Clinical trial NCT01696604 (phase 1, status: completed)
Conditions: cachexia
ICD codes: R64
Drugs: gsk2849466, 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:

          -  Males between 18 and 50 years of age (inclusive), at the time of signing the informed
             consent form.

          -  Body weight >=50 kilogram (kg) and Body Mass Index (BMI) within the range 19 - 32
             kg/meter (m)^2 (inclusive), where BMI = (weight in kg)/(height in meters)^2.

          -  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 GlaxoSmithKline (GSK) Medical Monitor agree that the finding
             is unlikely to introduce additional risk factors and will not interfere with the study
             procedures.

          -  Male subjects with female partners of child-bearing potential must agree to use one of
             the contraception methods listed in the Lifestyle Section of the protocol. This
             criterion must be followed through the completion of the follow-up visit.

          -  Capable of giving written informed consent, which includes compliance with the
             requirements and restrictions listed in the consent form.

          -  Average corrected QT interval using Fridericia's formulas (QTcF) <450 milliseconds
             (msec); or QTcF <480 msec in subjects with Bundle Branch Block.

        Exclusion Criteria:

          -  Subjects with a history of clinically significant endocrine, gastrointestinal,
             hepatic, cardiovascular, neurological, hematological, immunological, renal,
             respiratory, or genitourinary abnormalities or diseases.

          -  Subjects with a history at any time in the past of coronary artery disease, congestive
             heart failure, angina, myocardial infarction, any cardiac surgery, valvular heart
             disease, clinically significant arrhythmia, dyspnea, pulmonary edema, stroke, or
             transient ischemic attack.

          -  ECG exclusion criteria: Heart rate <40 and >100 beats per minute; PR Interval <120 and
             >200 msec; QRS duration <70 and >110 msec.

          -  Subjects with a history of malignancy that is not in complete remission for at least 5
             years or 1 year for non-melanoma skin carcinoma.

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

          -  History of drug or alcohol abuse within 5 years prior to the Screening Period.

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

          -  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.

          -  Subjects with a family history of early onset prostate cancer or multiple members with
             prostate cancer.

          -  A positive pre-study drug or alcohol screen.

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

          -  Subjects with values outside the specified ranges for the following Key Clinical
             Laboratory Tests must be excluded from the study: Liver function tests - Alanine
             transaminase (ALT), Direct Bilirubin, or Albumin >10% outside the normal reference
             range (<0.9 x lower limit of normal [LLN] or >1.1 x Upper Limit of Normal [ULN]),
             Renal function - Creatinine <1.6 mg/ deciliter (dl) with an age appropriate Glomerular
             filtration rate (GFR) >=60 mL/min/1.73 m^2), Electrolytes - Sodium > +,- 5
             milliequivalents of solute per litre of solvent (mEq/L) outside the normal reference
             range, Potassium or Calcium >10% outside the normal reference range (<0.9 x LLN or
             >1.1 x ULN), Metabolic - Glucose >10% outside the normal reference range (<0.9 x LLN
             or >1.1 x ULN) and Total Cholesterol >240 mg/dl, Muscle - creatine phosphokinase >2.0
             x ULN, Hematology - Hemoglobin, WBC, Neutrophils, or Platelets >10% outside the normal
             reference range (<0.9 x LLN or >1.1 x ULN), Prostate Specific Antigen (PSA) >=2.5
             nanogram (ng)/mL.

          -  A positive test for human immunodeficiency virus (HIV) antibody.

          -  A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
             result within 3 months of screening.

          -  Exposure to more than four new chemical entities within 12 months prior to the first
             dosing day.

          -  Unable to refrain from 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 and throughout the study, unless in the opinion of
             the Investigator and GSK Medical Monitor the medication will not interfere with the
             study procedures or compromise subject safety.

          -  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: 3 months (12 weeks), 5 half-lives or twice the duration of the biological
             effect of the investigational product (whichever is longer).

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

          -  Unable to refrain from consumption of red wine, seville oranges, grapefruit or
             grapefruit juice from 7 days prior to the first dose of study medication.

          -  Unwillingness or inability to follow the procedures outlined in the protocol