Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
Phase II clinical study, losmapimod, exacerbations, COPD, eosinophil sub-group
Brief summary
This is a randomised, double-blind, parallel-group, multi-centre study evaluating 15 milligram (mg) twice daily/ Bi-daily (BID) of losmapimod versus placebo, in addition to standard of care (SoC). The primary objective of this study is to explore the therapeutic potential of losmapimod as a treatment to reduce the rate of exacerbations in the subset of participants with moderate-to-severe COPD who are at high risk of exacerbation, having experienced two or more moderate/severe exacerbations in the preceding 12 months, and who have \<=2% of blood eosinophils at screening. As secondary objectives safety, effects on lung function, quality of life, pharmacokinetic (PK), biomarkers of both disease and inflammation shall be evaluated. The duration of the treatment period is variable but will be at least 26 weeks and up to a maximum of 52 weeks, with the end of study date being established once the final participant has been randomized. The purpose of the variable dosing regimen is to enable participants to remain in the study for a longer duration, as it is anticipated that this will increase the likelihood of observing exacerbation events without increasing the overall study duration. It will also enable safety data on dosing periods beyond 6 months to be generated. Approximately 200 participants in a 1:1 ratio between losmapimod and placebo will be randomized to the study. Sample size re-estimation will be performed during the course of the study to potentially increase the sample size up to a maximum of 600 participants.
Interventions
DRUGLosmapimod tablets
Losmapimod tablets will be provided as 15 mg strength in a formulation containing lactose. Administered orally, twice daily approximately 12 hours apart and with food and water for the duration of the treatment period. Participants will be instructed to take their medication with a full glass of water twice-daily within 30 minutes after meals for the duration of their treatment period.
DRUGPlacebo tablets
Placebo tablets will be provided in a formulation containing lactose and visually matching the losmapimod tablets. Administered orally, twice daily approximately 12 hours apart and with food and water for the duration of the treatment period. Participants will be instructed to take their medication with a full glass of water twice-daily within 30 minutes after meals for the duration of their treatment period
DRUGSalbutamol MDI
Salbutamol MDI will be provided as a rescue medication.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* COPD diagnosis and severity: Participants with a clinical history of COPD (established by a physician) in accordance with the following definition by the American Thoracic Society/European Respiratory Society, for at least 6 months prior to enrolment. Participants must have evidence of airflow obstruction, defined as post-bronchodilator FEV1 equal to or less than 80% of predicted normal value calculated using Third National Health and Nutrition Examination Survey (NHANES III) reference equation at Visit 1 and a FEV1 / FVC ratio \<=70% at Screening (Visit 1). Note: Post-bronchodilator spirometry will be performed approximately 10-15 minutes after the participants has self-administered 4 inhalations (i.e., total 400/360 \[microgram\] mcg) of salbutamol/albuterol via a Metered Dose Inhaler (MDI) (use of spacer will be optional). The study-provided central spirometry equipment will calculate the FEV1/FVC ratio and FEV1 percent predicted values. * Exacerbation History: A documented history (e.g., medical record verification) in the 12 months prior to Visit 1 of \>=2 COPD exacerbations resulting in prescription for antibiotics and/or oral corticosteroids or hospitalisation or extended observation in a hospital emergency room or outpatient centre. Note: Prior use of antibiotics alone does not qualify as a moderate exacerbation unless the use was specifically for the treatment of worsening symptoms of COPD. * Existing COPD maintenance treatment: Participants must be receiving daily maintenance treatment for their COPD for at least 3 months prior to Screening. Notes: Participants receiving only pro re nata or as needed (PRN) COPD medications are not eligible for inclusion in the study. All participants will continue on their current Standard of Care (SoC) COPD medications throughout the entire duration of the study. * Tobacco use: Participants with a current or prior history of \>=10 pack-years of cigarette smoking at Screening (Visit 1). Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1. One pack year =20 cigarettes smoked per day for 1 year or the equivalent. Number of pack years=(number of cigarettes per day/20) x number of years smoked. * Sex: Male or female participants aged \>=40 years at Screening (Visit 1). A female participant is eligible to participate if she is of non-child bearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \>40 milli-international unit/milliliter (MIU/mL) and estradiol \<40 picogram/milliliter (pg/mL) (\<140 \[Picomoles per liter\] pmol/L) is confirmatory\] or if of child-bearing potential is using a highly effective method for avoidance of pregnancy from 30 days before the first dose, for the duration of dosing and until 2 weeks post last-dose. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * Corrected ECG QT interval (QTc)\<450 milliseconds(msec) or QTc\<480 msec for participants with bundle branch block. The QTc is the QT interval corrected for heart rate according to either Bazett's formula (QTcB), Fridericia's formula (QTcF), or another method, machine or manual over-read. For eligibility and withdrawal, ideally the same QT correction formula will be used for all participants. However, because this is not always possible, the same QT correction formula will be used for each individual participant to determine eligibility for and withdrawal from the study. The QTc will be based on single or averaged QTc values of triplicate ECGs obtained over a brief recording period.
Exclusion criteria
* Eosinophils: \>2.0% blood eosinophils at Screening (Visit 1) * Concomitant medication: COPD Medication: Participants currently on chronic treatment with macrolides or Roflumilast; Long term oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day. Oxygen PRN use (i.e. \<=12 hours per day) is not exclusionary. Multidrug and toxin extrusion (MATE) transporter 1 (MATE1) inhibitors: cimetidine, pyrimethamine, trimethoprim (short course treatment with trimethoprim is allowed). Other medications: Chronic maintenance therapy with anti-Tumor Necrosis Factor (anti-TNF), anti-Interleukin-1 (anti-IL1), phosphodiesterase type 4 (PDE4) inhibitors, or any other immunosuppressive therapy (not including steroids) within 60 days prior to dosing. Any other investigational drug within 30 days or 5 half lives, whichever is longer prior to Screening Visit. * Other respiratory disorders: Participants with asthma (as primary diagnosis) lung cancer, bronchiectasis, active sarcoidosis, active lung fibrosis, cystic fibrosis, idiopathic pulmonary hypertension, active interstitial lung diseases or other active pulmonary diseases. Participants with alpha-1-antitrypsin deficiency as the underlying cause of COPD. * Participants with clinically significant sleep apnea who require use of continuous positive airway pressure (CPAP) device. * Participants who require a non-invasive positive pressure ventilation (NIPPV) device (Note: Use of non invasive ventilation (NIV) in hospital as part of the medical management of an acute exacerbation is permitted.) * Lung resection: Participants who have undergone previous lung reduction surgery (e.g. lobectomy, pneumonectomy, or lung volume reduction). * COPD stability: Less than 30 days prior to Visit 1 have elapsed from completion of a course of antibiotics or oral corticosteroids for a recent COPD exacerbation. * Evidence of pneumonia or a clinically significant abnormality not believed to be due to the presence of COPD on chest X-ray (posteroanterior with lateral) or computerised tomography (CT) scan (historic data up to 1 year may be used). * Pulmonary rehabilitation program: Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1. Participants who are in the maintenance phase of a pulmonary rehabilitation program are not excluded. * Alanine aminotransferase (ALT) \>2x Upper limits of normal (ULN) and bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). * Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). * Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to Visit 1 (Participants that had localized carcinoma of the skin or cervix which was resected for cure will not be excluded). * Other diseases/abnormalities: History or current evidence of clinically significant or uncontrolled cardiovascular, pulmonary, metabolic, neurological, endocrine (including uncontrolled diabetes or thyroid disease), renal, hepatic, haematological (including agranulocytosis) or gastrointestinal conditions that are uncontrolled on permitted therapy and in the opinion of the investigator and/or GSK Medical Monitor, places the participant at an unacceptable risk as participant in this trial or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study * Viral infections: Presence of hepatitis B surface antigen (HBsAg), Hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. Note: Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C Ribonucleic acid (RNA) polymerase chain reaction (PCR) test is obtained. * A positive test for human immunodeficiency virus (HIV) antibody * Tuberculosis (TB): Participant with active TB or who have previously tested positive for latent TB and not received treatment or prophylaxis following the positive test. * Vaccination: Participants who have received live attenuated vaccines in the 6 weeks prior to randomization. The use of live attenuated vaccines during the treatment period and in the 4 weeks post-discontinuation of investigational product is prohibited. * Drug/food allergy: Participants with a history of hypersensitivity to any of the study medications (e.g., lactose, magnesium stearate). * Lactating females * Pregnant females (as determined by positive urine human chorionic gonadotropin (hCG) test prior to dosing). * Drug/alcohol abuse: Participants with a known or suspected history of alcohol or drug abuse within the last 2 years. * Prior use of study medication/other investigational drugs: Participants who have received an investigational drug within 30 days of entry into this study or within 5 drug half-lives of the investigational drug, whichever is longer. * Affiliation with investigator site: Study investigators, sub-investigators, study coordinators, employees of a participating investigator or immediate family members of the aforementioned are excluded from participating in this study. * Inability to read: In the opinion of the investigator, any participant who is unable to read and/or would not be able to complete study related materials. * Non-compliance: Participants at risk of non-compliance, or unable to comply with the study procedures. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits. * Questionable validity of consent: Participants with a history of psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annual Rate of Moderate and Severe Exacerbations of COPD | From the start of the study treatment up to 53 Weeks | An exacerbation of COPD, is defined as the worsening of 2 or more major symptoms (dyspnea, sputum volume, sputum purulence) or the worsening of any 1 major symptom together with any 1 of the minor symptoms (sore throat, cold, fever without other cause, increased cough and wheeze), for at least 2 consecutive days. Moderate-severe exacerbations were defined as use of antibiotics and/or oral steroids and/or hospitalization. Summary only included exacerbations for which a date of resolution or death was provided. Analysis was performed by using Bayesian inference assuming non-informative priors. The mean exacerbation rate was adjusted for treatment group, smoking status, ICS use and region. The adjusted posterior median was summarized per treatment group. The number of exacerbation events per participant was assumed to follow a negative binomial distribution. Modified Intent-to-Treat (mITT) Population comprised of all randomized par. who received at least one dose of study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Having Any Adverse Events (AEs), Serious Adverse Events (SAEs) | From the start of the study treatment up to 53 Weeks | An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinaemia were categorized as SAE. AEs were considered as on-treatment If AE onset date is on or after treatment start date & on or before treatment stop date. par. having any AE or SAE were included in analysis. |
| Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | Baseline and up to Week 52 | SGRQ-C is a health related quality of life questionnaire consisting of 14 questions. SGRQ-C total score was calculated as 100 multiplied by summed weights from all positive items divided by sum of weights for all items in questionnaire. Components (Activity, Symptoms, Impacts) were calculated as 100 multiplied by summed weights from all positive items in that component divided by sum of weights for all items in that component. Score range for SGRQ-C total is 0-100. Maximum weights for Activity, Symptoms and Impacts component is 982.9, 566.2 and 1652.8 respectively. SGRQ-C was transformed to SGRQ for reporting. Higher scores indicate greater disease impact. Score at Day 1, pre-dose (Week 0) was considered as Baseline. Change from Baseline was calculated as score at indicated time point minus Baseline value. Only those par. with analyzable data at the given time points (represented by n=X, X in category titles) were included in analysis. |
| Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | Baseline and up to Week 52 | Pre and post FEV1, FVC and FEV6 were performed at Screening, Day 1 pre-dose and Weeks 2, 4, 8, 12, 18, 26, 39 and 52. Par. were asked to withheld all bronchodilator therapy included ipratropiumn bromide and salbutamol/albuterol for at least 4 hours prior to prebronchodilator spirometric test. Post-bronchodilator spirometric assessment was performed after inhalation of 400/360 micograms (µg) of salbutamol/albuterol in 10-15 minutes. Day 1 (pre-dose) values were considered as Baseline values. Change from Baseline was calculated as value at the indicated time point minus Baseline value. The maximum value of the 3 replicate assessments were used. Analysis performed using a mixed-effects repeated measures model. The adjusted mean values were summarized per treatment group. Par. were included in the analysis if they had at least one post-baseline measurement. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | Baseline and up to Week 52 | Pre and post FEV1/FVC, PP FEV1, PP FEV6 and PP FVC were assessed at Screening, Day 1 pre-dose and Weeks 2, 4, 8, 12, 18, 26, 39 and 52. Par. were asked to withheld all bronchodilator therapy included ipratropiumn bromide and salbutamol/albuterol for at least 4 hours prior to the prebronchodilator spirometric test. Post-bronchodilator spirometric assessment was performed after inhalation of 400/360 µg of salbutamol/albuterol in 10-15 minutes. Day 1 (pre-dose) values were considered as Baseline values. Change from Baseline was calculated as value at indicated time point minus Baseline value. The maximum value of the 3 replicate assessments were used. Analysis performed using a mixed-effects repeated measures model. The adjusted mean values were summarized per treatment group. Par. were included in the analysis if they had at least one post-baseline measurement. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Number of Participants With Electrocardiogram (ECG) Findings | Up to 53 Weeks | 12-lead ECGs were obtained in triplicate at Screening then singly at Baseline (day 1, pre-dose) and post dose at Weeks 2, 4, 8, 12, 26, 39, 52 and at follow up (Week 53) using an ECG machine that automatically calculates the heart rate (HR) and measures PR, QRS, QT, and QT duration corrected for heart rate by Fridericia's formula (QTcF) or QT duration corrected for heart rate by Bazett's formula (QTcB) intervals. Change in ECG findings were categorized as normal and abnormal. Abnormal ECG values could be clinically significant (CS) or not clinically significant (NCS), as determined by the investigator. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | Baseline and up to Week 53 | SBP and DBP were taken at Screening, Baseline (day 1, pre-dose) and post dose at Weeks 2, 4, 8, 12, 26, 39, 52 and at follow up (Week 53). Measurements were taken in a semi-recumbent position after 5 minutes rest. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value of an assessment is defined as the value at day 1, pre-dose. Par. were included in the analysis if they had at least one post-baseline measurement. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points | Baseline and up to Week 53 | HR was assessed at Screening, Baseline (day 1, pre-dose) and post dose at Weeks 2, 4, 8, 12, 26, 39, 52 and at follow up (Week 53). Measurements were taken in a semi-recumbent position after 5 minutes rest. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value of an assessment is defined as the value at day 1, pre-dose. Par. were included in the analysis if they had at least one post-baseline measurement. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Plasma Losmapimod Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to the End of Dosing Interval (AUC[0-tau]) | Pre-dose at Weeks 2 and 12; pre-dose and at 2 hours post-dose at Week 26 | Pharmacokinetics (PK) of losmapimod was evaluated in participants with COPD using PK samples collected at pre-dose at Week 2 and Week 12. At Week 26, a sample was collected at pre-dose and a second sample was collected at 2 hours post-dose. Par. of mITT population that provided at least one observed concentration data in this study were considered for PK analysis. Drug plasma concentration-time data were modelled by nonlinear mixed effects modelling. AUC\[0-tau\] (tau=12 hours) was estimated from the model. |
| Plasma Losmapimod Maximum Concentration (Cmax) and Lowest Concentration (Ctrough) at Steady State | Pre-dose at Weeks 2 and 12; pre-dose and at 2 hours post-dose at Week 26 | Pharmacokinetics of losmapimod was evaluated in participants with COPD using PK samples collected at pre-dose at Week 2 and Week 12. At Week 26, a sample was collected at pre-dose and a second sample was collected at 2 hours post-dose. Par. of mITT population that provided at least one observed concentration data in this study were considered for PK analysis (represented by n=X, X in the category titles). Drug plasma concentration-time data were modelled by nonlinear mixed effects modelling to develop a Population PK model. Cmax and Ctrough were estimated from the PK model. |
| Change From Baseline in Frequency of Short Acting Beta-agonist or Anti-cholinergic Use | Baseline and up to Week 52 | Use of short acting bronchodilators (short-acting beta2-agonists or short-acting anti-cholinergic) was allowed and was recorded in daily patient diary. It included inhaled short-acting beta2-agonists (e.g. Ipratropium bromide, salbutamol, Ipratropium/salbutamol (albuterol) combination product) and short-acting anti-cholinergics (e.g., ipratropium bromide3). Use of these medications was allowed throughout the study except 4 hours prior to and during each clinic visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Time to First Occurrence of Moderate or Severe COPD Exacerbation | From the start of the study treatment up to 53 Weeks | The time to first moderate-severe COPD exacerbation in par. treated with losmapimod compared to placebo treated par. was evaluated. The time to the first on-treatment moderate-severe exacerbation was calculated as exacerbation onset date of first on-treatment exacerbation minus exposure start date plus 1. No statistical analysis was conducted. Data was summarized statistically only. |
| Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Baseline and up to Week 53 | Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate hemoglobin, total protein, albumin and MCHC. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in Hematocrit at the Indicated Time Points | Baseline and up to Week 53 | Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate hematocrit. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Baseline and up to Week 53 | Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate absolute WBC count, total neutrophil, total lymphocyte, basophil, absolute eosinophil, percentage eosinophil, monocyte and platelet count. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at the indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in Eosinophil Percentage at the Indicated Time Points | Baseline and up to Week 53 | Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate eosinophil percentage. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at the indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Baseline and up to Week 53 | Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate total bilirubin, direct bilirubin, urice acid and creatinine. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at the indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Baseline and up to Week 53 | Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma glutamyl transferase at the indicated time point. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at the indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Baseline and up to Week 53 | Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate calcium, chloride, glucose, potassium, sodium and blood urea nitrogenat the indicated time point. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at the indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in Red Blood Cell Count at the Indicated Time Points | Baseline and up to Week 53 | Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate Red blood cell count. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at the indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points | Baseline and up to Week 53 | Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate mean corpuscle hemoglobin. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at the indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points | Baseline and up to Week 53 | Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate mean corpuscle volume. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at the indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Number of Participants With Abnormal Liver Events During the Treatment Period | Up to Week 53 | Various liver chemistry parameters were monitored periodically to ensure the safety and tolerability of Losmapimod as compared to placebo. Study treatments were discontinued for par. if alanine aminotransferase (ALT) absolute \>= 5xupper limit of normal (ULN) or; ALT \>= 3xULN persists for \>=4 Weeks or; ALT\>=3x ULN and bilirubin \>=2xULN or; ALT\>=3x ULN and International normalized ratio (INR) \>=1.5 or; ALT\>=3x ULN and cannot be monitored weekly for 4 Weeks or; ALT\>=3x ULN symptomatic. |
Countries
Argentina, Brazil, Bulgaria, Chile, Germany, Slovakia, South Korea, Spain
Participant flow
Recruitment details
This was a randomized, double-blind (sponsor unblinded), parallel-group, multi-center study evaluating 15 milligrams (mg) twice daily (BID) of losmapimod versus placebo in addition to standard of care in male and female participants (par.) \>=40 years of age having chronic obstructive pulmonary disease (COPD).
