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

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: NCT00500331
Recruitment Status : Completed
First Posted : July 12, 2007
Results First Posted : December 6, 2017
Last Update Posted : December 6, 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: pioglitazone
Other: Placebo
Enrollment 334
Recruitment Details This study was conducted at 121 centers of which 95 randomized participants, in 18 countries (9 European, 8 International, and the United States) from 23 January 2007 to 14 February 2008.
Pre-assignment Details The Screening period was of 2 weeks. A glucose meter and detailed instructions for use were provided to all participants at the Screening visit for self- monitoring of fasting blood glucose levels and a Daily Glucose Monitoring Log for recording blood glucose information. Dietary and exercise advice was provided at randomization.
Arm/Group Title Placebo GSK189075 50 mg GSK189075 100 mg GSK189075 250 mg GSK189075 500 mg GSK189075 1000 mg Pioglitazone 30 mg
Hide Arm/Group Description Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks. Eligible participants received GSK189075 50 milligram (mg) tablets, orally, twice daily before breakfast and dinner for 12 weeks. Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks. Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks. Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks. Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks. Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Period Title: Overall Study
Started 48 47 48 48 48 47 48
Completed 33 42 43 38 44 42 46
Not Completed 15 5 5 10 4 5 2
Reason Not Completed
Adverse Event             0             2             0             1             2             2             0
Lost to Follow-up             1             1             1             2             1             0             0
Protocol Violation             3             1             1             0             1             1             1
Withdrawal by Subject             4             0             1             5             0             1             1
Lack of Efficacy             3             1             0             0             0             0             0
Liver function test abnormality             0             0             1             0             0             0             0
Increased serum creatinine from Baseline             0             0             0             0             0             1             0
Didn't return for continuation of study             1             0             0             0             0             0             0
Exclusion citeria not met on Visit 4             1             0             0             0             0             0             0
Sponsor decided to withdraw participant             1             0             0             0             0             0             0
Participant was randomized by mistake             1             0             0             0             0             0             0
Diabetologist nurse in the study             0             0             1             0             0             0             0
State ban of biological samples export             0             0             0             1             0             0             0
Protocol violated             0             0             0             1             0             0             0
Arm/Group Title Placebo GSK189075 50 mg GSK189075 100 mg GSK189075 250 mg GSK189075 500 mg GSK189075 1000 mg Pioglitazone 30 mg Total
Hide Arm/Group Description Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks. Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks. Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks. Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks. Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks. Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks. Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 48 47 48 48 48 47 48 334
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 48 participants 47 participants 48 participants 48 participants 48 participants 47 participants 48 participants 334 participants
55.9  (9.67) 54.3  (9.04) 56.0  (8.11) 55.7  (9.46) 54.6  (9.33) 52.4  (9.03) 54.5  (9.45) 54.8  (9.16)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 48 participants 47 participants 48 participants 48 participants 48 participants 47 participants 48 participants 334 participants
Female
18
  37.5%
23
  48.9%
17
  35.4%
19
  39.6%
20
  41.7%
20
  42.6%
24
  50.0%
141
  42.2%
Male
30
  62.5%
24
  51.1%
31
  64.6%
29
  60.4%
28
  58.3%
27
  57.4%
24
  50.0%
193
  57.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 48 participants 47 participants 48 participants 48 participants 48 participants 47 participants 48 participants 334 participants
American Indian or Alaska Native
1
   2.1%
4
   8.5%
4
   8.3%
3
   6.3%
0
   0.0%
3
   6.4%
4
   8.3%
19
   5.7%
Asian
1
   2.1%
2
   4.3%
3
   6.3%
1
   2.1%
2
   4.2%
1
   2.1%
3
   6.3%
13
   3.9%
Native Hawaiian or Other Pacific Islander
1
   2.1%
1
   2.1%
2
   4.2%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
4
   1.2%
Black or African American
0
   0.0%
1
   2.1%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.3%
White
41
  85.4%
37
  78.7%
36
  75.0%
41
  85.4%
42
  87.5%
40
  85.1%
39
  81.3%
276
  82.6%
More than one race
1
   2.1%
0
   0.0%
1
   2.1%
1
   2.1%
1
   2.1%
1
   2.1%
0
   0.0%
5
   1.5%
Unknown or Not Reported
3
   6.3%
2
   4.3%
2
   4.2%
2
   4.2%
3
   6.3%
2
   4.3%
2
   4.2%
16
   4.8%
1.Primary Outcome
Title Change From Baseline (Week 0) in Glycosylated Hemoglobin (HbA1c) (%) at Week 12
Hide Description Fasted blood samples for HbA1c were collected at Baseline and Week 12. Participants were required to fast for at least 8 hours prior to laboratory samples and were told not to take the morning dose of study medication on these visit days and to refrain from eating until instructed to do so by study personnel in the clinic. When the participant had not fasted, the participant was rescheduled to return to the clinic to have a fasted sample taken. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Only those participants with a value at Baseline and at Week 12 (after Last Observation Carried Forward [LOCF]) were used for this analysis. Adjusted mean is presented as least square mean.
