Trial Outcomes & Findings for A Phase II Clinical Study of SB-480848 in Dyslipidemic Patients (NCT NCT00734032)

Last Updated: 2018-01-12

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

107 participants

Primary outcome timeframe

Baseline (Week 0, Visit 2) and Week 4

Results posted on

2018-01-12

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Placebo Participants received oral dose of matching placebo tablet once daily, after breakfast in the morning for 4 weeks of treatment period.	SB-480848 40 mg 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.	SB-480848 80 mg 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.	SB-480848 160 mg 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 Study STARTED	25	28	28	26
Overall Study COMPLETED	25	27	28	26
Overall Study NOT COMPLETED	0	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received oral dose of matching placebo tablet once daily, after breakfast in the morning for 4 weeks of treatment period.	SB-480848 40 mg 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.	SB-480848 80 mg 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.	SB-480848 160 mg 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 Study Adverse Event	0	1	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=25 Participants Participants received oral dose of matching placebo tablet once daily, after breakfast in the morning for 4 weeks of treatment period.	SB-480848 40 mg n=28 Participants 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.	SB-480848 80 mg n=28 Participants 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.	SB-480848 160 mg n=26 Participants 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 n=107 Participants Total of all reporting groups
Age, Continuous	59.5 Years STANDARD_DEVIATION 11.71 • n=5 Participants	59.8 Years STANDARD_DEVIATION 10.17 • n=7 Participants	58.3 Years STANDARD_DEVIATION 9.54 • n=5 Participants	58.3 Years STANDARD_DEVIATION 10.48 • n=4 Participants	59.0 Years STANDARD_DEVIATION 10.34 • n=21 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	17 Participants n=7 Participants	18 Participants n=5 Participants	13 Participants n=4 Participants	65 Participants n=21 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	11 Participants n=7 Participants	10 Participants n=5 Participants	13 Participants n=4 Participants	42 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	25 Participants n=5 Participants	28 Participants n=7 Participants	28 Participants n=5 Participants	26 Participants n=4 Participants	107 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline (Week 0, Visit 2) and Week 4

Population: 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).

Outcome measures

Outcome measures
Measure	Placebo n=25 Participants Participants received oral dose of matching placebo tablet once daily, after breakfast in the morning for 4 weeks of treatment period.	SB-480848 40 mg n=28 Participants 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.	SB-480848 80 mg n=28 Participants 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.	SB-480848 160 mg n=26 Participants 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.
Change From Baseline to Week 4 in Plasma Lipoprotein-associated Phospholipase A2 (Lp-PLA2) Activity	0.961 Log(millimole per milliliter per minute) Geometric Coefficient of Variation 8.5	0.494 Log(millimole per milliliter per minute) Geometric Coefficient of Variation 24.6	0.404 Log(millimole per milliliter per minute) Geometric Coefficient of Variation 21.5	0.313 Log(millimole per milliliter per minute) Geometric Coefficient of Variation 24.7

SECONDARY outcome

Timeframe: Baseline (Week 0, Visit 2) up to Follow-up (up to Week 7)

Population: FAS Population with LOCF analysis.

Outcome measures

Outcome measures
Measure	Placebo n=25 Participants Participants received oral dose of matching placebo tablet once daily, after breakfast in the morning for 4 weeks of treatment period.	SB-480848 40 mg n=28 Participants 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.	SB-480848 80 mg n=28 Participants 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.	SB-480848 160 mg n=26 Participants 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.
Percent Inhibition of Lp-PLA2 Activity in Plasma Over Time Week 1	-4.06 Percent inhibiton of Lp-PLA2 activity Standard Deviation 7.025	-48.25 Percent inhibiton of Lp-PLA2 activity Standard Deviation 15.929	-55.83 Percent inhibiton of Lp-PLA2 activity Standard Deviation 11.031	-66.03 Percent inhibiton of Lp-PLA2 activity Standard Deviation 7.656
Percent Inhibition of Lp-PLA2 Activity in Plasma Over Time Week 2	-1.96 Percent inhibiton of Lp-PLA2 activity Standard Deviation 8.147	-49.05 Percent inhibiton of Lp-PLA2 activity Standard Deviation 11.094	-58.95 Percent inhibiton of Lp-PLA2 activity Standard Deviation 8.258	-67.52 Percent inhibiton of Lp-PLA2 activity Standard Deviation 9.402
Percent Inhibition of Lp-PLA2 Activity in Plasma Over Time Week 4	-3.59 Percent inhibiton of Lp-PLA2 activity Standard Deviation 7.822	-49.05 Percent inhibiton of Lp-PLA2 activity Standard Deviation 13.472	-58.67 Percent inhibiton of Lp-PLA2 activity Standard Deviation 9.438	-67.73 Percent inhibiton of Lp-PLA2 activity Standard Deviation 8.310
Percent Inhibition of Lp-PLA2 Activity in Plasma Over Time Week 7 (Follow-up)	-3.16 Percent inhibiton of Lp-PLA2 activity Standard Deviation 9.018	-7.65 Percent inhibiton of Lp-PLA2 activity Standard Deviation 11.408	-9.40 Percent inhibiton of Lp-PLA2 activity Standard Deviation 8.667	-13.36 Percent inhibiton of Lp-PLA2 activity Standard Deviation 10.244

SECONDARY outcome

Timeframe: Baseline (Week 0, Visit 2), Week 1, Week 2 and Follow-up ( Week 7)

Population: FAS Population with LOCF analysis.

