
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change=Baseline+Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.64
Confidence Interval (2-Sided) 95%
-1.46 to 0.19
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 1000 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.023
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change=Baseline+Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.95
Confidence Interval (2-Sided) 95%
-1.77 to -0.13
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change=Baseline+Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.13
Confidence Interval (2-Sided) 95%
-1.95 to -0.32
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Pioglitazone 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.223
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change=Baseline+Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.51
Confidence Interval (2-Sided) 95%
-1.34 to 0.32
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Mean Change From Baseline to Week 12 in Fructosamine (Corrected)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK189075 100 mg QD GSK189075 250 mg QD GSK189075 500 mg QD GSK189075 1000 mg QD GSK189075 250 mg BID Pioglitazone 30 mg QD
Hide Arm/Group Description:
Participants received 2 placebo tablets matching for GSK189075 BID before breakfast and dinner and 1 placebo capsule matching for Pioglitazone QD before breakfast for 12 weeks.
Participants received 2 tablets of GSK189075 50 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 250 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 500 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 tablets of GSK189075 125 mg each before dinner daily for 12 weeks.
Participants received 2 placebo tablets matching GSK189075, 1 capsule of Pioglitazone 30 mg before breakfast and 2 placebo tablets matching GSK189075 before dinner daily for 12 weeks.
Overall Number of Participants Analyzed 33 36 30 33 33 35 33
Least Squares Mean (Standard Error)
Unit of Measure: micromoles per liter (µmol/L)
-1.4  (6.12) -25.5  (5.94) -36.3  (6.44) -31.2  (6.12) -37.9  (6.12) -30.9  (5.94) -15.2  (6.18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 100 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change=Baseline+Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -24.1
Confidence Interval (2-Sided) 95%
-40.9 to -7.4
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change=Baseline+Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -35.0
Confidence Interval (2-Sided) 95%
-52.5 to -17.4
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 500 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change=Baseline+Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -29.8
Confidence Interval (2-Sided) 95%
-46.9 to -12.7
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 1000 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change=Baseline+Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -36.5
Confidence Interval (2-Sided) 95%
-53.6 to -19.5
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change=Baseline+Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -29.5
Confidence Interval (2-Sided) 95%
-46.3 to -12.7
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Pioglitazone 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.114
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change=Baseline+Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -13.8
Confidence Interval (2-Sided) 95%
-31.0 to 3.4
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Number of Participants Who Were HbA1c Responders at Week 12
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK189075 100 mg QD GSK189075 250 mg QD GSK189075 500 mg QD GSK189075 1000 mg QD GSK189075 250 mg BID Pioglitazone 30 mg QD
Hide Arm/Group Description:
Participants received 2 placebo tablets matching for GSK189075 BID before breakfast and dinner and 1 placebo capsule matching for Pioglitazone QD before breakfast for 12 weeks.
Participants received 2 tablets of GSK189075 50 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 250 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 500 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 tablets of GSK189075 125 mg each before dinner daily for 12 weeks.
Participants received 2 placebo tablets matching GSK189075, 1 capsule of Pioglitazone 30 mg before breakfast and 2 placebo tablets matching GSK189075 before dinner daily for 12 weeks.
