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A Phase II Clinical Study of SB-480848 in Dyslipidemic Patients

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ClinicalTrials.gov Identifier: NCT00734032
Recruitment Status : Completed
First Posted : August 13, 2008
Results First Posted : January 12, 2018
Last Update Posted : January 12, 2018
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 Atherosclerosis
Interventions Drug: SB480848 40mg EC Tablet
Drug: SB480848 80mg EC Tablet
Drug: SB480848 160mg EC Tablet
Drug: SB480848 Placebo Tablet
Enrollment 107

Recruitment Details The study was planned in 100 dyslipidemic male or female participants, aged 20 to 80 years, undergoing statin therapy and no change in lipid-lowering medication or dose during the 4 weeks prior to randomization from 26 August 2008 to 16 January 2009 at 7 centers in Japan.
Pre-assignment Details Out of 116 participants screened, 9 were screen failures; 107 participants were randomized in a ratio of 1:1:1:1, to receive placebo or any 1 of the 3 doses of SB-480848 (40 milligram [mg], 80 mg, 160 mg), prior to which they continued their statin therapy with no change in lipid-lowering medication or dose during 4 weeks of Run-in period.
Arm/Group Title Placebo SB-480848 40 mg SB-480848 80 mg SB-480848 160 mg
Hide Arm/Group Description Participants received oral dose of matching placebo tablet once daily, after breakfast in the morning for 4 weeks of treatment period. Participants received oral dose of SB-480848 40 mg enteric-coated tablet once daily, after breakfast in the morning for 4 weeks of treatment period. Participants received oral dose of SB-480848 80 mg enteric-coated tablet once daily, after breakfast in the morning for 4 weeks of treatment period. Participants received oral dose of SB-480848 160 mg enteric-coated tablet once daily, after breakfast in the morning for 4 weeks of treatment period.
Period Title: Overall Study
Started 25 28 28 26
Completed 25 27 28 26
Not Completed 0 1 0 0
Reason Not Completed
Adverse Event             0             1             0             0
Arm/Group Title Placebo SB-480848 40 mg SB-480848 80 mg SB-480848 160 mg Total
Hide Arm/Group Description Participants received oral dose of matching placebo tablet once daily, after breakfast in the morning for 4 weeks of treatment period. Participants received oral dose of SB-480848 40 mg enteric-coated tablet once daily, after breakfast in the morning for 4 weeks of treatment period. Participants received oral dose of SB-480848 80 mg enteric-coated tablet once daily, after breakfast in the morning for 4 weeks of treatment period. Participants received oral dose of SB-480848 160 mg enteric-coated tablet once daily, after breakfast in the morning for 4 weeks of treatment period. Total of all reporting groups
Overall Number of Baseline Participants 25 28 28 26 107
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 25 participants 28 participants 28 participants 26 participants 107 participants
59.5  (11.71) 59.8  (10.17) 58.3  (9.54) 58.3  (10.48) 59.0  (10.34)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 28 participants 28 participants 26 participants 107 participants
Female
17
  68.0%
17
  60.7%
18
  64.3%
13
  50.0%
65
  60.7%
Male
8
  32.0%
11
  39.3%
10
  35.7%
13
  50.0%
42
  39.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 28 participants 28 participants 26 participants 107 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
25
 100.0%
28
 100.0%
28
 100.0%
26
 100.0%
107
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Change From Baseline to Week 4 in Plasma Lipoprotein-associated Phospholipase A2 (Lp-PLA2) Activity
Hide Description Blood sample for Lp-PLA2 activity was collected before administration of study medication on the sampling day. Participants were instructed to visit without meal and study medication in the morning. The study medication was administered with food following test. Baseline value was defined as the assessment done on Week 0 (Visit 2). Change from Baseline was calculated as the post-Baseline (Week 4) assessment value minus the Baseline assessment value. If either value was missing, then the change from Baseline was set to be missing. The natural logarithm (log) was used for transformation in Lp-PLA2 activity. In case of zero values, an offset of 0.0001 was added to the zero values to ensure that the log transformation was successfully applied. The log transformation was conducted on the original value and then taken the change from Baseline on that log original value, calculated as log (post-Baseline value [week 4]) minus log (Baseline value).
Time Frame Baseline (Week 0, Visit 2) and Week 4
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) Population was defined as all randomized participants who received at least one dose of study medication during treatment period and who had at least one evaluable assessment of Lp-PLA2 activity after randomization. Missing values during treatment period, except for Baseline were imputed by last observed response (LOCF).
