Clinical trial NCT01756495 (phase 1, status: completed)
Conditions: acute coronary syndrome
ICD codes: I24.0
Drugs: losmapimod, moxifloxacin, losmapimod matched placebo, moxifloxacin placebo
SMILES: CC1=C(C=C(C=C1F)C(=O)NC1CC1)C1=CC=C(C=N1)C(=O)NCC(C)(C)C, [H][C@@]12C[C@@H](C)[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C, CC1=C(C=C(C=C1F)C(=O)NC1CC1)C1=CC=C(C=N1)C(=O)NCC(C)(C)C, [H][C@@]12C[C@@H](C)[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C
Eligibility criteria:

        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 safety 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 GlaxoSmithKline (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 18 and 65 years of age inclusive, at the time of signing the
             informed consent

          -  A female subject is eligible to participate if she is of

               1. Non-childbearing 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 MIU/mL and estradiol <40 pg/mL [<147
                  pmol/L] is confirmatory)

               2. Child-bearing potential and is abstinent or agrees to use one of the allowed
                  contraception methods with a failure rate of <1% (Oral contraceptive, either
                  combined or progestogen alone, Injectable progestogen, Implants of etonogestrel
                  or levonorgestrel, Estrogenic vaginal ring, Percutaneous contraceptive patches,
                  Intrauterine device [IUD] or intrauterine system [IUS], Male partner
                  sterilization [vasectomy with documentation of azoospermia] prior to the female
                  subject's entry into the study, and this male is the sole partner for that
                  subject, Male condom combined with a female diaphragm, either with or without a
                  vaginal spermicide [foam, gel, cream or suppository], Male condom combined with a
                  vaginal spermicide [foam, gel, cream or suppository]) for an appropriate period
                  of time (as determined by the product label or investigator) prior to the start
                  of dosing to sufficiently minimize the risk of pregnancy at that point. Female
                  subjects must agree to use contraception until the follow-up visit

          -  Body weight >=50 kg and Body mass index (BMI) within the range 19 to 28 kg/m^2
             (inclusive)

          -  Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1.5 x upper limit
             of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is
             fractionated and direct bilirubin <35%)

        Exclusion Criteria:

          -  Subjects with cardiac conduction abnormalities on the screening 12-lead ECG denoted by
             any of the following

               1. QTcB or QTcF >450 msec

               2. PR interval >200 msec or <=110 msec

               3. evidence of second- or third- degree atrioventricular block (AVB)

               4. clinically significant pathological Q-waves (defined as Q-wave >40 msec or depth
                  greater than 0.4 to 0.5 mV)

               5. evidence of ventricular pre-excitation

               6. electrocardiographic evidence of complete left bundle branch block (LBBB), right
                  bundle branch block (RBBB), incomplete LBBB

               7. intraventricular conduction delay with QRS duration >110 msec

               8. bradycardia as defined by sinus rate <45 beats per minute (BPM) or tachycardia as
                  defined by sinus rate >100 BPM

          -  Any clinically relevant abnormality identified on the screening medical assessment,
             laboratory examination or ECG

          -  Subjects with a personal or family history of QTc prolongation, symptomatic cardiac
             arrhythmias or cardiac arrest

          -  History of hypersensitivity to moxifloxacin or components thereof or a history of drug
             or other allergy that, in the opinion of the physician responsible, contraindicates
             their participation

          -  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 Human immunodeficiency virus (HIV) antibody result within 3 months
             of screening

          -  History of regular alcohol consumption within 6 months of the study defined as (For US
             sites) an average weekly intake of >14 drinks for males or >7 drinks for females. One
             drink is equivalent to 12 g of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL)
             of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits

          -  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

          -  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 serum human chorionic gonadotropin (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 of sensitivity to heparin or heparin-induced thrombocytopenia