Overall Number of Participants Analyzed 33 36 32 34 35 35 34
Measure Type: Count of Participants
Unit of Measure: Participants
Responders (<=6.5%)
3
   9.1%
5
  13.9%
4
  12.5%
4
  11.8%
7
  20.0%
6
  17.1%
4
  11.8%
Responders (<7%)
7
  21.2%
11
  30.6%
12
  37.5%
10
  29.4%
13
  37.1%
15
  42.9%
11
  32.4%
Responders (reduction>=0.7%)
9
  27.3%
13
  36.1%
18
  56.3%
13
  38.2%
18
  51.4%
21
  60.0%
13
  38.2%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 100 mg QD
Comments Placebo vs GSK189075 100 mg QD: Responders (<=6.5%)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.757
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.28
Confidence Interval (2-Sided) 95%
0.27 to 6.06
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg QD
Comments Placebo vs GSK189075 250 mg QD: Responders (<=6.5%)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.580
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.58
Confidence Interval (2-Sided) 95%
0.31 to 8.01
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 500 mg QD
Comments Placebo vs GSK189075 500 mg QD: Responders (<=6.5%)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.881
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.22 to 5.73
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 1000 mg QD
Comments Placebo vs GSK189075 1000 mg QD: Responders (<=6.5%)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.382
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.95
Confidence Interval (2-Sided) 95%
0.44 to 8.75
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg BID
Comments Placebo vs GSK189075 250 mg BID: Responders (<=6.5%)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.409
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.90
Confidence Interval (2-Sided) 95%
0.42 to 8.68
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Pioglitazone 30 mg QD
Comments Placebo vs Pioglitazone 30 mg QD: Responders (<=6.5%)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.795
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.24
Confidence Interval (2-Sided) 95%
0.24 to 6.29
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 100 mg QD
Comments Placebo vs GSK189075 100 mg QD: Responders (<7%)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.765
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.20
Confidence Interval (2-Sided) 95%
0.36 to 3.95
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg QD
Comments Placebo vs GSK189075 250 mg QD: Responders (<7%)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.100
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.74
Confidence Interval (2-Sided) 95%
0.82 to 9.09
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 500 mg QD
Comments Placebo vs GSK189075 500 mg QD: Responders (<7%)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.687
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.28
Confidence Interval (2-Sided) 95%
0.38 to 4.30
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 1000 mg QD
Comments Placebo vs GSK189075 1000 mg QD: Responders (<7%)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.409
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.66
Confidence Interval (2-Sided) 95%
0.50 to 5.52
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg BID
Comments Placebo vs GSK189075 250 mg BID: Responders (<7%)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.086
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.81
Confidence Interval (2-Sided) 95%
0.86 to 9.15
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, Pioglitazone 30 mg QD
Comments Placebo vs Pioglitazone 30 mg QD: Responders (<7%)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.369
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.75
Confidence Interval (2-Sided) 95%
0.52 to 5.88
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 100 mg QD
Comments Placebo vs GSK189075 100 mg QD: Responders (reduction>=0.7%)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.160
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.17
Confidence Interval (2-Sided) 95%
0.74 to 6.40
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg QD
Comments Placebo vs GSK189075 250 mg QD: Responders (reduction>=0.7%)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.87
Confidence Interval (2-Sided) 95%
1.31 to 11.42
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 500 mg QD
Comments Placebo vs GSK189075 250 mg QD: Responders (reduction>=0.7%)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.162
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.17
Confidence Interval (2-Sided) 95%
0.73 to 6.44
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 1000 mg QD
Comments Placebo vs GSK189075 1000 mg QD: Responders (reduction>=0.7%)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.09
Confidence Interval (2-Sided) 95%
1.38 to 12.17
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg BID
Comments Placebo vs GSK189075 250 mg BID: Responders (reduction>=0.7%)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.31
Confidence Interval (2-Sided) 95%
1.79 to 15.73
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Placebo, Pioglitazone 30 mg QD
Comments Placebo vs Pioglitazone 30 mg QD: Responders (reduction>=0.7%)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.264
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.86
Confidence Interval (2-Sided) 95%
0.63 to 5.49
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Number of Participants Who Were Fasting Plasma Glucose (FPG) Responders at Week 12
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK189075 100 mg QD GSK189075 250 mg QD GSK189075 500 mg QD GSK189075 1000 mg QD GSK189075 250 mg BID Pioglitazone 30 mg QD
Hide Arm/Group Description:
Participants received 2 placebo tablets matching for GSK189075 BID before breakfast and dinner and 1 placebo capsule matching for Pioglitazone QD before breakfast for 12 weeks.
