Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
LOSMAPIMOD · 7 trials · 5 indications
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.
Proteinuria is defined as the presence of an excess of serum proteins in the urine. Participant was considered as a responder on achieving \>=50 percent reduction in proteinuria from Baseline (measured as 24 hour total protein) and also having a stable renal function of \>=70 percent of Baseline estimated glomerular filtration rate (eGFR) at end of treatment (\>=16 Weeks). Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.
Exercise tolerance was assessed using the 6MWD. If a participant was recorded as having used supplemental oxygen or a walking aid (including sitting down then continuing walking) or a technical problem during a 6MWD then that walk was considered as invalid; otherwise the 6MWD was considered as valid. The baseline 6MWD value was defined as the longest distance walked, for a valid walk, at Visit 2. Variability between the distances walked during the first six-minute walk test (6MWD1) and the second six-minute walk test (6MWD2) being compared was defined as: Variability = \[100 x (6MWD2 - 6MWD1)\]/6MWD1. Change from Baseline was calculated as the endpoint value minus the Baseline value. Baseline visit was Visit 2 (Week 0).
Qualifying artery was defined as the artery (left or right carotid or ascending aorta) with the highest segmental mean of maximum (max) TBR at Baseline. The TBR of the qualifying segment was to be ≥ 1.6. If more than one artery qualified, the hottest (greatest mean of max TBR) artery was the qualifying artery. Baseline was defined as the value between Days -14 to -1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-treatment values.
Triplicate ECGs will be collected at three baseline pre-dose time points (at -45 min, -30 min and -15 min) on Day 1 of the corresponding study period. Period baseline will be the average of triplicate pre-dose assessments. Triplicate Holter ECGs measurements will be evaluated at 14 post-dose time points (0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18 and 24 hours) on Day 5 of the corresponding study period and will be averaged prior to calculation of changes from period baseline and statistical analyses
Number of participants with adverse events as a measure of safety and tolerability (evaluated by the result of Clinical safety laboratory tests, vital signs and 12-lead ECG).
Area under the concentration-time curve from pre-dose to last time of quantifiable concentration of losmapimod and GSK198602 (inactive metabolite) (Single dose only).
Area under the concentration-time curve from time pre-dose extrapolated to infinite time of losmapimod and GSK198602 (Single dose only).
Area under the concentration-time curve over the dosing interval of losmapimod and GSK198602 (Repeat dose only).
Maximum observed concentration of losmapimod and GSK198602.
Time of occurrence of Cmax of losmapimod and GSK198602.
Terminal phase half-life of losmapimod and GSK198602
accumulation ratios of losmapimod and GSK198602 (Repeat dose only).
| Arm | Type | Description |
|---|---|---|
| Losmapimod 15 mg | EXPERIMENTAL | Subjects with COPD will receive 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 inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) will be provided as a rescue medication. |
| Placebo | EXPERIMENTAL | Subjects with COPD will receive 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 ICS. Salbutamol MDI will be provided as a rescue medication. |
| Losmapimod (GW856553X) | EXPERIMENTAL | The subjects will be administered with 7.5 mg (1 tablet) of losmapimod following the completion of the Baseline (time zero) assessments. Subjects will continue to take one tablet in the morning and one tablet in the evening for approximately 2 weeks. After all the pre-dose assessments are completed at the Week 2 visit, subjects will be administered the first 15 mg (2 tablets) dose. Subjects will continue to take two tablets in the morning and two tablets in the evening every day for approximately 22 weeks. Doses of study treatment will be separated by at least 6 hours |
| losmapimod 2.5 mg | EXPERIMENTAL | losmapimod 2.5 mg |
| losmapimod 7.5 mg | EXPERIMENTAL | losmapimod 7.5 mg |
| LOSMAPIMOD 7.5 MG TWICE DAILY | EXPERIMENTAL | Participants received 1 tablet of 7.5 mg Losmapimod orally twice daily, each morning and evening for a period of 12 weeks |
