Clinical trial NCT01245426 (phase 2, status: completed)
Conditions: asthma
ICD codes: J45.998, J82.83, J45.909, J45.991, J45.20, J45.30, J45.40
Drugs: gw870086 2mg, gw870086 4mg, gw870086 placebo, gw870086 1mg, gw870086 3mg
SMILES: C[C@@H]1C[C@H]2[C@@H]3C[C@H](F)C4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@]2(C)[C@@]1(OC(=O)C1C(C)(C)C1(C)C)C(=O)OCC#N, C[C@@H]1C[C@H]2[C@@H]3C[C@H](F)C4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@]2(C)[C@@]1(OC(=O)C1C(C)(C)C1(C)C)C(=O)OCC#N, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, C[C@@H]1C[C@H]2[C@@H]3C[C@H](F)C4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@]2(C)[C@@]1(OC(=O)C1C(C)(C)C1(C)C)C(=O)OCC#N, C[C@@H]1C[C@H]2[C@@H]3C[C@H](F)C4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@]2(C)[C@@]1(OC(=O)C1C(C)(C)C1(C)C)C(=O)OCC#N
Eligibility criteria:

        Inclusion Criteria:

          -  Male or female between 18 and 65 years

          -  A female subject is eligible to participate if she is of: Non-childbearing potential.
             Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt
             will be required to discontinue HRT to allow confirmation of post-menopausal status
             prior to study enrollment.

          -  Male subjects must agree to use one of the protocol contraception methods.

          -  Body weight, men ≥ 50 kg, women ≥ 45 kg and BMI within the range 18.5 - 29.0 kg/m2
             (inclusive).

          -  Documented history of bronchial asthma, first diagnosed at least 6 months prior to the
             screening visit and currently being treated only with intermittent short-acting beta-2
             agonist therapy

          -  Severity of Disease: A best FEV1 of 60%-85% of the predicted normal value during the
             Visit 1 screening period.

          -  No history of smoking within 6 months of the start of the study and with a total pack
             year history of ≤10 pack years

          -  Capable of giving written informed consent

          -  Single QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch
             Block.

          -  AST and ALT < 2xULN; alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin
             >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

        Exclusion Criteria:

          -  A positive test for Hepatitis B or Hepatitis C antibody.

          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities

          -  The subject has a positive pre-study drug/alcohol screen unless a positive can be
             explained by the patients' medication.

          -  Past or present disease, which as judged by the investigator, may affect the outcome
             of this study.

          -  Clinically significant abnormalities in safety laboratory analysis at screening, as
             determined by the investigator.

          -  Subject is hypertensive at screening.

          -  History of life-threatening asthma, defined as an asthma episode that required
             intubation and/or was associated with hypercapnoea, respiratory arrest and/or hypoxic
             seizures.

          -  Administration of oral, injectable or dermal steroids within 8 weeks of screening.

          -  Exacerbation of asthma within 4 weeks prior to the first dose of study medication.

          -  Respiratory Infection that is not resolved within the 4 weeks before screening and led
             to a change in asthma management, or in the opinion of the Investigator is expected to
             affect the subjects asthma status or the subjects ability to participate in the study.

          -  Any asthma exacerbation requiring oral corticosteroids within 8 weeks of screening. A
             subject must not have had any hospitalisation for asthma within 6 months prior to
             screening

          -  A positive test for HIV antibody.

          -  History of regular alcohol consumption within 6 months of the study.

          -  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.

          -  Use of prescription or non-prescription drugs 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. Paracetamol is an exception and will be permitted at daily doses of up
             to 4 g from screening to follow-up.

          -  Has taken Xanthines (including theophylline, but not including caffeine),
             anticholinergics, cromoglycates and/or long-acting beta-2 agonists within 1 week prior
             to screening and is unable to abstain from them throughout the study.

          -  Unable to abstain from other medications other than short acting inhaled beta-2
             agonists and paracetamol (up to 4 g per day) 7 days before screening until the
             follow-up visit.

          -  Unable to abstain from medication or supplements that significantly inhibit the
             cytochrome P450 subfamily enzyme CYP3A4, from screening and throughout the study.

          -  Unable to use the DISKHALER® device correctly.

          -  History of sensitivity to any of the study medications.

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

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

          -  The subject is not able to understand or comply with protocol requirements,
             instructions and protocol stated restrictions.

          -  Vulnerable subjects.

          -  Subject is mentally or legally incapacitated.

          -  Urinary cotinine levels indicative of smoking or history within 6 months prior to
             screening.

          -  Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or
             pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior
             to the first dose of study medication.