Clinical trial NCT02262689 (phase 1, status: completed)
Conditions: pulmonary disease, chronic obstructive
ICD codes: J44.9, J44.1, J44.0
Drugs: gsk2256294, placebo
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          -  AGE: Between 18 and 65 years of age inclusive, at the time of signing the informed
             consent

          -  Screening echocardiogram of at least good quality, without clinically significant
             abnormalities, and with mild-moderate tricuspid regurgitation sufficient for the
             reliable estimation of PASP, as determined by the echocardiography core laboratory or
             responsible cardiologist.

          -  Screening PASP within the normal range according to site standards

          -  Healthy as determined by the investigator or medically qualified designee based on a
             medical evaluation including medical history, physical examination, laboratory tests
             and cardiac monitoring.

          -  A subject with a clinical abnormality or laboratory parameter(s) which is/are not
             specifically listed in the inclusion or exclusion criteria, outside the reference
             range for the population being studied may be included only if the investigator [in
             consultation with the Medical Monitor if required] agree and document that the finding
             is unlikely to introduce additional risk factors and will not interfere with the study
             procedures.

          -  Body weight >= 60 kilogram and body mass index within the range 19 - 35 kilogram per
             square meter (inclusive)

          -  Female subject is eligible to participate if she is of non-reproductive potential
             defined as: Pre-menopausal females with one of the following: documented tubal
             ligation, documented hysteroscopic tubal occlusion procedure with follow-up
             confirmation of bilateral tubal occlusion, hysterectomy, and documented bilateral
             oophorectomy. Postmenopausal criteria is defined as 12 months of spontaneous
             amenorrhea [in questionable cases a blood sample with simultaneous follicle
             stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to
             laboratory reference ranges for confirmatory levels)]; females on hormone replacement
             therapy (HRT) must discontinue their HRT before the start of the study; for those
             whose menopausal status is in doubt, they will be required to use one of the highly
             effective contraception methods and may need to have a blood sample taken to check
             FSH/estradiol levels.

          -  Male subjects with female partners of child bearing potential must comply with the
             following contraception requirements from the time of first dose of study medication
             until two weeks after the last dose of study medication; vasectomy with documentation
             of azoospermia; male condom plus partner use of one of the contraceptive options
             below: Contraceptive subdermal implant that meets the Standard Operating Procedure
             (SOP)effectiveness criteria including a <1% rate of failure per year, as stated in the
             product label, Intrauterine device or intrauterine system that meets SOP effectiveness
             criteria including a <1% rate of failure per year, as stated in the product label,
             Oral Contraceptive, either combined or progestogen alone, Injectable progestogen,
             Contraceptive vaginal ring; percutaneous contraceptive patches. These allowed methods
             of contraception are only effective when used consistently, correctly and in
             accordance with the product label. The investigator is responsible for ensuring that
             subjects understand how to properly use these methods of contraception.

          -  Capable of giving signed informed consent as described in protocol, which includes
             compliance with the requirements and restrictions listed in the consent form and in
             protocol

        Exclusion Criteria:

          -  Subjects with sickle cell trait.

          -  History of pulmonary hypertension.

          -  Alanine aminotransferase (ALT) and bilirubin >1.5x Upper limit of normal (ULN)
             (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct
             bilirubin <35%).

          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).

          -  QTcF > 450 milliseconds (msec) NOTE: The QTc is the QT interval corrected for heart
             rate according to Fridericia's formula (QTcF). The specific formula that will be used
             to determine eligibility and discontinuation for an individual subject should be
             determined prior to initiation of the study. In other words, several different
             formulae cannot be used to calculate the QTc for an individual subject and then the
             lowest QTc value used to include or discontinue the subject from the trial. For
             purposes of data analysis, QTcF will be used as specified in the Reporting and
             Analysis Plan (RAP).

          -  Permitted Medications and Non-Drug Therapies: Acetaminophen, at doses of =< 2
             grams/day is permitted for use any time during the study. Other concomitant medication
             may be considered on a case by case basis by the investigator in consultation with the
             GSK Medical Monitor. All concomitant medications taken during the study will be
             recorded in the case report form. The minimum requirement is that drug name, dose
             administered and the dates of administration be recorded.

          -  Prohibited Medications and Non-Drug Therapies: Subjects must abstain from taking
             prescription or non-prescription drugs (including vitamins and dietary or herbal
             supplements), 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 until
             completion of the follow-up visit, unless in the opinion of the Investigator and
             sponsor the medication will not interfere with the study. - 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
             grams of alcohol: 12 ounces (360 milliliter [ml]) of beer, 5 ounces (150 ml) of wine
             or 1.5 ounces (45 ml) of 80 proof distilled spirits.

          -  Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or
             nicotine-containing products within 6 months prior to screening

          -  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 Medical
             Monitor, contraindicates their participation

          -  Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test
             result at screening or within 3 months prior to first dose of study treatment. For
             potent immunosuppressive agents, subjects with presence of hepatitis B core antibody
             (HBcAb) should also be excluded.

          -  A positive pre-study drug/alcohol screen.

          -  A positive test for Human Immunodeficiency Virus (HIV) antibody.

          -  Where participation in the study would result in donation of blood or blood products
             in excess of 500 mL within 56 days.

          -  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