A Study To Investigate The Effect Of Inhaling A Single Dose Of GW642444M In COPD Patients.

NCT00519376 | Completed Phase 2 Results

• 1 other identifier: B2C110165
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 4

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.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

pharmacodynamics,; Chronic Obstructive Pulmonary Disease (COPD); safety,; COPD patients; pharmacokinetics,; tolerability,; GW642444,

Outcome Measures

Primary Outcomes (15)

• Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) During the Treatment Period

  An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment should be exercised in deciding whether reporting is appropriate in other situations. Refer to the General Adverse AE/SAE module for a complete list of AEs and SAEs.

  From the first dose of the study medication until the Follow-up Visit (up to Study Day 60)

• 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

  Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count, and white blood cell (WBC) count at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

  Baseline and Day 1 of each treatment period (up to Study Day 54)

• Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at 24 Hours Post-dose on Day 1 of Each Treatment Period

  Blood samples were collected for the measurement of hemoglobin and MCHC at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

  Baseline and Day 1 of each treatment period (up to Study Day 54)

• Change From Baseline in Reticulocyte and Red Blood Cell (RBC) Count at 24 Hours Post-dose on Day 1 of Each Treatment Period

  Blood samples were collected for the measurement of reticulocyte and RBCs at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

  Baseline and Day 1 of each treatment period (up to Study Day 54)

• Change From Baseline in Hematocrit at 24 Hours Post-dose on Day 1 of Each Treatment Period

  Blood samples were collected for the measurement of hematocrit at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

  Baseline and Day 1 of each treatment period (up to Study Day 54)

• Change From Baseline in Mean Corpuscle Volume (MCV) at 24 Hours Post-dose on Day 1 of Each Treatment Period

  Blood samples were collected for the measurement of MCV at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

  Baseline and Day 1 of each treatment period (up to Study Day 54)

• Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Values at 24 Hours Post-dose on Day 1 of Each Treatment Period

  Blood samples were collected for the measurement of MCH at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

  Baseline and Day 1 of each treatment period (up to Study Day 54)

• 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

  Blood samples were collected for the measurement of ALT, ALP, AST, and GGT at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

  Baseline and Day 1 of each treatment period (up to Study Day 54)

• Change From Baseline in Albumin and Total Protein at 24 Hours Post-dose on Day 1 of Each Treatment Period

  Blood samples were collected for the measurement of albumin and total protein at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

  Baseline and Day 1 of each treatment period (up to Study Day 54)

• Change From Baseline in Cholesterol, Chloride, Potassium, Sodium, Triglycerides, and Urea at 24 Hours Post-dose on Day 1 of Each Treatment Period

  Blood samples were collected for the measurement of cholesterol, chloride, potassium, sodium, triglycerides, and urea at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

  Baseline and Day 1 of each treatment period (up to Study Day 54)

• Change From Baseline in Total Bilirubin and Creatinine at 24 Hours Post-dose on Day 1 of Each Treatment Period

  Blood samples were collected for the measurement of total bilirubin and creatinine at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

  Baseline and Day 1 of each treatment period (up to Study Day 54)

• Change From Baseline in C-reactive Protein at 24 Hours Post-dose on Day 1 of Each Treatment Period

  Blood samples were collected for the measurement of c-reactive protein at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

  Baseline and Day 1 of each treatment period (up to Study Day 54)

• Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over the Post-dose 24 Hour (h) Period

  SBP and DBP were measured at Baseline and over the post-dose 24 h period at the following scheduled time points: 20 minutes (M), 45 M, 1h, 2h, 3h, 4h, 6h, and 24 h. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

  Baseline and Day 1 of each treatment period (up to Study Day 54)

• Change From Baseline in Heart Rate Over the Post-dose 24 Hour (h) Period

  Heart rate (HR) was measured at Baseline and over the post-dose 24 h period at the following scheduled time points: 20 minutes (M), 45 M, 1 h, 2 h, 3 h, 4 h, 6 h, and 24 h. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

  Baseline and Day 1 of each treatment period (up to Study Day 54)

• Change From Baseline in Electrocardiographic (ECG) Parameters Over the Post-dose 24 Hour (h) Period

  ECG parameters \[PR, QRS, RR, QT (uncorrected), QTcB (QT corrected by Bazett's formula) and QTcF (QT corrected by Fridericia's formula) intervals\] were measured at Baseline and over the post-dose 24h period at the following scheduled time points: 20 minutes (min), 45 min, 1 h, 2 h, 3 h, 4 h, 6 h, and 24 h. Baseline was defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

  Baseline and Day 1 of each treatment period (up to Study Day 54)

Secondary Outcomes (8)

• Mean FEV1 Over 23 and 24 Hours After Dosing

  Baseline and Day 1 of each treatment period (up to Study Day 54)

• Weighted Mean and Maximum Value (0 - 4 Hours) QTc(B) and QTc(F)

  Baseline and Day 1 of each treatment period (up to Study Day 54)

• Weighted Mean and Maximum Value (0 - 4 Hours) Supine Heart Rate

  Baseline and Day 1 of each treatment period (up to Study Day 54)

• Weighted Mean and Maximum Value (0 - 4 Hours) of Supine Systolic and Diastolic Blood Pressure

  Baseline and Day 1 of each treatment period (up to Study Day 54)

• Weighted Mean and Maximum/Minimum Value (0 - 4 Hours) for Glucose and Potassium

  Baseline and Day 1 of each treatment period (up to Study Day 54)

Study Arms (5)

GW642444M 25mcg

EXPERIMENTAL

Drug: GW642444M; Drug: placebo

GW642444M 50mcg

EXPERIMENTAL

Drug: GW642444M

GW642444M 100mcg

EXPERIMENTAL

Drug: GW642444M; Drug: placebo

GW642444H 100mcg

EXPERIMENTAL

Drug: GW642444H; Drug: placebo

placebo

EXPERIMENTAL

Drug: placebo

Interventions

GW642444M DRUG

drug

GW642444M 100mcg; GW642444M 25mcg; GW642444M 50mcg

GW642444H DRUG

drug

GW642444H 100mcg

placebo DRUG

GW642444H 100mcg; GW642444M 100mcg; GW642444M 25mcg; placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (4)

GSK Investigational Site

Wiesbaden, Hesse, 65187, Germany

Location

GSK Investigational Site

Mainz, Rhineland-Palatinate, 55131, Germany

Location

GSK Investigational Site

Berlin, State of Berlin, 14050, Germany

Location

GSK Investigational Site

Berlin, State of Berlin, 14057, Germany

Location

Related Publications (1)

• 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.

  PMID: 23232038 BACKGROUND

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2007
• First Posted: August 22, 2007
• Study Start: August 1, 2007
• Primary Completion: November 1, 2007
• Study Completion: November 1, 2007
• Last Updated: March 23, 2017
• Results First Posted: December 30, 2013

Record last verified: 2016-12

Data Sharing

• IPD Sharing: Will share

Locations

DE (4)