Pre-assignment details
This study consisted of a 28 day screening period followed by treatment period (TP) of minimum 26 weeks. Total duration of TP was variable from 26 weeks to 52 weeks, and safety follow-up after 1 week. Total 365 par. were screened (175 par. failed), of which 190 par. passed screening and 184 par. were randomized in a TP.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication. | 94 |
| Losmapimod 15 mg Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication. | 90 |
| Total | 184 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event, non-fatal | 8 | 9 |
| Overall Study | Adverse Event, serious fatal | 1 | 3 |
| Overall Study | Lack of Efficacy | 1 | 3 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Other: Met stopping criteria | 1 | 0 |
| Overall Study | Other: Study closed/terminated | 66 | 55 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Protocol Violation | 1 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 4 |
Baseline characteristics
| Characteristic | Losmapimod 15 mg | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 66.4 Years STANDARD_DEVIATION 6.66 | 65.5 Years STANDARD_DEVIATION 7.55 | 64.6 Years STANDARD_DEVIATION 8.27 |
| Race/Ethnicity, Customized Race/ Ethnicity Japanese/East Asian /South East Asian Heritage | 9 Participants | 19 Participants | 10 Participants |
| Race/Ethnicity, Customized Race/ Ethnicity White | 81 Participants | 165 Participants | 84 Participants |
| Sex: Female, Male Female | 26 Participants | 59 Participants | 33 Participants |
| Sex: Female, Male Male | 64 Participants | 125 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 94 | 3 / 90 |
| other Total, other adverse events | 9 / 94 | 13 / 90 |
| serious Total, serious adverse events | 8 / 94 | 19 / 90 |
Outcome results
Primary
Annual Rate of Moderate and Severe Exacerbations of COPD
An exacerbation of COPD, is defined as the worsening of 2 or more major symptoms (dyspnea, sputum volume, sputum purulence) or the worsening of any 1 major symptom together with any 1 of the minor symptoms (sore throat, cold, fever without other cause, increased cough and wheeze), for at least 2 consecutive days. Moderate-severe exacerbations were defined as use of antibiotics and/or oral steroids and/or hospitalization. Summary only included exacerbations for which a date of resolution or death was provided. Analysis was performed by using Bayesian inference assuming non-informative priors. The mean exacerbation rate was adjusted for treatment group, smoking status, ICS use and region. The adjusted posterior median was summarized per treatment group. The number of exacerbation events per participant was assumed to follow a negative binomial distribution. Modified Intent-to-Treat (mITT) Population comprised of all randomized par. who received at least one dose of study treatment.
Time frame: From the start of the study treatment up to 53 Weeks
Population: mITT Population
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Annual Rate of Moderate and Severe Exacerbations of COPD | 0.84 Exacerbations per participant per year | Standard Deviation 0.19 |
| Losmapimod 15 mg | Annual Rate of Moderate and Severe Exacerbations of COPD | 0.88 Exacerbations per participant per year | Standard Deviation 0.22 |
95% CI: [0.63, 1.73]
Secondary
Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point
Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate absolute WBC count, total neutrophil, total lymphocyte, basophil, absolute eosinophil, percentage eosinophil, monocyte and platelet count. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at the indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline and up to Week 53
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Absolute WBC count, Week 2 (n=85,82) | -0.04 Giga cells per liter (G/L) | Standard Deviation 1.586 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Absolute WBC count, Week 4 (n=86,80) | 0.03 Giga cells per liter (G/L) | Standard Deviation 1.742 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Absolute WBC count, Week 8 (n=80,77) | 0.04 Giga cells per liter (G/L) | Standard Deviation 1.474 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Absolute WBC count, Week 12 (n=76,70) | -0.07 Giga cells per liter (G/L) | Standard Deviation 1.628 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Absolute WBC count, Week 18 (n=66,60) | 0.29 Giga cells per liter (G/L) | Standard Deviation 1.921 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Absolute WBC count, Week 26 (n=52,50) | -0.07 Giga cells per liter (G/L) | Standard Deviation 1.625 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Absolute WBC count, Week 39 (n=28,29) | 0.29 Giga cells per liter (G/L) | Standard Deviation 1.777 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Absolute WBC count, Week 52 (n=14,11) | 0.86 Giga cells per liter (G/L) | Standard Deviation 1.687 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Absolute WBC count, Follow up (n=79,67) | 0.73 Giga cells per liter (G/L) | Standard Deviation 1.691 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total neutrophils, Week 2 (n=85,82) | -0.038 Giga cells per liter (G/L) | Standard Deviation 1.598 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total neutrophils, Week 4 (n=86,80) | -0.014 Giga cells per liter (G/L) | Standard Deviation 1.7572 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total neutrophils, Week 8 (n=80,77) | -0.052 Giga cells per liter (G/L) | Standard Deviation 1.606 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total neutrophils, Week 12 (n=76,70) | 0.023 Giga cells per liter (G/L) | Standard Deviation 1.7039 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total neutrophils, Week 18 (n=66,60) | 0.189 Giga cells per liter (G/L) | Standard Deviation 1.9556 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total neutrophils, Week 26 (n=52,50) | -0.067 Giga cells per liter (G/L) | Standard Deviation 1.4529 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total neutrophils, Week 39 (n=28,29) | 0.240 Giga cells per liter (G/L) | Standard Deviation 1.7846 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total neutrophils, Week 52 (n=14,11) | 1.001 Giga cells per liter (G/L) | Standard Deviation 1.8753 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total neutrophils, Follow up (n=79,67) | 0.555 Giga cells per liter (G/L) | Standard Deviation 1.7317 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total lymphocyte, Week 2 (n=85,82) | 0.022 Giga cells per liter (G/L) | Standard Deviation 0.4739 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total lymphocyte, Week 4 (n=86,80) | 0.043 Giga cells per liter (G/L) | Standard Deviation 0.6599 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total lymphocyte, Week 8 (n=80,77) | 0.089 Giga cells per liter (G/L) | Standard Deviation 0.5532 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total lymphocyte, Week 12 (n=76,70) | -0.083 Giga cells per liter (G/L) | Standard Deviation 0.5983 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total lymphocyte, Week 18 (n=66,60) | 0.076 Giga cells per liter (G/L) | Standard Deviation 0.4751 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total lymphocyte, Week 26 (n=52,50) | -0.042 Giga cells per liter (G/L) | Standard Deviation 0.6673 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total lymphocyte, Week 39 (n=28,29) | 0.019 Giga cells per liter (G/L) | Standard Deviation 0.4731 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total lymphocyte, Week 52 (n=14,11) | -0.107 Giga cells per liter (G/L) | Standard Deviation 0.4707 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total lymphocyte, Follow up (n=79,67) | 0.100 Giga cells per liter (G/L) | Standard Deviation 0.5969 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Basophils, Week 2 (n=85,82) | 0.000 Giga cells per liter (G/L) | Standard Deviation 0.0194 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Basophils, Week 4 (n=86,80) | -0.001 Giga cells per liter (G/L) | Standard Deviation 0.0332 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Basophils, Week 8 (n=80,77) | -0.003 Giga cells per liter (G/L) | Standard Deviation 0.0288 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Basophils, Week 12 (n=76,70) | 0.001 Giga cells per liter (G/L) | Standard Deviation 0.0328 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Basophils, Week 18 (n=66,60) | -0.002 Giga cells per liter (G/L) | Standard Deviation 0.0249 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Basophils, Week 26 (n=52,50) | 0.001 Giga cells per liter (G/L) | Standard Deviation 0.0241 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Basophils, Week 39 (n=28,29) | -0.001 Giga cells per liter (G/L) | Standard Deviation 0.018 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Basophils, Week 52 (n=14,11) | -0.006 Giga cells per liter (G/L) | Standard Deviation 0.0109 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Basophils, Follow up (n=79,67) | -0.004 Giga cells per liter (G/L) | Standard Deviation 0.0305 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Eosinophil, Week 2 (n=85,82) | 0.000 Giga cells per liter (G/L) | Standard Deviation 0.066 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Eosinophil, Week 4 (n=86,80) | -0.002 Giga cells per liter (G/L) | Standard Deviation 0.1092 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Eosinophil, Week 8 (n=80,77) | 0.008 Giga cells per liter (G/L) | Standard Deviation 0.0948 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Eosinophil, Week 12 (n=76,70) | -0.001 Giga cells per liter (G/L) | Standard Deviation 0.0817 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Eosinophil, Week 18 (n=66,60) | 0.030 Giga cells per liter (G/L) | Standard Deviation 0.1287 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Eosinophil, Week 26 (n=52,50) | 0.037 Giga cells per liter (G/L) | Standard Deviation 0.1554 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Eosinophil, Week 39 (n=28,29) | 0.037 Giga cells per liter (G/L) | Standard Deviation 0.0628 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Eosinophil, Week 52 (n=14,11) | -0.001 Giga cells per liter (G/L) | Standard Deviation 0.0539 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Eosinophil, Follow up (n=79,67) | 0.011 Giga cells per liter (G/L) | Standard Deviation 0.0935 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Monocytes, Week 2 (n=85,82) | -0.029 Giga cells per liter (G/L) | Standard Deviation 0.1598 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Monocytes, Week 4 (n=86,80) | 0.002 Giga cells per liter (G/L) | Standard Deviation 0.1404 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Monocytes, Week 8 (n=80,77) | 0.001 Giga cells per liter (G/L) | Standard Deviation 0.1785 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Monocytes, Week 12 (n=76,70) | -0.007 Giga cells per liter (G/L) | Standard Deviation 0.1709 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Monocytes, Week 18 (n=66,60) | -0.010 Giga cells per liter (G/L) | Standard Deviation 0.2023 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Monocytes, Week 26 (n=52,50) | 0.001 Giga cells per liter (G/L) | Standard Deviation 0.2093 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Monocytes, Week 39 (n=28,29) | -0.005 Giga cells per liter (G/L) | Standard Deviation 0.121 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Monocytes, Week 52 (n=14,11) | -0.034 Giga cells per liter (G/L) | Standard Deviation 0.1075 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Monocytes, Follow up (n=79,67) | 0.071 Giga cells per liter (G/L) | Standard Deviation 0.2319 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Platelet count, Week 2 (n=85,82) | -3.3 Giga cells per liter (G/L) | Standard Deviation 45.84 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Platelet count, Week 4 (n=87,80) | -6.4 Giga cells per liter (G/L) | Standard Deviation 41.43 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Platelet count, Week 8 (n=79,77) | -2.2 Giga cells per liter (G/L) | Standard Deviation 40.51 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Platelet count, Week 12 (n=75,70) | -10.0 Giga cells per liter (G/L) | Standard Deviation 44.01 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Platelet count, Week 18 (n=66,59) | 5.3 Giga cells per liter (G/L) | Standard Deviation 53.14 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Platelet count, Week 26 (n=52,50) | -2.7 Giga cells per liter (G/L) | Standard Deviation 48.66 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Platelet count, Week 39 (n=28,29) | -3.4 Giga cells per liter (G/L) | Standard Deviation 35.47 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Platelet count, Week 52 (n=14,11) | -13.6 Giga cells per liter (G/L) | Standard Deviation 34.98 |
| Placebo | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Platelet count, Follow up (n=80,67) | 9.7 Giga cells per liter (G/L) | Standard Deviation 58.86 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Basophils, Week 18 (n=66,60) | -0.002 Giga cells per liter (G/L) | Standard Deviation 0.0191 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Absolute WBC count, Week 2 (n=85,82) | 0.21 Giga cells per liter (G/L) | Standard Deviation 1.71 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Monocytes, Week 8 (n=80,77) | -0.014 Giga cells per liter (G/L) | Standard Deviation 0.1653 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Absolute WBC count, Week 4 (n=86,80) | 0.12 Giga cells per liter (G/L) | Standard Deviation 2.116 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Basophils, Week 26 (n=52,50) | -0.006 Giga cells per liter (G/L) | Standard Deviation 0.0173 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Absolute WBC count, Week 8 (n=80,77) | 0.32 Giga cells per liter (G/L) | Standard Deviation 1.939 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Platelet count, Week 4 (n=87,80) | -0.4 Giga cells per liter (G/L) | Standard Deviation 35.5 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Absolute WBC count, Week 12 (n=76,70) | 0.51 Giga cells per liter (G/L) | Standard Deviation 1.905 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Basophils, Week 39 (n=28,29) | -0.005 Giga cells per liter (G/L) | Standard Deviation 0.019 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Absolute WBC count, Week 18 (n=66,60) | 0.17 Giga cells per liter (G/L) | Standard Deviation 1.842 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Monocytes, Week 12 (n=76,70) | -0.026 Giga cells per liter (G/L) | Standard Deviation 0.2145 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Absolute WBC count, Week 26 (n=52,50) | 0.09 Giga cells per liter (G/L) | Standard Deviation 1.876 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Basophils, Week 52 (n=14,11) | -0.000 Giga cells per liter (G/L) | Standard Deviation 0.0184 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Absolute WBC count, Week 39 (n=28,29) | 1.08 Giga cells per liter (G/L) | Standard Deviation 2.857 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Platelet count, Week 26 (n=52,50) | -0.4 Giga cells per liter (G/L) | Standard Deviation 42.21 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Absolute WBC count, Week 52 (n=14,11) | 0.75 Giga cells per liter (G/L) | Standard Deviation 1.637 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Basophils, Follow up (n=79,67) | -0.000 Giga cells per liter (G/L) | Standard Deviation 0.0234 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Absolute WBC count, Follow up (n=79,67) | 0.50 Giga cells per liter (G/L) | Standard Deviation 2.195 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Monocytes, Week 18 (n=66,60) | -0.025 Giga cells per liter (G/L) | Standard Deviation 0.2235 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total neutrophils, Week 2 (n=85,82) | -0.080 Giga cells per liter (G/L) | Standard Deviation 1.7982 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Eosinophil, Week 2 (n=85,82) | 0.025 Giga cells per liter (G/L) | Standard Deviation 0.0941 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total neutrophils, Week 4 (n=86,80) | -0.012 Giga cells per liter (G/L) | Standard Deviation 2.0753 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Platelet count, Week 8 (n=79,77) | 6.3 Giga cells per liter (G/L) | Standard Deviation 53.31 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total neutrophils, Week 8 (n=80,77) | 0.060 Giga cells per liter (G/L) | Standard Deviation 2.0525 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Eosinophil, Week 4 (n=86,80) | 0.013 Giga cells per liter (G/L) | Standard Deviation 0.0713 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total neutrophils, Week 12 (n=76,70) | 0.316 Giga cells per liter (G/L) | Standard Deviation 2.0173 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Monocytes, Week 26 (n=52,50) | -0.057 Giga cells per liter (G/L) | Standard Deviation 0.179 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total neutrophils, Week 18 (n=66,60) | -0.161 Giga cells per liter (G/L) | Standard Deviation 1.7378 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Eosinophil, Week 8 (n=80,77) | 0.014 Giga cells per liter (G/L) | Standard Deviation 0.0918 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total neutrophils, Week 26 (n=52,50) | -0.190 Giga cells per liter (G/L) | Standard Deviation 1.8779 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Platelet count, Week 52 (n=14,11) | -0.5 Giga cells per liter (G/L) | Standard Deviation 30.06 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total neutrophils, Week 39 (n=28,29) | 0.689 Giga cells per liter (G/L) | Standard Deviation 2.9389 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Eosinophil, Week 12 (n=76,70) | 0.013 Giga cells per liter (G/L) | Standard Deviation 0.1173 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total neutrophils, Week 52 (n=14,11) | 0.248 Giga cells per liter (G/L) | Standard Deviation 1.4497 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Monocytes, Week 39 (n=28,29) | -0.020 Giga cells per liter (G/L) | Standard Deviation 0.2376 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total neutrophils, Follow up (n=79,67) | 0.309 Giga cells per liter (G/L) | Standard Deviation 2.3168 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Eosinophil, Week 18 (n=66,60) | 0.046 Giga cells per liter (G/L) | Standard Deviation 0.1926 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total lymphocyte, Week 2 (n=85,82) | 0.282 Giga cells per liter (G/L) | Standard Deviation 0.7058 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Platelet count, Week 12 (n=75,70) | 5.1 Giga cells per liter (G/L) | Standard Deviation 55.82 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total lymphocyte, Week 4 (n=86,80) | 0.161 Giga cells per liter (G/L) | Standard Deviation 0.5497 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Eosinophil, Week 26 (n=52,50) | 0.051 Giga cells per liter (G/L) | Standard Deviation 0.1646 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total lymphocyte, Week 8 (n=80,77) | 0.263 Giga cells per liter (G/L) | Standard Deviation 0.7366 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Monocytes, Week 52 (n=14,11) | 0.020 Giga cells per liter (G/L) | Standard Deviation 0.1511 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total lymphocyte, Week 12 (n=76,70) | 0.210 Giga cells per liter (G/L) | Standard Deviation 0.6986 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Eosinophil, Week 39 (n=28,29) | 0.028 Giga cells per liter (G/L) | Standard Deviation 0.1035 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total lymphocyte, Week 18 (n=66,60) | 0.321 Giga cells per liter (G/L) | Standard Deviation 0.6855 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Platelet count, Week 39 (n=28,29) | 0.0 Giga cells per liter (G/L) | Standard Deviation 45.29 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total lymphocyte, Week 26 (n=52,50) | 0.296 Giga cells per liter (G/L) | Standard Deviation 0.7236 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Eosinophil, Week 52 (n=14,11) | 0.006 Giga cells per liter (G/L) | Standard Deviation 0.1688 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total lymphocyte, Week 39 (n=28,29) | 0.387 Giga cells per liter (G/L) | Standard Deviation 0.6355 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Monocytes, Follow up (n=79,67) | 0.083 Giga cells per liter (G/L) | Standard Deviation 0.219 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total lymphocyte, Week 52 (n=14,11) | 0.449 Giga cells per liter (G/L) | Standard Deviation 0.5762 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Eosinophil, Follow up (n=79,67) | 0.025 Giga cells per liter (G/L) | Standard Deviation 0.0903 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Total lymphocyte, Follow up (n=79,67) | 0.090 Giga cells per liter (G/L) | Standard Deviation 0.6346 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Platelet count, Week 18 (n=66,59) | 3.2 Giga cells per liter (G/L) | Standard Deviation 50.43 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Basophils, Week 2 (n=85,82) | 0.002 Giga cells per liter (G/L) | Standard Deviation 0.029 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Monocytes, Week 2 (n=85,82) | -0.024 Giga cells per liter (G/L) | Standard Deviation 0.1898 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Basophils, Week 4 (n=86,80) | -0.002 Giga cells per liter (G/L) | Standard Deviation 0.0231 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Platelet count, Week 2 (n=85,82) | -2.3 Giga cells per liter (G/L) | Standard Deviation 47.94 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Basophils, Week 8 (n=80,77) | 0.003 Giga cells per liter (G/L) | Standard Deviation 0.0254 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Monocytes, Week 4 (n=86,80) | -0.029 Giga cells per liter (G/L) | Standard Deviation 0.1975 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Basophils, Week 12 (n=76,70) | 0.000 Giga cells per liter (G/L) | Standard Deviation 0.0212 |
