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SB-480848 In Subjects With Coronary Heart Disease

Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT00269048
Collaborator
(none)
969
Enrollment
120
Locations
2
Arms
10
Duration (Months)
8.1
Patients Per Site
0.8
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This trial of SB-480848 in approximately 920 subjects with Coronary Heart Disease (CHD) or CHD-risk equivalent will examine whether SB-480848 produces sustained inhibition of plasma Lp-PLA2 activity, explore the effects of SB-480848 on other circulating biomarkers associated with cardiovascular risk, and evaluate the pharmacokinetics, safety and tolerability of SB-480848 over 12 weeks of once-daily oral dosing. Subjects will first be randomized 1:1 to double-blind atorvastatin 20 mg or 80 mg once daily for a minimum of 3 weeks. Subjects will then be randomized 1:1:1:1 to oral doses of SB-480848 40 mg, 80 mg, 160 mg or placebo once daily for 12 weeks. Blood samples will be collected at various timepoints. Vital signs, electrocardiograms, clinical laboratory safety tests and adverse event assessments will be performed to evaluate the safety and tolerability of SB-480848.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

A multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study of SB-480848, an oral lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, in subjects with stable coronary heart disease (CHD) or CHD-risk equivalent to examine chronic inhibition of Lp-PLA2, effects on circulating biomarkers associated with cardiovascular risk, safety and tolerability over 12 weeks

Study Design

Study Type:
Interventional
Actual Enrollment :
969 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Care Provider)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-ranging Study of SB-480848, an Oral Lipoprotein-associated Phospholipase A2 (Lp-PLA2) Inhibitor, in Subjects With Stable Coronary Heart Disease (CHD) or CHD-risk Equivalent to Examine Chronic Inhibition of Lp-PLA2 Effects on Circulating Biomarkers Associated With Cardiovascular Risk, Safety and Tolerability Over 12 Weeks
Study Start Date :
Nov 1, 2005
Actual Primary Completion Date :
Sep 1, 2006
Actual Study Completion Date :
Sep 1, 2006

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm 1

SB-480848

Drug: SB-480848
SB-480848
Placebo Comparator: Arm 2

placebo

Drug: placebo
placebo

Outcome Measures

Primary Outcome Measures

  1. On treatment sustained inhibition of plasma Lp-PLA2 activity. [12 Weeks]

Secondary Outcome Measures

  1. Difference in dose-dependent effects of SB-480848 on plasma Lp-PLA2 activity, other biomarkers, and safety. [12 Weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion criteria:

  • Female subjects must be of non-childbearing potential.

  • Stable CHD or CHD-risk equivalent.

  • Must have been on a stable dose of a statin for =4 weeks with LDL <130 mg/dL (3.4 mmol/L) or off statin therapy for =4 weeks with LDL <160 mg/dL (4.1 mmol/L).

  • On a stable dose of at least one oral antiplatelet agent (e.g., aspirin, clopidogrel, or ticlopidine).

Exclusion criteria:

  • Recent cardiovascular event and / or vascular procedure.

  • History of difficult to manage dyslipidemia.

  • Planned cardiac surgery or PCI (percutaneous coronary intervention) or planned major non-cardiac surgery.

  • Inadequately controlled hypertension.

  • Poorly controlled diabetes mellitus.

  • Serum triglycerides >400 mg/dL (4.52 mmol/L).

  • Recent or ongoing acute infection.

  • History of chronic inflammatory disease.

  • Receiving topical, oral, inhaled or injectable corticosteroids.

  • History of chronic viral hepatitis, or other chronic hepatic disorders.

  • History of kidney transplant.

  • History of myopathy or inflammatory muscle disease, or elevated total serum CK (3 x ULN).

  • Severe heart failure (NYHA class III or IV), or severe left ventricular dysfunction (ejection fraction <30%).

  • Asthma manifested by bronchospasm in the past 6 months, or currently taking inhaled bronchodilator on regular basis.

  • History of anaphylaxis, anaphylactoid reactions or severe allergic responses within the past 6 months.

  • Malignancy within the past 2 years, other than non-melanoma skin cancer.

  • Current life-threatening condition other than vascular disease that may prevent a subject from completing the study.

  • QTc interval >440 msec (males) or >450 msec (females).

  • Alcohol or drug abuse within the past 6 months.

  • Previous exposure to SB-480848.