Time Frame Baseline (Week 0) and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) Population with LOCF comprised of all randomized participants who received at least one dose of randomized study medication, had a Baseline assessment and had at least one corresponding on-therapy (scheduled or unscheduled) efficacy assessment. One extreme outlier participant had withdrawn from Placebo arm (lack of efficacy).
Arm/Group Title Placebo GSK189075 50 mg GSK189075 100 mg GSK189075 250 mg GSK189075 500 mg GSK189075 1000 mg Pioglitazone 30 mg
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Overall Number of Participants Analyzed 43 45 43 44 47 45 47
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of hemoglobin
-0.31  (0.107) -1.04  (0.105) -0.96  (0.107) -1.05  (0.106) -1.21  (0.102) -1.38  (0.104) -1.07  (0.102)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 50 mg, GSK189075 100 mg, GSK189075 250 mg, GSK189075 500 mg, GSK189075 1000 mg
Comments Placebo, GSK189075 50 mg, GSK189075 100 mg, GSK189075 250 mg, GSK189075 500 mg, GSK189075 1000 mg
Type of Statistical Test Other
Comments Tukey’s trend test for dose response: Change= Baseline+Treatment
Statistical Test of Hypothesis P-Value <0.001
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 50 mg, GSK189075 100 mg, GSK189075 250 mg, GSK189075 500 mg
Comments Placebo, GSK189075 50 mg, GSK189075 100 mg, GSK189075 250 mg, GSK189075 500 mg
Type of Statistical Test Other
Comments Tukey’s trend test for dose response
Statistical Test of Hypothesis P-Value <0.001
Comments Tukey’s trend test adjusts for multiplicity with statistical significance based on p-value <0.05
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 50 mg, GSK189075 100 mg, GSK189075 250 mg
Comments Placebo, GSK189075 50 mg, GSK189075 100 mg, GSK189075 250 mg
Type of Statistical Test Other
Comments Tukey’s trend test for dose response
Statistical Test of Hypothesis P-Value <0.001
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 50 mg, GSK189075 100 mg
Comments Placebo, GSK189075 50 mg, GSK189075 100 mg
Type of Statistical Test Other
Comments Tukey’s trend test for dose response
Statistical Test of Hypothesis P-Value <0.001
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 50 mg
Comments Placebo, GSK189075 50 mg
Type of Statistical Test Other
Comments Tukey’s trend test for dose response
Statistical Test of Hypothesis P-Value <0.001
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 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 50 mg
Comments Placebo vs. GSK189075 50 mg
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 -0.73
Confidence Interval (2-Sided) 95%
-1.02 to -0.44
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 100 mg
Comments Placebo vs. GSK189075 100 mg
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 -0.64
Confidence Interval (2-Sided) 95%
-0.94 to -0.35
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 250 mg
Comments Placebo vs. GSK189075 250 mg
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 -0.74
Confidence Interval (2-Sided) 95%
-1.03 to -0.44
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 500 mg
Comments Placebo vs. GSK189075 500 mg
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 -0.90
Confidence Interval (2-Sided) 95%
-1.19 to -0.61
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 1000 mg
Comments Placebo vs. GSK189075 1000 mg
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 -1.07
Confidence Interval (2-Sided) 95%
-1.36 to -0.77
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, Pioglitazone 30 mg
Comments Placebo vs. Pioglitazone 30 mg
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 -0.76
Confidence Interval (2-Sided) 95%
-1.05 to -0.47
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in HbA1c (%) at Weeks 4 and 8
Hide Description Fasted blood samples for HbA1c were collected at Baseline and Weeks 4 and 8. Participants were required to fast for at least 8 hours prior to laboratory samples and were told not to take the morning dose of study medication on these visit days and to refrain from eating until instructed to do so by study personnel in the clinic. When the participant had not fasted, the participant was rescheduled to return to the clinic to have a fasted sample taken. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time Frame Baseline (Week 0) and Week 4 and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population with LOCF. Only those participants with a value at Baseline and at specified visits (after LOCF) were used for this analysis. One extreme outlier participant had withdrawn from Placebo arm due to lack of efficacy.
Arm/Group Title Placebo GSK189075 50 mg GSK189075 100 mg GSK189075 250 mg GSK189075 500 mg GSK189075 1000 mg Pioglitazone 30 mg
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Overall Number of Participants Analyzed 47 46 44 45 47 47 47
Mean (Standard Deviation)
Unit of Measure: Percentage of hemoglobin
Week 4 Number Analyzed 41 participants 45 participants 42 participants 44 participants 45 participants 45 participants 46 participants
-0.30  (0.535) -0.77  (0.541) -0.69  (0.583) -0.64  (0.535) -0.83  (0.639) -0.84  (0.551) -0.39  (0.557)
Week 8 Number Analyzed 43 participants 45 participants 43 participants 44 participants 47 participants 45 participants 47 participants
-0.41  (0.689) -0.98  (0.712) -0.96  (0.827) -0.99  (0.751) -1.07  (0.747) -1.28  (0.636) -0.88  (0.713)
3.Secondary Outcome
Title Change From Baseline to Week 12 in Fasting Plasma Glucose (FPG) at Weeks 4, 8 and 12
Hide Description Fasted blood samples for FPG were collected up to Week 12. Participants were required to fast for at least 8 hours prior to laboratory samples and were told not to take the morning dose of study medication on these visit days and to refrain from eating until instructed to do so by study personnel in the clinic. When the participant had not fasted, the participant was rescheduled to return to the clinic to have a fasted sample taken. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time Frame Baseline (Week 0) and Week 4, Week 8 and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population with LOCF. Only those participants with a value at Baseline and at specified visits (after LOCF) were used for this analysis. One extreme outlier participant had withdrawn from Placebo arm due to lack of efficacy.
