Clinical trial NCT00372112: A Study To Assess The Safety And Tolerability Of GW642444 In Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Official title: A 2-wk Study to Evaluate the Safety, Tolerability,Pharmacodynamics and Pharmacokinetics of GW642444H(100 Administered Once Daily in the Morning Via DISKUS™ Dry-powder Inhaler)Compared With SEREVENT(Salmeterol)(50mcg Administered Twice Daily Via DISKUS Dry-powder Inhaler)and Placebo in Subject w/COPD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: Chronic Obstructive Pulmonary Disease (COPD)
COPD
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-09-06
Enrollment: 68
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The compound GW642444 has previously been found to be well tolerated with no significant side effects in subjects with asthma and healthy volunteers. This study will assess the safety and tolerability of GW642444 in subjects with COPD in order to obtain information to support dosing in a broader population of subjects with COPD

Detailed description: A multicentre, randomised, placebo-controlled, double-blind, 4-arm parallel-group, 2-week study to evaluate the safety, tolerability, pharmacodynamics and pharmacokinetics of GW642444H (100 administered once daily in the morning via DISKUS™ dry-powder inhaler) compared with SEREVENT (salmeterol) (50mcg administered twice daily via DISKUS dry-powder inhaler) and placebo in subjects with moderate COPD.

Eligibility criteria: Inclusion criteria:

* females must be of non-childbearing potential
* moderately severe COPD

Exclusion criteria:

* Subjects with a main diagnosis of asthma
* subjects with poorly controlled COPD
* subjects with significant heart, renal, endocrine, psychiatric, immunological or neurological disease.

Primary outcomes:
measure: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
timeFrame: Up to Follow-up (17 days)
Secondary outcomes:
measure: Change From Baseline in Pre-dose Weighted Mean Heart Rate (HR) Derived From 28.5 Hour (h) Ambulatory Blood Pressure Monitoring (ABPM) at Day 7 and 14
timeFrame: Baseline (Day 1, pre-dose) up to Day 14
measure: Change From Baseline in 0-4 h Weighted Mean HR Derived From 28.5 h ABPM at Day 1, 2, 7, 8, 14 and 15
timeFrame: Baseline (Day 1, pre-dose) up to Day 15
measure: Change From Baseline in 0-24 h Weighted Mean HR Derived From 28.5 ABPM at Day 7 and 14
timeFrame: Baseline (Day 1, pre-dose) up to Day 15
measure: Change From Baseline in Maximum HR During 0-4 h Derived From 28.5 h ABPM at Day 1, 2, 7, 8, 14 and 15
timeFrame: Baseline (Day 1, pre-dose) up to Day 15
measure: Mean Weighted Mean HR at 0-4 h, Weighted Mean HR at 0-24 h and Maximum HR at 0-4 h Derived From 28.5 h ABPM
timeFrame: Day 1 up to Day 15
measure: Mean Hourly HR 0-24 h at Day 1, 7 and 14
timeFrame: Day 1 up to Day 14
measure: Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
timeFrame: Day 1 up to Day 14
measure: Change From Baseline in Weighted Mean Systolic and Diastolic Blood Pressure (SBP and DBP) Derived From 28.5 h ABPM Over Time
timeFrame: Baseline (Day 1, pre-dose) up to Day 15
measure: Change From Baseline in Maximum SBP and Minimum DBP Derived From 28.5 h ABPM Over Time
timeFrame: Baseline (Day 1, pre-dose) up to Day 15
measure: Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
timeFrame: Day 1 up to Day 15
measure: Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
timeFrame: Baseline (Day 1, pre-dose) up to Day 15
measure: Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
timeFrame: Day 1 up to Day 15
measure: Mean of Hourly Maximums QTcF and QTcB Derived From 24 h 3-lead Holter ECG Monitoring Over Time
timeFrame: Day 1 up to Day 14
measure: Number of Events of Supra Ventricular Ectopics, Ventricular Ectopics and Ventricular Runs Per 24 h Derived From 3-lead Holter ECG Monitoring Over Time
timeFrame: Day 1 up to Day 14
measure: Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
timeFrame: Baseline (Day 1) up to Day 14
measure: Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
timeFrame: Baseline (Day 1) up to Day 14
measure: Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Pre-dose, Weighted Mean FEV1 at 0-4 h and Maximum FEV1 0-4 h Over Time
timeFrame: Baseline (Day 1, pre-dose) up to Day 15
measure: Mean FEV1 Weighted Mean FEV1 at 0-4 h and Maximum FEV1 at 0-4 h Over Time
timeFrame: Day 1 up to Day 15
measure: Change From Baseline in Weighted Mean FEV1 Over 22- 24 h on Days 1, 7 and 14
timeFrame: Baseline (Day 1, pre-dose) up to Day 15
measure: Mean Morning and Evening Peak Expiratory Flow Rate (PEFR) Over Time
timeFrame: Up to Follow-up (Day 17)
measure: Mean Use of Rescue Medication Over Period
timeFrame: Up to Follow-up (Day 17)
measure: Number of Participants With Rescue Free Days
timeFrame: Up to Follow-up (Day 17)
measure: Change From Baseline in Pre-dose Fasting Glucose and Potassium at Day 7 and 14
timeFrame: Baseline (Day 1, pre-dose) up to Day 14
measure: Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
timeFrame: Baseline (Day 1, pre-dose) up to Day 15
measure: Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
timeFrame: Day 1 up to Day 15
measure: AUC of GW642444H Over 0 to 4 h (AUC [0-4]) on Day 1, 7 and 14
timeFrame: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose)
measure: Maximum Concentration (Cmax) of GW642444H at Day 1, 7 and 14
timeFrame: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose)
measure: Time to Maximum Concentration (Tmax) and Time of Last Quantifiable Concentration (Tlast) of GW642444H at Day 1, 7 and 14
timeFrame: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose)
measure: AUC (0-4) of CCI2189 at Day 1, 7 and 14
timeFrame: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose)
measure: Cmax of CCI2189 at Day 1, 7 and 14
timeFrame: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose)
measure: AUC (0-4) of GW630200 and GSK932009 at Day 1, 7 and 14
timeFrame: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose)
measure: Cmax of GW630200 and GSK932009 at Day 1, 7 and 14
timeFrame: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose)
measure: Time to Maximum Concentration (Tmax) of CCI2189, GW630200 and GSK932009 at Day 1, 7 and 14
timeFrame: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose)
measure: AUC (0-4) of Salmeterol at Day 1, 7 and 14
timeFrame: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose)
measure: Cmax of Salmeterol at Day 1, 7 and 14
timeFrame: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose)
measure: Tmax of Salmeterol at Day 1, 7 and 14
timeFrame: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose)
Other outcomes:
Locations:
city: Camperdown
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Nedlands
country: Australia
facility: GSK Investigational Site
state: Western Australia
city: Ruse
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Weinheim
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Geesthacht
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Breda
country: Netherlands
facility: GSK Investigational Site
city: Hoorn
country: Netherlands
facility: GSK Investigational Site
city: Auckland
country: New Zealand
facility: GSK Investigational Site
city: Tauranga
country: New Zealand
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Iasi
country: Romania
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: