A Study to Evaluate the Effects of 3 Months Dosing With GW856553, as Assessed FDG-PET/CT Imaging

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00633022
• Collaborator: (none)
• Enrollment: 99
• Locations: 4
• Arms: 3
• Actual Duration (Months): 18
• Patients Per Site: 24.8
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

This study is being conducted to assess the potential anti-inflammatory effects of a 3-month treatment with GW856553, on the inflammatory activity within the aorta and carotid plaques, as assessed by FDG-PET/CT.

Condition or Disease	Intervention/Treatment	Phase
Atherosclerosis	Drug: LOSMAPIMOD 7.5 MG; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 99 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Effects of Two Regimens of GW856553, Over a Period of 3 Month, on In-vivo Macrophage Activity, as Assessed by FDG-PET/CT Imaging, in the Carotid Arteries and Aorta of Subjects With Established Atherosclerosis
• Actual Study Start Date: Jun 2, 2008
• Actual Primary Completion Date: Dec 3, 2009
• Actual Study Completion Date: Dec 3, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LOSMAPIMOD 7.5 MG TWICE DAILY Participants received 1 tablet of 7.5 mg Losmapimod orally twice daily, each morning and evening for a period of 12 weeks	Drug: LOSMAPIMOD 7.5 MG; GW856553 tablets (wet granulation formulation) are available as white, film coated, round, convex tablets manufactured using micronised GW856553X active substance. Tablets are available containing 7.5 mg of GW856553X and are packed into high-density polyethylene (HDPE) bottles.
Placebo Comparator: Placebo Participants received 1 tablet of placebo matching Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.	Drug: Placebo; Placebo tablets (wet granulation formulation) are available as white, film coated, round, convex tablets manufactured using micronised substance to visually match the active GW856553 tablets are also available. Tablets are packed into high-density polyethylene (HDPE) bottles.
Experimental: LOSMAPIMOD 7.5 MG ONCE DAILY Participants received 1 tablet of 7.5 mg Losmapimod each morning once daily and placebo tablet each evening once daily orally for a period of 12 weeks.	Drug: LOSMAPIMOD 7.5 MG; GW856553 tablets (wet granulation formulation) are available as white, film coated, round, convex tablets manufactured using micronised GW856553X active substance. Tablets are available containing 7.5 mg of GW856553X and are packed into high-density polyethylene (HDPE) bottles.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline of Mean of Maximum Tissue to Background Ratio (TBR) in the Qualifying Artery, Following 12 Weeks of Treatment in the Setting of Chronic Statin Therapy [Baseline (Days -14 to -1) and up to Week 12]

   Qualifying artery was defined as the artery (left or right carotid or ascending aorta) with the highest segmental mean of maximum (max) TBR at Baseline. The TBR of the qualifying segment was to be ≥ 1.6. If more than one artery qualified, the hottest (greatest mean of max TBR) artery was the qualifying artery. Baseline was defined as the value between Days -14 to -1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-treatment values.

Secondary Outcome Measures

1. Change From Baseline of the 'Most Diseased Segment (MSD)' Average Maximum TBR in the Qualifying Artery Following 12 Weeks of Treatment With GW856553 or Placebo in the Setting of Chronic Statin Therapy [Baseline (Days -14 to -1) and up to Week 12]

   Most diseased segment (MDS) mean of max TBR was mean of all the slice max TBR that compose the most diseased segment. TBR was derived by dividing the arterial vessel wall SUV (tissue) by the background venous blood pool SUV. Unless noted otherwise, the tissue max SUV value for each ROI was used as inputs to the TBR. Baseline was defined as the value between Days -14 to -1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-treatment values.

2. Change From Baseline in Blood Concentration of High Sensitivity C-reactive Protein (Hs-CRP) [Baseline (Day 1) and Days 7, 14, 21, 28, 42, 56, 70, 84]

   CRP is a protein that the liver makes when there is inflammation in the body. It's also called a marker of inflammation, and can be measured with an hs-CRP test. Blood samples were collected to analyze hs-CRP. Baseline was defined as the value on Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-treatment values.

3. Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points [Day 1, 7, 14, 21, 28, 42, 56, 70, 84, 98]

   Blood pressure measurements were taken to observe vital signs and included SBP and DBP. SBP and DBP measurements were obtained at Day 1, 7, 14, 21, 28, 42, 56, 70, 84 and follow-up (1-2 weeks post last dose on Day 84).

4. Mean Heart Rate at Indicated Time Points [Day 1, 7, 14, 21, 28, 42, 56, 70, 84, 98]

   Vital sign monitoring included heart rate measurement. Heart rate measurements were obtained at Day 1, 7, 14, 21, 28, 42, 56, 70, 84 and follow-up (1-2 weeks post last dose on Day 84).

5. Number of Participants With 12-lead Electrocardiogram (ECG) Findings [Days 1, 7, 14, 21, 28, 42, 56, 70, 84, 98]

   All 12-lead ECGs were obtained after the participant had rested in the supine position for at least 15 minutes. All ECGs were evaluated by the principal investigator or designee for any other abnormality of potential clinical importance (PCI). Data for abnormal ECG findings have been reported under abnormal - Not clinically significant (NCS) and Abnormal - Clinically significant (CS) categories. Data only for categories with values have been presented.

6. Number of Participants With Clinical Chemistry Abnormalities of PCI [Up to Follow-up (Day 98)]

   Clinical chemistry range for PCI was calcium low <1.5 mill mole per litre (mmol/L), high > 3.24 mmol/L; creatinine high 155 mmol/L; glucose low < 2.2 (age: 13-99) mmol/L, high > 27.8 (age: 13-99) mmol/L; phosphorus low < 2.8 mmol/L, high > 6.5 mmol/L; sodium low < 125 mmol/L, high > 150 mmol/L. Categories with values have been presented.

7. Number of Participants With Hematology Abnormalities of PCI [Up to Follow-up (Day 98)]

   Hematology range for PCI was: white blood cell count (WBC) low < 1.1 x109/ L; hemoglobin low <71 (age: 18-99) grams per litre (g/L), high >199 (age: 18-99) g/L; hematocrit low 0.201 (age: 18-99) ratio of 1 high 0.599 (age: 18-99) ratio of 1 and platelet count low < 80 x109/ L, high > 500 x109/ L. Categories with values have been presented.

8. Number of Participants With Urinalysis Dipstick Results [Day 1, 7, 14, 21, 28, 42, 56, 70, 84, 98]

   A urine dipstick test is a basic diagnostic tool used to determine pathological changes in a participant's urine in standard urinalysis. Data was analyzed for urine occult blood, urine glucose, urine ketones and urine protein ranging from 2+, trace, 1+, 3+, 1+or 1/4, 3+ or 1 and trace or 1/10, indicating proportional concentrations in the urine sample. Data has been presented for categories with values for positive findings.

9. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Up to Follow-up (Day 98)]

   An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria for Main Study:

1. Adult male and female subjects, between 50 and 80 years of age, inclusive, with a body weight > 50 kg and body mass index (BMI) between 19 and 35 kg/m2

2. Subjects who have:

• experienced a CV event (acute coronary syndrome, unstable angina, CABG, PCI, stroke, MI, TIA, carotid endarterectomy), but have been clinically stable for at least 6 months since that event,

• or, have peripheral vascular disease (PVD), as indicated by

• symptoms of claudication and either a positive imaging/treadmill test, or

• reduced ankle branchial pressure index,

• or, have a diagnosis of CAD corroborated by stress testing (exercise or pharmacological) or any other confirmed diagnosis of atherosclerotic arterial disease

• Individuals who have experienced a CV event or have PVD will be given preference for enrolment in the study, if they also have one of the following:

• metabolic syndrome, as defined by NCEP ATP III

• Framingham score > 20

• Current smokers (at least 1pack/day)

• Well-controlled diabetes, defined for the purposes of this study as HbA1c <= 8%, or fasting blood glucose <= 126mg/dL (7mmol/L)

1. Subjects must be on a stable dose of statin for at least 3 months prior to first dose of study medication. Subjects must be capable of continuing statin therapy from screening until the final follow up visit.

2. Either carotid or aortic TBR ³ 1.6, as measured on FDG-PET/CT, signifying active inflammation.

3. AST and ALT < 2xULN at screening; alkaline phosphatase and bilirubin <= 1.5xULN at screening (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

4. A signed and dated written informed consent prior to admission to the study

5. The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.

Exclusion Criteria for Main Study:

1. Any medical history or clinically relevant abnormality identified on the screening medical examination, vital sign measurement, 12-lead ECG recording and/or clinical laboratory examination that is deemed by the principal investigator and/or medical monitor to make the subject ineligible for inclusion because of a safety concern.

2. History of heart failure defined as NYHA class II - IV or those with known severe LV systolic dysfunction (EF<30%) regardless of symptomatic status

3. Subjects with atrial fibrillation (AF) at screening will be excluded.

4. Insulin controlled Type 1 or Type 2 diabetics

5. Diabetics with fasting glucose > 126mg/dL (7mmol/L) or HbAc1 levels > 8%, at screening. [note: fasting glucose to be checked again at first FDG-PET scan, and if glucose > 11mmol/L at that visit, subject will be excluded from study]

6. Positive pre-study hepatitis B surface antigen or positive hepatitis C antibody results within 3 months of screening.

7. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

8. Renal impairment with creatinine clearance of <40 ml/min at screening, or history of kidney transplant or history of contrast nephropathy.

9. Subjects with rheumatoid arthritis, connective tissue disorders and other conditions known to be associated with active chronic inflammation (e.g. Inflammatory Bowel Disease).

10. Subjects with chronic infections such as HIV, gingivitis, periodonitis, prostatitis, gastritis, and urinary tract infections, or any active diseases, including active tuberculosis or a history of active tuberculosis.

11. Subjects with any acute infection, symptoms suggestive of sinusitis, or significant trauma (burns, fractures)

12. History of malignancy within the past 5 years, other than non-melanoma skin cancer.

13. History of skeletal muscle myopathy or rhabdomyolysis

14. Previous exposure to GW856553.

15. Current use of steroids (inhaled or oral)

16. Subjects who have donated more than 500 mL of blood within 56 days prior to the study medication administration.

17. Participation in a clinical study where the subject has received a drug or new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of the drug (whichever is longer) prior to the first dose of study medication

18. History of alcohol/drug abuse or dependence within 12 months of the study

19. The subject has a three month prior history of regular alcohol consumption exceeding an average weekly intake of >28 units (or an average daily intake of greater than 3 units) for males, or an average weekly intake of > 21 units (or an average daily intake of greater than 2 units) for females. 1 unit is equivalent to a half-pint (284mL) of beer/lager; 25mL measure of spirits or 125mL of wine; or a positive alcohol breath test at the screening visit

20. A positive urine test for drugs of abuse (not related to known medications the subject is taking, e.g. codeine for pain management) or alcohol at screening or prior to study medication administration.

21. QTc interval > 450 msec (using average value of triplicate ECGs)

22. Subjects will be excluded if they have participated in clinical research studies involving radiation in the past three years

23. Women must be of non-childbearing potential [i.e. either postmenopausal or documented hysterectomy - tubal ligation is not sufficient]. For the purposes of this study, post menopausal is defined as being amenorrhoeic for greater than 2 years with an appropriate clinical profile, e.g. age appropriate, history of vasomotor symptoms. Postmenopausal status will be confirmed by serum or urine FSH and oestradiol concentrations at screening, if appropriate. Surgical sterility will be defined as females who have had a hysterectomy and/or bilateral oophorectomy.

24. An unwillingness of male subjects to abstain from sexual intercourse with pregnant or lactating women; or an unwillingness of the subject to use a condom/spermicide in addition to having their female partner use another form of contraception such as an IUD, diaphragm with spermicide, injectable progesterone, sub-dermal implants or a tubal ligation if the women could become pregnant from the time of the first dose of the study medication until 3 months after administration of last dose of study medication.

Inclusion Criteria for Subjects in MRI Sub-study

1. Recent (in approximately last 12 months) echocardiogram with ejection fraction between 30 and 50%.

Exclusion Criteria for Subjects in MRI Sub-study

1. Contraindication to MRI scanning (as assessed by local MRI safety questionnaire) which includes but not limited to:

• Intracranial aneurysm clips (except Sugita) or other metallic objects,

• History of intra- orbital metal fragments that have not been removed by an MD,

• Pacemakers, implantable cardiac defibrillators and non-MR compatible heart valves,

• Inner ear implants,

• History of claustrophobia in MR.

1. Allergy to MRI contrast enhancement agent (gadolinium).

2. Serum creatinine clearance < 60 mL/min (At the discretion of the physician, the subject may progress to a formal assessment based on 24 hour urine collection should serum creatinine limits fall below limits.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Oxford	Oxfordshire	United Kingdom	OX3 9DU
2	GSK Investigational Site	Cambridge		United Kingdom	CB2 2GG
3	GSK Investigational Site	London		United Kingdom	E1 1B3
4	GSK Investigational Site	London		United Kingdom	Se1 7EH

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

• Elkhawad M, Rudd JH, Sarov-Blat L, Cai G, Wells R, Davies LC, Collier DJ, Marber MS, Choudhury RP, Fayad ZA, Tawakol A, Gleeson FV, Lepore JJ, Davis B, Willette RN, Wilkinson IB, Sprecher DL, Cheriyan J. Effects of p38 mitogen-activated protein kinase inhibition on vascular and systemic inflammation in patients with atherosclerosis. JACC Cardiovasc Imaging. 2012 Sep;5(9):911-22. doi: 10.1016/j.jcmg.2012.02.016.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00633022
• Other Study ID Numbers: PM1111138
• First Posted: Mar 11, 2008
• Last Update Posted: Oct 17, 2018
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: FDG-PET/CT, atherosclerosis
• Additional relevant MeSH terms: Atherosclerosis

Study Results

Participant Flow

Recruitment Details	Participants with established atherosclerosis were planned to be enrolled across 4 sites in the United Kingdom from 02 June 2008 to 03 December 2009. Participants were screened within 45 days prior to the first dose and underwent radiological scan within 14 days prior to the first dose.
Pre-assignment Detail	Participants were randomized in the study to receive oral dose of Losmapimod 7.5 milligram (mg) twice daily, Losmapimod 7.5 mg once daily or placebo.

Arm/Group Title	Losmapimod 7.5 mg Twice Daily	Losmapimod 7.5 mg Once Daily	Placebo
Arm/Group Description	Participants received 1 tablet of 7.5 mg Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.	Participants received 1 tablet of 7.5 mg Losmapimod each morning once daily and placebo tablet each evening once daily orally for a period of 12 weeks.	Participants received 1 tablet of placebo matching Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.
Period Title: Overall Study
STARTED	34	33	32
COMPLETED	33	32	27
NOT COMPLETED	1	1	5

Baseline Characteristics

Arm/Group Title	Losmapimod 7.5 mg Twice Daily	Losmapimod 7.5 mg Once Daily	Placebo	Total
Arm/Group Description	Participants received 1 tablet of 7.5 mg Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.	Participants received 1 tablet of 7.5 mg Losmapimod each morning once daily and placebo tablet each evening once daily orally for a period of 12 weeks.	Participants received 1 tablet of placebo matching Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.	Total of all reporting groups
Overall Participants	34	33	32	99
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	62.3 (5.90)	65.3 (5.94)	63.7 (6.37)	63.8 (6.13)
Sex: Female, Male (Count of Participants)
Female	5 14.7%	5 15.2%	4 12.5%	14 14.1%
Male	29 85.3%	28 84.8%	28 87.5%	85 85.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	1 2.9%	1 3%	1 3.1%	3 3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	1 2.9%	2 6.1%	1 3.1%	4 4%
White	32 94.1%	30 90.9%	30 93.8%	92 92.9%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline of Mean of Maximum Tissue to Background Ratio (TBR) in the Qualifying Artery, Following 12 Weeks of Treatment in the Setting of Chronic Statin Therapy
Description	Qualifying artery was defined as the artery (left or right carotid or ascending aorta) with the highest segmental mean of maximum (max) TBR at Baseline. The TBR of the qualifying segment was to be ≥ 1.6. If more than one artery qualified, the hottest (greatest mean of max TBR) artery was the qualifying artery. Baseline was defined as the value between Days -14 to -1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-treatment values.
Time Frame	Baseline (Days -14 to -1) and up to Week 12

Outcome Measure Data

Analysis Population Description

Pharmacodynamic (PD) Population comprised of all participants who provided PD data. Only those participants with data available at the indicated time points were analyzed.

Arm/Group Title	Losmapimod 7.5 mg Twice Daily	Losmapimod 7.5 mg Once Daily	Placebo
Arm/Group Description	Participants received 1 tablet of 7.5 mg Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.	Participants received 1 tablet of 7.5 mg Losmapimod each morning once daily and placebo tablet each evening once daily orally for a period of 12 weeks.	Participants received 1 tablet of placebo matching Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.
Measure Participants	32	32	29
Mean (Standard Deviation) [Maximum tissue to background ratio]	-0.146 (0.2483)	-0.122 (0.1839)	-0.070 (0.1632)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Losmapimod 7.5 mg Twice Daily, Placebo
	Comments	Losmapimod 7.5 mg BID versus Placebo
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4519
	Comments
	Method	ANCOVA
	Comments	ANCOVA model, fitting fixed effect treatment term, and including baseline TBR value as a covariate.ANCOVA model, fitting fixed effect treatment term,
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.14 to 0.06
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (final values) of Losmapimod 7.5 mg twice daily and Placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Losmapimod 7.5 mg Once Daily, Placebo
	Comments	Losmapimod 7.5 mg once daily versus Placebo
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5789
	Comments
	Method	ANCOVA
	Comments	ANCOVA model, fitting fixed effect treatment term, and including baseline TBR value as a covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.11 to 0.06
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (final values) of Losmapimod 7.5 mg once daily and Placebo.

2. Secondary Outcome

Title	Change From Baseline of the 'Most Diseased Segment (MSD)' Average Maximum TBR in the Qualifying Artery Following 12 Weeks of Treatment With GW856553 or Placebo in the Setting of Chronic Statin Therapy
Description	Most diseased segment (MDS) mean of max TBR was mean of all the slice max TBR that compose the most diseased segment. TBR was derived by dividing the arterial vessel wall SUV (tissue) by the background venous blood pool SUV. Unless noted otherwise, the tissue max SUV value for each ROI was used as inputs to the TBR. Baseline was defined as the value between Days -14 to -1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-treatment values.
Time Frame	Baseline (Days -14 to -1) and up to Week 12

Outcome Measure Data

Analysis Population Description

PD Population. Only those participants with data available at the indicated time points were analyzed.

Arm/Group Title	Losmapimod 7.5 mg Twice Daily	Losmapimod 7.5 mg Once Daily	Placebo
Arm/Group Description	Participants received 1 tablet of 7.5 mg Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.	Participants received 1 tablet of 7.5 mg Losmapimod each morning once daily and placebo tablet each evening once daily orally for a period of 12 weeks.	Participants received 1 tablet of placebo matching Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.
Measure Participants	31	32	28
Mean (Standard Deviation) [Ratio]	-0.294 (0.3169)	-0.250 (0.2892)	-0.221 (0.2132)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Losmapimod 7.5 mg Twice Daily, Placebo
	Comments	Losmapimod 7.5 mg twice daily versus placebo
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6986
	Comments
	Method	ANCOVA
	Comments	ANCOVA model, fitting fixed effect treatment term, and including baseline TBR value as a covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.15 to 0.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (final values) of Losmapimod 7.5 mg twice daily and Placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Losmapimod 7.5 mg Once Daily, Placebo
	Comments	Losmapimod 7.5 mg once daily versus Placebo
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9486
	Comments
	Method	ANCOVA
	Comments	ANCOVA model, fitting fixed effect treatment term, and including baseline TBR value as a covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.00
	Confidence Interval	(2-Sided) 95%; -0.13 to 0.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (final values) of Losmapimod 7.5 mg once daily and Placebo.

3. Secondary Outcome

Title	Change From Baseline in Blood Concentration of High Sensitivity C-reactive Protein (Hs-CRP)
Description	CRP is a protein that the liver makes when there is inflammation in the body. It's also called a marker of inflammation, and can be measured with an hs-CRP test. Blood samples were collected to analyze hs-CRP. Baseline was defined as the value on Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-treatment values.
Time Frame	Baseline (Day 1) and Days 7, 14, 21, 28, 42, 56, 70, 84

Outcome Measure Data

Analysis Population Description

PD Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Losmapimod 7.5 mg Twice Daily	Losmapimod 7.5 mg Once Daily	Placebo
Arm/Group Description	Participants received 1 tablet of 7.5 mg Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.	Participants received 1 tablet of 7.5 mg Losmapimod each morning once daily and placebo tablet each evening once daily orally for a period of 12 weeks.	Participants received 1 tablet of placebo matching Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.
Measure Participants	34	33	32
Day 7	-2.293 (6.0389)	-0.446 (0.5547)	0.079 (0.6886)
Day 14	-0.756 (4.8068)	-0.617 (2.0800)	-0.352 (1.9871)
Day 21	-2.250 (5.9883)	0.130 (1.1586)	0.242 (1.3125)
Day 28	-1.394 (3.9276)	1.953 (13.6807)	0.197 (3.7474)
Day 42	-0.085 (10.3631)	-0.145 (0.6186)	-0.009 (0.8105)
Day 56	0.012 (6.0287)	0.077 (4.6724)	0.563 (5.0270)
Day 70	1.313 (2.8216)	0.086 (0.9118)	-0.657 (1.3011)
Day 84	-0.100 (1.5281)	1.452 (5.3392)	-0.313 (1.9369)

4. Secondary Outcome

Title	Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points
Description	Blood pressure measurements were taken to observe vital signs and included SBP and DBP. SBP and DBP measurements were obtained at Day 1, 7, 14, 21, 28, 42, 56, 70, 84 and follow-up (1-2 weeks post last dose on Day 84).
Time Frame	Day 1, 7, 14, 21, 28, 42, 56, 70, 84, 98

Outcome Measure Data

Analysis Population Description

Safety Population comprised of all participants who received at least one dose of study drug. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Losmapimod 7.5 mg Twice Daily	Losmapimod 7.5 mg Once Daily	Placebo
Arm/Group Description	Participants received 1 tablet of 7.5 mg Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.	Participants received 1 tablet of 7.5 mg Losmapimod each morning once daily and placebo tablet each evening once daily orally for a period of 12 weeks.	Participants received 1 tablet of placebo matching Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.
Measure Participants	34	33	32
DBP: Day 1	78.9 (8.67)	76.7 (11.08)	75.8 (7.64)
DBP: Day 7	79.4 (8.00)	73.6 (11.04)	73.9 (6.81)
DBP: Day 14	76.6 (9.01)	76.1 (10.55)	76.4 (9.03)
DBP: Day 21	77.9 (8.44)	73.8 (12.05)	74.5 (7.60)
DBP: Day 28	77.4 (9.64)	76.5 (9.63)	76.4 (8.96)
DBP: Day 42	80.6 (11.12)	72.8 (8.96)	74.6 (7.94)
DBP: Day 56	77.5 (10.95)	75.7 (9.09)	75.9 (7.50)
DBP: Day 70	76.3 (4.54)	73.8 (10.71)	75.0 (6.30)
DBP: Day 84	75.6 (8.68)	75.4 (9.51)	76.2 (8.90)
DBP: Day 98	78.0 (9.81)	76.6 (10.58)	73.6 (8.26)
SBP: Day 1	134.9 (16.67)	132.6 (16.00)	129.5 (19.22)
SBP: Day 7	132.4 (19.40)	123.1 (13.58)	122.4 (13.99)
SBP: Day 14	128.2 (17.08)	133.3 (19.05)	130.3 (17.87)
SBP: Day 21	136.9 (15.12)	132.8 (20.80)	126.6 (15.76)
SBP: Day 28	131.7 (21.94)	132.3 (17.79)	128.5 (18.76)
SBP: Day 42	140.7 (19.78)	126.5 (17.94)	128.3 (20.10)
SBP: Day 56	130.1 (17.88)	130.5 (16.91)	127.4 (16.69)
SBP: Day 70	136.3 (11.46)	122.8 (14.56)	135.4 (19.48)
SBP: Day 84	129.5 (17.78)	128.1 (14.32)	126.4 (19.84)
SBP: Day 98	131.2 (18.06)	130.9 (17.61)	125.1 (15.87)

5. Secondary Outcome

Title	Mean Heart Rate at Indicated Time Points
Description	Vital sign monitoring included heart rate measurement. Heart rate measurements were obtained at Day 1, 7, 14, 21, 28, 42, 56, 70, 84 and follow-up (1-2 weeks post last dose on Day 84).
Time Frame	Day 1, 7, 14, 21, 28, 42, 56, 70, 84, 98

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Losmapimod 7.5 mg Twice Daily	Losmapimod 7.5 mg Once Daily	Placebo
Arm/Group Description	Participants received 1 tablet of 7.5 mg Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.	Participants received 1 tablet of 7.5 mg Losmapimod each morning once daily and placebo tablet each evening once daily orally for a period of 12 weeks.	Participants received 1 tablet of placebo matching Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.
Measure Participants	34	33	32
Heart rate: Day 1	57.6 (11.39)	56.3 (9.84)	56.5 (9.79)
Heart rate: Day 7	60.8 (13.97)	52.5 (6.81)	54.6 (6.11)
Heart rate: Day 14	57.7 (11.80)	56.7 (7.66)	55.4 (10.32)
Heart rate: Day 21	63.9 (12.44)	54.3 (6.59)	54.8 (8.97)
Heart rate: Day 28	58.7 (12.25)	56.4 (9.17)	57.2 (10.91)
Heart rate: Day 42	60.1 (9.31)	52.1 (6.46)	56.8 (10.80)
Heart rate: Day 56	58.6 (11.48)	56.1 (10.12)	56.5 (10.73)
Heart rate: Day 70	57.3 (7.67)	53.8 (5.26)	54.3 (9.52)
Heart rate: Day 84	58.7 (12.07)	59.2 (10.35)	55.8 (11.53)
Heart rate: Day 98	61.5 (12.09)	58.2 (9.00)	56.1 (9.76)

6. Secondary Outcome

Title	Number of Participants With 12-lead Electrocardiogram (ECG) Findings
Description	All 12-lead ECGs were obtained after the participant had rested in the supine position for at least 15 minutes. All ECGs were evaluated by the principal investigator or designee for any other abnormality of potential clinical importance (PCI). Data for abnormal ECG findings have been reported under abnormal - Not clinically significant (NCS) and Abnormal - Clinically significant (CS) categories. Data only for categories with values have been presented.
Time Frame	Days 1, 7, 14, 21, 28, 42, 56, 70, 84, 98

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Losmapimod 7.5 mg Twice Daily	Losmapimod 7.5 mg Once Daily	Placebo
Arm/Group Description	Participants received 1 tablet of 7.5 mg Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.	Participants received 1 tablet of 7.5 mg Losmapimod each morning once daily and placebo tablet each evening once daily orally for a period of 12 weeks.	Participants received 1 tablet of placebo matching Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.
Measure Participants	34	33	32
Day 1 pre-dose 1: Abnormal-NCS	19 55.9%	17 51.5%	15 46.9%
Day 1 pre-dose 2:Abnormal-NCS	19 55.9%	16 48.5%	15 46.9%
Day 1 pre-dose 3: Abnormal-NCS	18 52.9%	16 48.5%	15 46.9%
Day 7 pre-dose 1: Abnormal-NCS	8 23.5%	8 24.2%	7 21.9%
Day 14 pre-dose 1: Abnormal-NCS	16 47.1%	17 51.5%	16 50%
Day 28 pre-dose 1: Abnormal-NCS	16 47.1%	14 42.4%	13 40.6%
Day 28 pre-dose 1: Abnormal-CS	0 0%	0 0%	1 3.1%
Day 56 pre-dose 1: Abnormal-NCS	17 50%	15 45.5%	12 37.5%
Day 70 pre-dose 1: Abnormal-NCS	4 11.8%	4 12.1%	4 12.5%
Day 84 pre-dose 1: Abnormal-NCS	15 44.1%	17 51.5%	11 34.4%
Day 98: Abnormal-NCS	15 44.1%	18 54.5%	13 40.6%
Day 98: Abnormal-CS	0 0%	0 0%	1 3.1%