Arm/Group Title Placebo GSK189075 50 mg GSK189075 100 mg GSK189075 250 mg GSK189075 500 mg GSK189075 1000 mg Pioglitazone 30 mg
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Overall Number of Participants Analyzed 46 46 44 43 46 46 46
Mean (Standard Deviation)
Unit of Measure: Millimoles per Liter (mmol/L)
Week 4 -0.49  (1.991) -0.56  (1.512) -1.43  (2.005) -1.49  (2.314) -1.90  (2.232) -2.48  (2.491) -1.26  (1.294)
Week 8 -0.62  (1.859) -0.91  (2.073) -1.30  (1.821) -1.76  (2.137) -2.14  (2.547) -2.78  (2.531) -1.73  (1.340)
Week 12 -0.51  (1.700) -0.89  (1.960) -1.63  (2.145) -1.80  (2.107) -2.07  (2.459) -2.76  (2.821) -1.71  (1.978)
4.Secondary Outcome
Title Change From Baseline to Week 12 in Fructosamine
Hide Description Fasted blood samples for fructosamine were collected up to Week 12. Participants were required to fast for at least 8 hours prior to laboratory samples and were told not to take the morning dose of study medication on these visit days and to refrain from eating until instructed to do so by study personnel in the clinic. When the participant had not fasted, the participant was rescheduled to return to the clinic to have a fasted sample taken. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time Frame Baseline (Week 0) to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population with LOCF. Only those participants with a value at Baseline up to Week 12 (after LOCF) were used for this analysis.
Arm/Group Title Placebo GSK189075 50 mg GSK189075 100 mg GSK189075 250 mg GSK189075 500 mg GSK189075 1000 mg Pioglitazone 30 mg
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Overall Number of Participants Analyzed 39 37 37 36 41 39 43
Mean (Standard Deviation)
Unit of Measure: Micromol per Liter (mcmol/L)
5.7  (51.24) -33.8  (38.20) -35.7  (41.69) -38.9  (29.62) -41.9  (35.54) -55.2  (30.31) -34.7  (38.84)
5.Secondary Outcome
Title Change From Baseline to Week 12 in Fasting Insulin
Hide Description Fasted blood samples for insulin were collected up to Week 12. Participants were required to fast for at least 8 hours prior to laboratory samples and were told not to take the morning dose of study medication on these visit days and to refrain from eating until instructed to do so by study personnel in the clinic. When the participant had not fasted, the participant was rescheduled to return to the clinic to have a fasted sample taken. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time Frame Baseline (Week 0) to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population with LOCF. Only those participants with a value at Baseline and up to Week 12 (after LOCF) were used for this analysis.
Arm/Group Title Placebo GSK189075 50 mg GSK189075 100 mg GSK189075 250 mg GSK189075 500 mg GSK189075 1000 mg Pioglitazone 30 mg
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Overall Number of Participants Analyzed 38 40 40 39 41 43 42
Mean (Standard Deviation)
Unit of Measure: Picomol per Liter (pmol/L)
-30.6  (171.35) 0.3  (58.69) -20.7  (60.75) -9.7  (43.95) -25.8  (60.94) -15.1  (57.59) -2.1  (49.60)
6.Secondary Outcome
Title Number of Participants at Week 12 With: HbA1c <= 6.5%, HbA1c <7.0%; FPG <7 Mmo/L, FPG <7.8 mmol/L; FPG <5.5 mmol/L; a Decrease From Baseline of HbA1c >= 0.7%; a Decrease From Baseline of FPG ≥1.7 mmol/L
Hide Description Fasted blood samples for HbA1c were collected at Week 12. Participants were required to fast for at least 8 hours prior to laboratory samples and were told not to take the morning dose of study medication on these visit days and to refrain from eating until instructed to do so by study personnel in the clinic. When the participant had not fasted, the participant was rescheduled to return to the clinic to have a fasted sample taken. Number of participants at Week 12 with: HbA1c <= 6.5%, HbA1c <7.0%; FPG <7 mmo/L (126 milligram/deciliter [mg/dL]), FPG <7.8 mmol/L (140 mg/dL); FPG <5.5 mmol/L (100 mg/dL); a decrease from Baseline of HbA1c >= 0.7%; a decrease from Baseline of FPG ≥1.7 mmol/L (30 mg/dL) are presented.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population with Last Observation Carried Forward (LOCF). Only those participants with a value at Baseline and at Week 12 (after LOCF) were used for this analysis.
Arm/Group Title Placebo GSK189075 50 mg GSK189075 100 mg GSK189075 250 mg GSK189075 500 mg GSK189075 1000 mg Pioglitazone 30 mg
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Overall Number of Participants Analyzed 47 46 44 45 47 47 47
Measure Type: Count of Participants
Unit of Measure: Participants
HbA1c <= 6.5% Number Analyzed 44 participants 45 participants 43 participants 44 participants 47 participants 45 participants 47 participants
3
   6.8%
10
  22.2%
8
  18.6%
11
  25.0%
17
  36.2%
17
  37.8%
8
  17.0%
HbA1c <7.0% Number Analyzed 44 participants 45 participants 43 participants 44 participants 47 participants 45 participants 47 participants
9
  20.5%
20
  44.4%
18
  41.9%
22
  50.0%
28
  59.6%
29
  64.4%
21
  44.7%
FPG <7 mmo/L Number Analyzed 47 participants 46 participants 44 participants 43 participants 46 participants 46 participants 46 participants
4
   8.5%
16
  34.8%
20
  45.5%
18
  41.9%
22
  47.8%
22
  47.8%
21
  45.7%
FPG <7.8 mmol/L Number Analyzed 47 participants 46 participants 44 participants 43 participants 46 participants 46 participants 46 participants
13
  27.7%
24
  52.2%
26
  59.1%
27
  62.8%
33
  71.7%
34
  73.9%
31
  67.4%
FPG <5.5 mmol/L Number Analyzed 47 participants 46 participants 44 participants 43 participants 46 participants 46 participants 46 participants
0
   0.0%
4
   8.7%
2
   4.5%
5
  11.6%
4
   8.7%
3
   6.5%
2
   4.3%
Decrease from Baseline of HbA1c >= 0.7% Number Analyzed 44 participants 45 participants 43 participants 44 participants 47 participants 45 participants 47 participants
16
  36.4%
33
  73.3%
27
  62.8%
33
  75.0%
36
  76.6%
39
  86.7%
28
  59.6%
Decrease from Baseline of FPG ≥1.7 mmol/L Number Analyzed 47 participants 46 participants 44 participants 43 participants 46 participants 46 participants 46 participants
8
  17.0%
15
  32.6%
19
  43.2%
21
  48.8%
24
  52.2%
30
  65.2%
23
  50.0%
7.Secondary Outcome
Title Percent Change From Baseline in Lipid Parameters at Weeks 4, 8 and 12(Triglycerides [TG], Total Cholesterol [TC], Low-density Lipoprotein Cholesterol [LDL-C] and High-density Lipoprotein Cholesterol [HDL-C])
Hide Description Fasted samples for TC, LDL-C, HDL-C and TG were collected at Week 12. When the participant had not fasted, the participant was rescheduled to return to the clinic to have a fasted sample taken. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Percent Change based on log-transformed data: 100*(exponentiated(mean change on log scale)-1)
Time Frame Baseline (Week 0) and Week 4, Week 8 and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population with LOCF. Only those participants with a value at Baseline and at specified visits (after LOCF) were used for this analysis.
Arm/Group Title Placebo GSK189075 50 mg GSK189075 100 mg GSK189075 250 mg GSK189075 500 mg GSK189075 1000 mg Pioglitazone 30mg
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Overall Number of Participants Analyzed 47 46 44 45 47 47 47
Median (Full Range)
Unit of Measure: Percent change
TG: Week 4 Number Analyzed 44 participants 45 participants 42 participants 44 participants 44 participants 46 participants 46 participants
-8.35
(-44.3 to 110.1)
-3.45
(-48.1 to 177.8)
6.32
(-55.1 to 112.1)
-13.42
(-56.8 to 133.6)
-13.04
(-74.8 to 207.1)
-4.62
(-48.2 to 256.3)
-7.22
(-68.6 to 76.9)
TG: Week 8 Number Analyzed 46 participants 45 participants 43 participants 44 participants 47 participants 46 participants 47 participants
-1.66
(-67.2 to 135.2)
-9.09
(-61.3 to 88.8)
0.59
(-47.4 to 122.5)
-10.01
(-57.9 to 100.0)
-13.35
(-51.9 to 207.1)
-7.30
(-60.9 to 121.6)
-0.79
(-71.1 to 82.5)
TG: Week 12 Number Analyzed 46 participants 45 participants 43 participants 44 participants 47 participants 46 participants 47 participants
3.32
(-58.6 to 135.2)
-10.91
(-60.2 to 213.0)
10.92
(-45.3 to 232.5)
-4.71
(-56.8 to 73.6)
-15.28
(-66.8 to 255.7)
-9.97
(-58.4 to 123.4)
-7.19
(-58.2 to 116.7)
TC: Week 4 Number Analyzed 44 participants 45 participants 42 participants 44 participants 44 participants 46 participants 46 participants
0.47
(-57.4 to 25.8)
1.85
(-22.9 to 65.0)
1.62
(-17.6 to 34.8)
4.13
(-40.1 to 63.9)
4.43
(-37.9 to 36.6)
2.39
(-22.7 to 54.4)
2.29
(-42.0 to 29.5)
TC: Week 8 Number Analyzed 46 participants 45 participants 43 participants 44 participants 47 participants 46 participants 47 participants
0.82
(-48.4 to 48.4)
3.49
(-31.3 to 43.1)
3.64
(-31.5 to 30.0)
4.49
(-14.0 to 73.7)
5.31
(-19.9 to 41.2)
0.00
(-24.3 to 49.9)
1.06
(-40.2 to 34.9)
TC: Week 12 Number Analyzed 46 participants 45 participants 43 participants 44 participants 47 participants 46 participants 47 participants
4.75
(-46.5 to 76.6)
3.39
(-28.1 to 43.4)
5.45
(-19.0 to 84.6)
3.97
(-16.8 to 67.1)
9.82
(-16.3 to 43.3)
2.77
(-17.5 to 52.5)
-2.05
(-48.3 to 31.4)
LDL-C: Week 4 Number Analyzed 42 participants 43 participants 40 participants 43 participants 43 participants 41 participants 45 participants
0.82
(-75.6 to 68.5)
0.83
(-27.3 to 117.0)
0.37
(-30.9 to 75.0)
6.91
(-52.9 to 84.1)
10.03
(-39.0 to 59.6)
7.02
(-37.0 to 130.3)
0.00
(-54.0 to 50.0)
LDL-C: Week 8 Number Analyzed 45 participants 44 participants 42 participants 43 participants 46 participants 44 participants 46 participants
3.17
(-63.0 to 56.4)
8.67
(-38.7 to 53.1)
3.62
(-32.6 to 125.0)
8.96
(-37.9 to 118.8)
7.57
(-24.8 to 67.2)
4.44
(-39.5 to 119.5)
-2.24
(-47.8 to 55.2)
LDL-C: Week 12 Number Analyzed 45 participants 44 participants 43 participants 44 participants 47 participants 44 participants 46 participants
3.17
(-60.4 to 56.4)
6.69
(-39.4 to 90.2)
3.57
(-29.7 to 355.0)
3.93
(-23.0 to 102.9)
11.43
(-36.7 to 92.0)
14.89
(-23.7 to 125.6)
1.18
(-61.9 to 51.8)
HDL-C: Week 4 Number Analyzed 44 participants 45 participants 42 participants 44 participants 44 participants 46 participants 46 participants
-1.97
(-23.5 to 23.5)
5.43
(-11.5 to 45.8)
3.69
(-31.3 to 54.2)
5.13
(-29.3 to 93.3)
5.69
(-17.0 to 56.2)
0.00
(-33.0 to 32.9)
9.18
(-17.6 to 57.5)
HDL-C: Week 8 Number Analyzed 46 participants 45 participants 43 participants 44 participants 47 participants 46 participants 47 participants
0.00
(-31.6 to 19.1)
6.20
(-20.6 to 40.6)
5.00
(-20.7 to 58.3)
3.09
(-41.4 to 93.5)
7.14
(-15.8 to 59.2)
0.00
(-42.7 to 52.2)
8.20
(-13.2 to 48.1)
HDL-C: Week 12 Number Analyzed 46 participants 45 participants 43 participants 44 participants 47 participants 46 participants 47 participants
0.00
(-31.6 to 32.6)
5.56
(-28.6 to 42.2)
4.96
(-16.7 to 70.8)
6.70
(-14.4 to 90.3)
11.93
(-15.8 to 51.7)
4.27
(-50.2 to 36.4)
10.00
(-12.6 to 46.2)
8.Secondary Outcome
Title Change From Baseline to Week 12 in Body Weight
Hide Description Weight of participants was measured from Baseline (Week 0) to Week 12 and recorded in the case report form (CRF). Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time Frame Baseline (Week 0) to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population with LOCF for withdrawn participants or missing values.
Arm/Group Title Placebo GSK189075 50 mg GSK189075 100 mg GSK189075 250 mg GSK189075 500 mg GSK189075 1000 mg Pioglitazone 30 mg
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Overall Number of Participants Analyzed 47 46 44 45 47 47 47
Mean (Standard Deviation)
Unit of Measure: Kilograms
-0.49  (1.719) -1.78  (3.197) -2.41  (2.850) -2.38  (2.875) -3.52  (2.874) -4.00  (2.945) 0.96  (2.425)
9.Secondary Outcome
Title Change From Baseline to Week 12 in Waist Circumference
Hide Description Waist circumference of participants was measured from Baseline (Week 0) to Week 12 and recorded in the CRF. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time Frame Baseline (Week 0) to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population with LOCF for withdrawn participants or missing values.
