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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00269048




Registration number
NCT00269048
Ethics application status
Date submitted
21/12/2005
Date registered
23/12/2005
Date last updated
8/08/2016

Titles & IDs
Public title
SB-480848 In Subjects With Coronary Heart Disease
Scientific 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
Secondary ID [1] 0 0
LPL104884
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atherosclerosis 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SB-480848
Treatment: Drugs - placebo

Experimental: Arm 1 - SB-480848

Placebo Comparator: Arm 2 - placebo


Treatment: Drugs: SB-480848
SB-480848

Treatment: Drugs: placebo
placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
On treatment sustained inhibition of plasma Lp-PLA2 activity.
Timepoint [1] 0 0
12 Weeks
Secondary outcome [1] 0 0
Difference in dose-dependent effects of SB-480848 on plasma Lp-PLA2 activity, other biomarkers, and safety.
Timepoint [1] 0 0
12 Weeks

Eligibility
Key inclusion criteria
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).
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/09/2006
Sample size
Target
Accrual to date
Final
969
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Kippa Ring
Recruitment hospital [2] 0 0
GSK Investigational Site - Caulfield
Recruitment hospital [3] 0 0
GSK Investigational Site - Geelong
Recruitment postcode(s) [1] 0 0
4021 - Kippa Ring
Recruitment postcode(s) [2] 0 0
3162 - Caulfield
Recruitment postcode(s) [3] 0 0
3220 - Geelong
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
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Arizona
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United States of America
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California
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United States of America
State/province [4] 0 0
Florida
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United States of America
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Illinois
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United States of America
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Indiana
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United States of America
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Louisiana
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United States of America
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Maine
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United States of America
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New York
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United States of America
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North Carolina
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United States of America
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Ohio
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United States of America
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Oklahoma
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United States of America
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Pennsylvania
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United States of America
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Texas
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United States of America
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Utah
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United States of America
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Virginia
Country [17] 0 0
Argentina
State/province [17] 0 0
Buenos Aires
Country [18] 0 0
Argentina
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Ciudad Autónoma de Buenos Aires
Country [19] 0 0
Bulgaria
State/province [19] 0 0
Pleven
Country [20] 0 0
Bulgaria
State/province [20] 0 0
Sofia
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Canada
State/province [21] 0 0
Ontario
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Canada
State/province [22] 0 0
Quebec
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Denmark
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Koebenhavn N
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Estonia
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Tallinn
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Estonia
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Tartu
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France
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Anzin
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France
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Bron Cedex
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France
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Créteil
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France
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Dommartin-les-Toul
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France
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Gières
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France
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Montbrison
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France
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Montpellier Cedex 5
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France
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Pessac cedex
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France
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Toulouse
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Germany
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Baden-Wuerttemberg
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Germany
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Bayern
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Germany
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Mecklenburg-Vorpommern
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Germany
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Nordrhein-Westfalen
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Germany
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Rheinland-Pfalz
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Germany
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Sachsen
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Germany
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Berlin
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Germany
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Hamburg
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Hungary
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Budapest
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Hungary
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Debrecen
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Hungary
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Szeged
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Hungary
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Szolnok
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India
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Banglore
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India
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Hyderabad
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India
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New Delhi
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Netherlands
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Den Helder
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Netherlands
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EDE
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Netherlands
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Enschede
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Netherlands
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Haarlem
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Netherlands
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Hoofddorp
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Netherlands
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Rotterdam
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Netherlands
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Sneek
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Netherlands
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Zeist
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New Zealand
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Hamilton
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New Zealand
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Takapuna
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Pakistan
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Karachi
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Romania
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Bucharest
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Romania
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Bucuresti
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Romania
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Targu-Mures
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Spain
State/province [64] 0 0
Alicante
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Spain
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Barcelona
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Spain
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Cáceres
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Spain
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Madrid
Country [68] 0 0
Spain
State/province [68] 0 0
Móstoles/Madrid
Country [69] 0 0
Spain
State/province [69] 0 0
Oviedo
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Spain
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Palma de Mallorca
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Spain
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Quart de Poblet, Valencia
Country [72] 0 0
Spain
State/province [72] 0 0
San Juan De Alicante
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Spain
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Santiago de Compostela/La Coruña
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Spain
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Santiago de Compostela
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Spain
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Sta. Coloma de Gramanet/Barcelona
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Spain
State/province [76] 0 0
Tarrasa, Barcelona

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00269048
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00269048