Participants received 2 tablets of GSK189075 50 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 250 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 500 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 tablets of GSK189075 125 mg each before dinner daily for 12 weeks.
Participants received 2 placebo tablets matching GSK189075, 1 capsule of Pioglitazone 30 mg before breakfast and 2 placebo tablets matching GSK189075 before dinner daily for 12 weeks.
Overall Number of Participants Analyzed 33 36 33 34 35 35 34
Measure Type: Count of Participants
Unit of Measure: Participants
Responders (<7 mmol/L)
6
  18.2%
10
  27.8%
14
  42.4%
11
  32.4%
12
  34.3%
14
  40.0%
13
  38.2%
Responders (<7.8 mmol/L)
13
  39.4%
20
  55.6%
19
  57.6%
17
  50.0%
21
  60.0%
22
  62.9%
15
  44.1%
Responders (reduction >=1.7 mmol/L)
5
  15.2%
9
  25.0%
13
  39.4%
11
  32.4%
14
  40.0%
19
  54.3%
17
  50.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 100 mg QD
Comments Placebo vs GSK189075 100 mg QD: Responders (<7 mmol/L)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.480
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.55
Confidence Interval (2-Sided) 95%
0.46 to 5.28
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg QD
Comments Placebo vs GSK189075 250 mg QD: Responders (<7 mmol/L)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.87
Confidence Interval (2-Sided) 95%
1.44 to 16.46
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 500 mg QD
Comments Placebo vs GSK189075 500 mg QD: Responders (<7 mmol/L)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.087
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.92
Confidence Interval (2-Sided) 95%
0.85 to 9.96
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 1000 mg QD
Comments Placebo vs GSK189075 1000 mg QD: Responders (<7 mmol/L)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.082
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.92
Confidence Interval (2-Sided) 95%
0.87 to 9.78
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg BID
Comments Placebo vs GSK189075 250 mg BID: Responders (<7 mmol/L)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.024
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.00
Confidence Interval (2-Sided) 95%
1.20 to 13.27
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Pioglitazone 30 mg QD
Comments Placebo vs Pioglitazone 30 mg QD: Responders (<7 mmol/L)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.85
Confidence Interval (2-Sided) 95%
1.41 to 16.66
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 100 mg QD
Comments Placebo vs GSK189075 100 mg QD: Responders (<7.8 mmol/L)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.270
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.85
Confidence Interval (2-Sided) 95%
0.62 to 5.54
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg QD
Comments Placebo vs GSK189075 250 mg QD: Responders (<7.8 mmol/L)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.043
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.18
Confidence Interval (2-Sided) 95%
1.04 to 9.72
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 500 mg QD
Comments Placebo vs GSK189075 500 mg QD: Responders (<7.8 mmol/L)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.169
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.17
Confidence Interval (2-Sided) 95%
0.72 to 6.53
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 1000 mg QD
Comments Placebo vs GSK189075 1000 mg QD: Responders (<7.8 mmol/L)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.042
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.12
Confidence Interval (2-Sided) 95%
1.04 to 9.36
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg BID
Comments Placebo vs GSK189075 250 mg BID: Responders (<7.8 mmol/L)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.020
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.69
Confidence Interval (2-Sided) 95%
1.23 to 11.06
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, Pioglitazone 30 mg QD
Comments Placebo vs Pioglitazone 30 mg QD: Responders (<7.8 mmol/L)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.211
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.04
Confidence Interval (2-Sided) 95%
0.67 to 6.24
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 100 mg QD
Comments Placebo vs GSK189075 100 mg QD: Responders (reduction >=1.7 mmol/L)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.179
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.90
Confidence Interval (2-Sided) 95%
0.61 to 13.75
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg QD
Comments Placebo vs GSK189075 250 mg QD: Responders (reduction >=1.7 mmol/L)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.030
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.93
Confidence Interval (2-Sided) 95%
1.17 to 20.87
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 500 mg QD
Comments Placebo vs GSK189075 500 mg QD: Responders (reduction >=1.7 mmol/L)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.142
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.99
Confidence Interval (2-Sided) 95%
0.69 to 12.86
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 1000 mg QD
Comments Placebo vs GSK189075 1000 mg QD: Responders (reduction >=1.7 mmol/L)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.21
Confidence Interval (2-Sided) 95%
1.49 to 25.83
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg BID
Comments Placebo vs GSK189075 250 mg BID: Responders (reduction >=1.7 mmol/L)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 13.01
Confidence Interval (2-Sided) 95%
