Acute Coronary SyndromePhase 1NCT01648192
Phase I Study of GW856553 (Losmapimod)
A Phase 1 study testing Losmapimod for single dose and Losmapimod for repeat dose in people with Acute Coronary Syndrome, run by GlaxoSmithKline at 1 site in Australia.
Trial summary
This study is the first study of losmapimod in Japanese subjects. This study will be a single-center, single blind, phase I and two part study to characterize the safety, tolerability, pharmacokinetic and pharmacodynamic profiles in healthy Japanese volunteers (male and female of non-childbearing potential). Read more about this study
- Who is it for?
- Ages 20 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Acute Coronary Syndrome
- What is being tested?
- Losmapimod for single dose and Losmapimod for repeat dose
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteAustralia
- Study dates
- 24 Jul 2012to 26 Oct 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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).
Show all 15Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
This study is the first study of losmapimod in Japanese subjects. This study will be a single-center, single blind, phase I and two part study to characterize the safety, tolerability, pharmacokinetic and pharmacodynamic profiles in healthy Japanese volunteers (male and female of non-childbearing potential). Part1 will be a single dose, randomized, three-period, placebo-controlled and dose escalation part. Each subject will participate in 3 dosing sessions, and receive, on separate days, three of four treatments of losmapimod 2.5, 7.5 and 20 mg, and the matching placebo in the fasted state after overnight fast (at least 10 hours). The design incorporates sufficient washout between treatments (at least 7 days after the previous administration), and is an efficient design for the study objectives. Part 2 will be a fixed dose and placebo-controlled part. Each subject will participate in one dosing session, and receive losmapimod 7.5 mg or the matching placebo twice daily in the fasted state for 14 days. Only subjects will be blind to the sequence and dose studied. The study will include the placebo treatment to allow a valid evaluation of adverse events attributable to treatment versus those independent of treatment. Approximately 18 subjects in each part will receive treatments of losmapimod and/or placebo in the design. The primary objective of the study is to characterize the safety and tolerability of single doses and repeat doses of losmapimod in healthy Japanese subjects. Serial pharmacokinetic samples will be collected and safety assessments will be performed following each dose.
- Conditions
- Acute Coronary Syndrome
- Being tested
- Losmapimod for single dose, Losmapimod for repeat dose
- Medical subject headings
- Acute Coronary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Losmapimod for single doseDrug
Film coated white tablet
Losmapimod for repeat doseDrug
Film coated white tablet
| Study group | Role | What they receive |
|---|---|---|
| 2.5 mg | Experimental | Losmapimod for single dose Receives: Drug: Losmapimod for single dose |
| 7.5 mg | Experimental | Losmapimod for single dose Receives: Drug: Losmapimod for single dose |
| 20 mg | Experimental | Losmapimod for single dose Receives: Drug: Losmapimod for single dose |
| Placebo | Placebo comparator | Placebo Receives: Drug: Losmapimod for single dose |
| 7.5 mg BID | Experimental | Losmapimod for repeat dose (14 days) Receives: Drug: Losmapimod for repeat dose |
| Placebo BID | Placebo comparator | Placebo Receives: Drug: Losmapimod for repeat dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events
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).
Measured: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
AUC(0-t)
Area under the concentration-time curve from pre-dose to last time of quantifiable concentration of losmapimod and GSK198602 (inactive metabolite) (Single dose only).
Measured: up to 96h post dose.
AUC(0-inf)
Area under the concentration-time curve from time pre-dose extrapolated to infinite time of losmapimod and GSK198602 (Single dose only).
Measured: up to 96h post dose.
AUC(0-tau)
Area under the concentration-time curve over the dosing interval of losmapimod and GSK198602 (Repeat dose only).
Measured: up to 17 days post dose.
Cmax
Maximum observed concentration of losmapimod and GSK198602.
Measured: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
tmax
Time of occurrence of Cmax of losmapimod and GSK198602.
Measured: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
t1/2
Terminal phase half-life of losmapimod and GSK198602
Measured: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
accumulation ratios
accumulation ratios of losmapimod and GSK198602 (Repeat dose only).
Measured: up to 17 days post dose.
Secondary outcomes (8)
hsCRP
Change from baseline in hsCRP after the oral dose of losmapimod.