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).

Outcome measures

Outcome measures
Measure	Placebo n=25 Participants Participants received oral dose of matching placebo tablet once daily, after breakfast in the morning for 4 weeks of treatment period.	SB-480848 40 mg n=28 Participants 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.	SB-480848 80 mg n=28 Participants 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.	SB-480848 160 mg n=26 Participants 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.
Change From Baseline in Lp-PLA2 Activity at Week 1, 2 and Follow-up Week 1	0.957 Log(millimole per milliliter per minute) Geometric Coefficient of Variation 7.4	0.495 Log(millimole per milliliter per minute) Geometric Coefficient of Variation 30.9	0.430 Log(millimole per milliliter per minute) Geometric Coefficient of Variation 24.1	0.332 Log(millimole per milliliter per minute) Geometric Coefficient of Variation 22.5
Change From Baseline in Lp-PLA2 Activity at Week 1, 2 and Follow-up Week 2	0.977 Log(millimole per milliliter per minute) Geometric Coefficient of Variation 8.4	0.499 Log(millimole per milliliter per minute) Geometric Coefficient of Variation 20.9	0.403 Log(millimole per milliliter per minute) Geometric Coefficient of Variation 19.0	0.313 Log(millimole per milliliter per minute) Geometric Coefficient of Variation 28.3
Change From Baseline in Lp-PLA2 Activity at Week 1, 2 and Follow-up Week 7 (Follow-up)	0.964 Log(millimole per milliliter per minute) Geometric Coefficient of Variation 9.6	0.917 Log(millimole per milliliter per minute) Geometric Coefficient of Variation 11.6	0.902 Log(millimole per milliliter per minute) Geometric Coefficient of Variation 9.8	0.860 Log(millimole per milliliter per minute) Geometric Coefficient of Variation 12.1

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

SB-480848 40 mg

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

SB-480848 80 mg

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

SB-480848 160 mg

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=25 participants at risk Participants received oral dose of matching placebo tablet once daily, after breakfast in the morning for 4 weeks of treatment period.	SB-480848 40 mg n=28 participants at risk 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.	SB-480848 80 mg n=28 participants at risk 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.	SB-480848 160 mg n=26 participants at risk 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.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/25 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	3.6% 1/28 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	0.00% 0/28 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	0.00% 0/26 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.

Other adverse events

Other adverse events
Measure	Placebo n=25 participants at risk Participants received oral dose of matching placebo tablet once daily, after breakfast in the morning for 4 weeks of treatment period.	SB-480848 40 mg n=28 participants at risk 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.	SB-480848 80 mg n=28 participants at risk 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.	SB-480848 160 mg n=26 participants at risk 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.
Gastrointestinal disorders Abnormal faeces	0.00% 0/25 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	17.9% 5/28 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	21.4% 6/28 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	19.2% 5/26 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.
Gastrointestinal disorders Diarrhoea	4.0% 1/25 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	3.6% 1/28 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	7.1% 2/28 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	11.5% 3/26 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/25 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	0.00% 0/28 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	0.00% 0/28 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	7.7% 2/26 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.
Gastrointestinal disorders Constipation	0.00% 0/25 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	7.1% 2/28 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	0.00% 0/28 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	0.00% 0/26 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.
Infections and infestations Nasopharyngitis	16.0% 4/25 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	10.7% 3/28 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	14.3% 4/28 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	19.2% 5/26 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/25 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	0.00% 0/28 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	7.1% 2/28 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	0.00% 0/26 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.
Nervous system disorders Headache	4.0% 1/25 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	7.1% 2/28 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	7.1% 2/28 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	0.00% 0/26 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.
Renal and urinary disorders Urine odour abnormal	0.00% 0/25 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	7.1% 2/28 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	17.9% 5/28 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	15.4% 4/26 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.
Skin and subcutaneous tissue disorders Eczema	8.0% 2/25 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	3.6% 1/28 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	3.6% 1/28 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	7.7% 2/26 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.
Skin and subcutaneous tissue disorders Skin odour abnormal	0.00% 0/25 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	7.1% 2/28 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	0.00% 0/28 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.	3.8% 1/26 • Adverse events (AEs) were recorded up to Follow-up (up to Week 7). Safety Population comprised of all participants who received at least one dose of the study medication during the treatment period.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER