Assessment of Lung Function After Single Inhalations of a Bronchodilator From 2 Configurations a Dry Powder Inhaler.

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT01521390
• Date of registration: 26/01/2012
• Primary sponsor: GlaxoSmithKline
• Public title: Assessment of Lung Function After Single Inhalations of a Bronchodilator From 2 Configurations a Dry Powder Inhaler.
• Scientific title: Randomized, Double-blind, 5 Period Cross Over Study Assessing Lung Function in Healthy Volunteers Following Single Inhalations of GSK573719 Inhalation Powder From Two Configurations of the Novel Dry Powder Inhaler
• Date of first enrolment: October 2011
• Target sample size: 15
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT01521390
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor)

Countries of recruitment

Germany

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 65 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Pulmonary Disease, Chronic Obstructive

Intervention(s)

Drug: GSK573719 125 mcg (one strip)

Drug: GSK573719 125 mcg(two strips)

Drug: GSK573719 62.5 mcg (one strip)

Drug: GSK573719 62.5 mcg(two strips)

Drug: Placebo

Primary Outcome(s)

Weighted mean and maximal change from baseline in sGaw [Time Frame: serial over 24 hr for each treatment period]

Secondary Outcome(s)

Blood pressure [Time Frame: over 24 hr for each treatment period]

Clinical lab safety tests [Time Frame: Over 24 hrs for each treatment period]

ECG [Time Frame: over 24 hrs for each treatment period]

Heart Rate [Time Frame: over 24 hr for each treatment period]

Plasma concentration of GSK573714 [Time Frame: over 24 hrs for each treatment period]

Serial FEV1 [Time Frame: over 24 hr]

Serial sGaw [Time Frame: over 24 hr for each treatment period]

Urine concentration of GSK573714 [Time Frame: over 24 hr for each treatment period]

Secondary ID(s)

115487

Source(s) of Monetary Support

Please refer to primary and secondary sponsors