Arm/Group Title Placebo SB-480848 40 mg SB-480848 80 mg SB-480848 160 mg
Hide Arm/Group Description:
Participants received oral dose of matching placebo tablet once daily, after breakfast in the morning for 4 weeks of treatment period.
Participants received oral dose of SB-480848 40 mg enteric-coated tablet once daily, after breakfast in the morning for 4 weeks of treatment period.
Participants received oral dose of SB-480848 80 mg enteric-coated tablet once daily, after breakfast in the morning for 4 weeks of treatment period.
Participants received oral dose of SB-480848 160 mg enteric-coated tablet once daily, after breakfast in the morning for 4 weeks of treatment period.
Overall Number of Participants Analyzed 25 28 28 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Log(millimole per milliliter per minute)
0.961
(8.5%)
0.494
(24.6%)
0.404
(21.5%)
0.313
(24.7%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, SB-480848 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.514
Confidence Interval (2-Sided) 95%
0.449 to 0.590
Estimation Comments The point estimate was calculated as adjusted geometric mean ratio of placebo and SB-480848 40 mg. Dunnett adjustment was used for comparison of each dose group to placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, SB-480848 80 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.421
Confidence Interval (2-Sided) 95%
0.367 to 0.483
Estimation Comments The point estimate was calculated as adjusted geometric mean ratio of placebo and SB-480848 80 mg. Dunnett adjustment was used for comparison of each dose group to placebo.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, SB-480848 160 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.326
Confidence Interval (2-Sided) 95%
0.284 to 0.375
Estimation Comments The point estimate was calculated as adjusted geometric mean ratio of placebo and SB-480848 160 mg. Dunnett adjustment was used for comparison of each dose group to placebo.
2.Secondary Outcome
Title Percent Inhibition of Lp-PLA2 Activity in Plasma Over Time
Hide Description Blood sample for Lp-PLA2 activity was collected before administration of study medication on the sampling day. Participants were instructed to visit without meal and study medication in the morning. The study medication was administered with food following test. Baseline value was defined as the assessment done on Week 0 (Visit 2). Percentage inhibition of Lp-PLA2 activity relative to a Baseline value was calculated as: 100 multiplied by (post-Baseline values (Week 1, 2, 4 and Follow-up–Baseline value) divided by [Baseline value]).
Time Frame Baseline (Week 0, Visit 2) up to Follow-up (up to Week 7)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS Population with LOCF analysis.
Arm/Group Title Placebo SB-480848 40 mg SB-480848 80 mg SB-480848 160 mg
Hide Arm/Group Description:
Participants received oral dose of matching placebo tablet once daily, after breakfast in the morning for 4 weeks of treatment period.
Participants received oral dose of SB-480848 40 mg enteric-coated tablet once daily, after breakfast in the morning for 4 weeks of treatment period.
Participants received oral dose of SB-480848 80 mg enteric-coated tablet once daily, after breakfast in the morning for 4 weeks of treatment period.
Participants received oral dose of SB-480848 160 mg enteric-coated tablet once daily, after breakfast in the morning for 4 weeks of treatment period.
Overall Number of Participants Analyzed 25 28 28 26
Mean (Standard Deviation)
Unit of Measure: Percent inhibiton of Lp-PLA2 activity
Week 1 -4.06  (7.025) -48.25  (15.929) -55.83  (11.031) -66.03  (7.656)
Week 2 -1.96  (8.147) -49.05  (11.094) -58.95  (8.258) -67.52  (9.402)
Week 4 -3.59  (7.822) -49.05  (13.472) -58.67  (9.438) -67.73  (8.310)
Week 7 (Follow-up) -3.16  (9.018) -7.65  (11.408) -9.40  (8.667) -13.36  (10.244)
3.Secondary Outcome
Title Change From Baseline in Lp-PLA2 Activity at Week 1, 2 and Follow-up
Hide Description Blood sample for Lp-PLA2 activity was collected before administration of study medication on the sampling day. Participants were instructed to visit without meal and study medication in the morning. The study medication was administered with food following test. Baseline value was defined as the assessment done on Week 0 (Visit 2). Change from Baseline was calculated as the post-Baseline (Week 1, Week 2 and Follow-up) assessment values minus the Baseline assessment value. If either value was missing, then the change from Baseline was set to be missing. The log was used for transformation in Lp-PLA2 activity. In case of zero values, an offset of 0.0001 was added to the zero values to ensure that the log transformation was successfully applied. The log transformation was conducted on the original value and then taken change from Baseline on that log original value, calculated as log (post-Baseline [Week 1, Week 2 and Follow-up] values) minus log (Baseline value).
