Clinical trial NCT01521390 (phase 1, status: completed)
Conditions: pulmonary disease, chronic obstructive
ICD codes: J44.9, J44.1, J44.0
Drugs: gsk573719 62.5 mcg (one strip), gsk573719 62.5 mcg(two strips), gsk573719 125 mcg (one strip), gsk573719 125 mcg(two strips), placebo
SMILES: OC(C1=CC=CC=C1)(C1=CC=CC=C1)C12CC[N+](CCOCC3=CC=CC=C3)(CC1)CC2, OC(C1=CC=CC=C1)(C1=CC=CC=C1)C12CC[N+](CCOCC3=CC=CC=C3)(CC1)CC2, OC(C1=CC=CC=C1)(C1=CC=CC=C1)C12CC[N+](CCOCC3=CC=CC=C3)(CC1)CC2, OC(C1=CC=CC=C1)(C1=CC=CC=C1)C12CC[N+](CCOCC3=CC=CC=C3)(CC1)CC2, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

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

          -  Healthy male or female 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 significant abnormality or
             laboratory parameters outside the reference range for the population being studied may
             be included only if the Investigator believes that the finding is unlikely to
             introduce additional risk factors and will not interfere with the study procedures.

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

               -  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 MlU/ml and estradiol < 40 pg/ml (<147
                  pmol/L) is confirmatory]. [Females on hormone replacement therapy (HRT) and whose
                  menopausal status is in doubt will be required to use one of the contraception
                  methods in Section 8.1 if they wish to continue their HRT during the study.
                  Otherwise, they must discontinue HRT to allow confirmation of post-menopausal
                  status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will
                  elapse between the cessation of therapy and the blood draw; this interval depends
                  on the type and dosage of HRT. Following confirmation of their post-menopausal
                  status, they can resume use of HRT during the study without use of a
                  contraceptive method.]

               -  Child-bearing potential and agrees to use one of the contraception methods listed
                  in Section 8.1 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 10 days after last dose.

          -  Body weight ≥ 50 kg and BMI within the range 19.0 - 29.9 kg/m2 (inclusive).

          -  Normal spirometry (FEV1 ≥ 80% of predicted, FEV1/FVC ≥ 70%).

          -  Response to ipratropium bromide defined as

               -  an increase in sGaw of ≥25% over pre-dose baseline at 2 h following 80μg
                  ipratropium bromide; or

               -  a documented increase in sGaw of ≥25% over pre-dose baseline at 2 h following
                  inhalation of 80 μg of ipratropium bromide within 3 months of screening.

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

          -  No significant abnormality on 12-lead ECG at screening, including QTcF < 450msec.

          -  Non-smokers (never smoked or not smoking for >6 months with <10 pack years history
             (Pack years = (cigarettes per day smoked/20) x number of years smoked))

          -  Subjects who are able to use the Novel DPI satisfactorily

          -  Subjects, who are capable of giving written informed consent, have signed and dated
             the informed consent form which includes compliance with the requirements and
             restrictions listed in the consent form.

        Exclusion Criteria:

          -  A supine mean heart rate outside the range 40-90 beats per minute (BPM) at screening.

          -  A supine blood pressure that is persistently higher than 140/90 millimetres of mercury
             (mmHG) at screening.

          -  History of symptomatic arrhythmias.

          -  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 HIV antibody.

          -  History of regular alcohol consumption within 6 months of the study defined as:

             • an average weekly intake of >21 units for males or >14 units for females. One unit
             is equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of
             wine or 1 (25 ml) measure of 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.

          -  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.

          -  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.

          -  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 or urine 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.

          -  Subject who has asthma or a history of asthma or bronchoconstriction.

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

          -  Subjects who are kept due to regulatory or juridical order in an institution.

          -  Subjects who are in military service.