3.14 to 54.00
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Placebo, Pioglitazone 30 mg QD
Comments Placebo vs Pioglitazone 30 mg QD: Responders (reduction >=1.7 mmol/L)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010
Comments Pairwise comparison not controlled for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.60
Confidence Interval (2-Sided) 95%
1.56 to 27.99
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Mean Change From Baseline to Week 12 in Triglycerides
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population with LOCF. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK189075 100 mg QD GSK189075 250 mg QD GSK189075 500 mg QD GSK189075 1000 mg QD GSK189075 250 mg BID Pioglitazone 30 mg QD
Hide Arm/Group Description:
Participants received 2 placebo tablets matching for GSK189075 BID before breakfast and dinner and 1 placebo capsule matching for Pioglitazone QD before breakfast for 12 weeks.
Participants received 2 tablets of GSK189075 50 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 250 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 500 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 tablets of GSK189075 125 mg each before dinner daily for 12 weeks.
Participants received 2 placebo tablets matching GSK189075, 1 capsule of Pioglitazone 30 mg before breakfast and 2 placebo tablets matching GSK189075 before dinner daily for 12 weeks.
Overall Number of Participants Analyzed 32 34 28 33 31 30 32
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-0.01  (0.142) 0.19  (0.138) -0.32  (0.152) -0.16  (0.140) -0.05  (0.144) -0.18  (0.147) -0.37  (0.142)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 100 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.318
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.20
Confidence Interval (2-Sided) 95%
-0.19 to 0.59
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.131
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.32
Confidence Interval (2-Sided) 95%
-0.73 to 0.10
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 500 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.452
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.54 to 0.24
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 1000 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.845
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.44 to 0.36
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.393
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.18
Confidence Interval (2-Sided) 95%
-0.58 to 0.23
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Pioglitazone 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.072
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.36
Confidence Interval (2-Sided) 95%
-0.76 to 0.03
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Mean Change From Baseline to Week 12 in Total Cholesterol
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population with LOCF. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK189075 100 mg QD GSK189075 250 mg QD GSK189075 500 mg QD GSK189075 1000 mg QD GSK189075 250 mg BID Pioglitazone 30 mg QD
Hide Arm/Group Description:
Participants received 2 placebo tablets matching for GSK189075 BID before breakfast and dinner and 1 placebo capsule matching for Pioglitazone QD before breakfast for 12 weeks.
Participants received 2 tablets of GSK189075 50 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 250 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 500 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 tablets of GSK189075 125 mg each before dinner daily for 12 weeks.
Participants received 2 placebo tablets matching GSK189075, 1 capsule of Pioglitazone 30 mg before breakfast and 2 placebo tablets matching GSK189075 before dinner daily for 12 weeks.
Overall Number of Participants Analyzed 32 34 28 33 31 30 32
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-0.03  (0.127) -0.08  (0.124) -0.12  (0.136) 0.10  (0.126) -0.02  (0.129) 0.22  (0.132) 0.00  (0.128)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 100 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.767
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-0.40 to 0.30
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.604
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.10
Confidence Interval (2-Sided) 95%
-0.46 to 0.27
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 500 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.483
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
-0.23 to 0.48
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 1000 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.956
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-0.35 to 0.37
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.185
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.24
Confidence Interval (2-Sided) 95%
-0.12 to 0.60
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Pioglitazone 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.863
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-0.32 to 0.39
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Mean Change From Baseline to Week 12 in Low Density Lipoprotein Cholesterol (LDL-c)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population with LOCF. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK189075 100 mg QD GSK189075 250 mg QD GSK189075 500 mg QD GSK189075 1000 mg QD GSK189075 250 mg BID Pioglitazone 30 mg QD
Hide Arm/Group Description:
Participants received 2 placebo tablets matching for GSK189075 BID before breakfast and dinner and 1 placebo capsule matching for Pioglitazone QD before breakfast for 12 weeks.