| LOSMAPIMOD 7.5 MG ONCE DAILY | EXPERIMENTAL | Participants received 1 tablet of 7.5 mg Losmapimod each morning once daily and placebo tablet each evening once daily orally for a period of 12 weeks. |
| Losmapimod 20 mg | EXPERIMENTAL | Each subject will receive losmapimod 20 mg QD orally for 5 days, in one of the 4 study periods (per randomization sequence) separated by a minimum washout period of 5 days |
| Moxifloxacin 400 mg | ACTIVE_COMPARATOR | Each subject will receive moxifloxacin 400 mg orally on Day 5, in one of the 4 study periods (per randomization sequence) separated by a minimum washout period of 5 days |
| 2.5 mg | EXPERIMENTAL | Losmapimod for single dose |
| 7.5 mg | EXPERIMENTAL | Losmapimod for single dose |
| 20 mg | EXPERIMENTAL | Losmapimod for single dose |
| 7.5 mg BID | EXPERIMENTAL | Losmapimod for repeat dose (14 days) |
| Placebo BID | PLACEBO_COMPARATOR | Placebo |
| 1 mg IV | EXPERIMENTAL | Unit Dose Strength: 0.4 mg/mL |
| ?mg IV | EXPERIMENTAL | dose to be determined based on PK of first IV dose |
| 15 mg (oral) | EXPERIMENTAL | two 7.5 mg tablets |
| Name | Type | Description |
|---|---|---|
| Losmapimod tablets | DRUG | 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. |
| Placebo tablets | DRUG | 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 |
| Salbutamol MDI | DRUG | Salbutamol MDI will be provided as a rescue medication. |
| Losmapimod | DRUG | Losmapimod (micronized GW856553X) will be supplied as a film coated white, 7 mm round, biconvex, plain faced, tablet. Oral doses of losmapimod, 7.5 mg (1 tablet) or 15 mg (2 tablets), will be taken twice daily (BID) with food and swallowed whole (not chewed or crushed) |
| placebo | DRUG | placebo comparison with active |
| LOSMAPIMOD 7.5 MG | DRUG | GW856553 tablets (wet granulation formulation) are available as white, film coated, round, convex tablets manufactured using micronised GW856553X active substance. Tablets are available containing 7.5 mg of GW856553X and are packed into high-density polyethylene (HDPE) bottles. |
| Moxifloxacin | DRUG | 17.2mm x 7.1 mm capsule shaped pink biconvex tablet of 400 mg unit dose strength. Taken orally 400 mg on Day 5 in one of the 4 study periods |
| Losmapimod matched Placebo | DRUG | Direct compression formulation (visually matched to GW856553), Film coated white, 7 mm round, biconvex, plain faced Tablet. Taken orally for 5 days in one of the 4 study periods |
| Moxifloxacin Placebo | DRUG | 16 mm x 8 mm capsule shaped to white film coated tablet. Taken orally for 5 days in one of the 4 study periods |
| Losmapimod for single dose | DRUG | Film coated white tablet |
| Losmapimod for repeat dose | DRUG | Film coated white tablet |
| losmapimod 1 mg | DRUG | IV infusion |
| losmapimod 15 mg | DRUG | oral, two 7.5 mg tablets |
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 ev...
LOSMAPIMOD is an investigational small molecule being developed for cardiovascular and related conditions, including atherosclerosis, focal segmental glomerulosclerosis, chronic obstructive pulmonary disease, acute coronary syndrome, and cardiovascular disease. It is not approved and remains in clinical development.
LOSMAPIMOD is a small molecule that targets p38 MAP kinase, a signaling protein involved in inflammatory responses. By inhibiting this pathway, it is being studied for potential effects in cardiovascular and inflammatory diseases, though its exact mechanism in these conditions is still under investigation.
LOSMAPIMOD is being developed by GSK plc, a global biopharmaceutical company listed on the London Stock Exchange under the ticker GSK. GSK is conducting clinical trials to evaluate the drug's safety and efficacy in various patient populations.
LOSMAPIMOD is in Phase 2 clinical development. It has completed two trials, including a Phase 2 study in atherosclerosis, and several Phase 1 studies. It remains investigational and has not received regulatory approval for any indication.
LOSMAPIMOD has been studied in clinical trials including NCT00633022, a Phase 2 FDG-PET/CT imaging study in atherosclerosis, and NCT01039961, a pharmacokinetic study of an IV formulation in cardiovascular disease. Additional Phase 1 trials include NCT01648192 and NCT01756495.
Yes, LOSMAPIMOD is also known as GW856553. Clinical trial records reference both names, with GW856553 appearing in earlier study titles and LOSMAPIMOD used in later trials. Both names refer to the same investigational drug being developed by GSK.