| Losmapimod 15 mg | Change From Baseline in Absolute White Blood Cell (WBC) Count, Total Neutrophil, Total Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Point | Platelet count, Follow up (n=80,67) | 10.5 Giga cells per liter (G/L) | Standard Deviation 50.76 |
Secondary
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points
Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma glutamyl transferase at the indicated time point. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at the indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline and up to Week 53
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alkaline phosphatase, Week 2 (n=90,84) | 0.3 International units (IU)/ L | Standard Deviation 9.14 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alanine aminotransferase, Week 26 (n=53,50) | -0.2 International units (IU)/ L | Standard Deviation 7.88 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alkaline phosphatase, Week 4 (n=88,81) | 0.0 International units (IU)/ L | Standard Deviation 10.43 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Aspartate aminotransferase, Week 4 (n=88,80) | 2.0 International units (IU)/ L | Standard Deviation 7.65 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alkaline phosphatase, Week 8 (n=81,79) | -2.5 International units (IU)/ L | Standard Deviation 10.46 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alanine aminotransferase, Week 12 (n=78,72) | 1.3 International units (IU)/ L | Standard Deviation 9.61 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alkaline phosphatase, Week 12 (n=78,72) | -2.9 International units (IU)/ L | Standard Deviation 12.67 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Aspartate aminotransferase, Week 8 (n=81,79) | -0.4 International units (IU)/ L | Standard Deviation 6.54 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alkaline phosphatase, Week 18 (n=67,60) | 1.0 International units (IU)/ L | Standard Deviation 9.87 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alanine aminotransferase, Week 39 (n=28,29) | 3.0 International units (IU)/ L | Standard Deviation 14.98 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alkaline phosphatase, Week 26 (n=53,50) | 0.2 International units (IU)/ L | Standard Deviation 13.06 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Aspartate aminotransferase, Week 12 (n=78,72) | 2.2 International units (IU)/ L | Standard Deviation 11.91 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alkaline phosphatase, Week 39 (n=28,29) | 0.9 International units (IU)/ L | Standard Deviation 9.77 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alanine aminotransferase, Week 8 (n=81,79) | -0.3 International units (IU)/ L | Standard Deviation 6 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alkaline phosphatase, Week 52 (n=14,11) | 0.1 International units (IU)/ L | Standard Deviation 6.39 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Aspartate aminotransferase, Week 18 (n=67,60) | 0.9 International units (IU)/ L | Standard Deviation 5.72 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alkaline phosphatase, Follow up (n=80,68) | -4.2 International units (IU)/ L | Standard Deviation 15.26 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alanine aminotransferase, Week 52 (n=14,11) | -1.1 International units (IU)/ L | Standard Deviation 5.79 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Gamma glutamyl transferase, Week 2 (n=90,84) | -0.3 International units (IU)/ L | Standard Deviation 11.45 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Aspartate aminotransferase, Week 26 (n=53,49) | 0.3 International units (IU)/ L | Standard Deviation 5.75 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Gamma glutamyl transferase, Week 4 (n=88,81) | 1.4 International units (IU)/ L | Standard Deviation 19.82 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alanine aminotransferase, Week 18 (n=67,60) | 0.3 International units (IU)/ L | Standard Deviation 8.03 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Gamma glutamyl transferase, Week 8 (n=81,79) | -1.8 International units (IU)/ L | Standard Deviation 17.32 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Aspartate aminotransferase, Week 39 (n=28,29) | 1.3 International units (IU)/ L | Standard Deviation 6.5 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Gamma glutamyl transferase, Week 12 (n=78,72) | -0.1 International units (IU)/ L | Standard Deviation 17.11 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alanine aminotransferase, Follow up (n=80,68) | 0.7 International units (IU)/ L | Standard Deviation 12.02 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Gamma glutamyl transferase, Week 18 (n=67,60) | 0.6 International units (IU)/ L | Standard Deviation 15.42 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Aspartate aminotransferase, Week 52 (n=14,11) | -1.1 International units (IU)/ L | Standard Deviation 9.22 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Gamma glutamyl transferase, Week 26 (n=53,50) | -1.8 International units (IU)/ L | Standard Deviation 13.53 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alanine aminotransferase, Week 4 (n=88,81) | 1.8 International units (IU)/ L | Standard Deviation 8.22 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Gamma glutamyl transferase, Week 39 (n=28,29) | -1.7 International units (IU)/ L | Standard Deviation 10.4 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Aspartate aminotransferase, Follow up (n=80,67) | 0.3 International units (IU)/ L | Standard Deviation 6.55 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Gamma glutamyl transferase, Week 52 (n=14,11) | -0.5 International units (IU)/ L | Standard Deviation 13.39 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Aspartate aminotransferase, Week 2 (n=90,84) | -0.5 International units (IU)/ L | Standard Deviation 3.68 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Gamma glutamyl transferase, Follow up (n=80,68) | -2.5 International units (IU)/ L | Standard Deviation 17.16 |
| Placebo | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alanine aminotransferase, Week 2 (n=90,84) | -0.3 International units (IU)/ L | Standard Deviation 3.78 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Gamma glutamyl transferase, Follow up (n=80,68) | 0.1 International units (IU)/ L | Standard Deviation 14.92 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alanine aminotransferase, Week 2 (n=90,84) | 1.2 International units (IU)/ L | Standard Deviation 5.52 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alanine aminotransferase, Week 4 (n=88,81) | 0.3 International units (IU)/ L | Standard Deviation 6.56 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alanine aminotransferase, Week 8 (n=81,79) | -0.1 International units (IU)/ L | Standard Deviation 6.53 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alanine aminotransferase, Week 12 (n=78,72) | 1.7 International units (IU)/ L | Standard Deviation 7.48 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alanine aminotransferase, Week 18 (n=67,60) | 2.4 International units (IU)/ L | Standard Deviation 7.67 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alanine aminotransferase, Week 26 (n=53,50) | 3.0 International units (IU)/ L | Standard Deviation 10.79 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alanine aminotransferase, Week 39 (n=28,29) | 1.9 International units (IU)/ L | Standard Deviation 9.74 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alanine aminotransferase, Week 52 (n=14,11) | 1.9 International units (IU)/ L | Standard Deviation 3.24 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alanine aminotransferase, Follow up (n=80,68) | 0.7 International units (IU)/ L | Standard Deviation 6.86 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Aspartate aminotransferase, Week 2 (n=90,84) | 1.4 International units (IU)/ L | Standard Deviation 4.25 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Aspartate aminotransferase, Week 4 (n=88,80) | 0.5 International units (IU)/ L | Standard Deviation 5.16 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Aspartate aminotransferase, Week 8 (n=81,79) | 0.5 International units (IU)/ L | Standard Deviation 5.13 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Aspartate aminotransferase, Week 12 (n=78,72) | 2.0 International units (IU)/ L | Standard Deviation 7.73 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Aspartate aminotransferase, Week 18 (n=67,60) | 2.9 International units (IU)/ L | Standard Deviation 6.25 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Aspartate aminotransferase, Week 26 (n=53,49) | 4.7 International units (IU)/ L | Standard Deviation 9.94 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Aspartate aminotransferase, Week 39 (n=28,29) | 2.4 International units (IU)/ L | Standard Deviation 9.79 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Aspartate aminotransferase, Week 52 (n=14,11) | 1.7 International units (IU)/ L | Standard Deviation 3.23 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Aspartate aminotransferase, Follow up (n=80,67) | 0.1 International units (IU)/ L | Standard Deviation 4.56 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alkaline phosphatase, Week 2 (n=90,84) | -2.0 International units (IU)/ L | Standard Deviation 11.62 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alkaline phosphatase, Week 4 (n=88,81) | -2.8 International units (IU)/ L | Standard Deviation 10.32 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alkaline phosphatase, Week 8 (n=81,79) | -5.3 International units (IU)/ L | Standard Deviation 12.71 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alkaline phosphatase, Week 12 (n=78,72) | -4.7 International units (IU)/ L | Standard Deviation 12.64 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alkaline phosphatase, Week 18 (n=67,60) | -4.9 International units (IU)/ L | Standard Deviation 13.57 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alkaline phosphatase, Week 26 (n=53,50) | -4.4 International units (IU)/ L | Standard Deviation 16.89 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alkaline phosphatase, Week 39 (n=28,29) | -4.1 International units (IU)/ L | Standard Deviation 22.29 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alkaline phosphatase, Week 52 (n=14,11) | -9.5 International units (IU)/ L | Standard Deviation 9.37 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Alkaline phosphatase, Follow up (n=80,68) | -4.4 International units (IU)/ L | Standard Deviation 13.57 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Gamma glutamyl transferase, Week 2 (n=90,84) | -1.5 International units (IU)/ L | Standard Deviation 16.55 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Gamma glutamyl transferase, Week 4 (n=88,81) | -3.7 International units (IU)/ L | Standard Deviation 19.85 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Gamma glutamyl transferase, Week 8 (n=81,79) | -5.3 International units (IU)/ L | Standard Deviation 20.2 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Gamma glutamyl transferase, Week 12 (n=78,72) | -1.1 International units (IU)/ L | Standard Deviation 24.97 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Gamma glutamyl transferase, Week 18 (n=67,60) | -1.7 International units (IU)/ L | Standard Deviation 21.15 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Gamma glutamyl transferase, Week 26 (n=53,50) | 2.5 International units (IU)/ L | Standard Deviation 19.87 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Gamma glutamyl transferase, Week 39 (n=28,29) | 1.4 International units (IU)/ L | Standard Deviation 25.46 |
| Losmapimod 15 mg | Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points | Gamma glutamyl transferase, Week 52 (n=14,11) | 0.1 International units (IU)/ L | Standard Deviation 9.06 |
Secondary
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points
Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate calcium, chloride, glucose, potassium, sodium and blood urea nitrogenat the indicated time point. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at the indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline and up to Week 53
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Potassium, Week 2 (n=90,84) | 0.02 Millimole (MMOL)/L | Standard Deviation 0.349 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Chloride, Week 39 (n=28,29) | -0.8 Millimole (MMOL)/L | Standard Deviation 2.45 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Potassium, Week 4 (n=88,80) | 0.01 Millimole (MMOL)/L | Standard Deviation 0.498 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Calcium, Week 26 (n=53,49) | -0.024 Millimole (MMOL)/L | Standard Deviation 0.0855 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Potassium, Week 8 (n=81,79) | 0.05 Millimole (MMOL)/L | Standard Deviation 0.406 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Chloride, Week 52 (n=14,11) | -1.8 Millimole (MMOL)/L | Standard Deviation 2.12 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Potassium, Week 12 (n=77,72) | 0.02 Millimole (MMOL)/L | Standard Deviation 0.352 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Calcium, Week 39 (n=28,29) | -0.017 Millimole (MMOL)/L | Standard Deviation 0.0922 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Potassium, Week 18 (n=67,60) | 0.02 Millimole (MMOL)/L | Standard Deviation 0.39 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Chloride, Week 12 (n=77,72) | 0.0 Millimole (MMOL)/L | Standard Deviation 2.48 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Potassium, Week 26 (n=53,49) | 0.02 Millimole (MMOL)/L | Standard Deviation 0.309 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Calcium, Week 52 (n=14,11) | 0.002 Millimole (MMOL)/L | Standard Deviation 0.1004 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Potassium, Week 39 (n=28,29) | 0.13 Millimole (MMOL)/L | Standard Deviation 0.395 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Chloride, Follow up (n=80,68) | -0.2 Millimole (MMOL)/L | Standard Deviation 2.87 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Potassium, Week 52 (n=14,11) | 0.10 Millimole (MMOL)/L | Standard Deviation 0.39 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Calcium, Follow up (n=80,67) | -0.018 Millimole (MMOL)/L | Standard Deviation 0.1042 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Potassium, Follow up (n=80,67) | 0.01 Millimole (MMOL)/L | Standard Deviation 0.385 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Chloride, Week 2 (n=90,84) | 0.3 Millimole (MMOL)/L | Standard Deviation 2.59 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Sodium, Week 2 (n=90,84) | 0.1 Millimole (MMOL)/L | Standard Deviation 2.16 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Glucose, Week 2 (n=90,84) | -0.13 Millimole (MMOL)/L | Standard Deviation 1.456 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Sodium, Week 4 (n=88,81) | -0.1 Millimole (MMOL)/L | Standard Deviation 2.18 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Calcium, Week 2 (n=90,84) | -0.002 Millimole (MMOL)/L | Standard Deviation 0.1031 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Sodium, Week 8 (n=81,79) | 0.0 Millimole (MMOL)/L | Standard Deviation 2.33 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Glucose, Week 4 (n=88,81) | -0.01 Millimole (MMOL)/L | Standard Deviation 1.5 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Sodium, Week 12 (n=77,72) | -0.1 Millimole (MMOL)/L | Standard Deviation 1.96 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Chloride, Week 18 (n=67,60) | 0.2 Millimole (MMOL)/L | Standard Deviation 2.73 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Sodium, Week 18 (n=67,60) | 0.1 Millimole (MMOL)/L | Standard Deviation 2.8 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Glucose, Week 8 (n=81,79) | 0.01 Millimole (MMOL)/L | Standard Deviation 1.33 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Sodium, Week 26 (n=53,50) | 0.1 Millimole (MMOL)/L | Standard Deviation 2.92 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Calcium, Week 4 (n=88,80) | -0.024 Millimole (MMOL)/L | Standard Deviation 0.1007 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Sodium, Week 39 (n=28,29) | -0.4 Millimole (MMOL)/L | Standard Deviation 2.33 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Glucose, Week 12 (n=78,72) | -0.08 Millimole (MMOL)/L | Standard Deviation 1.661 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Sodium, Week 52 (n=14,11) | -0.6 Millimole (MMOL)/L | Standard Deviation 1.28 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Chloride, Week 8 (n=81,79) | 0.3 Millimole (MMOL)/L | Standard Deviation 2.88 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Sodium, Follow up (n=80,68) | -0.2 Millimole (MMOL)/L | Standard Deviation 2.4 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Glucose, Week 18 (n=67,60) | 0.22 Millimole (MMOL)/L | Standard Deviation 1.607 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Blood urea nitrogen, Week 2 (n=90,84) | -0.04 Millimole (MMOL)/L | Standard Deviation 1.368 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Calcium, Week 8 (n=81,79) | -0.017 Millimole (MMOL)/L | Standard Deviation 0.0934 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Blood urea nitrogen, Week 4 (n=88,81) | -0.21 Millimole (MMOL)/L | Standard Deviation 1.399 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Glucose, Week 26 (n=53,50) | -0.08 Millimole (MMOL)/L | Standard Deviation 1.518 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Blood urea nitrogen, Week 8 (n=81,79) | -0.11 Millimole (MMOL)/L | Standard Deviation 1.635 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Chloride, Week 26 (n=53,50) | -0.3 Millimole (MMOL)/L | Standard Deviation 3.35 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Blood urea nitrogen, Week 12 (n=78,72) | -0.12 Millimole (MMOL)/L | Standard Deviation 1.511 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Glucose, Week 39 (n=28,29) | -0.11 Millimole (MMOL)/L | Standard Deviation 1.553 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Blood urea nitrogen, Week 18 (n=67,60) | -0.41 Millimole (MMOL)/L | Standard Deviation 1.332 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Calcium, Week 12 (n=78,72) | -0.008 Millimole (MMOL)/L | Standard Deviation 0.1106 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Blood urea nitrogen, Week 26 (n=53,50) | -0.34 Millimole (MMOL)/L | Standard Deviation 1.267 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Glucose, Week 52 (n=14,11) | 0.31 Millimole (MMOL)/L | Standard Deviation 1.075 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Blood urea nitrogen, Week 39 (n=28,29) | -0.26 Millimole (MMOL)/L | Standard Deviation 1.385 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Chloride, Week 4 (n=88,81) | -0.2 Millimole (MMOL)/L | Standard Deviation 2.42 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Blood urea nitrogen, Week 52 (n=14,11) | 0.01 Millimole (MMOL)/L | Standard Deviation 0.975 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Glucose, Follow up (n=80,68) | 0.20 Millimole (MMOL)/L | Standard Deviation 1.645 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Blood urea nitrogen, Follow up (n=80,68) | 0.07 Millimole (MMOL)/L | Standard Deviation 1.577 |