  • Use of an investigational drug within 30 days or 5 half-lives (whichever is the longer) preceding the first dose of study medication (blinded atorvastatin).

Contacts and Locations

Locations

Site City State Country Postal Code
1 GSK Investigational Site Birmingham Alabama United States 35294
2 GSK Investigational Site Northport Alabama United States 35476
3 GSK Investigational Site Phoenix Arizona United States 85014
4 GSK Investigational Site Tucson Arizona United States 85715
5 GSK Investigational Site Spring Valley California United States 91978
6 GSK Investigational Site Torrance California United States 90509
7 GSK Investigational Site Walnut Creek California United States 94598
8 GSK Investigational Site Fort Lauderdale Florida United States 33308
9 GSK Investigational Site Jacksonville Florida United States 32205
10 GSK Investigational Site Pembroke Pines Florida United States 33024
11 GSK Investigational Site Chicago Illinois United States 60607
12 GSK Investigational Site Chicago Illinois United States 60610
13 GSK Investigational Site Indianapolis Indiana United States 46260
14 GSK Investigational Site Lacombe Louisiana United States 70445
15 GSK Investigational Site Slidell Louisiana United States 70458
16 GSK Investigational Site Auburn Maine United States 04210
17 GSK Investigational Site New York New York United States 10016
18 GSK Investigational Site Statesville North Carolina United States 28677
19 GSK Investigational Site Cincinnati Ohio United States 45219
20 GSK Investigational Site Oklahoma City Oklahoma United States 73132
21 GSK Investigational Site Camp Hill Pennsylvania United States 17011
22 GSK Investigational Site Philadelphia Pennsylvania United States 19104
23 GSK Investigational Site Bryan Texas United States 77802
24 GSK Investigational Site Houston Texas United States 77030
25 GSK Investigational Site San Antonio Texas United States 78229
26 GSK Investigational Site Salt Lake City Utah United States 84143
27 GSK Investigational Site Norfolk Virginia United States 23502
28 GSK Investigational Site Richmond Virginia United States 23294
29 GSK Investigational Site Buenos Aires Argentina 1425
30 GSK Investigational Site Buenos Aires Argentina 1704
31 GSK Investigational Site Ciudad Autónoma de Buenos Aires Argentina C1408INH
32 GSK Investigational Site Kippa Ring Queensland Australia 4021
33 GSK Investigational Site Caulfield Victoria Australia 3162
34 GSK Investigational Site Geelong Victoria Australia 3220
35 GSK Investigational Site Pleven Bulgaria 5800
36 GSK Investigational Site Sofia Bulgaria 1000
37 GSK Investigational Site Sofia Bulgaria 1309
38 GSK Investigational Site Sofia Bulgaria 1572
39 GSK Investigational Site Oakville Ontario Canada L6H 3P1
40 GSK Investigational Site Ottawa Ontario Canada K1Y 4W7
41 GSK Investigational Site Sainte-Foy Quebec Canada G1V 4G2
42 GSK Investigational Site Sainte-Foy Quebec Canada G1V 4G5
43 GSK Investigational Site Koebenhavn N Denmark 2100
44 GSK Investigational Site Tallinn Estonia 1162
45 GSK Investigational Site Tallinn Estonia 13419
46 GSK Investigational Site Tartu Estonia 51014
47 GSK Investigational Site Anzin France 59410
48 GSK Investigational Site Bron Cedex France 69677
49 GSK Investigational Site Créteil France 94000
50 GSK Investigational Site Dommartin-les-Toul France 54201
51 GSK Investigational Site Gières France 38610
52 GSK Investigational Site Montbrison France 42600
53 GSK Investigational Site Montpellier Cedex 5 France 34295
54 GSK Investigational Site Pessac cedex France 33604
55 GSK Investigational Site Toulouse France 31300
56 GSK Investigational Site Kippenheim Baden-Wuerttemberg Germany 77971
57 GSK Investigational Site Haag Bayern Germany 83527
58 GSK Investigational Site Kuenzing Bayern Germany 94550
59 GSK Investigational Site Muenchen Bayern Germany 81241