Arm/Group Title Placebo GSK189075 50 mg GSK189075 100 mg GSK189075 250 mg GSK189075 500 mg GSK189075 1000 mg Pioglitazone 30 mg
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Overall Number of Participants Analyzed 41 43 43 43 42 44 47
Mean (Standard Deviation)
Unit of Measure: Centimeters
-0.7  (2.92) -1.2  (3.58) -2.0  (4.51) -2.2  (3.43) -2.6  (3.31) -2.4  (4.26) 1.3  (4.82)
10.Secondary Outcome
Title Change From Baseline in 24-hour Percent of Filtered Glucose Excreted in Urine
Hide Description A 24-hour urine collection was obtained from all participants at Baseline (Week 0) and Week 12 to measure glucose. Participants were provided with urine collection bottles and cooler prior to these visits and instructed that the urine collections must be kept cold and dropped off at the clinic prior to or at the scheduled visits. Site staff queried participants to determine whether the sample represented a full 24-hour collection. The total volume and the sample date and time were recorded. The entire 24-hour urine collection was well mixed in one container and a urine aliquot obtained. Samples were assayed for glucose. The 24-hour collections were used to derive 24-hour urine glucose excretion corrected for filtered load. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time Frame Baseline (Week 0) and Week 12 (24-hour urine collection)
Hide 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 50 mg GSK189075 100 mg GSK189075 250 mg GSK189075 500 mg GSK189075 1000 mg Pioglitazone 30 mg
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Overall Number of Participants Analyzed 23 28 27 27 25 27 37
Mean (Standard Deviation)
Unit of Measure: Percentage of filtered glucose molecules
-1.09  (5.731) 27.96  (15.693) 40.43  (16.144) 38.98  (19.006) 42.41  (22.708) 52.39  (15.264) -0.99  (2.313)
11.Secondary Outcome
Title Change From Baseline in Plasma Glucose Area Under the Curve (AUC) During a 2-hour Oral Glucose Tolerance Test (OGTT)
Hide Description Post-prandial assessments of glucose were performed at Baseline (Week 0) and at Week 12 using a 2-hour OGTT in a subgroup of participants at selected sites who agreed to participate. Participants were required to fast for at least 8 hours prior to the test. Seventy-five (75) g of standard oral glucose solution was administered 15 minutes after the morning administration of study medication (Week 12) and in the place of breakfast at Week 0 (i.e., at Week 0 the OGTT was completed prior to administration of study medication). Time “0” started when the participants drank the glucose solution. Blood samples were collected at the following times relative to the administration of oral glucose: -30 min (pre-glucose), -20 min (pre-glucose), 20 min, 30 min, 1 hour, 1.5 hour and 2 hour post glucose administration. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time Frame Baseline (Week 0) and Week 12 (0 to 2 hour OGTT)
Hide Outcome Measure Data
Hide Analysis Population Description
The OGTT Population with LOCF which comprised of participants in the ITT population having evaluable Baseline and corresponding on-therapy OGTT measurements (for at least one of the measured parameters of FPG, C-Peptide or Insulin). Only those participants with a value at Baseline and at Week 12 (after LOCF) were used for this analysis.
Arm/Group Title Placebo GSK189075 50 mg GSK189075 100 mg GSK189075 250 mg GSK189075 500 mg GSK189075 1000 mg Pioglitazone 30 mg
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Overall Number of Participants Analyzed 9 8 12 8 10 14 7
Mean (Standard Deviation)
Unit of Measure: Millimol*hour per Liter (mmol*hr/L)
-0.90  (5.739) -6.31  (5.907) -6.71  (7.326) -7.69  (3.791) -6.06  (2.837) -7.59  (3.065) -6.55  (3.841)
12.Secondary Outcome
Title Change From Baseline in Insulin AUC During a 2-hour OGTT
Hide Description Post-prandial assessments of insulin were performed at Baseline (Week 0) and at Week 12 using a 2-hour OGTT in a subgroup of participants at selected sites who agreed to participate. Participants were required to fast for at least 8 hours prior to the test. Seventy-five (75) g of standard oral glucose solution was administered 15 minutes after the morning administration of study medication (Week 12) and in the place of breakfast at Week 0 (i.e., at Week 0 the OGTT was completed prior to administration of study medication). Time “0” started when the participants drank the glucose solution. Blood samples were collected at the following times relative to the administration of oral glucose: -30 min (pre-glucose), -20 min (pre-glucose), 20 min, 30 min, 1 hour, 1.5 hour and 2 hour post glucose administration. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time Frame Baseline (Week 0) and Week 12 (0 to 2-hour OGTT)
Hide Outcome Measure Data
Hide Analysis Population Description
OGTT with LOCF Population. Only those participants with a value at Baseline and at Week 12 (after LOCF) were used for this analysis.
