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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LOSMAPIMOD 7.5 MG TWICE DAILY | Experimental | Participants received 1 tablet of 7.5 mg Losmapimod orally twice daily, each morning and evening for a period of 12 weeks |
|
| Placebo | Placebo Comparator | Participants received 1 tablet of placebo matching Losmapimod orally twice daily, each morning and evening for a period of 12 weeks. |
|
| LOSMAPIMOD 7.5 MG ONCE DAILY | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LOSMAPIMOD 7.5 MG | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. | Baseline (Days -14 to -1) and up to Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. |
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Inclusion Criteria for Main Study:
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
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
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:
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.
Either carotid or aortic TBR ³ 1.6, as measured on FDG-PET/CT, signifying active inflammation.
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%).
A signed and dated written informed consent prior to admission to the study
The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
Exclusion Criteria for Main Study:
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
Contraindication to MRI scanning (as assessed by local MRI safety questionnaire) which includes but not limited to:
Allergy to MRI contrast enhancement agent (gadolinium).
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.
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Oxford | Oxfordshire | OX3 9DU | United Kingdom | ||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22974804 | Background | 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. |
| Label | URL |
|---|---|
| Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| PM1111138 | Study Protocol | View IPD |
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | Placebo | Participants received 1 tablet of placebo matching Losmapimod orally twice daily, each morning and evening for a period of 12 weeks. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Losmapimod 7.5 mg Once Daily |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | 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. | Pharmacodynamic (PD) Population comprised of all participants who provided PD data. Only those participants with data available at the indicated time points were analyzed. | Posted | Mean | Standard Deviation | Maximum tissue to background ratio | Baseline (Days -14 to -1) and up to Week 12 |
|
SAEs and non-serious AEs were collected up to Follow-up visit (Day 98)
SAEs and non-serious AEs are reported for Safety Population.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Meningitis herpes | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
Not provided
| ID | Term |
|---|---|
| D050197 | Atherosclerosis |
| ID | Term |
|---|---|
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C543534 | 6-(5-((cyclopropylamino)carbonyl)-3-fluoro-2-methylphenyl)-N-(2,2-dimethylprpyl)-3-pyridinecarboxamide |
Not provided
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|
| Placebo | Drug | 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. |
|
| Baseline (Days -14 to -1) and up to Week 12 |
| Change From Baseline in Blood Concentration of High Sensitivity C-reactive Protein (Hs-CRP) | 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. | Baseline (Day 1) and Days 7, 14, 21, 28, 42, 56, 70, 84 |
| Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | 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). | Day 1, 7, 14, 21, 28, 42, 56, 70, 84, 98 |
| Mean Heart Rate at Indicated Time Points | 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). | Day 1, 7, 14, 21, 28, 42, 56, 70, 84, 98 |
| Number of Participants With 12-lead Electrocardiogram (ECG) Findings | 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. | Days 1, 7, 14, 21, 28, 42, 56, 70, 84, 98 |
| Number of Participants With Clinical Chemistry Abnormalities of PCI | 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. | Up to Follow-up (Day 98) |
| Number of Participants With Hematology Abnormalities of PCI | 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. | Up to Follow-up (Day 98) |
| Number of Participants With Urinalysis Dipstick Results | 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. | Day 1, 7, 14, 21, 28, 42, 56, 70, 84, 98 |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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. | Up to Follow-up (Day 98) |
| Cambridge |
| CB2 2GG |
| United Kingdom |
| GSK Investigational Site | London | E1 1B3 | United Kingdom |
| GSK Investigational Site | London | Se1 7EH | United Kingdom |
For additional information about this study please refer to the GSK Clinical Study Register |
| PM1111138 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| PM1111138 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| PM1111138 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| PM1111138 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| PM1111138 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| PM1111138 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
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.