60 GSK Investigational Site Nuernberg Bayern Germany 90402
61 GSK Investigational Site Rednitzhembach Bayern Germany 91126
62 GSK Investigational Site Schwerin Mecklenburg-Vorpommern Germany 19055
63 GSK Investigational Site Bochum Nordrhein-Westfalen Germany 44787
64 GSK Investigational Site Essen Nordrhein-Westfalen Germany 45359
65 GSK Investigational Site Goch Nordrhein-Westfalen Germany 47574
66 GSK Investigational Site Koeln Nordrhein-Westfalen Germany 51069
67 GSK Investigational Site Witten Nordrhein-Westfalen Germany 58455
68 GSK Investigational Site Rhaunen Rheinland-Pfalz Germany 55624
69 GSK Investigational Site Dresden Sachsen Germany 01307
70 GSK Investigational Site Leipzig Sachsen Germany 04229
71 GSK Investigational Site Leipzig Sachsen Germany 04315
72 GSK Investigational Site Berlin Germany 10249
73 GSK Investigational Site Berlin Germany 10367
74 GSK Investigational Site Berlin Germany 12163
75 GSK Investigational Site Berlin Germany 13125
76 GSK Investigational Site Hamburg Germany 20249
77 GSK Investigational Site Hamburg Germany 22041
78 GSK Investigational Site Hamburg Germany 22143
79 GSK Investigational Site Hamburg Germany 22335
80 GSK Investigational Site Budapest Hungary 1032
81 GSK Investigational Site Budapest Hungary 1135
82 GSK Investigational Site Debrecen Hungary 4004
83 GSK Investigational Site Szeged Hungary 6720
84 GSK Investigational Site Szolnok Hungary 5000
85 GSK Investigational Site Banglore India
86 GSK Investigational Site Hyderabad India 500034
87 GSK Investigational Site New Delhi India 110044
88 GSK Investigational Site Den Helder Netherlands 1782 GZ
89 GSK Investigational Site EDE Netherlands 6716 RP
90 GSK Investigational Site Enschede Netherlands 7511JX
91 GSK Investigational Site Haarlem Netherlands 2035 RC
92 GSK Investigational Site Hoofddorp Netherlands 2130 AT
93 GSK Investigational Site Rotterdam Netherlands 3011 TD
94 GSK Investigational Site Sneek Netherlands 8601 ZK
95 GSK Investigational Site Zeist Netherlands 3707 HL
96 GSK Investigational Site Hamilton New Zealand 2001
97 GSK Investigational Site Takapuna New Zealand
98 GSK Investigational Site Karachi Pakistan 74800
99 GSK Investigational Site Karachi Pakistan 75510
100 GSK Investigational Site Bucharest Romania
101 GSK Investigational Site Bucuresti Romania
102 GSK Investigational Site Targu-Mures Romania
103 GSK Investigational Site Alicante Spain 03114
104 GSK Investigational Site Barcelona Spain 080018
105 GSK Investigational Site Barcelona Spain 08022
106 GSK Investigational Site Cáceres Spain 10004
107 GSK Investigational Site Madrid Spain 28034
108 GSK Investigational Site Madrid Spain 28035
109 GSK Investigational Site Madrid Spain 28037
110 GSK Investigational Site Madrid Spain 28041
111 GSK Investigational Site Madrid Spain 28046
112 GSK Investigational Site Móstoles/Madrid Spain 28935
113 GSK Investigational Site Oviedo Spain 33006
114 GSK Investigational Site Palma de Mallorca Spain 07014
115 GSK Investigational Site Quart de Poblet, Valencia Spain 46930
116 GSK Investigational Site San Juan De Alicante Spain 3550
117 GSK Investigational Site Santiago de Compostela/La Coruña Spain 15706
118 GSK Investigational Site Santiago de Compostela Spain 15706
119 GSK Investigational Site Sta. Coloma de Gramanet/Barcelona Spain 08923
120 GSK Investigational Site Tarrasa, Barcelona Spain 08221

Sponsors and Collaborators

  • GlaxoSmithKline

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00269048
Other Study ID Numbers:
  • LPL104884
First Posted:
Dec 23, 2005
Last Update Posted:
Aug 8, 2016
Last Verified:
Aug 1, 2016
Keywords provided by GlaxoSmithKline
CHD
Lp-PLA2
SB-480848
Additional relevant MeSH terms:
Heart Diseases
Atherosclerosis
Coronary Disease
Coronary Artery Disease
Myocardial Ischemia

Study Results

No Results Posted as of Aug 8, 2016