Measured: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
phosphorylated HSP27
Change from baseline in phosphorylated HSP27 assayed following ex vivo stimulation of cells in wholeblood.
Measured: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
%AUCex
Percentage of AUC(0-inf) obtained by extrapolation of losmapimod and GSK198602.
Measured: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
tlast
Time of last quantifiable concentration of losmapimod and GSK198602.
Measured: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
λz
Terminal phase rate constant of losmapimod and GSK198602.
Measured: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
CL/F
Apparent clearance following oral dosing of losmapimod.
Measured: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
Vz/F
Apparent volume of distribution following oral dosing of losmapimod.
Measured: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
AUC(0-inf)
Area under the concentration-time curve from time pre-dose extrapolated to infinite time of losmapimod and GSK198602 (Repeat dose only).
Measured: up to 17 days post dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2012 (estimated)
- Study start24 Jul 2012
- Primary completion26 Oct 2012
- Study completion26 Oct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Coronary SyndromeStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01648192
- Sponsor's protocol ID
- 116681
- Status last verified
- Jul 2017
- First submitted
- 12 Jul 2012
- Last updated
- 26 Jul 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01648192
- Acronym / sponsor ID
- 116681
- Conditions
- Acute Coronary Syndrome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 24 Jul 2012 (actual)
- Primary completion
- 26 Oct 2012 (actual)
- Study completion
- 26 Oct 2012 (actual)
- First posted
- 24 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is the first study of losmapimod in Japanese subjects. This study will be a single-center, single blind, phase I and two part study to characterize the safety, tolerability, pharmacokinetic and pharmacodynamic profiles in healthy Japanese volunteers (male and female of non-childbearing potential). Part1 will be a single dose, randomized, three-period, placebo-controlled and dose escalation part. Each subject will participate in 3 dosing sessions, and receive, on separate days, three of four treatments of losmapimod 2.5, 7.5 and 20 mg, and the matching placebo in the fasted state after overnight fast (at least 10 hours). The design incorporates sufficient washout between treatments (at least 7 days after the previous administration), and is an efficient design for the study objectives. Part 2 will be a fixed dose and placebo-controlled part. Each subject will participate in one dosing session, and receive losmapimod 7.5 mg or the matching placebo twice daily in the fasted state for 14 days. Only subjects will be blind to the sequence and dose studied. The study will include the placebo treatment to allow a valid evaluation of adverse events attributable to treatment versus those independent of treatment. Approximately 18 subjects in each part will receive treatments of losmapimod and/or placebo in the design. The primary objective of the study is to characterize the safety and tolerability of single doses and repeat doses of losmapimod in healthy Japanese subjects. Serial pharmacokinetic samples will be collected and safety assessments will be performed following each dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| 2.5 mg | Experimental | Drug: Losmapimod for single doseLosmapimod for single dose |
| 7.5 mg | Experimental | Drug: Losmapimod for single doseLosmapimod for single dose |
| 20 mg | Experimental | Drug: Losmapimod for single doseLosmapimod for single dose |
| Placebo | Placebo comparator | Drug: Losmapimod for single dosePlacebo |
| 7.5 mg BID | Experimental | Drug: Losmapimod for repeat doseLosmapimod for repeat dose (14 days) |
| Placebo BID | Placebo comparator | Drug: Losmapimod for repeat dosePlacebo |
Who may qualify
- Ages
- 20 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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).
Key exclusion criteria (15 listed)
- 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])
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Losmapimod for single doseFilm coated white tablet | Drug | 2.5 mg, 20 mg, 7.5 mg, Placebo |
| Losmapimod for repeat doseFilm coated white tablet | Drug | 7.5 mg BID, Placebo BID |
Primary outcome
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).
8 secondary outcomes
hsCRP
Time frame: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
phosphorylated HSP27
Time frame: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
%AUCex
Time frame: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
tlast
Time frame: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
λz
Time frame: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
CL/F
Time frame: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
Vz/F
Time frame: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
AUC(0-inf)
Time frame: up to 17 days post dose.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2017.
- Results for study 116681 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Losmapimod for single dose and Losmapimod for repeat dose in people with Acute Coronary Syndrome, run by GlaxoSmithKline at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events (time frame: Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2017.