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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01648192




Registration number
NCT01648192
Ethics application status
Date submitted
12/07/2012
Date registered
24/07/2012
Date last updated
26/07/2017

Titles & IDs
Public title
Phase I Study of GW856553 (Losmapimod)
Scientific 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.
Secondary ID [1] 0 0
116681
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Coronary Syndrome 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Losmapimod for single dose
Treatment: Drugs - Losmapimod for repeat dose

Experimental: 2.5 mg - Losmapimod for single dose

Experimental: 7.5 mg - Losmapimod for single dose

Experimental: 20 mg - Losmapimod for single dose

Placebo Comparator: Placebo - Placebo

Experimental: 7.5 mg BID - Losmapimod for repeat dose (14 days)

Placebo Comparator: Placebo BID - Placebo


Treatment: Drugs: Losmapimod for single dose
Film coated white tablet

Treatment: Drugs: Losmapimod for repeat dose
Film coated white tablet
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adverse events
Timepoint [1] 0 0
Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
Primary outcome [2] 0 0
AUC(0-t)
Timepoint [2] 0 0
up to 96h post dose.
Primary outcome [3] 0 0
AUC(0-inf)
Timepoint [3] 0 0
up to 96h post dose.
Primary outcome [4] 0 0
AUC(0-tau)
Timepoint [4] 0 0
up to 17 days post dose.
Primary outcome [5] 0 0
Cmax
Timepoint [5] 0 0
Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
Primary outcome [6] 0 0
tmax
Timepoint [6] 0 0
Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
Primary outcome [7] 0 0
t1/2
Timepoint [7] 0 0
Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
Primary outcome [8] 0 0
accumulation ratios
Timepoint [8] 0 0
up to 17 days post dose.
Secondary outcome [1] 0 0
hsCRP
Timepoint [1] 0 0
Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
Secondary outcome [2] 0 0
phosphorylated HSP27
Timepoint [2] 0 0
Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
Secondary outcome [3] 0 0
%AUCex
Timepoint [3] 0 0
Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
Secondary outcome [4] 0 0
tlast
Timepoint [4] 0 0
Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
Secondary outcome [5] 0 0
?z
Timepoint [5] 0 0
Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
Secondary outcome [6] 0 0
CL/F
Timepoint [6] 0 0
Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
Secondary outcome [7] 0 0
Vz/F
Timepoint [7] 0 0
Single dose: up to 96h post dose. Repeat dose: up to 17 days post dose.
Secondary outcome [8] 0 0
AUC(0-inf)
Timepoint [8] 0 0
up to 17 days post dose.

Eligibility
Key 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.
Minimum age
20 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/07/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/10/2012
Sample size
Target
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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). 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01648192
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01648192