Phase I Study of GW856553 (Losmapimod)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT01648192 |
Recruitment Status :
Completed
First Posted : July 24, 2012
Last Update Posted : July 26, 2017
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Acute Coronary Syndrome | Drug: Losmapimod for single dose Drug: Losmapimod for repeat dose | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 20 participants |
Allocation: | Randomized |
Intervention Model: | Crossover Assignment |
Masking: | Single (Participant) |
Primary Purpose: | Treatment |
Official Title: | A Phase I, Randomized, Single-Blind, Three-Period Cross-Over, Placebo-Controlled, Single Oral Dose, Dose-Escalation (Part 1), Fixed Sequence, and Repeat Dose (Part 2) Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Losmapimod in Healthy Japanese Subjects. |
Actual Study Start Date : | July 24, 2012 |
Actual Primary Completion Date : | October 26, 2012 |
Actual Study Completion Date : | October 26, 2012 |

Arm | Intervention/treatment |
---|---|
Experimental: 2.5 mg
Losmapimod for single dose
|
Drug: Losmapimod for single dose
Film coated white tablet |
Experimental: 7.5 mg
Losmapimod for single dose
|
Drug: Losmapimod for single dose
Film coated white tablet |
Experimental: 20 mg
Losmapimod for single dose
|
Drug: Losmapimod for single dose
Film coated white tablet |
Placebo Comparator: Placebo
Placebo
|
Drug: Losmapimod for single dose
Film coated white tablet |
Experimental: 7.5 mg BID
Losmapimod for repeat dose (14 days)
|
Drug: Losmapimod for repeat dose
Film coated white tablet |
Placebo Comparator: Placebo BID
Placebo
|
Drug: Losmapimod for repeat dose
Film coated white tablet |
- Adverse events [ Time Frame: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose. ]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).
- AUC(0-t) [ Time Frame: up to 96h post dose. ]Area under the concentration-time curve from pre-dose to last time of quantifiable concentration of losmapimod and GSK198602 (inactive metabolite) (Single dose only).
- AUC(0-inf) [ Time Frame: up to 96h post dose. ]Area under the concentration-time curve from time pre-dose extrapolated to infinite time of losmapimod and GSK198602 (Single dose only).
- AUC(0-tau) [ Time Frame: up to 17 days post dose. ]Area under the concentration-time curve over the dosing interval of losmapimod and GSK198602 (Repeat dose only).
- Cmax [ Time Frame: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose. ]Maximum observed concentration of losmapimod and GSK198602.
- tmax [ Time Frame: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose. ]Time of occurrence of Cmax of losmapimod and GSK198602.
- t1/2 [ Time Frame: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose. ]Terminal phase half-life of losmapimod and GSK198602
- accumulation ratios [ Time Frame: up to 17 days post dose. ]accumulation ratios of losmapimod and GSK198602 (Repeat dose only).
- hsCRP [ Time Frame: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose. ]Change from baseline in hsCRP after the oral dose of losmapimod.
- phosphorylated HSP27 [ Time Frame: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose. ]Change from baseline in phosphorylated HSP27 assayed following ex vivo stimulation of cells in wholeblood.
- %AUCex [ Time Frame: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose. ]Percentage of AUC(0-inf) obtained by extrapolation of losmapimod and GSK198602.
- tlast [ Time Frame: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose. ]Time of last quantifiable concentration of losmapimod and GSK198602.
- λz [ Time Frame: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose. ]Terminal phase rate constant of losmapimod and GSK198602.
- CL/F [ Time Frame: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose. ]Apparent clearance following oral dosing of losmapimod.
- Vz/F [ Time Frame: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose. ]Apparent volume of distribution following oral dosing of losmapimod.
- AUC(0-inf) [ Time Frame: up to 17 days post dose. ]Area under the concentration-time curve from time pre-dose extrapolated to infinite time of losmapimod and GSK198602 (Repeat dose only).

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 20 Years to 55 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Male or female between 20 and 55 years of age inclusive, at the time of signing the informed consent.
- A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females.
- Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods. This criterion must be followed from the time of the first dose of study medication until follow-up visit.
- Body weight >= 45 kg and BMI within the range 18.5 - 29.0 kg/m2 (inclusive).
- Japanese defined as being born in Japan, having four ethnic Japanese grandparents, holding a Japanese passport or identity papers and being able to speak Japanese. Japanese subjects must not have lived outside of Japan for more than 10 years.
- ALT, alkaline phosphatase and bilirubin <= 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Single QTc, QTcB or QTcF < 450 msec.
Exclusion Criteria:
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A positive pre-study drug/alcohol screen.
- A positive test for HIV antibody.
- History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of greater than 21 units for men and 14 for women or an average daily intake of greater than 3 units. One unit is equivalent to a 285 mL glass of full strength beer or 425 mL schooner of light beer or 1 (30 mL) measure of spirits or 1 glass (100 mL) of wine (NHMRC Guidelines [NHMRC, 2009])
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- Pregnant females as determined by positive urine hCG test at screening or prior to dosing.
- Lactating females.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subject is mentally or legally incapacitated.
- History or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01648192
Australia, New South Wales | |
GSK Investigational Site | |
Randwick, New South Wales, Australia, 2031 |
Study Director: | GSK Clinical Trials | GlaxoSmithKline |
Study Data/Documents: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

For additional information about this study please refer to the GSK Clinical Study Register

For additional information about this study please refer to the GSK Clinical Study Register

For additional information about this study please refer to the GSK Clinical Study Register

For additional information about this study please refer to the GSK Clinical Study Register

For additional information about this study please refer to the GSK Clinical Study Register

For additional information about this study please refer to the GSK Clinical Study Register
Responsible Party: | GlaxoSmithKline |
ClinicalTrials.gov Identifier: | NCT01648192 |
Other Study ID Numbers: |
116681 |
First Posted: | July 24, 2012 Key Record Dates |
Last Update Posted: | July 26, 2017 |
Last Verified: | July 2017 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site. |
Acute Coronary Syndrome Myocardial Ischemia Heart Diseases Cardiovascular Diseases Vascular Diseases |