| Placebo | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Calcium, Week 18 (n=67,60) | -0.017 Millimole (MMOL)/L | Standard Deviation 0.0891 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Blood urea nitrogen, Follow up (n=80,68) | 0.11 Millimole (MMOL)/L | Standard Deviation 1.545 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Chloride, Week 2 (n=90,84) | 0.5 Millimole (MMOL)/L | Standard Deviation 2.4 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Chloride, Week 4 (n=88,81) | 1.1 Millimole (MMOL)/L | Standard Deviation 2.51 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Chloride, Week 8 (n=81,79) | 0.7 Millimole (MMOL)/L | Standard Deviation 2.85 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Chloride, Week 12 (n=77,72) | 0.2 Millimole (MMOL)/L | Standard Deviation 2.93 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Chloride, Week 18 (n=67,60) | 0.3 Millimole (MMOL)/L | Standard Deviation 2.66 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Chloride, Week 26 (n=53,50) | 0.5 Millimole (MMOL)/L | Standard Deviation 2.57 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Chloride, Week 52 (n=14,11) | -1.4 Millimole (MMOL)/L | Standard Deviation 2.66 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Chloride, Follow up (n=80,68) | -0.5 Millimole (MMOL)/L | Standard Deviation 2.24 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Calcium, Week 2 (n=90,84) | -0.042 Millimole (MMOL)/L | Standard Deviation 0.0774 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Calcium, Week 4 (n=88,80) | -0.31 Millimole (MMOL)/L | Standard Deviation 0.0908 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Calcium, Week 8 (n=81,79) | -0.039 Millimole (MMOL)/L | Standard Deviation 0.0843 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Calcium, Week 12 (n=78,72) | -0.029 Millimole (MMOL)/L | Standard Deviation 0.0982 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Calcium, Week 18 (n=67,60) | -0.033 Millimole (MMOL)/L | Standard Deviation 0.0928 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Calcium, Week 26 (n=53,49) | -0.023 Millimole (MMOL)/L | Standard Deviation 0.1014 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Calcium, Week 39 (n=28,29) | -0.032 Millimole (MMOL)/L | Standard Deviation 0.0927 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Calcium, Week 52 (n=14,11) | -0.061 Millimole (MMOL)/L | Standard Deviation 0.0791 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Calcium, Follow up (n=80,67) | -0.010 Millimole (MMOL)/L | Standard Deviation 0.0959 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Glucose, Week 2 (n=90,84) | 0.22 Millimole (MMOL)/L | Standard Deviation 1.619 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Glucose, Week 4 (n=88,81) | 0.04 Millimole (MMOL)/L | Standard Deviation 1.204 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Glucose, Week 8 (n=81,79) | 0.28 Millimole (MMOL)/L | Standard Deviation 1.272 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Glucose, Week 12 (n=78,72) | 0.24 Millimole (MMOL)/L | Standard Deviation 1.439 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Glucose, Week 18 (n=67,60) | 0.50 Millimole (MMOL)/L | Standard Deviation 1.974 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Glucose, Week 26 (n=53,50) | 0.00 Millimole (MMOL)/L | Standard Deviation 1.117 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Glucose, Week 39 (n=28,29) | -0.16 Millimole (MMOL)/L | Standard Deviation 1.202 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Glucose, Week 52 (n=14,11) | -0.09 Millimole (MMOL)/L | Standard Deviation 0.896 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Glucose, Follow up (n=80,68) | 0.34 Millimole (MMOL)/L | Standard Deviation 2.104 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Potassium, Week 2 (n=90,84) | -0.01 Millimole (MMOL)/L | Standard Deviation 0.391 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Potassium, Week 4 (n=88,80) | 0.06 Millimole (MMOL)/L | Standard Deviation 0.393 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Potassium, Week 8 (n=81,79) | -0.03 Millimole (MMOL)/L | Standard Deviation 0.306 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Potassium, Week 12 (n=77,72) | -0.06 Millimole (MMOL)/L | Standard Deviation 0.354 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Potassium, Week 18 (n=67,60) | 0.14 Millimole (MMOL)/L | Standard Deviation 0.525 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Potassium, Week 26 (n=53,49) | -0.02 Millimole (MMOL)/L | Standard Deviation 0.381 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Potassium, Week 39 (n=28,29) | -0.03 Millimole (MMOL)/L | Standard Deviation 0.415 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Potassium, Week 52 (n=14,11) | -0.13 Millimole (MMOL)/L | Standard Deviation 0.422 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Potassium, Follow up (n=80,67) | -0.02 Millimole (MMOL)/L | Standard Deviation 0.395 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Sodium, Week 2 (n=90,84) | -0.2 Millimole (MMOL)/L | Standard Deviation 2.06 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Sodium, Week 4 (n=88,81) | 0.3 Millimole (MMOL)/L | Standard Deviation 2.37 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Sodium, Week 8 (n=81,79) | -0.1 Millimole (MMOL)/L | Standard Deviation 2.5 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Sodium, Week 12 (n=77,72) | -0.4 Millimole (MMOL)/L | Standard Deviation 2.39 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Sodium, Week 18 (n=67,60) | -0.7 Millimole (MMOL)/L | Standard Deviation 2.49 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Sodium, Week 26 (n=53,50) | -0.2 Millimole (MMOL)/L | Standard Deviation 1.83 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Sodium, Week 39 (n=28,29) | -0.3 Millimole (MMOL)/L | Standard Deviation 2.18 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Sodium, Week 52 (n=14,11) | -0.9 Millimole (MMOL)/L | Standard Deviation 1.45 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Sodium, Follow up (n=80,68) | -0.1 Millimole (MMOL)/L | Standard Deviation 2.14 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Blood urea nitrogen, Week 2 (n=90,84) | 0.46 Millimole (MMOL)/L | Standard Deviation 1.474 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Blood urea nitrogen, Week 4 (n=88,81) | 0.14 Millimole (MMOL)/L | Standard Deviation 1.392 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Blood urea nitrogen, Week 8 (n=81,79) | 0.15 Millimole (MMOL)/L | Standard Deviation 1.464 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Blood urea nitrogen, Week 12 (n=78,72) | 0.62 Millimole (MMOL)/L | Standard Deviation 1.993 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Blood urea nitrogen, Week 18 (n=67,60) | 0.72 Millimole (MMOL)/L | Standard Deviation 2.31 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Blood urea nitrogen, Week 26 (n=53,50) | 0.24 Millimole (MMOL)/L | Standard Deviation 1.636 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Blood urea nitrogen, Week 39 (n=28,29) | 0.62 Millimole (MMOL)/L | Standard Deviation 1.68 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Blood urea nitrogen, Week 52 (n=14,11) | 1.07 Millimole (MMOL)/L | Standard Deviation 1.209 |
| Losmapimod 15 mg | Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points | Chloride, Week 39 (n=28,29) | 0.1 Millimole (MMOL)/L | Standard Deviation 2.15 |
Secondary
Change From Baseline in Eosinophil Percentage at the Indicated Time Points
Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate eosinophil percentage. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at the indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline and up to Week 53
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Eosinophil Percentage at the Indicated Time Points | Eosinophil percentage, Week 4 (n=86,80) | 0.03 Percent change | Standard Deviation 1.583 |
| Placebo | Change From Baseline in Eosinophil Percentage at the Indicated Time Points | Eosinophil percentage, Week 26 (n=52,50) | 0.58 Percent change | Standard Deviation 2.39 |
| Placebo | Change From Baseline in Eosinophil Percentage at the Indicated Time Points | Eosinophil percentage, Week 12 (n=76,70) | 0.08 Percent change | Standard Deviation 1.087 |
| Placebo | Change From Baseline in Eosinophil Percentage at the Indicated Time Points | Eosinophil percentage, Week 39 (n=28,29) | 0.39 Percent change | Standard Deviation 0.865 |
| Placebo | Change From Baseline in Eosinophil Percentage at the Indicated Time Points | Eosinophil percentage, Week 8 (n=80,77) | 0.14 Percent change | Standard Deviation 1.419 |
| Placebo | Change From Baseline in Eosinophil Percentage at the Indicated Time Points | Eosinophil percentage, Week 52 (n=14,11) | -0.11 Percent change | Standard Deviation 0.805 |
| Placebo | Change From Baseline in Eosinophil Percentage at the Indicated Time Points | Eosinophil percentage, Week 18 (n=66,60) | 0.30 Percent change | Standard Deviation 1.513 |
| Placebo | Change From Baseline in Eosinophil Percentage at the Indicated Time Points | Eosinophil percentage, Follow up (n=79,67) | -0.01 Percent change | Standard Deviation 1.245 |
| Placebo | Change From Baseline in Eosinophil Percentage at the Indicated Time Points | Eosinophil percentage, Week 2 (n=85,82) | 0.09 Percent change | Standard Deviation 0.969 |
| Losmapimod 15 mg | Change From Baseline in Eosinophil Percentage at the Indicated Time Points | Eosinophil percentage, Follow up (n=79,67) | 0.29 Percent change | Standard Deviation 1.215 |
| Losmapimod 15 mg | Change From Baseline in Eosinophil Percentage at the Indicated Time Points | Eosinophil percentage, Week 2 (n=85,82) | 0.30 Percent change | Standard Deviation 0.995 |
| Losmapimod 15 mg | Change From Baseline in Eosinophil Percentage at the Indicated Time Points | Eosinophil percentage, Week 4 (n=86,80) | 0.16 Percent change | Standard Deviation 0.93 |
| Losmapimod 15 mg | Change From Baseline in Eosinophil Percentage at the Indicated Time Points | Eosinophil percentage, Week 8 (n=80,77) | 0.11 Percent change | Standard Deviation 1.248 |
| Losmapimod 15 mg | Change From Baseline in Eosinophil Percentage at the Indicated Time Points | Eosinophil percentage, Week 12 (n=76,70) | 0.08 Percent change | Standard Deviation 1.517 |
| Losmapimod 15 mg | Change From Baseline in Eosinophil Percentage at the Indicated Time Points | Eosinophil percentage, Week 18 (n=66,60) | 0.60 Percent change | Standard Deviation 2.387 |
| Losmapimod 15 mg | Change From Baseline in Eosinophil Percentage at the Indicated Time Points | Eosinophil percentage, Week 26 (n=52,50) | 0.58 Percent change | Standard Deviation 2.082 |
| Losmapimod 15 mg | Change From Baseline in Eosinophil Percentage at the Indicated Time Points | Eosinophil percentage, Week 39 (n=28,29) | 0.21 Percent change | Standard Deviation 1.434 |
| Losmapimod 15 mg | Change From Baseline in Eosinophil Percentage at the Indicated Time Points | Eosinophil percentage, Week 52 (n=14,11) | 0.05 Percent change | Standard Deviation 2.819 |
Secondary
Change From Baseline in Frequency of Short Acting Beta-agonist or Anti-cholinergic Use
Use of short acting bronchodilators (short-acting beta2-agonists or short-acting anti-cholinergic) was allowed and was recorded in daily patient diary. It included inhaled short-acting beta2-agonists (e.g. Ipratropium bromide, salbutamol, Ipratropium/salbutamol (albuterol) combination product) and short-acting anti-cholinergics (e.g., ipratropium bromide3). Use of these medications was allowed throughout the study except 4 hours prior to and during each clinic visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline and up to Week 52
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Frequency of Short Acting Beta-agonist or Anti-cholinergic Use | Week 18; n=65, 61 | 0.3163 Average number of puffs per 24 hours | Standard Deviation 1.26883 |
| Placebo | Change From Baseline in Frequency of Short Acting Beta-agonist or Anti-cholinergic Use | Week 4; n=85, 82 | -0.0029 Average number of puffs per 24 hours | Standard Deviation 0.73616 |
| Placebo | Change From Baseline in Frequency of Short Acting Beta-agonist or Anti-cholinergic Use | Week 26; n=51, 53 | 0.2725 Average number of puffs per 24 hours | Standard Deviation 1.43462 |
| Placebo | Change From Baseline in Frequency of Short Acting Beta-agonist or Anti-cholinergic Use | Week 39; n=27, 27 | 0.7109 Average number of puffs per 24 hours | Standard Deviation 1.61447 |
| Placebo | Change From Baseline in Frequency of Short Acting Beta-agonist or Anti-cholinergic Use | Week 12; n=76, 70 | 0.0904 Average number of puffs per 24 hours | Standard Deviation 1.0692 |
| Placebo | Change From Baseline in Frequency of Short Acting Beta-agonist or Anti-cholinergic Use | Week 52; n=14, 10 | 0.4368 Average number of puffs per 24 hours | Standard Deviation 1.22619 |
| Placebo | Change From Baseline in Frequency of Short Acting Beta-agonist or Anti-cholinergic Use | Week 8; n=79, 79 | 0.1143 Average number of puffs per 24 hours | Standard Deviation 0.77946 |
| Losmapimod 15 mg | Change From Baseline in Frequency of Short Acting Beta-agonist or Anti-cholinergic Use | Week 52; n=14, 10 | -0.2881 Average number of puffs per 24 hours | Standard Deviation 0.98057 |
| Losmapimod 15 mg | Change From Baseline in Frequency of Short Acting Beta-agonist or Anti-cholinergic Use | Week 4; n=85, 82 | -0.0400 Average number of puffs per 24 hours | Standard Deviation 0.93329 |
| Losmapimod 15 mg | Change From Baseline in Frequency of Short Acting Beta-agonist or Anti-cholinergic Use | Week 8; n=79, 79 | -0.1473 Average number of puffs per 24 hours | Standard Deviation 1.26462 |
| Losmapimod 15 mg | Change From Baseline in Frequency of Short Acting Beta-agonist or Anti-cholinergic Use | Week 12; n=76, 70 | 0.0022 Average number of puffs per 24 hours | Standard Deviation 1.10426 |
| Losmapimod 15 mg | Change From Baseline in Frequency of Short Acting Beta-agonist or Anti-cholinergic Use | Week 18; n=65, 61 | 0.1489 Average number of puffs per 24 hours | Standard Deviation 0.97966 |
| Losmapimod 15 mg | Change From Baseline in Frequency of Short Acting Beta-agonist or Anti-cholinergic Use | Week 39; n=27, 27 | 0.3418 Average number of puffs per 24 hours | Standard Deviation 1.39346 |
| Losmapimod 15 mg | Change From Baseline in Frequency of Short Acting Beta-agonist or Anti-cholinergic Use | Week 26; n=51, 53 | 0.2098 Average number of puffs per 24 hours | Standard Deviation 1.25768 |
Secondary
Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points
HR was assessed at Screening, Baseline (day 1, pre-dose) and post dose at Weeks 2, 4, 8, 12, 26, 39, 52 and at follow up (Week 53). Measurements were taken in a semi-recumbent position after 5 minutes rest. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value of an assessment is defined as the value at day 1, pre-dose. Par. were included in the analysis if they had at least one post-baseline measurement. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline and up to Week 53
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points | HR, Week 2, (n=90,84) | 1.2 Beats per minute (bpm) | Standard Deviation 7.99 |
| Placebo | Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points | HR, Week 4, (n=89,82) | 1.4 Beats per minute (bpm) | Standard Deviation 7.18 |
| Placebo | Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points | HR, Week 8, (n=81,80) | 1.0 Beats per minute (bpm) | Standard Deviation 8.39 |
| Placebo | Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points | HR, Week 12, (n=78,72) | 3.3 Beats per minute (bpm) | Standard Deviation 8.8 |
| Placebo | Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points | HR, Week 26, (n=53,53) | 4.1 Beats per minute (bpm) | Standard Deviation 10.99 |
| Placebo | Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points | HR, Week 39, (n=28,29) | 3.3 Beats per minute (bpm) | Standard Deviation 9.48 |
| Placebo | Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points | HR, Week 52, (n=14,11) | 4.3 Beats per minute (bpm) | Standard Deviation 9.55 |
| Placebo | Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points | HR, Follow up, (n=83,68) | 3.6 Beats per minute (bpm) | Standard Deviation 6.72 |
| Losmapimod 15 mg | Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points | HR, Follow up, (n=83,68) | 4.2 Beats per minute (bpm) | Standard Deviation 10.99 |
| Losmapimod 15 mg | Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points | HR, Week 2, (n=90,84) | 1.5 Beats per minute (bpm) | Standard Deviation 9.92 |
| Losmapimod 15 mg | Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points | HR, Week 26, (n=53,53) | 1.8 Beats per minute (bpm) | Standard Deviation 8.32 |
| Losmapimod 15 mg | Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points | HR, Week 4, (n=89,82) | 0.6 Beats per minute (bpm) | Standard Deviation 8.72 |
| Losmapimod 15 mg | Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points | HR, Week 52, (n=14,11) | 1.3 Beats per minute (bpm) | Standard Deviation 8.72 |
| Losmapimod 15 mg | Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points | HR, Week 8, (n=81,80) | 1.6 Beats per minute (bpm) | Standard Deviation 9.5 |
| Losmapimod 15 mg | Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points | HR, Week 39, (n=28,29) | 4.4 Beats per minute (bpm) | Standard Deviation 12.64 |
| Losmapimod 15 mg | Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points | HR, Week 12, (n=78,72) | 2.2 Beats per minute (bpm) | Standard Deviation 8.89 |
Secondary
Change From Baseline in Hematocrit at the Indicated Time Points
Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate hematocrit. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline and up to Week 53
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Hematocrit at the Indicated Time Points | Hematocrit, Week 4 (n=87,80) | -0.002 L | Standard Deviation 0.0236 |
| Placebo | Change From Baseline in Hematocrit at the Indicated Time Points | Hematocrit, Week 26 (n=52,50) | 0.003 L | Standard Deviation 0.0302 |
| Placebo | Change From Baseline in Hematocrit at the Indicated Time Points | Hematocrit, Week 12 (n=76,70) | 0.002 L | Standard Deviation 0.0251 |
| Placebo | Change From Baseline in Hematocrit at the Indicated Time Points | Hematocrit, Week 39 (n=28,29) | 0.003 L | Standard Deviation 0.0373 |
| Placebo | Change From Baseline in Hematocrit at the Indicated Time Points | Hematocrit, Week 8 (n=80,77) | -0.001 L | Standard Deviation 0.0274 |
| Placebo | Change From Baseline in Hematocrit at the Indicated Time Points | Hematocrit, Week 52 (n=14,11) | 0.014 L | Standard Deviation 0.0231 |
| Placebo | Change From Baseline in Hematocrit at the Indicated Time Points | Hematocrit, Week 18 (n=66,61) | 0.007 L | Standard Deviation 0.0296 |
| Placebo | Change From Baseline in Hematocrit at the Indicated Time Points | Hematocrit, Follow up (n=80,67) | -0.003 L | Standard Deviation 0.0305 |
| Placebo | Change From Baseline in Hematocrit at the Indicated Time Points | Hematocrit, Week 2 (n=85,82) | -0.001 L | Standard Deviation 0.0238 |