Arm/Group Title Placebo GSK189075 50 mg GSK189075 100 mg GSK189075 250 mg GSK189075 500 mg GSK189075 1000 mg Pioglitazone 30 mg
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Overall Number of Participants Analyzed 8 8 12 8 9 13 9
Mean (Standard Deviation)
Unit of Measure: Picomol*hour per Liter (pmol*hr/L)
-5.3  (177.23) 162.4  (362.82) -70.9  (193.77) 66.6  (213.07) -173.9  (143.52) -97.8  (224.24) 10.0  (128.77)
13.Secondary Outcome
Title Change From Baseline in C-peptide AUC During a 2-hr OGTT
Hide Description Post-prandial assessments of C-peptide were performed at Baseline (Week 0) and at Week 12 using a 2-hour OGTT in a subgroup of participants at selected sites who agreed to participate. Participants were required to fast for at least 8 hours prior to the test. Seventy-five (75) g of standard oral glucose solution was administered 15 minutes after the morning administration of study medication (Week 12) and in the place of breakfast at Week 0 (i.e., at Week 0 the OGTT was completed prior to administration of study medication). Time “0” started when the participants drank the glucose solution. Blood samples were collected at the following times relative to the administration of oral glucose: -30 min (pre-glucose), -20 min (pre-glucose), 20 min, 30 min, 1 hour, 1.5 hour and 2 hour post glucose administration. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time Frame Baseline (Week 0) and Week 12 (0 to 2 hour OGTT)
Hide Outcome Measure Data
Hide Analysis Population Description
OGTT with LOCF Population. Only those participants with a value at Baseline and at Week 12 (after LOCF) were used for this analysis.
Arm/Group Title Placebo GSK189075 50 mg GSK189075 100 mg GSK189075 250 mg GSK189075 500 mg GSK189075 1000 mg Pioglitazone 30 mg
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Overall Number of Participants Analyzed 8 8 12 7 9 12 9
Mean (Standard Deviation)
Unit of Measure: Nanomol*hour per Liter (nmol*hr/L)
-0.140  (0.7348) 0.654  (1.4023) -0.156  (1.0566) -0.026  (0.9606) -0.476  (0.4668) -0.175  (0.8322) -0.239  (0.6732)
14.Secondary Outcome
Title Number of Participants With On-therapy Adverse Events (AE) and Serious Adverse Events (SAE)
Hide Description AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.
Time Frame Up to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population which comprised of all participants who received at least one dose of study medication.
Arm/Group Title Placebo GSK189075 50 mg GSK189075 100 mg GSK189075 250 mg GSK189075 500 mg GSK189075 1000 mg Pioglitazone 30 mg
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Overall Number of Participants Analyzed 48 47 48 48 48 47 48
Measure Type: Count of Participants
Unit of Measure: Participants
AE
18
  37.5%
18
  38.3%
17
  35.4%
19
  39.6%
18
  37.5%
22
  46.8%
22
  45.8%
SAE
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
15.Secondary Outcome
Title Number of Participants With On-therapy Hypoglycemia
Hide Description Hypoglycemia is low blood glucose or low blood sugar. Hypoglycemic events were collected separately and reported separately from AE, including supplemental data which were not collected for AE. However, any hypoglycemic event which met the criteria for a SAE was included in the SAE summaries. The number of participants in each group that experienced a hypoglycemic event was summarized by frequency of the events.
Time Frame Up to 14 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population.
Arm/Group Title Placebo GSK189075 50 mg GSK189075 100 mg GSK189075 250 mg GSK189075 500 mg GSK189075 1000 mg Pioglitazone 30 mg
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Overall Number of Participants Analyzed 48 47 48 48 48 47 48
Measure Type: Count of Participants
Unit of Measure: Participants
1
   2.1%
1
   2.1%
0
   0.0%
0
   0.0%
1
   2.1%
0
   0.0%
0
   0.0%
16.Secondary Outcome
Title Number of Participants With Change From Baseline Vital Signs of Potential Clinical Concern
Hide Description Vital signs included heart rate and blood pressure. Heart rate and blood pressure were taken before blood draws were performed. Participants were asked to refrain from smoking for at least 30 minutes prior to vital sign measurements. Heart rate and blood pressure was measured pre-dose in duplicate at the specified visits, after the participant had been lying quietly for 5 minutes, and then in duplicate 3 minutes after standing up. Heart rate was measured at the same time as blood pressure using the standardized blood pressure equipment that was provided. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time Frame Up to 14 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo GSK189075 50 mg GSK189075 100 mg GSK189075 250 mg GSK189075 500 mg GSK189075 1000 mg Pioglitazone 30 mg
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Overall Number of Participants Analyzed 48 47 48 48 48 47 48
Measure Type: Count of Participants
Unit of Measure: Participants
High SBP Number Analyzed 47 participants 46 participants 44 participants 45 participants 47 participants 47 participants 47 participants
3
   6.4%
0
   0.0%
2
   4.5%
0
   0.0%
0
   0.0%
1
   2.1%
0
   0.0%
Low SBP Number Analyzed 47 participants 46 participants 44 participants 45 participants 47 participants 47 participants 47 participants
0
   0.0%
0
   0.0%
1
   2.3%
2
   4.4%
2
   4.3%
2
   4.3%
0
   0.0%
High DBP Number Analyzed 47 participants 46 participants 44 participants 45 participants 47 participants 47 participants 47 participants
1
   2.1%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   4.3%
0
   0.0%
Low DBP Number Analyzed 47 participants 46 participants 44 participants 45 participants 47 participants 47 participants 47 participants
0
   0.0%
1
   2.2%
2
   4.5%
0
   0.0%
0
   0.0%
1
   2.1%
3
   6.4%
High heart rate Number Analyzed 47 participants 46 participants 44 participants 45 participants 47 participants 47 participants 47 participants
0
   0.0%
1
   2.2%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Low heart rate Number Analyzed 47 participants 46 participants 44 participants 45 participants 47 participants 47 participants 47 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.1%
1
   2.1%
0
   0.0%
17.Secondary Outcome
Title Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern
Hide Description Full 12-lead ECGs were recorded at screening, Baseline (Week 0), Week 4, Week 12 or early withdrawal, and Week 14 (Follow-up) using an ECG machine that automatically calculated the heart rate and measured the PR, QRS, QT and corrected QT (QTc) intervals. All 12-lead ECGs were read locally by the Investigator or his/her designate and were forwarded electronically to the central reader for interpretation. If the QTc was >500 milliseconds (msec) on the locally read ECG recording, an additional 2 ECG recordings at 10 minute intervals were made at that visit. If the average QTc for the 3 recordings was >500 msec, the participant was withdrawn from the study.