7. Secondary Outcome

Title	Number of Participants With Clinical Chemistry Abnormalities of PCI
Description	Clinical chemistry range for PCI was calcium low <1.5 mill mole per litre (mmol/L), high > 3.24 mmol/L; creatinine high 155 mmol/L; glucose low < 2.2 (age: 13-99) mmol/L, high > 27.8 (age: 13-99) mmol/L; phosphorus low < 2.8 mmol/L, high > 6.5 mmol/L; sodium low < 125 mmol/L, high > 150 mmol/L. Categories with values have been presented.
Time Frame	Up to Follow-up (Day 98)

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Losmapimod 7.5 mg Twice Daily	Losmapimod 7.5 mg Once Daily	Placebo
Arm/Group Description	Participants received 1 tablet of 7.5 mg Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.	Participants received 1 tablet of 7.5 mg Losmapimod each morning once daily and placebo tablet each evening once daily orally for a period of 12 weeks.	Participants received 1 tablet of placebo matching Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.
Measure Participants	34	33	32
Calcium low	2 5.9%	0 0%	0 0%
Calcium high	0 0%	0 0%	1 3.1%
Glucose low	1 2.9%	0 0%	0 0%
Glucose high	7 20.6%	2 6.1%	3 9.4%
Potassium low	1 2.9%	2 6.1%	0 0%
Sodium low	1 2.9%	3 9.1%	3 9.4%
Creatinine high	0 0%	2 6.1%	4 12.5%
Chloride low	0 0%	2 6.1%	0 0%

8. Secondary Outcome

Title	Number of Participants With Hematology Abnormalities of PCI
Description	Hematology range for PCI was: white blood cell count (WBC) low < 1.1 x109/ L; hemoglobin low <71 (age: 18-99) grams per litre (g/L), high >199 (age: 18-99) g/L; hematocrit low 0.201 (age: 18-99) ratio of 1 high 0.599 (age: 18-99) ratio of 1 and platelet count low < 80 x109/ L, high > 500 x109/ L. Categories with values have been presented.
Time Frame	Up to Follow-up (Day 98)

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Losmapimod 7.5 mg Twice Daily	Losmapimod 7.5 mg Once Daily	Placebo
Arm/Group Description	Participants received 1 tablet of 7.5 mg Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.	Participants received 1 tablet of 7.5 mg Losmapimod each morning once daily and placebo tablet each evening once daily orally for a period of 12 weeks.	Participants received 1 tablet of placebo matching Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.
Measure Participants	34	33	32
Eosinophils high	3 8.8%	1 3%	1 3.1%
Eosinophils low	0 0%	0 0%	1 3.1%
Haemoglobin low	1 2.9%	0 0%	1 3.1%
Lymphocytes low	4 11.8%	2 6.1%	2 6.3%
Lymphocytes high	1 2.9%	0 0%	2 6.3%
MCH high	0 0%	0 0%	1 3.1%
Monocytes high	1 2.9%	0 0%	1 3.1%
Neutrophils low	0 0%	0 0%	1 3.1%
Neutrophils high	3 8.8%	1 3%	0 0%
RBC count low	1 2.9%	0 0%	1 3.1%
Reticulocytes low	4 11.8%	4 12.1%	9 28.1%
Reticulocytes high	18 52.9%	10 30.3%	13 40.6%
Platelet count low	0 0%	1 3%	0 0%
WBC count low	0 0%	1 3%	0 0%

9. Secondary Outcome

Title	Number of Participants With Urinalysis Dipstick Results
Description	A urine dipstick test is a basic diagnostic tool used to determine pathological changes in a participant's urine in standard urinalysis. Data was analyzed for urine occult blood, urine glucose, urine ketones and urine protein ranging from 2+, trace, 1+, 3+, 1+or 1/4, 3+ or 1 and trace or 1/10, indicating proportional concentrations in the urine sample. Data has been presented for categories with values for positive findings.
Time Frame	Day 1, 7, 14, 21, 28, 42, 56, 70, 84, 98