| BG002 | Placebo | Participants received 1 tablet of placebo matching Losmapimod orally twice daily, each morning and evening for a period of 12 weeks. |
| BG003 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
Participants received 1 tablet of 7.5 mg Losmapimod orally twice daily, each morning and evening for a period of 12 weeks. |
| OG001 | 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. |
| OG002 | Placebo | Participants received 1 tablet of placebo matching Losmapimod orally twice daily, each morning and evening for a period of 12 weeks. |
|
|
|
| Secondary | 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 | 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. | PD Population. Only those participants with data available at the indicated time points were analyzed. | Posted | Mean | Standard Deviation | Ratio | Baseline (Days -14 to -1) and up to Week 12 |
|
|
|
|
| Secondary | Change From Baseline in Blood Concentration of High Sensitivity C-reactive Protein (Hs-CRP) | 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. | PD Population. Only those participants with data available at the specified time points were analyzed. | Posted | Mean | Standard Deviation | milligram per litre (mg/L) | Baseline (Day 1) and Days 7, 14, 21, 28, 42, 56, 70, 84 |
|
|
|
| Secondary | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | 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). | 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. | Posted | Mean | Standard Deviation | millimeter of mercury (mm/Hg) | Day 1, 7, 14, 21, 28, 42, 56, 70, 84, 98 |
|
|
|
| Secondary | Mean Heart Rate at Indicated Time Points | 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). | Safety Population. Only those participants with data available at the specified time points were analyzed. | Posted | Mean | Standard Deviation | beats per minute (bpm) | Day 1, 7, 14, 21, 28, 42, 56, 70, 84, 98 |
|
|
|
| Secondary | Number of Participants With 12-lead Electrocardiogram (ECG) Findings | 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. | Safety Population. Only those participants with data available at the specified time points were analyzed. | Posted | Count of Participants | Participants | Days 1, 7, 14, 21, 28, 42, 56, 70, 84, 98 |
|
|
|
| Secondary | Number of Participants With Clinical Chemistry Abnormalities of PCI | 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. | Safety Population. | Posted | Count of Participants | Participants | Up to Follow-up (Day 98) |
|
|
|
| Secondary | Number of Participants With Hematology Abnormalities of PCI | 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. | Safety Population. | Posted | Count of Participants | Participants | Up to Follow-up (Day 98) |
|
|
|
| Secondary | Number of Participants With Urinalysis Dipstick Results | 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. | Safety Population. | Posted | Count of Participants | Participants | Day 1, 7, 14, 21, 28, 42, 56, 70, 84, 98 |
|
|
|
| Secondary | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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. | Safety Population. | Posted | Count of Participants | Participants | Up to Follow-up (Day 98) |
|
|
|
| 0 |
| 34 |
| 4 |
| 34 |
| 25 |
| 34 |
| EG001 | 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. | 0 | 33 | 1 | 33 | 24 | 33 |
| EG002 | Placebo | Participants received 1 tablet of placebo matching Losmapimod orally twice daily, each morning and evening for a period of 12 weeks. | 1 | 32 | 3 | 32 | 28 | 32 |
| Costochondritis | Musculoskeletal and connective tissue disorders | MedDRA 12.1 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 12.1 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 12.1 | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 12.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Road trafic accident | Injury, poisoning and procedural complications | MedDRA 12.1 | Systematic Assessment |
|
| Bundle branch block left | Cardiac disorders | MedDRA 12.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 12.1 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 12.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 12.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 12.1 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 12.1 | Systematic Assessment |
|
| Joint stiffness | Musculoskeletal and connective tissue disorders | MedDRA 12.1 | Systematic Assessment |
|
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA 12.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 12.1 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 12.1 | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA 12.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 12.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Hyperventilation | Respiratory, thoracic and mediastinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA 12.1 | Systematic Assessment |
|
| Angina pectoris | Cardiac disorders | MedDRA 12.1 | Systematic Assessment |
|
| Arthropod sting | Injury, poisoning and procedural complications | MedDRA 12.1 | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 12.1 | Systematic Assessment |
|
| Muscle strain | Injury, poisoning and procedural complications | MedDRA 12.1 | Systematic Assessment |
|
| C-reactive protein increased | Investigations | MedDRA 12.1 | Systematic Assessment |
|
| Blood urine present | Investigations | MedDRA 12.1 | Systematic Assessment |
|
| Lung neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 12.1 | Systematic Assessment |
|
| Eye pain | Eye disorders | MedDRA 12.1 | Systematic Assessment |
|
| Seasonal allergy | Immune system disorders | MedDRA 12.1 | Systematic Assessment |
|
| Gout | Metabolism and nutrition disorders | MedDRA 12.1 | Systematic Assessment |
|
| Depressed mood | Psychiatric disorders | MedDRA 12.1 | Systematic Assessment |
|
| Nocturia | Renal and urinary disorders | MedDRA 12.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 12.1 | Systematic Assessment |
|
| Tooth extraction | Surgical and medical procedures | MedDRA 12.1 | Systematic Assessment |
|
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.