Participants received 2 tablets of GSK189075 50 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 250 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 500 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 tablets of GSK189075 125 mg each before dinner daily for 12 weeks.
Participants received 2 placebo tablets matching GSK189075, 1 capsule of Pioglitazone 30 mg before breakfast and 2 placebo tablets matching GSK189075 before dinner daily for 12 weeks.
Overall Number of Participants Analyzed 32 31 28 31 31 30 32
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-0.02  (0.111) -0.17  (0.113) -0.03  (0.119) 0.08  (0.114) -0.04  (0.113) 0.23  (0.115) 0.07  (0.112)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 100 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.348
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.46 to 0.16
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.952
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.33 to 0.31
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 500 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.523
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.10
Confidence Interval (2-Sided) 95%
-0.21 to 0.42
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 1000 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.889
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.34 to 0.29
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.124
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
-0.07 to 0.56
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Pioglitazone 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.581
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
-0.22 to 0.40
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Mean Change From Baseline to Week 12 in High Density Lipoprotein Cholesterol (HDL-c)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population with LOCF. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK189075 100 mg QD GSK189075 250 mg QD GSK189075 500 mg QD GSK189075 1000 mg QD GSK189075 250 mg BID Pioglitazone 30 mg QD
Hide Arm/Group Description:
Participants received 2 placebo tablets matching for GSK189075 BID before breakfast and dinner and 1 placebo capsule matching for Pioglitazone QD before breakfast for 12 weeks.
Participants received 2 tablets of GSK189075 50 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 250 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 500 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 tablets of GSK189075 125 mg each before dinner daily for 12 weeks.
Participants received 2 placebo tablets matching GSK189075, 1 capsule of Pioglitazone 30 mg before breakfast and 2 placebo tablets matching GSK189075 before dinner daily for 12 weeks.
Overall Number of Participants Analyzed 32 34 28 33 31 30 32
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-0.02  (0.027) 0.00  (0.026) 0.02  (0.028) 0.06  (0.026) 0.05  (0.027) 0.04  (0.027) 0.09  (0.026)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 100 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.518
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-0.05 to 0.10
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.352
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-0.04 to 0.11
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 500 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.026
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
0.01 to 0.16
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 1000 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.069
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.07
Confidence Interval (2-Sided) 95%
-0.01 to 0.14
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.154
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.02 to 0.13
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Pioglitazone 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.11
Confidence Interval (2-Sided) 95%
0.03 to 0.18
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Mean Change From Baseline to Week 12 in LDL-c/HDL-c Ratio
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population with LOCF. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK189075 100 mg QD GSK189075 250 mg QD GSK189075 500 mg QD GSK189075 1000 mg QD GSK189075 250 mg BID Pioglitazone 30 mg QD
Hide Arm/Group Description:
Participants received 2 placebo tablets matching for GSK189075 BID before breakfast and dinner and 1 placebo capsule matching for Pioglitazone QD before breakfast for 12 weeks.
Participants received 2 tablets of GSK189075 50 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 250 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 500 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 tablets of GSK189075 125 mg each before dinner daily for 12 weeks.
Participants received 2 placebo tablets matching GSK189075, 1 capsule of Pioglitazone 30 mg before breakfast and 2 placebo tablets matching GSK189075 before dinner daily for 12 weeks.
