Clinical trial NCT01797926 (phase 1, status: completed)
Conditions: hypertension
ICD codes: I15.0, I97.3, K76.6, P29.2, G93.2, H40.053, I10
Drugs: reference treatment: 5 mg amlodipine + 50 mg losartan, reference treatment:5 mg amlodipine + 100 mg losartan, fdc 5/50 amlodipine/ losartan, fdc 5/100 amlodipine /losartan
SMILES: COC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OC(C)(C)CN(C)CCC(C1=CC=CC=C1)C1=CC=CC=C1, COC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OC(C)(C)CN(C)CCC(C1=CC=CC=C1)C1=CC=CC=C1, CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=C1)C1=CC=CC=C1C1=NNN=N1, COC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OC(C)(C)CN(C)CCC(C1=CC=CC=C1)C1=CC=CC=C1
Eligibility criteria:

        Inclusion Criteria:

          -  Age & Gender: Male or female between 18 and 65 years of age inclusive, at the time of
             signing the informed consent.

          -  Body weight >= 50 kg and body mass index (BMI) within the range 18.5 to 24.9
             kilogram/meter squared.

          -  Alanine aminotransferase (ALT) alkaline phosphatase and bilirubin <or=1.5x upper limit
             of normal (ULN).

          -  Normal electrocardiogram (ECG) measurements. Average QT duration corrected for heart
             rate by Fridericia's formula (QTcF) <450 millisecond (msec) or QTcF <480 msec in
             subjects with Bundle Branch Block based on an average from three ECGs obtained over a
             brief recording period.

          -  Female subjects of non-child bearing potential. Females of child bearing potential are
             eligible to enter if they are not pregnant and willing to use protocol-specified
             methods of contraception to prevent pregnancy.

          -  Healthy as determined by a responsible and experienced physician, based on a medical
             Evaluation.

          -  Capable of giving written informed consent.

        Exclusion Criteria:

          -  The subject has a positive: drug/alcohol screen, Hepatitis, human immunodeficiency
             virus(HIV) screen

          -  Subject with systolic blood pressure less than 90 mmHg or diastolic less than 60 mm Hg
             irrespective of associated symptoms at the time of admission

          -  If there is a drop in 20 mmHg of systolic pressure (and a 10 mmHg drop in diastolic)
             and a 20 beats per minute increase in heart rate between supine measurement and after
             two minutes standing at the time of admission.

          -  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 at the time of admission.

          -  Abuse of alcohol

          -  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 GlaxoSmithKline (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.

          -  Donation of more than 500 milliliter (mL) blood within a 56 day period.

          -  Pregnant or 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.

          -  Subject having positive urinary cotinine levels indicative of use of tobacco or
             nicotine-containing products within 6 months prior to screening.

          -  Subjects who have asthma or a history of asthma including childhood asthma.

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