|
Losmapimod 7.5 mg once daily versus Placebo |
| ANCOVA |
ANCOVA model, fitting fixed effect treatment term, and including baseline TBR value as a covariate. |
| 0.9486 |
| Mean Difference (Final Values) |
| -0.00 |
| 2-Sided |
| 95 |
| -0.13 |
| 0.12 |
The point estimate was calculated as least square mean difference (final values) of Losmapimod 7.5 mg once daily and Placebo. |
| Superiority |
| Day 14 |
|
|
| Day 21 |
|
|
| Day 28 |
|
|
| Day 42 |
|
|
| Day 56 |
|
|
| Day 70 |
|
|
| Day 84 |
|
|
| DBP: Day 7 |
|
|
| DBP: Day 14 |
|
|
| DBP: Day 21 |
|
|
| DBP: Day 28 |
|
|
| DBP: Day 42 |
|
|
| DBP: Day 56 |
|
|
| DBP: Day 70 |
|
|
| DBP: Day 84 |
|
|
| DBP: Day 98 |
|
|
| SBP: Day 1 |
|
|
| SBP: Day 7 |
|
|
| SBP: Day 14 |
|
|
| SBP: Day 21 |
|
|
| SBP: Day 28 |
|
|
| SBP: Day 42 |
|
|
| SBP: Day 56 |
|
|
| SBP: Day 70 |
|
|
| SBP: Day 84 |
|
|
| SBP: Day 98 |
|
|
| Heart rate: Day 7 |
|
|
| Heart rate: Day 14 |
|
|
| Heart rate: Day 21 |
|
|
| Heart rate: Day 28 |
|
|
| Heart rate: Day 42 |
|
|
| Heart rate: Day 56 |
|
|
| Heart rate: Day 70 |
|
|
| Heart rate: Day 84 |
|
|
| Heart rate: Day 98 |
|
|
| Day 1 pre-dose 2:Abnormal-NCS |
|
|
| Day 1 pre-dose 3: Abnormal-NCS |
|
|
| Day 7 pre-dose 1: Abnormal-NCS |
|
|
| Day 14 pre-dose 1: Abnormal-NCS |
|
|
| Day 28 pre-dose 1: Abnormal-NCS |
|
|
| Day 28 pre-dose 1: Abnormal-CS |
|
|
| Day 56 pre-dose 1: Abnormal-NCS |
|
|
| Day 70 pre-dose 1: Abnormal-NCS |
|
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| Day 84 pre-dose 1: Abnormal-NCS |
|
|
| Day 98: Abnormal-NCS |
|
|
| Day 98: Abnormal-CS |
|
|
| Title | Measurements |
|---|---|
|
| Glucose low |
|
| Glucose high |
|
| Potassium low |
|
| Sodium low |
|
| Creatinine high |
|
| Chloride low |
|
| Title | Measurements |
|---|---|
|
| Haemoglobin low |
|
| Lymphocytes low |
|
| Lymphocytes high |
|
| MCH high |
|
| Monocytes high |
|
| Neutrophils low |
|
| Neutrophils high |
|
| RBC count low |
|
| Reticulocytes low |
|
| Reticulocytes high |
|
| Platelet count low |
|
| WBC count low |
|
|
| Day 1: Urine Glucose, 1+ |
|
| Day 1: Urine Protein, trace |
|
| Day 1: Urine Protein, 1+ |
|
| Day 7: Urine Occult Blood, 1+ |
|
| Day 7: Urine Occult Blood, 3+ |
|
| Day 7: Urine Protein, trace |
|
| Day 7: Urine Protein, 1+ |
|
| Day 14: Urine Occult Blood, 2+ |
|
| Day 14: Urine Occult Blood, trace |
|
| Day 14: Urine Occult Blood, 1+ |
|
| Day 14: Urine Ketones, trace |
|
| Day 14: Urine Protein, trace |
|
| Day 14: Urine Protein, 1+ |
|
| Day 21: Urine Occult Blood, trace |
|
| Day 21: Urine Ketones, trace |
|
| Day 21: Urine Protein, trace |
|
| Day 21: Urine Protein, 1+ |
|
| Day 28: Urine Occult Blood, 2+ |
|
| Day 28: Urine Occult Blood, trace |
|
| Day 28: Urine Protein, trace |
|
| Day 28: Urine Protein, 1+ |
|
| Day 42: Urine Occult Blood, 2+ |
|
| Day 42: Urine Protein, trace |
|
| Day 42: Urine Protein, 1+ |
|
| Day 56: Urine Occult Blood, 2+ |
|
| Day 56: Urine Occult Blood, trace |
|
| Day 56: Urine Occult Blood, 1+ |
|
| Day 56: Urine Glucose, Trace or 1/10 |
|
| Day 56: Urine Ketones, trace |
|
| Day 56: Urine Protein, trace |
|
| Day 56: Urine Protein, 1+ |
|
| Day 70: Urine Occult Blood, 2+ |
|
| Day 70: Urine Occult Blood, trace |
|
| Day 70: Urine Protein, 2+ |
|
| Day 70: Urine Protein, trace |
|
| Day 70: Urine Protein, 1+ |
|
| Day 84: Urine Occult Blood, 2+ |
|
| Day 84: Urine Occult Blood, trace |
|
| Day 84: Urine Occult Blood, 1+ |
|
| Day 84: Urine Ketones, trace |
|
| Day 84: Urine Protein, 2+ |
|
| Day 84: Urine Protein, trace |
|
| Day 84: Urine Protein, 1+ |
|
| Day 98: Urine Occult Blood, 2+ |
|
| Day 98: Urine Occult Blood, trace |
|
| Day 98: Urine Occult Blood, 1+ |
|
| Day 98: Urine Occult Blood, 3+ |
|
| Day 98: Urine Glucose, 3+ OR 1 |
|
| Day 98: Urine Protein, trace |
|
| Day 98: Urine Protein, 1+ |
|
| Title | Measurements |
|---|---|
|