| Losmapimod 15 mg | Change From Baseline in Hematocrit at the Indicated Time Points | Hematocrit, Follow up (n=80,67) | -0.015 L | Standard Deviation 0.0302 |
| Losmapimod 15 mg | Change From Baseline in Hematocrit at the Indicated Time Points | Hematocrit, Week 2 (n=85,82) | -0.002 L | Standard Deviation 0.0169 |
| Losmapimod 15 mg | Change From Baseline in Hematocrit at the Indicated Time Points | Hematocrit, Week 4 (n=87,80) | -0.002 L | Standard Deviation 0.0218 |
| Losmapimod 15 mg | Change From Baseline in Hematocrit at the Indicated Time Points | Hematocrit, Week 8 (n=80,77) | -0.006 L | Standard Deviation 0.0229 |
| Losmapimod 15 mg | Change From Baseline in Hematocrit at the Indicated Time Points | Hematocrit, Week 12 (n=76,70) | 0.000 L | Standard Deviation 0.0361 |
| Losmapimod 15 mg | Change From Baseline in Hematocrit at the Indicated Time Points | Hematocrit, Week 18 (n=66,61) | -0.000 L | Standard Deviation 0.0337 |
| Losmapimod 15 mg | Change From Baseline in Hematocrit at the Indicated Time Points | Hematocrit, Week 26 (n=52,50) | -0.000 L | Standard Deviation 0.0318 |
| Losmapimod 15 mg | Change From Baseline in Hematocrit at the Indicated Time Points | Hematocrit, Week 39 (n=28,29) | 0.001 L | Standard Deviation 0.0329 |
| Losmapimod 15 mg | Change From Baseline in Hematocrit at the Indicated Time Points | Hematocrit, Week 52 (n=14,11) | -0.001 L | Standard Deviation 0.0255 |
Secondary
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points
Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate hemoglobin, total protein, albumin and MCHC. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline and up to Week 53
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Total protein, Week 2 (n=90,84) | -0.4 Gram (G)/Liter (L) | Standard Deviation 3.68 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin, Week 26 (n=52,50) | -0.7 Gram (G)/Liter (L) | Standard Deviation 9.27 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Total protein, Week 4 (n=88,81) | -0.8 Gram (G)/Liter (L) | Standard Deviation 3.93 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Albumin, Week 4 (n=88,81) | -0.5 Gram (G)/Liter (L) | Standard Deviation 2.35 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Total protein, Week 8 (n=81,79) | -1.8 Gram (G)/Liter (L) | Standard Deviation 3.67 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin, Week 12 (n=76,70) | -0.5 Gram (G)/Liter (L) | Standard Deviation 7.61 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Total protein, Week 12 (n=78,72) | -0.6 Gram (G)/Liter (L) | Standard Deviation 4.14 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Albumin, Week 8 (n=81,79) | -1.1 Gram (G)/Liter (L) | Standard Deviation 2.43 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Total protein, Week 18 (n=67,60) | -0.8 Gram (G)/Liter (L) | Standard Deviation 4 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin, Week 39 (n=28,29) | 0.0 Gram (G)/Liter (L) | Standard Deviation 11.71 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Total protein, Week 26 (n=53,50) | -0.5 Gram (G)/Liter (L) | Standard Deviation 4.59 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Albumin, Week 12 (n=78,72) | -0.4 Gram (G)/Liter (L) | Standard Deviation 2.62 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Total protein, Week 39 (n=28,29) | -0.6 Gram (G)/Liter (L) | Standard Deviation 4.5 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin, Week 8 (n=80,77) | -0.9 Gram (G)/Liter (L) | Standard Deviation 8.38 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Total protein, Week 52 (n=14,11) | -0.8 Gram (G)/Liter (L) | Standard Deviation 4.66 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Albumin, Week 18 (n=67,60) | -1.1 Gram (G)/Liter (L) | Standard Deviation 2.53 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Total protein, Follow up (n=80,68) | -1.6 Gram (G)/Liter (L) | Standard Deviation 4.05 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin, Week 52 (n=14,11) | 2.9 Gram (G)/Liter (L) | Standard Deviation 8.43 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC, Week 2 (n=85,82) | 0.1 Gram (G)/Liter (L) | Standard Deviation 6.94 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Albumin, Week 26 (n=53,50) | -0.9 Gram (G)/Liter (L) | Standard Deviation 2.89 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC, Week 4 (n=87,80) | 0.3 Gram (G)/Liter (L) | Standard Deviation 6.31 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin, Week 18 (n=66,61) | 0.1 Gram (G)/Liter (L) | Standard Deviation 9.24 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC, Week 8 (n=80,77) | -1.0 Gram (G)/Liter (L) | Standard Deviation 7.63 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Albumin, Week 39 (n=28,29) | -0.8 Gram (G)/Liter (L) | Standard Deviation 2.76 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC, Week 12 (n=76,70) | -3.1 Gram (G)/Liter (L) | Standard Deviation 8.45 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin, Follow up (n=80,67) | -0.2 Gram (G)/Liter (L) | Standard Deviation 9.3 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC, Week 18 (n=66,61) | -5.0 Gram (G)/Liter (L) | Standard Deviation 10.38 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Albumin, Week 52 (n=14,11) | -0.4 Gram (G)/Liter (L) | Standard Deviation 2.95 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC, Week 26 (n=52,50) | -4.4 Gram (G)/Liter (L) | Standard Deviation 7.06 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin, Week 4 (n=87,80) | -0.6 Gram (G)/Liter (L) | Standard Deviation 7.01 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC, Week 39 (n=28,29) | -2.8 Gram (G)/Liter (L) | Standard Deviation 5.19 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Albumin, Follow up (n=80,68) | -0.8 Gram (G)/Liter (L) | Standard Deviation 2.49 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC, Week 52 (n=14,11) | -3.9 Gram (G)/Liter (L) | Standard Deviation 5.55 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Albumin, Week 2 (n=90,84) | -0.3 Gram (G)/Liter (L) | Standard Deviation 2.23 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC, Follow up (n=80,67) | 1.5 Gram (G)/Liter (L) | Standard Deviation 9.77 |
| Placebo | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin, Week 2 (n=85,82) | -0.3 Gram (G)/Liter (L) | Standard Deviation 7.12 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC, Follow up (n=80,67) | 0.6 Gram (G)/Liter (L) | Standard Deviation 8.73 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin, Week 2 (n=85,82) | 0.0 Gram (G)/Liter (L) | Standard Deviation 4.86 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin, Week 4 (n=87,80) | -1.0 Gram (G)/Liter (L) | Standard Deviation 6.34 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin, Week 8 (n=80,77) | -2.5 Gram (G)/Liter (L) | Standard Deviation 6.93 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin, Week 12 (n=76,70) | -1.4 Gram (G)/Liter (L) | Standard Deviation 9.9 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin, Week 18 (n=66,61) | -2.3 Gram (G)/Liter (L) | Standard Deviation 9.66 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin, Week 26 (n=52,50) | -2.9 Gram (G)/Liter (L) | Standard Deviation 8.86 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin, Week 39 (n=28,29) | -0.1 Gram (G)/Liter (L) | Standard Deviation 10.09 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin, Week 52 (n=14,11) | -1.8 Gram (G)/Liter (L) | Standard Deviation 7.9 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin, Follow up (n=80,67) | -4.5 Gram (G)/Liter (L) | Standard Deviation 9.42 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Albumin, Week 2 (n=90,84) | -0.6 Gram (G)/Liter (L) | Standard Deviation 2.55 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Albumin, Week 4 (n=88,81) | -0.3 Gram (G)/Liter (L) | Standard Deviation 2.28 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Albumin, Week 8 (n=81,79) | -1.2 Gram (G)/Liter (L) | Standard Deviation 2.38 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Albumin, Week 12 (n=78,72) | -0.8 Gram (G)/Liter (L) | Standard Deviation 2.64 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Albumin, Week 18 (n=67,60) | -1.1 Gram (G)/Liter (L) | Standard Deviation 2.32 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Albumin, Week 26 (n=53,50) | -1.1 Gram (G)/Liter (L) | Standard Deviation 2.25 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Albumin, Week 39 (n=28,29) | -1.2 Gram (G)/Liter (L) | Standard Deviation 2.35 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Albumin, Week 52 (n=14,11) | -1.5 Gram (G)/Liter (L) | Standard Deviation 2.07 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Albumin, Follow up (n=80,68) | -1.6 Gram (G)/Liter (L) | Standard Deviation 2.71 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Total protein, Week 2 (n=90,84) | -1.6 Gram (G)/Liter (L) | Standard Deviation 2.96 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Total protein, Week 4 (n=88,81) | -1.2 Gram (G)/Liter (L) | Standard Deviation 3.18 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Total protein, Week 8 (n=81,79) | -2.0 Gram (G)/Liter (L) | Standard Deviation 3.01 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Total protein, Week 12 (n=78,72) | -0.8 Gram (G)/Liter (L) | Standard Deviation 3.45 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Total protein, Week 18 (n=67,60) | -1.5 Gram (G)/Liter (L) | Standard Deviation 2.66 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Total protein, Week 26 (n=53,50) | -1.5 Gram (G)/Liter (L) | Standard Deviation 3.7 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Total protein, Week 39 (n=28,29) | -2.2 Gram (G)/Liter (L) | Standard Deviation 3.51 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Total protein, Week 52 (n=14,11) | -3.0 Gram (G)/Liter (L) | Standard Deviation 3.66 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Total protein, Follow up (n=80,68) | -2.0 Gram (G)/Liter (L) | Standard Deviation 3.87 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC, Week 2 (n=85,82) | 1.7 Gram (G)/Liter (L) | Standard Deviation 6.4 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC, Week 4 (n=87,80) | -0.6 Gram (G)/Liter (L) | Standard Deviation 6.8 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC, Week 8 (n=80,77) | -0.9 Gram (G)/Liter (L) | Standard Deviation 6.88 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC, Week 12 (n=76,70) | -3.3 Gram (G)/Liter (L) | Standard Deviation 10.7 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC, Week 18 (n=66,61) | -4.8 Gram (G)/Liter (L) | Standard Deviation 8.75 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC, Week 26 (n=52,50) | -5.3 Gram (G)/Liter (L) | Standard Deviation 8.48 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC, Week 39 (n=28,29) | -1.5 Gram (G)/Liter (L) | Standard Deviation 5.35 |
| Losmapimod 15 mg | Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC, Week 52 (n=14,11) | -3.3 Gram (G)/Liter (L) | Standard Deviation 6.15 |
Secondary
Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points
Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate mean corpuscle hemoglobin. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at the indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline and up to Week 53
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points | Mean corpuscle hemoglobin, Week 4 (n=87,80) | 0.09 Picograms | Standard Deviation 0.516 |
| Placebo | Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points | Mean corpuscle hemoglobin, Week 26 (n=52,50) | -0.25 Picograms | Standard Deviation 0.692 |
| Placebo | Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points | Mean corpuscle hemoglobin, Week 12 (n=76,70) | -0.22 Picograms | Standard Deviation 0.773 |
| Placebo | Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points | Mean corpuscle hemoglobin, Week 39 (n=28,29) | -0.55 Picograms | Standard Deviation 1.121 |
| Placebo | Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points | Mean corpuscle hemoglobin, Week 8 (n=80,77) | 0.02 Picograms | Standard Deviation 0.801 |
| Placebo | Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points | Mean corpuscle hemoglobin, Week 52 (n=14,11) | -0.72 Picograms | Standard Deviation 1.022 |
| Placebo | Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points | Mean corpuscle hemoglobin, Week 18 (n=66,61) | -0.27 Picograms | Standard Deviation 1.167 |
| Placebo | Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points | Mean corpuscle hemoglobin, Follow up (n=80,67) | -0.46 Picograms | Standard Deviation 1.13 |
| Placebo | Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points | Mean corpuscle hemoglobin, Week 2 (n=85,82) | 0.02 Picograms | Standard Deviation 0.551 |
| Losmapimod 15 mg | Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points | Mean corpuscle hemoglobin, Follow up (n=80,67) | -0.73 Picograms | Standard Deviation 1.279 |
| Losmapimod 15 mg | Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points | Mean corpuscle hemoglobin, Week 2 (n=85,82) | 0.03 Picograms | Standard Deviation 0.701 |
| Losmapimod 15 mg | Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points | Mean corpuscle hemoglobin, Week 4 (n=87,80) | -0.04 Picograms | Standard Deviation 0.48 |
| Losmapimod 15 mg | Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points | Mean corpuscle hemoglobin, Week 8 (n=80,77) | -0.20 Picograms | Standard Deviation 0.7 |
| Losmapimod 15 mg | Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points | Mean corpuscle hemoglobin, Week 12 (n=76,70) | -0.46 Picograms | Standard Deviation 0.964 |
| Losmapimod 15 mg | Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points | Mean corpuscle hemoglobin, Week 18 (n=66,61) | -0.52 Picograms | Standard Deviation 0.944 |
| Losmapimod 15 mg | Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points | Mean corpuscle hemoglobin, Week 26 (n=52,50) | -0.48 Picograms | Standard Deviation 0.983 |
| Losmapimod 15 mg | Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points | Mean corpuscle hemoglobin, Week 39 (n=28,29) | -0.60 Picograms | Standard Deviation 1.1 |
| Losmapimod 15 mg | Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points | Mean corpuscle hemoglobin, Week 52 (n=14,11) | -0.32 Picograms | Standard Deviation 0.676 |
Secondary
Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points
Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate mean corpuscle volume. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at the indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline and up to Week 53
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points | Mean corpuscle volume, Week 4 (n=87,80) | 0.1 Femtoliters | Standard Deviation 1.66 |
| Placebo | Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points | Mean corpuscle volume, Week 26 (n=52,50) | 0.5 Femtoliters | Standard Deviation 2.34 |
| Placebo | Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points | Mean corpuscle volume, Week 12 (n=76,70) | 0.3 Femtoliters | Standard Deviation 2.29 |
| Placebo | Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points | Mean corpuscle volume, Week 39 (n=28,29) | -1.0 Femtoliters | Standard Deviation 3.5 |
| Placebo | Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points | Mean corpuscle volume, Week 8 (n=80,77) | 0.2 Femtoliters | Standard Deviation 2.49 |
| Placebo | Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points | Mean corpuscle volume, Week 52 (n=14,11) | -1.4 Femtoliters | Standard Deviation 3.15 |
| Placebo | Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points | Mean corpuscle volume, Week 18 (n=66,61) | 0.6 Femtoliters | Standard Deviation 2.85 |
| Placebo | Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points | Mean corpuscle volume, Follow up (n=80,67) | -1.9 Femtoliters | Standard Deviation 2.73 |
| Placebo | Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points | Mean corpuscle volume, Week 2 (n=85,82) | 0.0 Femtoliters | Standard Deviation 1.72 |
| Losmapimod 15 mg | Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points | Mean corpuscle volume, Follow up (n=80,67) | -2.4 Femtoliters | Standard Deviation 3.36 |
| Losmapimod 15 mg | Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points | Mean corpuscle volume, Week 2 (n=85,82) | -0.4 Femtoliters | Standard Deviation 1.97 |
| Losmapimod 15 mg | Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points | Mean corpuscle volume, Week 4 (n=87,80) | 0.1 Femtoliters | Standard Deviation 1.88 |
| Losmapimod 15 mg | Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points | Mean corpuscle volume, Week 8 (n=80,77) | -0.4 Femtoliters | Standard Deviation 2.11 |
| Losmapimod 15 mg | Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points | Mean corpuscle volume, Week 12 (n=76,70) | -0.4 Femtoliters | Standard Deviation 2.45 |
| Losmapimod 15 mg | Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points | Mean corpuscle volume, Week 18 (n=66,61) | -0.1 Femtoliters | Standard Deviation 3.12 |
| Losmapimod 15 mg | Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points | Mean corpuscle volume, Week 26 (n=52,50) | 0.2 Femtoliters | Standard Deviation 3.07 |
| Losmapimod 15 mg | Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points | Mean corpuscle volume, Week 39 (n=28,29) | -1.4 Femtoliters | Standard Deviation 3.82 |
| Losmapimod 15 mg | Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points | Mean corpuscle volume, Week 52 (n=14,11) | 0.0 Femtoliters | Standard Deviation 2.05 |
Secondary
Change From Baseline in Red Blood Cell Count at the Indicated Time Points
Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate Red blood cell count. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at the indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline and up to Week 53
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Red Blood Cell Count at the Indicated Time Points | Red blood cell count, Week 4 (n=87,80) | -0.03 Trillion cells per liter (TI/L) | Standard Deviation 0.242 |
| Placebo | Change From Baseline in Red Blood Cell Count at the Indicated Time Points | Red blood cell count, Week 26 (n=52,50) | 0.01 Trillion cells per liter (TI/L) | Standard Deviation 0.318 |
| Placebo | Change From Baseline in Red Blood Cell Count at the Indicated Time Points | Red blood cell count, Week 12 (n=76,70) | 0.02 Trillion cells per liter (TI/L) | Standard Deviation 0.278 |
| Placebo | Change From Baseline in Red Blood Cell Count at the Indicated Time Points | Red blood cell count, Week 39 (n=28,29) | 0.08 Trillion cells per liter (TI/L) | Standard Deviation 0.352 |
| Placebo | Change From Baseline in Red Blood Cell Count at the Indicated Time Points | Red blood cell count, Week 8 (n=80,77) | -0.03 Trillion cells per liter (TI/L) | Standard Deviation 0.281 |
| Placebo | Change From Baseline in Red Blood Cell Count at the Indicated Time Points | Red blood cell count, Week 52 (n=14,11) | 0.23 Trillion cells per liter (TI/L) | Standard Deviation 0.32 |
| Placebo | Change From Baseline in Red Blood Cell Count at the Indicated Time Points | Red blood cell count, Week 18 (n=66,61) | 0.04 Trillion cells per liter (TI/L) | Standard Deviation 0.341 |
| Placebo | Change From Baseline in Red Blood Cell Count at the Indicated Time Points | Red blood cell count, Follow up (n=80,67) | 0.06 Trillion cells per liter (TI/L) | Standard Deviation 0.354 |
| Placebo | Change From Baseline in Red Blood Cell Count at the Indicated Time Points | Red blood cell count, Week 2 (n=85,82) | -0.01 Trillion cells per liter (TI/L) | Standard Deviation 0.248 |
| Losmapimod 15 mg | Change From Baseline in Red Blood Cell Count at the Indicated Time Points | Red blood cell count, Follow up (n=80,67) | -0.04 Trillion cells per liter (TI/L) | Standard Deviation 0.28 |
| Losmapimod 15 mg | Change From Baseline in Red Blood Cell Count at the Indicated Time Points | Red blood cell count, Week 2 (n=85,82) | -0.00 Trillion cells per liter (TI/L) | Standard Deviation 0.183 |
| Losmapimod 15 mg | Change From Baseline in Red Blood Cell Count at the Indicated Time Points | Red blood cell count, Week 4 (n=87,80) | -0.02 Trillion cells per liter (TI/L) | Standard Deviation 0.219 |