Time Frame Baseline (Week 0, Visit 2), Week 1, Week 2 and Follow-up ( Week 7)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS Population with LOCF analysis.
Arm/Group Title Placebo SB-480848 40 mg SB-480848 80 mg SB-480848 160 mg
Hide Arm/Group Description:
Participants received oral dose of matching placebo tablet once daily, after breakfast in the morning for 4 weeks of treatment period.
Participants received oral dose of SB-480848 40 mg enteric-coated tablet once daily, after breakfast in the morning for 4 weeks of treatment period.
Participants received oral dose of SB-480848 80 mg enteric-coated tablet once daily, after breakfast in the morning for 4 weeks of treatment period.
Participants received oral dose of SB-480848 160 mg enteric-coated tablet once daily, after breakfast in the morning for 4 weeks of treatment period.
Overall Number of Participants Analyzed 25 28 28 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Log(millimole per milliliter per minute)
Week 1
0.957
(7.4%)
0.495
(30.9%)
0.430
(24.1%)
0.332
(22.5%)
Week 2
0.977
(8.4%)
0.499
(20.9%)
0.403
(19.0%)
0.313
(28.3%)
Week 7 (Follow-up)
0.964
(9.6%)
0.917
(11.6%)
0.902
(9.8%)
0.860
(12.1%)
Time Frame Adverse events (AEs) were recorded up to Follow-up (up to Week 7).
Adverse Event Reporting Description Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.
 
Arm/Group Title Placebo SB-480848 40 mg SB-480848 80 mg SB-480848 160 mg
Hide Arm/Group Description Participants received oral dose of matching placebo tablet once daily, after breakfast in the morning for 4 weeks of treatment period. Participants received oral dose of SB-480848 40 mg enteric-coated tablet once daily, after breakfast in the morning for 4 weeks of treatment period. Participants received oral dose of SB-480848 80 mg enteric-coated tablet once daily, after breakfast in the morning for 4 weeks of treatment period. Participants received oral dose of SB-480848 160 mg enteric-coated tablet once daily, after breakfast in the morning for 4 weeks of treatment period.
All-Cause Mortality
Placebo SB-480848 40 mg SB-480848 80 mg SB-480848 160 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/25 (0.00%)   0/28 (0.00%)   0/28 (0.00%)   0/26 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo SB-480848 40 mg SB-480848 80 mg SB-480848 160 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/25 (0.00%)   1/28 (3.57%)   0/28 (0.00%)   0/26 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Pulmonary embolism  1  0/25 (0.00%)  1/28 (3.57%)  0/28 (0.00%)  0/26 (0.00%) 
1
Term from vocabulary, MedDRA 11.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo SB-480848 40 mg SB-480848 80 mg SB-480848 160 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/25 (32.00%)   12/28 (42.86%)   13/28 (46.43%)   13/26 (50.00%) 
Gastrointestinal disorders         
Abnormal faeces  1  0/25 (0.00%)  5/28 (17.86%)  6/28 (21.43%)  5/26 (19.23%) 
Diarrhoea  1  1/25 (4.00%)  1/28 (3.57%)  2/28 (7.14%)  3/26 (11.54%) 
Abdominal pain upper  1  0/25 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  2/26 (7.69%) 
Constipation  1  0/25 (0.00%)  2/28 (7.14%)  0/28 (0.00%)  0/26 (0.00%) 
Infections and infestations         
Nasopharyngitis  1  4/25 (16.00%)  3/28 (10.71%)  4/28 (14.29%)  5/26 (19.23%) 
Musculoskeletal and connective tissue disorders         
Muscle spasms  1  0/25 (0.00%)  0/28 (0.00%)  2/28 (7.14%)  0/26 (0.00%) 
Nervous system disorders         
Headache  1  1/25 (4.00%)  2/28 (7.14%)  2/28 (7.14%)  0/26 (0.00%) 
Renal and urinary disorders         
Urine odour abnormal  1  0/25 (0.00%)  2/28 (7.14%)  5/28 (17.86%)  4/26 (15.38%) 
Skin and subcutaneous tissue disorders         
Eczema  1  2/25 (8.00%)  1/28 (3.57%)  1/28 (3.57%)  2/26 (7.69%) 
Skin odour abnormal  1  0/25 (0.00%)  2/28 (7.14%)  0/28 (0.00%)  1/26 (3.85%) 
1
Term from vocabulary, MedDRA 11.1
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
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00734032     History of Changes
Other Study ID Numbers: LPL110118
First Submitted: August 12, 2008
First Posted: August 13, 2008
Results First Submitted: July 18, 2017
Results First Posted: January 12, 2018
Last Update Posted: January 12, 2018