Clinical trial NCT00519376: A Study To Investigate The Effect Of Inhaling A Single Dose Of GW642444M In COPD Patients.
Official title: A Randomised, Single-dose, Dose Ascending, Double-blind, Placebo Controlled, Four-way, Incomplete Block Crossover Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Inhaled Doses of GW642444M With Magnesium Stearate in COPD Patients.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: pharmacodynamics,
Chronic Obstructive Pulmonary Disease (COPD)
safety,
COPD patients
pharmacokinetics,
tolerability,
GW642444,
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-08-22
Enrollment: 20
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study will involve the use of a new compound, GW642444 that is being developed for the treatment of asthma and chronic obstructive pulmonary disease (COPD). It works by acting on cells in the lungs, causing some of the muscles around the lungs to relax and open up better (bronchodilation), making breathing easier. When a medicine is made into a form ready to be given to patients, the active ingredient is often prepared in the form of a salt, and inactive ingredients (excipients) are often added. Inactive ingredients might be used to help a medicine work better, to make it easier to produce the medicine, or to make it easier to get an accurate dose of medicine. In previous studies the study drug has been given as a dry powder in the form of either the 'H' salt (with the excipient lactose), or in the form of the 'M' salt (with the excipients lactose and cellobiose octaacetate). In this study the 'M' salt form of the study drug has been prepared with lactose and a new excipient called magnesium stearate (instead of cellobiose octaacetate). Participants in this study will receive both the 'H' salt (GW642444H) and the new 'M' salt (GW642444M) containing magnesium stearate. This study will be the first time the new 'M' salt form of the study drug will be given to COPD patients.


Eligibility criteria: Inclusion criteria:

* Male or female (of non-childbearing potential) \> or = 40 years
* History of COPD
* Smoker or ex-smoker
* Body weight \> or = 50 kg with BMI 18-32 kg/m2

Exclusion criteria:

* History of significant disease
* Subjects with a primary asthma diagnosis
* Alpha-1 antitrypsin deficiency as underlying cause of COPD
* Recent respiratory tract infection
* Poorly controlled COPD
* Blood potassium level \< 3.5mmol/L
* Short-term or long tern oxygen therapy
* Recent participation in another trial
* History of drug or alcohol abuse
* Known allergies
* Recent blood donation
* ECG abnormalities

Primary outcomes:
measure: Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) During the Treatment Period
timeFrame: From the first dose of the study medication until the Follow-up Visit (up to Study Day 60)
measure: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cell Count at 24 Hours Post-dose on Day 1 of Each Treatment Period
timeFrame: Baseline and Day 1 of each treatment period (up to Study Day 54)
measure: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at 24 Hours Post-dose on Day 1 of Each Treatment Period
timeFrame: Baseline and Day 1 of each treatment period (up to Study Day 54)
measure: Change From Baseline in Reticulocyte and Red Blood Cell (RBC) Count at 24 Hours Post-dose on Day 1 of Each Treatment Period
timeFrame: Baseline and Day 1 of each treatment period (up to Study Day 54)
measure: Change From Baseline in Hematocrit at 24 Hours Post-dose on Day 1 of Each Treatment Period
timeFrame: Baseline and Day 1 of each treatment period (up to Study Day 54)
measure: Change From Baseline in Mean Corpuscle Volume (MCV) at 24 Hours Post-dose on Day 1 of Each Treatment Period
timeFrame: Baseline and Day 1 of each treatment period (up to Study Day 54)
measure: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Values at 24 Hours Post-dose on Day 1 of Each Treatment Period
timeFrame: Baseline and Day 1 of each treatment period (up to Study Day 54)
measure: Change From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK) and Gamma Glutamyl Transferase (GGT) Values at 24 Hours Post-dose on Day 1 of Each Treatment Period
timeFrame: Baseline and Day 1 of each treatment period (up to Study Day 54)
measure: Change From Baseline in Albumin and Total Protein at 24 Hours Post-dose on Day 1 of Each Treatment Period
timeFrame: Baseline and Day 1 of each treatment period (up to Study Day 54)
measure: Change From Baseline in Cholesterol, Chloride, Potassium, Sodium, Triglycerides, and Urea at 24 Hours Post-dose on Day 1 of Each Treatment Period
timeFrame: Baseline and Day 1 of each treatment period (up to Study Day 54)
measure: Change From Baseline in Total Bilirubin and Creatinine at 24 Hours Post-dose on Day 1 of Each Treatment Period
timeFrame: Baseline and Day 1 of each treatment period (up to Study Day 54)
measure: Change From Baseline in C-reactive Protein at 24 Hours Post-dose on Day 1 of Each Treatment Period
timeFrame: Baseline and Day 1 of each treatment period (up to Study Day 54)
measure: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over the Post-dose 24 Hour (h) Period
timeFrame: Baseline and Day 1 of each treatment period (up to Study Day 54)
measure: Change From Baseline in Heart Rate Over the Post-dose 24 Hour (h) Period
timeFrame: Baseline and Day 1 of each treatment period (up to Study Day 54)
measure: Change From Baseline in Electrocardiographic (ECG) Parameters Over the Post-dose 24 Hour (h) Period
timeFrame: Baseline and Day 1 of each treatment period (up to Study Day 54)
Secondary outcomes:
measure: Mean FEV1 Over 23 and 24 Hours After Dosing
timeFrame: Baseline and Day 1 of each treatment period (up to Study Day 54)
measure: Weighted Mean and Maximum Value (0 - 4 Hours) QTc(B) and QTc(F)
timeFrame: Baseline and Day 1 of each treatment period (up to Study Day 54)
measure: Weighted Mean and Maximum Value (0 - 4 Hours) Supine Heart Rate
timeFrame: Baseline and Day 1 of each treatment period (up to Study Day 54)
measure: Weighted Mean and Maximum Value (0 - 4 Hours) of Supine Systolic and Diastolic Blood Pressure
timeFrame: Baseline and Day 1 of each treatment period (up to Study Day 54)
measure: Weighted Mean and Maximum/Minimum Value (0 - 4 Hours) for Glucose and Potassium
timeFrame: Baseline and Day 1 of each treatment period (up to Study Day 54)
measure: AUC(0- t) and up to 1 Hour Post-dose (AUC[0-1]) of GW642444 and Its Metabolites GI179710, GW630200, and GSK932009, After a Single Dose of GW642444
timeFrame: Baseline and Day 1 of each treatment period (up to Study Day 54)
measure: Cmax of GW642444 and Its Metabolites GI179710, GW630200, and GSK932009, After a Single Dose of GW642444
timeFrame: Day 1 of each treatment period (up to Study Day 54)
measure: Tmax of GW642444 and Its Metabolites GI179710, GW630200, and GSK932009, After a Single Dose of GW642444
timeFrame: Day 1 of each treatment period (up to Study Day 54)
Other outcomes:
Locations:
city: Wiesbaden
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Mainz
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Kempsford R, Norris V, Siederer S. Vilanterol trifenatate, a novel inhaled long-acting beta2 adrenoceptor agonist, is well tolerated in healthy subjects and demonstrates prolonged bronchodilation in subjects with asthma and COPD. Pulm Pharmacol Ther. 2013 Apr;26(2):256-64. doi: 10.1016/j.pupt.2012.12.001. Epub 2012 Dec 8.