| Losmapimod 15 mg | Change From Baseline in Red Blood Cell Count at the Indicated Time Points | Red blood cell count, Week 8 (n=80,77) | -0.05 Trillion cells per liter (TI/L) | Standard Deviation 0.205 |
| Losmapimod 15 mg | Change From Baseline in Red Blood Cell Count at the Indicated Time Points | Red blood cell count, Week 12 (n=76,70) | 0.02 Trillion cells per liter (TI/L) | Standard Deviation 0.328 |
| Losmapimod 15 mg | Change From Baseline in Red Blood Cell Count at the Indicated Time Points | Red blood cell count, Week 18 (n=66,61) | 0.00 Trillion cells per liter (TI/L) | Standard Deviation 0.287 |
| Losmapimod 15 mg | Change From Baseline in Red Blood Cell Count at the Indicated Time Points | Red blood cell count, Week 26 (n=52,50) | -0.02 Trillion cells per liter (TI/L) | Standard Deviation 0.268 |
| Losmapimod 15 mg | Change From Baseline in Red Blood Cell Count at the Indicated Time Points | Red blood cell count, Week 39 (n=28,29) | 0.09 Trillion cells per liter (TI/L) | Standard Deviation 0.265 |
| Losmapimod 15 mg | Change From Baseline in Red Blood Cell Count at the Indicated Time Points | Red blood cell count, Week 52 (n=14,11) | 0.01 Trillion cells per liter (TI/L) | Standard Deviation 0.23 |
Secondary
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC
Pre and post FEV1/FVC, PP FEV1, PP FEV6 and PP FVC were assessed at Screening, Day 1 pre-dose and Weeks 2, 4, 8, 12, 18, 26, 39 and 52. Par. were asked to withheld all bronchodilator therapy included ipratropiumn bromide and salbutamol/albuterol for at least 4 hours prior to the prebronchodilator spirometric test. Post-bronchodilator spirometric assessment was performed after inhalation of 400/360 µg of salbutamol/albuterol in 10-15 minutes. Day 1 (pre-dose) values were considered as Baseline values. Change from Baseline was calculated as value at indicated time point minus Baseline value. The maximum value of the 3 replicate assessments were used. Analysis performed using a mixed-effects repeated measures model. The adjusted mean values were summarized per treatment group. Par. were included in the analysis if they had at least one post-baseline measurement. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline and up to Week 52
Population: mITT Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV1, Week 4, n =88, 81 | -0.24 Percentage | Standard Error 0.877 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV1, Week 8, n =81, 78 | -1.14 Percentage | Standard Error 0.979 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FVC, Week 2, n =90, 82 | 0.72 Percentage | Standard Error 1.156 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FVC, Week 4, n =88, 81 | -0.73 Percentage | Standard Error 1.16 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FVC, Week 8, n =81, 78 | -2.05 Percentage | Standard Error 1.556 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FVC, Week 12 , n =78, 70 | -0.64 Percentage | Standard Error 1.324 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FVC, Week 18, n =67, 60 | -1.58 Percentage | Standard Error 1.286 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FVC, Week 26, n =53, 51 | -2.81 Percentage | Standard Error 1.518 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FVC, Week 39, n =28, 27 | -2.06 Percentage | Standard Error 1.548 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FVC, Week 52, n =14, 11 | -1.24 Percentage | Standard Error 2.017 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV1, Week 2, n =90, 82 | 0.28 Percentage | Standard Error 0.858 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV1, Week 12 , n =78, 70 | -0.10 Percentage | Standard Error 0.94 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV1, Week 18, n =67, 60 | -0.79 Percentage | Standard Error 1.094 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV1, Week 26, n =53, 51 | -2.07 Percentage | Standard Error 1.075 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV1, Week 39, n =28, 27 | -2.33 Percentage | Standard Error 1.307 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV1, Week 52, n =14, 11 | -0.32 Percentage | Standard Error 1.714 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV6, Week 2, n =87, 75 | 0.63 Percentage | Standard Error 1.163 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV6, Week 4, n =84, 75 | -0.72 Percentage | Standard Error 1.135 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV6, Week 8, n =79, 74 | -1.71 Percentage | Standard Error 1.332 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV6, Week 12 , n =76, 67 | -0.42 Percentage | Standard Error 1.214 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV6, Week 18, n =65, 56 | -1.47 Percentage | Standard Error 1.347 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV6, Week 26, n =51, 48 | -1.69 Percentage | Standard Error 1.359 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV6, Week 39, n =26, 24 | -2.10 Percentage | Standard Error 1.543 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV6, Week 52, n =13, 11 | 0.99 Percentage | Standard Error 2.936 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Pre-dose, Week 2, n =90, 83 | 0.22 Percentage | Standard Error 0.571 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Pre-dose, Week 4, n =88, 82 | 0.30 Percentage | Standard Error 0.674 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Pre-dose Week 8, n = 81, 79 | 0.10 Percentage | Standard Error 0.632 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Pre-dose, Week 12, n =78, 71 | 0.31 Percentage | Standard Error 0.649 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Pre-dose Week 18, n =67, 61 | 0.11 Percentage | Standard Error 0.735 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Pre dose Week 26, n=53, 52 | -0.48 Percentage | Standard Error 0.767 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Pre-dose Week 39, n =28, 28 | -1.36 Percentage | Standard Error 0.932 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Pre-dose Week 52, n =14, 11 | -0.18 Percentage | Standard Error 1.177 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Post-dose Week 2, n =89, 82 | 0.09 Percentage | Standard Error 0.682 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Post-dose Week 4, n =87, 81 | -0.90 Percentage | Standard Error 0.619 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Post-dose Week 8, n =80, 78 | 0.12 Percentage | Standard Error 0.646 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC,Post-dose Week 12, n =76, 69 | -0.51 Percentage | Standard Error 0.693 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Post-dose Week 18, n =66, 60 | -0.65 Percentage | Standard Error 0.643 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Post-dose Week 26, n=52, 51 | -0.60 Percentage | Standard Error 2.272 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Post-dose Week 39, n =27, 27 | -1.27 Percentage | Standard Error 0.939 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Post-dose Week 52, n =13, 10 | 0.34 Percentage | Standard Error 1.28 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Post-dose Week 26, n=52, 51 | 3.23 Percentage | Standard Error 2.292 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV6, Week 18, n =65, 56 | 1.87 Percentage | Standard Error 1.438 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Pre-dose Week 39, n =28, 28 | 0.70 Percentage | Standard Error 0.963 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FVC, Week 2, n =90, 82 | 1.31 Percentage | Standard Error 1.228 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV6, Week 26, n =51, 48 | 1.84 Percentage | Standard Error 1.436 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FVC, Week 4, n =88, 81 | 1.72 Percentage | Standard Error 1.228 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC,Post-dose Week 12, n =76, 69 | -0.97 Percentage | Standard Error 0.736 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FVC, Week 8, n =81, 78 | 0.47 Percentage | Standard Error 1.604 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV6, Week 39, n =26, 24 | 2.09 Percentage | Standard Error 1.652 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FVC, Week 12 , n =78, 70 | -0.78 Percentage | Standard Error 1.399 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Pre-dose Week 52, n =14, 11 | 1.26 Percentage | Standard Error 1.27 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FVC, Week 18, n =67, 60 | 1.12 Percentage | Standard Error 1.356 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV6, Week 52, n =13, 11 | 3.66 Percentage | Standard Error 3.209 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FVC, Week 26, n =53, 51 | 1.88 Percentage | Standard Error 1.575 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Post-dose Week 52, n =13, 10 | 1.51 Percentage | Standard Error 1.397 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FVC, Week 39, n =28, 27 | 1.24 Percentage | Standard Error 1.604 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Pre-dose, Week 2, n =90, 83 | 0.43 Percentage | Standard Error 0.611 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FVC, Week 52, n =14, 11 | 0.92 Percentage | Standard Error 2.137 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Post-dose Week 2, n =89, 82 | 0.51 Percentage | Standard Error 0.726 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV1, Week 2, n =90, 82 | 2.03 Percentage | Standard Error 0.932 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV1, Week 4, n =88, 81 | 1.52 Percentage | Standard Error 0.95 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV1, Week 8, n =81, 78 | 1.04 Percentage | Standard Error 1.037 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Pre-dose, Week 4, n =88, 82 | 0.43 Percentage | Standard Error 0.716 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV1, Week 12 , n =78, 70 | 0.12 Percentage | Standard Error 1.013 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Post-dose Week 18, n =66, 60 | -0.23 Percentage | Standard Error 0.682 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV1, Week 18, n =67, 60 | 0.58 Percentage | Standard Error 1.172 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Pre-dose Week 8, n = 81, 79 | 0.46 Percentage | Standard Error 0.663 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV1, Week 26, n =53, 51 | 1.26 Percentage | Standard Error 1.134 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Post-dose Week 4, n =87, 81 | -0.23 Percentage | Standard Error 0.662 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV1, Week 39, n =28, 27 | 0.79 Percentage | Standard Error 1.37 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Pre-dose, Week 12, n =78, 71 | 0.02 Percentage | Standard Error 0.688 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV1, Week 52, n =14, 11 | 2.03 Percentage | Standard Error 1.901 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Post-dose Week 39, n =27, 27 | 0.18 Percentage | Standard Error 0.961 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV6, Week 2, n =87, 75 | 3.45 Percentage | Standard Error 1.252 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Pre-dose Week 18, n =67, 61 | 0.34 Percentage | Standard Error 0.78 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV6, Week 4, n =84, 75 | 2.15 Percentage | Standard Error 1.212 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Post-dose Week 8, n =80, 78 | 0.28 Percentage | Standard Error 0.679 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV6, Week 8, n =79, 74 | 2.04 Percentage | Standard Error 1.395 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | FEV1/FVC, Pre dose Week 26, n=53, 52 | 0.84 Percentage | Standard Error 0.803 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC | PP FEV6, Week 12 , n =76, 67 | -0.02 Percentage | Standard Error 1.284 |
p-value: 0.66195% CI: [-2.08, 3.27]MMRM
p-value: 0.07495% CI: [-0.24, 5.12]MMRM
p-value: 0.2195% CI: [-1.43, 6.46]MMRM
p-value: 0.93395% CI: [-3.4, 3.12]MMRM
p-value: 0.09195% CI: [-0.43, 5.82]MMRM
p-value: 0.01895% CI: [0.82, 8.56]MMRM
p-value: 0.10395% CI: [-0.69, 7.29]MMRM
p-value: 0.44895% CI: [-3.5, 7.82]MMRM
p-value: 0.08995% CI: [-0.27, 3.77]MMRM
p-value: 0.09595% CI: [-0.31, 3.84]MMRM
p-value: 0.07395% CI: [-0.2, 4.58]MMRM
p-value: 0.85395% CI: [-2.08, 2.51]MMRM
p-value: 0.33495% CI: [-1.43, 4.17]MMRM
p-value: 0.01795% CI: [0.61, 6.05]MMRM
p-value: 0.07795% CI: [-0.34, 6.59]MMRM
p-value: 0.35595% CI: [-2.7, 7.38]MMRM
p-value: 0.04495% CI: [0.08, 5.55]MMRM
p-value: 0.03295% CI: [0.25, 5.49]MMRM
p-value: 0.02595% CI: [0.49, 7.01]MMRM
p-value: 0.78595% CI: [-2.5, 3.29]MMRM
p-value: 0.05295% CI: [-0.03, 6.7]MMRM
p-value: 0.04195% CI: [0.14, 6.92]MMRM
p-value: 0.04395% CI: [0.13, 8.25]MMRM
p-value: 0.56295% CI: [-6.58, 11.92]MMRM
p-value: 0.74695% CI: [-1.09, 1.52]MMRM
p-value: 0.87895% CI: [-1.53, 1.79]MMRM
p-value: 0.64495% CI: [-1.15, 1.85]MMRM
p-value: 0.71595% CI: [-1.86, 1.28]MMRM
p-value: 0.80395% CI: [-1.62, 2.1]MMRM
p-value: 0.18495% CI: [-0.63, 3.27]MMRM
p-value: 0.10295% CI: [-0.42, 4.52]MMRM
p-value: 0.38395% CI: [-1.85, 4.73]MMRM
p-value: 0.60795% CI: [-1.2, 2.06]MMRM
p-value: 0.34895% CI: [-0.74, 2.08]MMRM
p-value: 0.82695% CI: [-1.32, 1.65]MMRM
p-value: 0.58895% CI: [-2.13, 1.21]MMRM
p-value: 0.58595% CI: [-1.08, 1.91]MMRM
p-value: 0.23195% CI: [-2.48, 10.12]MMRM
p-value: 0.2495% CI: [-0.99, 3.89]MMRM
p-value: 0.51795% CI: [-2.49, 4.84]MMRM
Secondary
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6).
Pre and post FEV1, FVC and FEV6 were performed at Screening, Day 1 pre-dose and Weeks 2, 4, 8, 12, 18, 26, 39 and 52. Par. were asked to withheld all bronchodilator therapy included ipratropiumn bromide and salbutamol/albuterol for at least 4 hours prior to prebronchodilator spirometric test. Post-bronchodilator spirometric assessment was performed after inhalation of 400/360 micograms (µg) of salbutamol/albuterol in 10-15 minutes. Day 1 (pre-dose) values were considered as Baseline values. Change from Baseline was calculated as value at the indicated time point minus Baseline value. The maximum value of the 3 replicate assessments were used. Analysis performed using a mixed-effects repeated measures model. The adjusted mean values were summarized per treatment group. Par. were included in the analysis if they had at least one post-baseline measurement. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline and up to Week 52
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 post-dose, Week 18, n=66, 60 | -0.035 Liters | Standard Error 0.0256 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 Pre-dose, Week 4, n=88, 82 | -0.010 Liters | Standard Error 0.0242 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 Pre-dose, Week 8, n=81, 79 | -0.031 Liters | Standard Error 0.0247 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 Pre-dose, Week 12, n=78, 71 | -0.011 Liters | Standard Error 0.025 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 Pre-dose, Week 18, n=67, 61 | -0.037 Liters | Standard Error 0.026 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 Pre-dose, Week 26, n=53, 52 | -0.059 Liters | Standard Error 0.0278 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 Pre-dose, Week 39, n=28, 28 | -0.085 Liters | Standard Error 0.0342 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 Pre-dose, Week 52, n=14, 11 | -0.034 Liters | Standard Error 0.0485 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 post-dose, Week 2, n=89, 82 | 0.012 Liters | Standard Error 0.0188 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 post-dose, Week 4, n=87, 81 | -0.022 Liters | Standard Error 0.0193 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 post-dose, Week 8, n=80, 78 | -0.010 Liters | Standard Error 0.0232 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 post-dose, Week 12, n=76, 69 | -0.008 Liters | Standard Error 0.0217 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 pre-dose, Week 2, n = 90, 83 | 0.002 Liters | Standard Error 0.0241 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 post-dose, Week 26, n=52, 51 | -0.070 Liters | Standard Error 0.0273 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 post-dose, Week 39, n=27, 27 | -0.086 Liters | Standard Error 0.0346 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 post-dose, Week 52, n=13, 10 | -0.018 Liters | Standard Error 0.0419 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 pre-dose, Week 2, n = 90,82 | -0.007 Liters | Standard Error 0.0353 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 Pre-dose, Week 4, n=87, 81 | -0.034 Liters | Standard Error 0.0353 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 Pre-dose, Week 8, n=81, 78 | -0.043 Liters | Standard Error 0.04 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 Pre-dose, Week 12, n=78, 71 | -0.036 Liters | Standard Error 0.0366 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 Pre-dose, Week 18, n=67, 60 | -0.073 Liters | Standard Error 0.0413 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 Pre-dose, Week 26, n=53, 52 | -0.076 Liters | Standard Error 0.0405 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 Pre-dose, Week 39, n=28, 28 | -0.102 Liters | Standard Error 0.0486 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 Pre-dose, Week 52, n=14, 11 | -0.101 Liters | Standard Error 0.0731 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 post-dose, Week 2, n=89, 81 | -0.003 Liters | Standard Error 0.0296 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 post-dose, Week 4, n=86, 80 | -0.027 Liters | Standard Error 0.0273 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 post-dose, Week 8, n=80, 76 | -0.039 Liters | Standard Error 0.0313 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 post-dose, Week 12, n=76, 69 | -0.028 Liters | Standard Error 0.0308 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 post-dose, Week 18, n=66, 59 | -0.060 Liters | Standard Error 0.0367 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 post-dose, Week 26, n=51, 51 | -0.081 Liters | Standard Error 0.036 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 post-dose, Week 39, n=27, 27 | -0.095 Liters | Standard Error 0.0428 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 post-dose, Week 52, n=13, 10 | -0.119 Liters | Standard Error 0.0607 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Pre-dose, Week 2, n =90, 83 | -0.018 Liters | Standard Error 0.0389 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Pre-dose, Week 4, n =88, 82 | -0.039 Liters | Standard Error 0.0392 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Pre-dose Week 8, n = 81, 79 | -0.061 Liters | Standard Error 0.0401 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Pre-dose, Week 12, n =78, 71 | -0.046 Liters | Standard Error 0.0405 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Pre-dose Week 18, n =67, 61 | -0.093 Liters | Standard Error 0.0422 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Pre-dose Week 26, n=53, 52 | -0.095 Liters | Standard Error 0.0451 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Pre-dose Week 39, n =28, 28 | -0.115 Liters | Standard Error 0.0558 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Pre-dose Week 52, n =14, 11 | -0.052 Liters | Standard Error 0.0806 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Post-dose Week 2, n =89, 82 | -0.007 Liters | Standard Error 0.0359 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Post-dose Week 4, n =87, 81 | -0.021 Liters | Standard Error 0.0316 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Post-dose Week 8, n =80, 78 | -0.052 Liters | Standard Error 0.0366 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC,Post-dose Week 12, n =76, 69 | -0.020 Liters | Standard Error 0.0361 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Post-dose Week 18, n =66, 60 | -0.075 Liters | Standard Error 0.0422 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Post-dose Week 26, n=52, 51 | -0.135 Liters | Standard Error 0.0495 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Post-dose Week 39, n =27, 27 | -0.092 Liters | Standard Error 0.0499 |