Overall Number of Participants Analyzed 32 31 28 31 31 30 32
Least Squares Mean (Standard Error)
Unit of Measure: Ratio
0.06  (0.119) -0.19  (0.121) -0.06  (0.127) -0.13  (0.120) -0.07  (0.121) 0.10  (0.122) -0.07  (0.120)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 100 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.143
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.25
Confidence Interval (2-Sided) 95%
-0.58 to 0.08
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.495
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.12
Confidence Interval (2-Sided) 95%
-0.46 to 0.22
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 500 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.261
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-0.52 to 0.14
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 1000 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.446
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.13
Confidence Interval (2-Sided) 95%
-0.46 to 0.20
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.783
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.29 to 0.38
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Pioglitazone 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.454
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.13
Confidence Interval (2-Sided) 95%
-0.46 to 0.21
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Mean Change From Baseline to Week 12 in Total Cholesterol/HDL-c Ratio
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population with LOCF. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK189075 100 mg QD GSK189075 250 mg QD GSK189075 500 mg QD GSK189075 1000 mg QD GSK189075 250 mg BID Pioglitazone 30 mg QD
Hide Arm/Group Description:
Participants received 2 placebo tablets matching for GSK189075 BID before breakfast and dinner and 1 placebo capsule matching for Pioglitazone QD before breakfast for 12 weeks.
Participants received 2 tablets of GSK189075 50 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 250 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 500 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 tablets of GSK189075 125 mg each before dinner daily for 12 weeks.
Participants received 2 placebo tablets matching GSK189075, 1 capsule of Pioglitazone 30 mg before breakfast and 2 placebo tablets matching GSK189075 before dinner daily for 12 weeks.
Overall Number of Participants Analyzed 32 34 28 33 31 30 32
Least Squares Mean (Standard Error)
Unit of Measure: Ratio
0.14  (0.146) -0.05  (0.142) -0.20  (0.156) -0.22  (0.144) -0.09  (0.149) 0.01  (0.151) -0.26  (0.147)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 100 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.363
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-0.59 to 0.22
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.111
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.34
Confidence Interval (2-Sided) 95%
-0.76 to 0.08
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 500 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.080
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.36
Confidence Interval (2-Sided) 95%
-0.77 to 0.04
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 1000 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.267
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.23
Confidence Interval (2-Sided) 95%
-0.64 to 0.18
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.549
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.13
Confidence Interval (2-Sided) 95%
-0.54 to 0.29
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Pioglitazone 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.056
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.40
Confidence Interval (2-Sided) 95%
-0.81 to 0.01
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Mean Change From Baseline to Week 12 in Body Weight
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population with LOCF.
Arm/Group Title Placebo GSK189075 100 mg QD GSK189075 250 mg QD GSK189075 500 mg QD GSK189075 1000 mg QD GSK189075 250 mg BID Pioglitazone 30 mg QD
Hide Arm/Group Description:
Participants received 2 placebo tablets matching for GSK189075 BID before breakfast and dinner and 1 placebo capsule matching for Pioglitazone QD before breakfast for 12 weeks.
Participants received 2 tablets of GSK189075 50 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 250 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 500 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 tablets of GSK189075 125 mg each before dinner daily for 12 weeks.
Participants received 2 placebo tablets matching GSK189075, 1 capsule of Pioglitazone 30 mg before breakfast and 2 placebo tablets matching GSK189075 before dinner daily for 12 weeks.
Overall Number of Participants Analyzed 33 37 33 34 35 35 34
Least Squares Mean (Standard Error)
Unit of Measure: kilograms
-1.03  (0.426) -1.52  (0.402) -2.54  (0.425) -2.46  (0.419) -2.47  (0.413) -2.11  (0.413) 0.00  (0.419)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 100 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.396
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.50
Confidence Interval (2-Sided) 95%
-1.65 to 0.66
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.013
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.51
Confidence Interval (2-Sided) 95%
-2.70 to -0.33
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 500 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.017
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.44
Confidence Interval (2-Sided) 95%
-2.61 to -0.26
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 1000 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.45
Confidence Interval (2-Sided) 95%
-2.61 to -0.28
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.069
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.09
Confidence Interval (2-Sided) 95%
-2.26 to 0.08
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Pioglitazone 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.086
Comments Pairwise comparison not controlled for multiplicity.