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Losmapimod 7.5 mg Twice Daily	Losmapimod 7.5 mg Once Daily	Placebo
Arm/Group Description	Participants received 1 tablet of 7.5 mg Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.	Participants received 1 tablet of 7.5 mg Losmapimod each morning once daily and placebo tablet each evening once daily orally for a period of 12 weeks.	Participants received 1 tablet of placebo matching Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.
Measure Participants	34	33	32
Day 1: Urine Occult Blood, trace	1 2.9%	1 3%	2 6.3%
Day 1: Urine Occult Blood, 3+	0 0%	0 0%	1 3.1%
Day 1: Urine Glucose, 1+	0 0%	0 0%	1 3.1%
Day 1: Urine Protein, trace	4 11.8%	1 3%	2 6.3%
Day 1: Urine Protein, 1+	2 5.9%	0 0%	5 15.6%
Day 7: Urine Occult Blood, 1+	0 0%	0 0%	1 3.1%
Day 7: Urine Occult Blood, 3+	0 0%	0 0%	1 3.1%
Day 7: Urine Protein, trace	0 0%	1 3%	3 9.4%
Day 7: Urine Protein, 1+	1 2.9%	0 0%	1 3.1%
Day 14: Urine Occult Blood, 2+	0 0%	0 0%	1 3.1%
Day 14: Urine Occult Blood, trace	1 2.9%	2 6.1%	0 0%
Day 14: Urine Occult Blood, 1+	0 0%	0 0%	3 9.4%
Day 14: Urine Ketones, trace	0 0%	1 3%	0 0%
Day 14: Urine Protein, trace	1 2.9%	1 3%	3 9.4%
Day 14: Urine Protein, 1+	3 8.8%	0 0%	2 6.3%
Day 21: Urine Occult Blood, trace	1 2.9%	0 0%	0 0%
Day 21: Urine Ketones, trace	0 0%	0 0%	1 3.1%
Day 21: Urine Protein, trace	1 2.9%	0 0%	3 9.4%
Day 21: Urine Protein, 1+	1 2.9%	0 0%	1 3.1%
Day 28: Urine Occult Blood, 2+	0 0%	0 0%	2 6.3%
Day 28: Urine Occult Blood, trace	1 2.9%	1 3%	1 3.1%
Day 28: Urine Protein, trace	2 5.9%	3 9.1%	5 15.6%
Day 28: Urine Protein, 1+	3 8.8%	0 0%	1 3.1%
Day 42: Urine Occult Blood, 2+	0 0%	0 0%	1 3.1%
Day 42: Urine Protein, trace	0 0%	1 3%	2 6.3%
Day 42: Urine Protein, 1+	1 2.9%	0 0%	0 0%
Day 56: Urine Occult Blood, 2+	0 0%	0 0%	1 3.1%
Day 56: Urine Occult Blood, trace	0 0%	0 0%	2 6.3%
Day 56: Urine Occult Blood, 1+	0 0%	1 3%	2 6.3%
Day 56: Urine Glucose, Trace or 1/10	0 0%	0 0%	1 3.1%
Day 56: Urine Ketones, trace	1 2.9%	0 0%	0 0%
Day 56: Urine Protein, trace	2 5.9%	2 6.1%	1 3.1%
Day 56: Urine Protein, 1+	3 8.8%	0 0%	2 6.3%
Day 70: Urine Occult Blood, 2+	0 0%	0 0%	1 3.1%
Day 70: Urine Occult Blood, trace	1 2.9%	0 0%	0 0%
Day 70: Urine Protein, 2+	1 2.9%	0 0%	0 0%
Day 70: Urine Protein, trace	0 0%	0 0%	1 3.1%
Day 70: Urine Protein, 1+	0 0%	0 0%	1 3.1%
Day 84: Urine Occult Blood, 2+	0 0%	1 3%	1 3.1%
Day 84: Urine Occult Blood, trace	0 0%	0 0%	1 3.1%
Day 84: Urine Occult Blood, 1+	0 0%	0 0%	2 6.3%
Day 84: Urine Ketones, trace	0 0%	0 0%	1 3.1%
Day 84: Urine Protein, 2+	0 0%	1 3%	0 0%
Day 84: Urine Protein, trace	2 5.9%	3 9.1%	5 15.6%
Day 84: Urine Protein, 1+	3 8.8%	0 0%	0 0%
Day 98: Urine Occult Blood, 2+	0 0%	0 0%	1 3.1%
Day 98: Urine Occult Blood, trace	1 2.9%	1 3%	0 0%
Day 98: Urine Occult Blood, 1+	0 0%	1 3%	1 3.1%
Day 98: Urine Occult Blood, 3+	0 0%	0 0%	1 3.1%
Day 98: Urine Glucose, 3+ OR 1	0 0%	1 3%	0 0%
Day 98: Urine Protein, trace	2 5.9%	1 3%	3 9.4%
Day 98: Urine Protein, 1+	3 8.8%	0 0%	3 9.4%

10. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.
Time Frame	Up to Follow-up (Day 98)

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Losmapimod 7.5 mg Twice Daily	Losmapimod 7.5 mg Once Daily	Placebo
Arm/Group Description	Participants received 1 tablet of 7.5 mg Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.	Participants received 1 tablet of 7.5 mg Losmapimod each morning once daily and placebo tablet each evening once daily orally for a period of 12 weeks.	Participants received 1 tablet of placebo matching Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.
Measure Participants	34	33	32
Any AE	29 85.3%	28 84.8%	31 96.9%
Any SAE	4 11.8%	1 3%	3 9.4%