| Placebo | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Post-dose Week 52, n =13, 10 | -0.081 Liters | Standard Error 0.0612 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Post-dose Week 39, n =27, 27 | -0.043 Liters | Standard Error 0.0518 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 pre-dose, Week 2, n = 90, 83 | 0.028 Liters | Standard Error 0.0258 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 post-dose, Week 2, n=89, 81 | 0.023 Liters | Standard Error 0.0319 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 Pre-dose, Week 4, n=88, 82 | 0.025 Liters | Standard Error 0.0259 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Pre-dose Week 18, n =67, 61 | -0.021 Liters | Standard Error 0.0447 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 Pre-dose, Week 8, n=81, 79 | 0.028 Liters | Standard Error 0.0261 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 post-dose, Week 4, n=86, 80 | 0.010 Liters | Standard Error 0.0295 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 Pre-dose, Week 12, n=78, 71 | -0.014 Liters | Standard Error 0.0267 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Post-dose Week 8, n =80, 78 | 0.019 Liters | Standard Error 0.0385 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 Pre-dose, Week 18, n=67, 61 | 0.013 Liters | Standard Error 0.0277 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 post-dose, Week 8, n=80, 76 | 0.012 Liters | Standard Error 0.0331 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 Pre-dose, Week 26, n=53, 52 | 0.020 Liters | Standard Error 0.0289 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Pre-dose Week 26, n=53, 52 | -0.028 Liters | Standard Error 0.0468 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 Pre-dose, Week 39, n=28, 28 | 0.001 Liters | Standard Error 0.0353 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 post-dose, Week 12, n=76, 69 | -0.029 Liters | Standard Error 0.033 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 Pre-dose, Week 52, n=14, 11 | 0.016 Liters | Standard Error 0.0513 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Post-dose Week 26, n=52, 51 | 0.003 Liters | Standard Error 0.0513 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 post-dose, Week 2, n=89, 82 | 0.026 Liters | Standard Error 0.0203 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 post-dose, Week 18, n=66, 59 | -0.035 Liters | Standard Error 0.0392 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 post-dose, Week 4, n=87, 81 | 0.019 Liters | Standard Error 0.0207 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Pre-dose Week 39, n =28, 28 | -0.033 Liters | Standard Error 0.0574 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 post-dose, Week 8, n=80, 78 | 0.023 Liters | Standard Error 0.0242 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 post-dose, Week 26, n=51, 51 | 0.003 Liters | Standard Error 0.0373 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 post-dose, Week 12, n=76, 69 | -0.020 Liters | Standard Error 0.0231 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC,Post-dose Week 12, n =76, 69 | -0.008 Liters | Standard Error 0.0385 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 post-dose, Week 18, n=66, 60 | -0.012 Liters | Standard Error 0.0271 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 post-dose, Week 39, n=27, 27 | -0.067 Liters | Standard Error 0.0443 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 post-dose, Week 26, n=52, 51 | 0.030 Liters | Standard Error 0.0282 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Pre-dose Week 52, n =14, 11 | 0.031 Liters | Standard Error 0.0837 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 post-dose, Week 39, n=27, 27 | -0.031 Liters | Standard Error 0.0356 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 post-dose, Week 52, n=13, 10 | -0.017 Liters | Standard Error 0.0674 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV1 post-dose, Week 52, n=13, 10 | 0.024 Liters | Standard Error 0.0472 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Post-dose Week 52, n =13, 10 | -0.039 Liters | Standard Error 0.0671 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 pre-dose, Week 2, n = 90,82 | 0.045 Liters | Standard Error 0.0381 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Pre-dose, Week 2, n =90, 83 | 0.038 Liters | Standard Error 0.0417 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 Pre-dose, Week 4, n=87, 81 | 0.012 Liters | Standard Error 0.038 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Post-dose Week 2, n =89, 82 | 0.037 Liters | Standard Error 0.0385 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 Pre-dose, Week 8, n=81, 78 | 0.032 Liters | Standard Error 0.0424 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Pre-dose, Week 4, n =88, 82 | 0.006 Liters | Standard Error 0.0418 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 Pre-dose, Week 12, n=78, 71 | -0.034 Liters | Standard Error 0.0392 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Post-dose Week 18, n =66, 60 | -0.016 Liters | Standard Error 0.0449 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 Pre-dose, Week 18, n=67, 60 | -0.014 Liters | Standard Error 0.0441 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Pre-dose Week 8, n = 81, 79 | 0.011 Liters | Standard Error 0.0422 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 Pre-dose, Week 26, n=53, 52 | -0.003 Liters | Standard Error 0.0425 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Post-dose Week 4, n =87, 81 | 0.033 Liters | Standard Error 0.0341 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 Pre-dose, Week 39, n=28, 28 | 0.013 Liters | Standard Error 0.0507 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FVC, Pre-dose, Week 12, n =78, 71 | -0.058 Liters | Standard Error 0.043 |
| Losmapimod 15 mg | Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). | FEV6 Pre-dose, Week 52, n=14, 11 | 0.071 Liters | Standard Error 0.0745 |
p-value: 0.62295% CI: [-0.085, 0.141]MMRM
p-value: 0.27795% CI: [-0.086, 0.291]MMRM
p-value: 0.24195% CI: [-0.038, 0.15]MMRM
p-value: 0.34895% CI: [-0.049, 0.14]MMRM
p-value: 0.13895% CI: [-0.024, 0.169]MMRM
p-value: 0.81395% CI: [-0.111, 0.087]MMRM
p-value: 0.17295% CI: [-0.032, 0.177]MMRM
p-value: 0.24295% CI: [-0.045, 0.18]MMRM
p-value: 0.26795% CI: [-0.063, 0.228]MMRM
p-value: 0.47195% CI: [-0.143, 0.309]MMRM
p-value: 0.31595% CI: [-0.043, 0.132]MMRM
p-value: 0.14395% CI: [-0.018, 0.126]MMRM
p-value: 0.11195% CI: [-0.017, 0.16]MMRM
p-value: 0.52195% CI: [-0.03, 0.059]MMRM
p-value: 0.37195% CI: [-0.031, 0.084]MMRM
p-value: 0.24495% CI: [-0.024, 0.093]MMRM
p-value: 0.0595% CI: [0, 0.119]MMRM
p-value: 0.94295% CI: [-0.063, 0.058]MMRM
p-value: 0.12795% CI: [-0.014, 0.114]MMRM
p-value: 0.02495% CI: [0.011, 0.148]MMRM
p-value: 0.05795% CI: [-0.003, 0.174]MMRM
p-value: 0.48195% CI: [-0.09, 0.191]MMRM
p-value: 0.08495% CI: [-0.005, 0.086]MMRM
p-value: 0.26695% CI: [-0.025, 0.09]MMRM
p-value: 0.66595% CI: [-0.066, 0.042]MMRM
p-value: 0.48995% CI: [-0.043, 0.09]MMRM
p-value: 0.00795% CI: [0.028, 0.17]MMRM
p-value: 0.24895% CI: [-0.039, 0.148]MMRM
p-value: 0.50695% CI: [-0.087, 0.172]MMRM
p-value: 0.22395% CI: [-0.032, 0.134]MMRM
p-value: 0.27695% CI: [-0.037, 0.129]MMRM
p-value: 0.13195% CI: [-0.023, 0.173]MMRM
p-value: 0.94995% CI: [-0.084, 0.09]MMRM
p-value: 0.25995% CI: [-0.044, 0.163]MMRM
p-value: 0.15295% CI: [-0.027, 0.172]MMRM
p-value: 0.07695% CI: [-0.012, 0.241]MMRM
p-value: 0.10795% CI: [-0.038, 0.381]MMRM
p-value: 0.48495% CI: [-0.046, 0.097]MMRM
p-value: 0.25695% CI: [-0.027, 0.1]MMRM
p-value: 0.18495% CI: [-0.025, 0.128]MMRM
p-value: 0.07195% CI: [-0.007, 0.175]MMRM
p-value: 0.9795% CI: [-0.077, 0.074]MMRM
p-value: 0.60895% CI: [-0.07, 0.12]MMRM
p-value: 0.78395% CI: [-0.075, 0.1]MMRM
p-value: 0.28395% CI: [-0.049, 0.167]MMRM
p-value: 0.03895% CI: [0.008, 0.267]MMRM
p-value: 0.46795% CI: [-0.083, 0.18]MMRM
p-value: 0.6495% CI: [-0.138, 0.222]MMRM
Secondary
Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time
SGRQ-C is a health related quality of life questionnaire consisting of 14 questions. SGRQ-C total score was calculated as 100 multiplied by summed weights from all positive items divided by sum of weights for all items in questionnaire. Components (Activity, Symptoms, Impacts) were calculated as 100 multiplied by summed weights from all positive items in that component divided by sum of weights for all items in that component. Score range for SGRQ-C total is 0-100. Maximum weights for Activity, Symptoms and Impacts component is 982.9, 566.2 and 1652.8 respectively. SGRQ-C was transformed to SGRQ for reporting. Higher scores indicate greater disease impact. Score at Day 1, pre-dose (Week 0) was considered as Baseline. Change from Baseline was calculated as score at indicated time point minus Baseline value. Only those par. with analyzable data at the given time points (represented by n=X, X in category titles) were included in analysis.
Time frame: Baseline and up to Week 52
Population: mITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Total, Week 12, (n=74, 71) | -0.75 Scores on a scale | Standard Error 1.541 |
| Placebo | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Total, Week 26, (n=50, 49) | -2.20 Scores on a scale | Standard Error 1.833 |
| Placebo | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Total, Week 39, (n=28, 28) | -0.37 Scores on a scale | Standard Error 2.451 |
| Placebo | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Total, Week 52, (n=14, 11) | -2.95 Scores on a scale | Standard Error 2.769 |
| Placebo | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Symptoms, Week 12, (n=78, 72) | -2.41 Scores on a scale | Standard Error 1.999 |
| Placebo | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Symptoms, Week 26, (n=52, 52) | -5.04 Scores on a scale | Standard Error 2.264 |
| Placebo | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Symptoms, Week 39, (n=28, 29) | -4.61 Scores on a scale | Standard Error 3.411 |
| Placebo | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Symptoms, Week 52, (n=14, 11) | -3.69 Scores on a scale | Standard Error 3.99 |
| Placebo | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Activity, Week 12, (n=77, 71) | -0.08 Scores on a scale | Standard Error 1.968 |
| Placebo | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Activity, Week 26, (n=50, 49) | -0.33 Scores on a scale | Standard Error 2.217 |
| Placebo | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Activity, Week 39, (n=28, 28) | 1.41 Scores on a scale | Standard Error 3.027 |
| Placebo | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Activity, Week 52, (n=14, 11) | -1.80 Scores on a scale | Standard Error 3.308 |
| Placebo | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Impact, Week 12, (n=75, 71) | -0.53 Scores on a scale | Standard Error 1.78 |
| Placebo | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Impact, Week 26, (n=52, 50) | -1.84 Scores on a scale | Standard Error 2.169 |
| Placebo | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Impact, Week 39, (n=28, 28) | -0.59 Scores on a scale | Standard Error 2.868 |
| Placebo | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Impact, Week 52, (n=14, 11) | -2.01 Scores on a scale | Standard Error 3.693 |
| Losmapimod 15 mg | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Impact, Week 52, (n=14, 11) | -3.31 Scores on a scale | Standard Error 4.099 |
| Losmapimod 15 mg | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Total, Week 12, (n=74, 71) | -1.42 Scores on a scale | Standard Error 1.638 |
| Losmapimod 15 mg | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Activity, Week 12, (n=77, 71) | 1.15 Scores on a scale | Standard Error 2.097 |
| Losmapimod 15 mg | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Total, Week 26, (n=50, 49) | -1.31 Scores on a scale | Standard Error 1.904 |
| Losmapimod 15 mg | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Impact, Week 12, (n=75, 71) | -2.22 Scores on a scale | Standard Error 1.893 |
| Losmapimod 15 mg | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Total, Week 39, (n=28, 28) | -3.19 Scores on a scale | Standard Error 2.502 |
| Losmapimod 15 mg | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Activity, Week 26, (n=50, 49) | 0.70 Scores on a scale | Standard Error 2.303 |
| Losmapimod 15 mg | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Total, Week 52, (n=14, 11) | -3.43 Scores on a scale | Standard Error 3.098 |
| Losmapimod 15 mg | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Impact, Week 39, (n=28, 28) | -2.80 Scores on a scale | Standard Error 2.931 |
| Losmapimod 15 mg | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Symptoms, Week 12, (n=78, 72) | -4.08 Scores on a scale | Standard Error 2.115 |
| Losmapimod 15 mg | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Activity, Week 39, (n=28, 28) | -1.00 Scores on a scale | Standard Error 3.095 |
| Losmapimod 15 mg | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Symptoms, Week 26, (n=52, 52) | -4.30 Scores on a scale | Standard Error 2.335 |
| Losmapimod 15 mg | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Impact, Week 26, (n=52, 50) | -2.19 Scores on a scale | Standard Error 2.255 |
| Losmapimod 15 mg | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Symptoms, Week 39, (n=28, 29) | -8.21 Scores on a scale | Standard Error 3.37 |
| Losmapimod 15 mg | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Activity, Week 52, (n=14, 11) | 2.59 Scores on a scale | Standard Error 3.65 |
| Losmapimod 15 mg | Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time | SGRQ Symptoms, Week 52, (n=14, 11) | -11.67 Scores on a scale | Standard Error 4.296 |
p-value: 0.70695% CI: [-4.2, 2.85]Mixed Models Analysis
p-value: 0.69495% CI: [-3.58, 5.36]Mixed Models Analysis
p-value: 0.38295% CI: [-9.23, 3.58]Mixed Models Analysis
p-value: 0.90395% CI: [-8.54, 7.57]Mixed Models Analysis
p-value: 0.48195% CI: [-6.33, 2.99]Mixed Models Analysis
p-value: 0.79395% CI: [-4.79, 6.25]Mixed Models Analysis
p-value: 0.42195% CI: [-12.45, 5.26]Mixed Models Analysis
p-value: 0.16295% CI: [-19.35, 3.4]Mixed Models Analysis
p-value: 0.59295% CI: [-3.31, 5.78]Mixed Models Analysis
p-value: 0.70495% CI: [-4.31, 6.36]Mixed Models Analysis
p-value: 0.54695% CI: [-10.32, 5.5]Mixed Models Analysis
p-value: 0.3595% CI: [-5.06, 13.84]Mixed Models Analysis
p-value: 0.41195% CI: [-5.75, 2.37]Mixed Models Analysis
p-value: 0.89695% CI: [-5.67, 4.97]Mixed Models Analysis
p-value: 0.55995% CI: [-9.73, 5.3]Mixed Models Analysis
p-value: 0.80995% CI: [-12.19, 9.6]Mixed Models Analysis
Secondary
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points
SBP and DBP were taken at Screening, Baseline (day 1, pre-dose) and post dose at Weeks 2, 4, 8, 12, 26, 39, 52 and at follow up (Week 53). Measurements were taken in a semi-recumbent position after 5 minutes rest. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value of an assessment is defined as the value at day 1, pre-dose. Par. were included in the analysis if they had at least one post-baseline measurement. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline and up to Week 53
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | SBP, Week 2, (n=90,84) | 0.2 Millimeter of mercury (mmHg) | Standard Deviation 12 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | SBP, Week 4, (n=89,82) | -0.8 Millimeter of mercury (mmHg) | Standard Deviation 11.49 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | SBP, Week 8, (n=81,80) | -1.9 Millimeter of mercury (mmHg) | Standard Deviation 14.53 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | SBP, Week 12, (n=78,72) | 0.5 Millimeter of mercury (mmHg) | Standard Deviation 12.97 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | SBP, Week 26, (n=53,53) | -1.5 Millimeter of mercury (mmHg) | Standard Deviation 15.39 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | SBP, Week 39, (n=28,29) | 0.3 Millimeter of mercury (mmHg) | Standard Deviation 16.3 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | SBP, Week 52, (n=14,11) | 6.1 Millimeter of mercury (mmHg) | Standard Deviation 17.81 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | SBP, Follow up, (n=83,68) | 1.8 Millimeter of mercury (mmHg) | Standard Deviation 14.46 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | DBP, Week 2, (n=90,84) | -0.0 Millimeter of mercury (mmHg) | Standard Deviation 7.18 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | DBP, Week 4, (n=89,82) | -0.3 Millimeter of mercury (mmHg) | Standard Deviation 8.57 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | DBP, Week 8, (n=81,80) | -1.4 Millimeter of mercury (mmHg) | Standard Deviation 8.75 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | DBP, Week 12, (n=78,72) | 1.5 Millimeter of mercury (mmHg) | Standard Deviation 9.79 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | DBP, Week 26, (n=53,53) | 0.9 Millimeter of mercury (mmHg) | Standard Deviation 8.33 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | DBP, Week 39, (n=28,29) | -0.5 Millimeter of mercury (mmHg) | Standard Deviation 10.4 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | DBP, Week 52, (n=14,11) | 3.4 Millimeter of mercury (mmHg) | Standard Deviation 8.08 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | DBP, Follow up, (n=83,68) | 1.5 Millimeter of mercury (mmHg) | Standard Deviation 10.57 |
| Losmapimod 15 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | DBP, Follow up, (n=83,68) | -1.7 Millimeter of mercury (mmHg) | Standard Deviation 9.94 |
| Losmapimod 15 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | SBP, Week 2, (n=90,84) | -2.9 Millimeter of mercury (mmHg) | Standard Deviation 11.85 |
| Losmapimod 15 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | DBP, Week 2, (n=90,84) | -3.8 Millimeter of mercury (mmHg) | Standard Deviation 9.81 |
| Losmapimod 15 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | SBP, Week 4, (n=89,82) | -0.4 Millimeter of mercury (mmHg) | Standard Deviation 12.49 |
| Losmapimod 15 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | DBP, Week 26, (n=53,53) | -1.2 Millimeter of mercury (mmHg) | Standard Deviation 7.87 |
| Losmapimod 15 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | SBP, Week 8, (n=81,80) | -0.3 Millimeter of mercury (mmHg) | Standard Deviation 11.48 |
| Losmapimod 15 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | DBP, Week 4, (n=89,82) | -2.2 Millimeter of mercury (mmHg) | Standard Deviation 9.32 |
| Losmapimod 15 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | SBP, Week 12, (n=78,72) | -1.6 Millimeter of mercury (mmHg) | Standard Deviation 13.84 |
| Losmapimod 15 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | DBP, Week 52, (n=14,11) | -0.2 Millimeter of mercury (mmHg) | Standard Deviation 8.46 |
| Losmapimod 15 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | SBP, Week 26, (n=53,53) | -1.3 Millimeter of mercury (mmHg) | Standard Deviation 13.25 |
| Losmapimod 15 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | DBP, Week 8, (n=81,80) | -1.5 Millimeter of mercury (mmHg) | Standard Deviation 7.92 |
| Losmapimod 15 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | SBP, Week 39, (n=28,29) | -3.4 Millimeter of mercury (mmHg) | Standard Deviation 10.99 |
| Losmapimod 15 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | DBP, Week 39, (n=28,29) | -1.9 Millimeter of mercury (mmHg) | Standard Deviation 9.58 |
| Losmapimod 15 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | SBP, Week 52, (n=14,11) | -7.6 Millimeter of mercury (mmHg) | Standard Deviation 12.89 |
| Losmapimod 15 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | DBP, Week 12, (n=78,72) | -1.5 Millimeter of mercury (mmHg) | Standard Deviation 9.59 |
| Losmapimod 15 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | SBP, Follow up, (n=83,68) | 0.2 Millimeter of mercury (mmHg) | Standard Deviation 13.41 |
Secondary
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point
Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate total bilirubin, direct bilirubin, urice acid and creatinine. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at the indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline and up to Week 53