Method ANCOVA
Comments Change = Baseline + Treatment
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
-0.15 to 2.20
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Number of Participants With Any On-therapy Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population consisted of all participants who received at least one dose of study medication.
Arm/Group Title Placebo GSK189075 100 mg QD GSK189075 250 mg QD GSK189075 500 mg QD GSK189075 1000 mg QD GSK189075 250 mg BID Pioglitazone 30 mg QD
Hide Arm/Group Description:
Participants received 2 placebo tablets matching for GSK189075 BID before breakfast and dinner and 1 placebo capsule matching for Pioglitazone QD before breakfast for 12 weeks.
Participants received 2 tablets of GSK189075 50 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 250 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 500 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 tablets of GSK189075 125 mg each before dinner daily for 12 weeks.
Participants received 2 placebo tablets matching GSK189075, 1 capsule of Pioglitazone 30 mg before breakfast and 2 placebo tablets matching GSK189075 before dinner daily for 12 weeks.
Overall Number of Participants Analyzed 36 37 34 36 36 36 35
Measure Type: Count of Participants
Unit of Measure: Participants
Any AEs
8
  22.2%
15
  40.5%
20
  58.8%
11
  30.6%
21
  58.3%
20
  55.6%
12
  34.3%
Any SAEs
0
   0.0%
1
   2.7%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.8%
0
   0.0%
15.Secondary Outcome
Title Number of Participants With On-therapy Hypoglycemia
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population.
Arm/Group Title Placebo GSK189075 100 mg QD GSK189075 250 mg QD GSK189075 500 mg QD GSK189075 1000 mg QD GSK189075 250 mg BID Pioglitazone 30 mg QD
Hide Arm/Group Description:
Participants received 2 placebo tablets matching for GSK189075 BID before breakfast and dinner and 1 placebo capsule matching for Pioglitazone QD before breakfast for 12 weeks.
Participants received 2 tablets of GSK189075 50 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 250 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 500 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 tablets of GSK189075 125 mg each before dinner daily for 12 weeks.
Participants received 2 placebo tablets matching GSK189075, 1 capsule of Pioglitazone 30 mg before breakfast and 2 placebo tablets matching GSK189075 before dinner daily for 12 weeks.
Overall Number of Participants Analyzed 36 37 34 36 36 36 35
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
1
   2.7%
0
   0.0%
2
   5.6%
1
   2.8%
1
   2.8%
0
   0.0%
16.Secondary Outcome
Title Number of Participants With Vital Signs of Potential Clinical Importance (PCI) at Any Time on Therapy
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK189075 100 mg QD GSK189075 250 mg QD GSK189075 500 mg QD GSK189075 1000 mg QD GSK189075 250 mg BID Pioglitazone 30 mg QD
Hide Arm/Group Description:
Participants received 2 placebo tablets matching for GSK189075 BID before breakfast and dinner and 1 placebo capsule matching for Pioglitazone QD before breakfast for 12 weeks.
Participants received 2 tablets of GSK189075 50 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 250 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 500 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 placebo tablets matching for GSK189075 before dinner daily for 12 weeks.
Participants received 2 tablets of GSK189075 125 mg each, 1 placebo capsule matching for Pioglitazone before breakfast and 2 tablets of GSK189075 125 mg each before dinner daily for 12 weeks.
Participants received 2 placebo tablets matching GSK189075, 1 capsule of Pioglitazone 30 mg before breakfast and 2 placebo tablets matching GSK189075 before dinner daily for 12 weeks.
Overall Number of Participants Analyzed 33 37 33 34 35 35 34
Measure Type: Count of Participants
Unit of Measure: Participants
SBP, supine, low