Adverse Events

Time Frame	SAEs and non-serious AEs were collected up to Follow-up visit (Day 98)
Adverse Event Reporting Description	SAEs and non-serious AEs are reported for Safety Population.
Arm/Group Title	Losmapimod 7.5 mg Twice Daily		Losmapimod 7.5 mg Once Daily		Placebo
Arm/Group Description	Participants received 1 tablet of 7.5 mg Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.		Participants received 1 tablet of 7.5 mg Losmapimod each morning once daily and placebo tablet each evening once daily orally for a period of 12 weeks.		Participants received 1 tablet of placebo matching Losmapimod orally twice daily, each morning and evening for a period of 12 weeks.
All Cause Mortality
	Losmapimod 7.5 mg Twice Daily		Losmapimod 7.5 mg Once Daily		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/33 (0%)		1/32 (3.1%)
Serious Adverse Events
	Losmapimod 7.5 mg Twice Daily		Losmapimod 7.5 mg Once Daily		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/34 (11.8%)		1/33 (3%)		3/32 (9.4%)
Cardiac disorders
Bundle branch block left	0/34 (0%)		0/33 (0%)		1/32 (3.1%)
Gastrointestinal disorders
Vomiting	0/34 (0%)		1/33 (3%)		0/32 (0%)
General disorders
Pain	1/34 (2.9%)		0/33 (0%)		0/32 (0%)
Chest pain	1/34 (2.9%)		0/33 (0%)		0/32 (0%)
Infections and infestations
Meningitis herpes	1/34 (2.9%)		0/33 (0%)		0/32 (0%)
Injury, poisoning and procedural complications
Road trafic accident	0/34 (0%)		0/33 (0%)		1/32 (3.1%)
Musculoskeletal and connective tissue disorders
Costochondritis	1/34 (2.9%)		0/33 (0%)		0/32 (0%)
Nervous system disorders
Presyncope	1/34 (2.9%)		0/33 (0%)		1/32 (3.1%)
Dizziness	0/34 (0%)		1/33 (3%)		0/32 (0%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	0/34 (0%)		1/33 (3%)		0/32 (0%)
Other (Not Including Serious) Adverse Events
	Losmapimod 7.5 mg Twice Daily		Losmapimod 7.5 mg Once Daily		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/34 (73.5%)		24/33 (72.7%)		28/32 (87.5%)
Cardiac disorders
Palpitations	2/34 (5.9%)		3/33 (9.1%)		1/32 (3.1%)
Angina pectoris	2/34 (5.9%)		1/33 (3%)		0/32 (0%)
Eye disorders
Eye pain	0/34 (0%)		3/33 (9.1%)		0/32 (0%)
Gastrointestinal disorders
Diarrhoea	8/34 (23.5%)		3/33 (9.1%)		3/32 (9.4%)
Nausea	3/34 (8.8%)		2/33 (6.1%)		2/32 (6.3%)
Constipation	3/34 (8.8%)		0/33 (0%)		3/32 (9.4%)
Dyspepsia	3/34 (8.8%)		0/33 (0%)		1/32 (3.1%)
Toothache	4/34 (11.8%)		0/33 (0%)		0/32 (0%)
Vomiting	2/34 (5.9%)		1/33 (3%)		1/32 (3.1%)
Flatulence	0/34 (0%)		1/33 (3%)		2/32 (6.3%)
Abdominal discomfort	0/34 (0%)		2/33 (6.1%)		0/32 (0%)
Abdominal distension	0/34 (0%)		0/33 (0%)		2/32 (6.3%)
Mouth ulceration	0/34 (0%)		2/33 (6.1%)		0/32 (0%)
General disorders
Fatigue	4/34 (11.8%)		2/33 (6.1%)		5/32 (15.6%)
Chest pain	3/34 (8.8%)		2/33 (6.1%)		2/32 (6.3%)
Chest discomfort	2/34 (5.9%)		1/33 (3%)		1/32 (3.1%)
Pyrexia	2/34 (5.9%)		0/33 (0%)		0/32 (0%)
Immune system disorders
Seasonal allergy	0/34 (0%)		2/33 (6.1%)		1/32 (3.1%)
Infections and infestations
Nasopharyngitis	5/34 (14.7%)		4/33 (12.1%)		2/32 (6.3%)
Urinary tract infection	0/34 (0%)		1/33 (3%)		2/32 (6.3%)
Injury, poisoning and procedural complications
Arthropod sting	1/34 (2.9%)		2/33 (6.1%)		0/32 (0%)
Contusion	0/34 (0%)		2/33 (6.1%)		1/32 (3.1%)
Muscle strain	0/34 (0%)		0/33 (0%)		2/32 (6.3%)
Investigations
C-reactive protein increased	1/34 (2.9%)		3/33 (9.1%)		0/32 (0%)
Blood urine present	0/34 (0%)		2/33 (6.1%)		0/32 (0%)
Metabolism and nutrition disorders
Gout	0/34 (0%)		2/33 (6.1%)		0/32 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/34 (8.8%)		1/33 (3%)		3/32 (9.4%)
Muscle spasms	1/34 (2.9%)		3/33 (9.1%)		3/32 (9.4%)
Pain in extremity	4/34 (11.8%)		2/33 (6.1%)		1/32 (3.1%)
Back pain	1/34 (2.9%)		0/33 (0%)		5/32 (15.6%)
Musculoskeletal pain	0/34 (0%)		2/33 (6.1%)		1/32 (3.1%)
Joint stiffness	0/34 (0%)		0/33 (0%)		2/32 (6.3%)
Joint swelling	2/34 (5.9%)		0/33 (0%)		0/32 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm	1/34 (2.9%)		1/33 (3%)		3/32 (9.4%)
Nervous system disorders
Headache	7/34 (20.6%)		10/33 (30.3%)		10/32 (31.3%)
Dizziness	2/34 (5.9%)		2/33 (6.1%)		4/32 (12.5%)
Lethargy	0/34 (0%)		0/33 (0%)		4/32 (12.5%)
Migraine	1/34 (2.9%)		2/33 (6.1%)		0/32 (0%)
Psychiatric disorders
Depressed mood	2/34 (5.9%)		0/33 (0%)		0/32 (0%)
Renal and urinary disorders
Nocturia	0/34 (0%)		2/33 (6.1%)		0/32 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	3/34 (8.8%)		3/33 (9.1%)		1/32 (3.1%)
Oropharyngeal pain	2/34 (5.9%)		3/33 (9.1%)		1/32 (3.1%)
Epistaxis	0/34 (0%)		3/33 (9.1%)		0/32 (0%)
Dyspnoea	2/34 (5.9%)		0/33 (0%)		0/32 (0%)
Hyperventilation	0/34 (0%)		2/33 (6.1%)		0/32 (0%)
Skin and subcutaneous tissue disorders
Rash	0/34 (0%)		0/33 (0%)		2/32 (6.3%)
Surgical and medical procedures
Tooth extraction	2/34 (5.9%)		0/33 (0%)		0/32 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.