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Uric acid, Week 2 (n=90,83) | 1.7 Micromole (UMOL)/ L | Standard Deviation 44.47 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Direct bilirubin, Week 2 (n=90,84) | -0.1 Micromole (UMOL)/ L | Standard Deviation 1.09 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Uric acid, Week 4 (n=88,80) | -3.8 Micromole (UMOL)/ L | Standard Deviation 53.43 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Total bilirubin, Week 12 (n=78,72) | -0.2 Micromole (UMOL)/ L | Standard Deviation 3.33 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Uric acid, Week 8 (n=81,78) | 2.1 Micromole (UMOL)/ L | Standard Deviation 47.41 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Direct bilirubin, Week 4 (n=88,81) | 0.1 Micromole (UMOL)/ L | Standard Deviation 0.89 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Uric acid, Week 12 (n=78,71) | 7.5 Micromole (UMOL)/ L | Standard Deviation 54.68 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Total bilirubin, Week 26 (n=53,50) | 0.0 Micromole (UMOL)/ L | Standard Deviation 3.03 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Uric acid, Week 18 (n=67,60) | 6.7 Micromole (UMOL)/ L | Standard Deviation 49.87 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Direct bilirubin, Week 8 (n=81,79) | -0.0 Micromole (UMOL)/ L | Standard Deviation 0.92 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Uric acid, Week 26 (n=53,50) | 0.6 Micromole (UMOL)/ L | Standard Deviation 54.09 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Total bilirubin, Week 4 (n=88,81) | 0.2 Micromole (UMOL)/ L | Standard Deviation 3.07 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Uric acid, Week 39 (n=28,29) | 13.7 Micromole (UMOL)/ L | Standard Deviation 50.99 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Direct bilirubin, Week 12 (n=78,72) | 0.1 Micromole (UMOL)/ L | Standard Deviation 0.92 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Uric acid, Week 52 (n=14,11) | 7.9 Micromole (UMOL)/ L | Standard Deviation 48.23 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Total bilirubin, Week 39 (n=28,29) | -0.0 Micromole (UMOL)/ L | Standard Deviation 2.06 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Uric acid, Follow up (n=80,67) | -2.6 Micromole (UMOL)/ L | Standard Deviation 62.22 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Direct bilirubin, Week 18 (n=67,60) | 0.1 Micromole (UMOL)/ L | Standard Deviation 1 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Creatinine, Week 2 (n=90,84) | 0.20 Micromole (UMOL)/ L | Standard Deviation 7.974 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Total bilirubin, Week 2 (n=90,84) | -0.5 Micromole (UMOL)/ L | Standard Deviation 3.12 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Creatinine, Week 4 (n=88,81) | 0.04 Micromole (UMOL)/ L | Standard Deviation 7.224 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Direct bilirubin, Week 26 (n=53,50) | -0.1 Micromole (UMOL)/ L | Standard Deviation 0.79 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Creatinine, Week 8 (n=81,79) | 0.53 Micromole (UMOL)/ L | Standard Deviation 11.111 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Total bilirubin, Week 52 (n=14,11) | 1.1 Micromole (UMOL)/ L | Standard Deviation 3.38 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Creatinine, Week 12 (n=78,72) | -0.11 Micromole (UMOL)/ L | Standard Deviation 9.917 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Direct bilirubin, Week 39 (n=28,29) | -0.1 Micromole (UMOL)/ L | Standard Deviation 0.72 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Creatinine, Week 18 (n=67,60) | 0.41 Micromole (UMOL)/ L | Standard Deviation 11.973 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Total bilirubin, Week 8 (n=81,79) | -0.4 Micromole (UMOL)/ L | Standard Deviation 3.03 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Creatinine, Week 26 (n=53,50) | 1.61 Micromole (UMOL)/ L | Standard Deviation 8.018 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Direct bilirubin, Week 52 (n=14,11) | -0.1 Micromole (UMOL)/ L | Standard Deviation 1.14 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Creatinine, Week 39 (n=28,29) | 2.16 Micromole (UMOL)/ L | Standard Deviation 6.164 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Total bilirubin, Follow up (n=80,68) | 0.2 Micromole (UMOL)/ L | Standard Deviation 3.62 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Creatinine, Week 52 (n=14,11) | 2.94 Micromole (UMOL)/ L | Standard Deviation 6.757 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Direct bilirubin, Follow up (n=80,68) | 0.1 Micromole (UMOL)/ L | Standard Deviation 1.09 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Creatinine, Follow up (n=80,68) | 0.62 Micromole (UMOL)/ L | Standard Deviation 12.075 |
| Placebo | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Total bilirubin, Week 18 (n=67,60) | 0.0 Micromole (UMOL)/ L | Standard Deviation 3.84 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Creatinine, Follow up (n=80,68) | 0.23 Micromole (UMOL)/ L | Standard Deviation 9.463 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Total bilirubin, Week 12 (n=78,72) | -0.1 Micromole (UMOL)/ L | Standard Deviation 3.56 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Total bilirubin, Week 2 (n=90,84) | 0.2 Micromole (UMOL)/ L | Standard Deviation 3.62 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Total bilirubin, Week 4 (n=88,81) | -0.1 Micromole (UMOL)/ L | Standard Deviation 2.97 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Total bilirubin, Week 18 (n=67,60) | 0.2 Micromole (UMOL)/ L | Standard Deviation 2.66 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Total bilirubin, Week 26 (n=53,50) | -0.5 Micromole (UMOL)/ L | Standard Deviation 3.05 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Total bilirubin, Week 39 (n=28,29) | 0.2 Micromole (UMOL)/ L | Standard Deviation 3.55 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Total bilirubin, Week 52 (n=14,11) | 0.9 Micromole (UMOL)/ L | Standard Deviation 2.91 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Total bilirubin, Follow up (n=80,68) | -0.4 Micromole (UMOL)/ L | Standard Deviation 2.67 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Direct bilirubin, Week 2 (n=90,84) | 0.2 Micromole (UMOL)/ L | Standard Deviation 1.04 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Direct bilirubin, Week 4 (n=88,81) | 0.0 Micromole (UMOL)/ L | Standard Deviation 0.94 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Direct bilirubin, Week 8 (n=81,79) | -0.1 Micromole (UMOL)/ L | Standard Deviation 0.98 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Direct bilirubin, Week 12 (n=78,72) | 0.3 Micromole (UMOL)/ L | Standard Deviation 1.17 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Direct bilirubin, Week 18 (n=67,60) | 0.2 Micromole (UMOL)/ L | Standard Deviation 0.98 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Direct bilirubin, Week 26 (n=53,50) | 0.0 Micromole (UMOL)/ L | Standard Deviation 1.14 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Direct bilirubin, Week 39 (n=28,29) | 0.1 Micromole (UMOL)/ L | Standard Deviation 0.88 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Direct bilirubin, Week 52 (n=14,11) | 0.1 Micromole (UMOL)/ L | Standard Deviation 0.7 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Direct bilirubin, Follow up (n=80,68) | 0.0 Micromole (UMOL)/ L | Standard Deviation 0.96 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Uric acid, Week 2 (n=90,83) | -7.0 Micromole (UMOL)/ L | Standard Deviation 45.87 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Uric acid, Week 4 (n=88,80) | -14.0 Micromole (UMOL)/ L | Standard Deviation 44.47 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Uric acid, Week 8 (n=81,78) | -12.1 Micromole (UMOL)/ L | Standard Deviation 52.91 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Uric acid, Week 12 (n=78,71) | -10.2 Micromole (UMOL)/ L | Standard Deviation 62.09 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Uric acid, Week 18 (n=67,60) | -5.9 Micromole (UMOL)/ L | Standard Deviation 54.33 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Uric acid, Week 26 (n=53,50) | -3.7 Micromole (UMOL)/ L | Standard Deviation 61.19 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Uric acid, Week 39 (n=28,29) | 16.6 Micromole (UMOL)/ L | Standard Deviation 87.59 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Uric acid, Week 52 (n=14,11) | 8.3 Micromole (UMOL)/ L | Standard Deviation 57.49 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Uric acid, Follow up (n=80,67) | 1.7 Micromole (UMOL)/ L | Standard Deviation 63.56 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Creatinine, Week 2 (n=90,84) | 3.22 Micromole (UMOL)/ L | Standard Deviation 9.14 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Creatinine, Week 4 (n=88,81) | 1.78 Micromole (UMOL)/ L | Standard Deviation 9.899 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Creatinine, Week 8 (n=81,79) | 2.23 Micromole (UMOL)/ L | Standard Deviation 10.424 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Creatinine, Week 12 (n=78,72) | 3.46 Micromole (UMOL)/ L | Standard Deviation 17.547 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Creatinine, Week 18 (n=67,60) | 5.32 Micromole (UMOL)/ L | Standard Deviation 18.863 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Creatinine, Week 26 (n=53,50) | 1.30 Micromole (UMOL)/ L | Standard Deviation 8.927 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Creatinine, Week 39 (n=28,29) | 5.64 Micromole (UMOL)/ L | Standard Deviation 12.546 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Creatinine, Week 52 (n=14,11) | 0.33 Micromole (UMOL)/ L | Standard Deviation 5.15 |
| Losmapimod 15 mg | Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point | Total bilirubin, Week 8 (n=81,79) | -0.7 Micromole (UMOL)/ L | Standard Deviation 3.28 |
Secondary
Number of Participants Having Any Adverse Events (AEs), Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinaemia were categorized as SAE. AEs were considered as on-treatment If AE onset date is on or after treatment start date & on or before treatment stop date. par. having any AE or SAE were included in analysis.
Time frame: From the start of the study treatment up to 53 Weeks
Population: mITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants Having Any Adverse Events (AEs), Serious Adverse Events (SAEs) | Non-serious AEs | 34 Participants |
| Placebo | Number of Participants Having Any Adverse Events (AEs), Serious Adverse Events (SAEs) | SAEs | 8 Participants |
| Losmapimod 15 mg | Number of Participants Having Any Adverse Events (AEs), Serious Adverse Events (SAEs) | Non-serious AEs | 38 Participants |
| Losmapimod 15 mg | Number of Participants Having Any Adverse Events (AEs), Serious Adverse Events (SAEs) | SAEs | 19 Participants |
Secondary
Number of Participants With Abnormal Liver Events During the Treatment Period
Various liver chemistry parameters were monitored periodically to ensure the safety and tolerability of Losmapimod as compared to placebo. Study treatments were discontinued for par. if alanine aminotransferase (ALT) absolute \>= 5xupper limit of normal (ULN) or; ALT \>= 3xULN persists for \>=4 Weeks or; ALT\>=3x ULN and bilirubin \>=2xULN or; ALT\>=3x ULN and International normalized ratio (INR) \>=1.5 or; ALT\>=3x ULN and cannot be monitored weekly for 4 Weeks or; ALT\>=3x ULN symptomatic.
Time frame: Up to Week 53
Population: mITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Abnormal Liver Events During the Treatment Period | 0 Participants |
| Losmapimod 15 mg | Number of Participants With Abnormal Liver Events During the Treatment Period | 0 Participants |
Secondary
Number of Participants With Electrocardiogram (ECG) Findings
12-lead ECGs were obtained in triplicate at Screening then singly at Baseline (day 1, pre-dose) and post dose at Weeks 2, 4, 8, 12, 26, 39, 52 and at follow up (Week 53) using an ECG machine that automatically calculates the heart rate (HR) and measures PR, QRS, QT, and QT duration corrected for heart rate by Fridericia's formula (QTcF) or QT duration corrected for heart rate by Bazett's formula (QTcB) intervals. Change in ECG findings were categorized as normal and abnormal. Abnormal ECG values could be clinically significant (CS) or not clinically significant (NCS), as determined by the investigator. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Up to 53 Weeks
Population: mITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Normal-Week 8, (n=80,80) | 42 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Normal-SCREENING, (n=94,90) | 49 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-NCS-SCREENING, (n=94,90) | 39 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-CS-SCREENING, (n=94,90) | 9 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Normal-Baseline, (n=94,90) | 44 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-NCS-Baseline, (n=94,90) | 46 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-CS-Baseline, (n=94,90) | 4 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Normal-Week 2, (n=90,84) | 40 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-NCS-Week 2, (n=90,84) | 45 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-CS-Week 2, (n=90,84) | 5 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Normal-Week 4, (n=89,82) | 45 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-NCS-Week 4, (n=89,82) | 40 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-CS-Week 4, (n=89,82) | 4 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-NCS-Week 8, (n=80,80) | 35 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-CS-Week 8, (n=80,80) | 3 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Normal-Week 12, (n=78,72) | 45 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-NCS-Week 12, (n=78,72) | 29 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-CS-Week 12, (n=78,72) | 4 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Normal-Week 26, (n=53,52) | 31 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-NCS-Week 26, (n=53,52) | 21 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-CS-Week 26, (n=53,52) | 1 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Normal-Week 39, (n=28,29) | 18 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-NCS-Week 39, (n=28,29) | 9 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-CS-Week 39, (n=28,29) | 1 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Normal-Week 52, (n=14,11) | 11 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-NCS-Week 52, (n=14,11) | 2 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-CS-Week 52, (n=14,11) | 1 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Normal-Follow up, (n=83,68) | 37 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-NCS-Follow up, (n=83,68) | 40 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-CS-Follow up, (n=83,68) | 6 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-NCS-Week 39, (n=28,29) | 8 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Normal-Week 12, (n=78,72) | 42 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Normal-SCREENING, (n=94,90) | 51 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-CS-Week 52, (n=14,11) | 0 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-NCS-SCREENING, (n=94,90) | 36 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-NCS-Week 12, (n=78,72) | 29 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-CS-SCREENING, (n=94,90) | 5 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-CS-Week 39, (n=28,29) | 1 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Normal-Baseline, (n=94,90) | 54 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-CS-Week 12, (n=78,72) | 1 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-NCS-Baseline, (n=94,90) | 31 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-NCS-Follow up, (n=83,68) | 25 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-CS-Baseline, (n=94,90) | 5 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Normal-Week 26, (n=53,52) | 35 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Normal-Week 2, (n=90,84) | 52 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Normal-Week 52, (n=14,11) | 7 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-NCS-Week 2, (n=90,84) | 29 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-NCS-Week 26, (n=53,52) | 16 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-CS-Week 2, (n=90,84) | 3 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Normal-Follow up, (n=83,68) | 42 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Normal-Week 4, (n=89,82) | 53 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-CS-Week 26, (n=53,52) | 1 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-NCS-Week 4, (n=89,82) | 27 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-NCS-Week 52, (n=14,11) | 4 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-CS-Week 4, (n=89,82) | 2 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Normal-Week 8, (n=80,80) | 50 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Normal-Week 39, (n=28,29) | 20 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-NCS-Week 8, (n=80,80) | 28 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-CS-Follow up, (n=83,68) | 1 Participants |
| Losmapimod 15 mg | Number of Participants With Electrocardiogram (ECG) Findings | Abnormal-CS-Week 8, (n=80,80) | 2 Participants |
Secondary
Plasma Losmapimod Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to the End of Dosing Interval (AUC[0-tau])
Pharmacokinetics (PK) of losmapimod was evaluated in participants with COPD using PK samples collected at pre-dose at Week 2 and Week 12. At Week 26, a sample was collected at pre-dose and a second sample was collected at 2 hours post-dose. Par. of mITT population that provided at least one observed concentration data in this study were considered for PK analysis. Drug plasma concentration-time data were modelled by nonlinear mixed effects modelling. AUC\[0-tau\] (tau=12 hours) was estimated from the model.
Time frame: Pre-dose at Weeks 2 and 12; pre-dose and at 2 hours post-dose at Week 26
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Plasma Losmapimod Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to the End of Dosing Interval (AUC[0-tau]) | 668.5 hour (h)*nanogram (ng)/milliliter (mL) |
Secondary
Plasma Losmapimod Maximum Concentration (Cmax) and Lowest Concentration (Ctrough) at Steady State
Pharmacokinetics of losmapimod was evaluated in participants with COPD using PK samples collected at pre-dose at Week 2 and Week 12. At Week 26, a sample was collected at pre-dose and a second sample was collected at 2 hours post-dose. Par. of mITT population that provided at least one observed concentration data in this study were considered for PK analysis (represented by n=X, X in the category titles). Drug plasma concentration-time data were modelled by nonlinear mixed effects modelling to develop a Population PK model. Cmax and Ctrough were estimated from the PK model.
Time frame: Pre-dose at Weeks 2 and 12; pre-dose and at 2 hours post-dose at Week 26
Population: PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Placebo | Plasma Losmapimod Maximum Concentration (Cmax) and Lowest Concentration (Ctrough) at Steady State | Cmax | 49.7 ng/ mL |
| Placebo | Plasma Losmapimod Maximum Concentration (Cmax) and Lowest Concentration (Ctrough) at Steady State | Ctrough | 23.7 ng/ mL |
Secondary
Time to First Occurrence of Moderate or Severe COPD Exacerbation
The time to first moderate-severe COPD exacerbation in par. treated with losmapimod compared to placebo treated par. was evaluated. The time to the first on-treatment moderate-severe exacerbation was calculated as exacerbation onset date of first on-treatment exacerbation minus exposure start date plus 1. No statistical analysis was conducted. Data was summarized statistically only.
Time frame: From the start of the study treatment up to 53 Weeks
Population: mITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time to First Occurrence of Moderate or Severe COPD Exacerbation | 168.01 Days | Standard Deviation 106.222 |
| Losmapimod 15 mg | Time to First Occurrence of Moderate or Severe COPD Exacerbation | 160.18 Days | Standard Deviation 117.142 |