Time Frame Up to Early withdrawal (Between Week 12 and Week 14)
Hide 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 50 mg GSK189075 100 mg GSK189075 250 mg GSK189075 500 mg GSK189075 1000 mg Pioglitazone 30 mg
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Overall Number of Participants Analyzed 46 45 43 44 47 46 47
Measure Type: Count of Participants
Unit of Measure: Participants
PR interval > 300 msec
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
QRS Duration > 200 msec
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
QTc(Bazett) > 500 msec
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
QTc(Fridericia) > 500 msec
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
18.Secondary Outcome
Title Number of Participants With Change From Baseline in Standard Laboratory Parameters of Potential Clinical Concern
Hide Description Participants were instructed to fast for at least 8 hours prior to all study visits for the collection of laboratory samples. An additional fasting blood sample (serum and plasma) was drawn at Week 0, Week 4, Week 6 and Week 12 or at early withdrawal (up to 14 weeks) and kept in long-term storage for future testing of biomarkers for diabetes and complications of the disease. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time Frame Up to 14 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo GSK189075 50 mg GSK189075 100 mg GSK189075 250 mg GSK189075 500 mg GSK189075 1000 mg Pioglitazone 30 mg
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.
Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Overall Number of Participants Analyzed 46 46 44 44 47 46 47
Measure Type: Count of Participants
Unit of Measure: Participants
Low Hemoglobin
1
   2.2%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Low Hematocrit
1
   2.2%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Time Frame Up to 12 weeks.
Adverse Event Reporting Description On-therapy SAE and non-SAEs are reported for the Safety population which comprised of all participants who received at least one dose of study medication.
 
Arm/Group Title Placebo GSK189075 50 mg GSK189075 100 mg GSK189075 250 mg GSK189075 500 mg GSK189075 1000 mg Pioglitazone 30 mg
Hide Arm/Group Description Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks. Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks. Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks. Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks. Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks. Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks. Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
All-Cause Mortality
Placebo GSK189075 50 mg GSK189075 100 mg GSK189075 250 mg GSK189075 500 mg GSK189075 1000 mg Pioglitazone 30 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/48 (0.00%)   0/47 (0.00%)   0/48 (0.00%)   0/48 (0.00%)   0/48 (0.00%)   0/47 (0.00%)   0/48 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo GSK189075 50 mg GSK189075 100 mg GSK189075 250 mg GSK189075 500 mg GSK189075 1000 mg Pioglitazone 30 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/48 (0.00%)   0/47 (0.00%)   0/48 (0.00%)   0/48 (0.00%)   0/48 (0.00%)   0/47 (0.00%)   0/48 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo GSK189075 50 mg GSK189075 100 mg GSK189075 250 mg GSK189075 500 mg GSK189075 1000 mg Pioglitazone 30 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/48 (6.25%)   5/47 (10.64%)   5/48 (10.42%)   4/48 (8.33%)   5/48 (10.42%)   3/47 (6.38%)   12/48 (25.00%) 
Gastrointestinal disorders               
Diarrhoea  1  3/48 (6.25%)  1/47 (2.13%)  1/48 (2.08%)  1/48 (2.08%)  0/48 (0.00%)  2/47 (4.26%)  3/48 (6.25%) 
Constipation  1  0/48 (0.00%)  1/47 (2.13%)  1/48 (2.08%)  2/48 (4.17%)  3/48 (6.25%)  0/47 (0.00%)  0/48 (0.00%) 
Infections and infestations               
Urinary tract infection  1  0/48 (0.00%)  2/47 (4.26%)  1/48 (2.08%)  0/48 (0.00%)  0/48 (0.00%)  0/47 (0.00%)  4/48 (8.33%) 
Nervous system disorders               
Headache  1  0/48 (0.00%)  1/47 (2.13%)  2/48 (4.17%)  1/48 (2.08%)  2/48 (4.17%)  1/47 (2.13%)  5/48 (10.42%) 
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00500331     History of Changes
Other Study ID Numbers: KG2105255
First Submitted: January 24, 2007
First Posted: July 12, 2007
Results First Submitted: September 26, 2017
Results First Posted: December 6, 2017
Last Update Posted: December 6, 2017