Trial Outcomes & Findings for Safety and Tolerability of Repeat Dosing of GSK233705/GW642444 in COPD (NCT NCT00749411)

Last Updated: 2020-09-01

Results Overview

Baseline was the most recent result taken on or before pre-dose (Day 1). The analysis was performed using a Repeated Measures Model. This model used all available weighted mean pulse rate values recorded. Change from Baseline was calculated as (Change from Baseline = Assessment value - Baseline value).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

61 participants

Primary outcome timeframe

Baseline (Pre-dose, Day 1) and Day 28

Results posted on

2020-09-01

Participant Flow

This study was conducted between 13 November 2008 and 12 February 2009, at 12 centers in the United States.

A total of 127 participants were screened out of which 61 participants were enrolled and randomized to receive at least one dose of study medication in the study.

Participant milestones

Participant milestones
Measure	Placebo Eligible participants received oral inhalation of matching Placebo via dry powder inhaler (DPI) once daily for 28 days.	GSK233705/GW642444 Eligible participants received oral inhalation of GSK233705 100 microgram (mcg)/GW642444 25 mcg via DPI once daily for 28 days.
Overall Study STARTED	21	40
Overall Study COMPLETED	20	35
Overall Study NOT COMPLETED	1	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Eligible participants received oral inhalation of matching Placebo via dry powder inhaler (DPI) once daily for 28 days.	GSK233705/GW642444 Eligible participants received oral inhalation of GSK233705 100 microgram (mcg)/GW642444 25 mcg via DPI once daily for 28 days.
Overall Study Adverse Event	0	2
Overall Study Lack of Efficacy	0	1
Overall Study Protocol Violation	1	1
Overall Study Protocol-defined stopping criteria	0	1

Baseline Characteristics

Safety and Tolerability of Repeat Dosing of GSK233705/GW642444 in COPD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=21 Participants Eligible participants received oral inhalation of matching Placebo via DPI once daily for 28 days.	GSK233705/GW642444 n=40 Participants Eligible participants received oral inhalation of GSK233705 100 mcg / GW642444 25 mcg via DPI once daily for 28 days.	Total n=61 Participants Total of all reporting groups
Age, Continuous	60.7 Years STANDARD_DEVIATION 10.09 • n=5 Participants	61.2 Years STANDARD_DEVIATION 9.55 • n=7 Participants	61.0 Years STANDARD_DEVIATION 9.66 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	29 Participants n=7 Participants	40 Participants n=5 Participants
Race/Ethnicity, Customized African American / African Heritage	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	20 Participants n=5 Participants	38 Participants n=7 Participants	58 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Pre-dose, Day 1) and Day 28

Population: Intent-to-Treat (ITT) Population comprised of all participants who were randomized to study treatment and took at least one dose of study medication. Only those participants available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Eligible participants received oral inhalation of matching Placebo via DPI once daily for 28 days.	GSK233705/GW642444 n=35 Participants Eligible participants received oral inhalation of GSK233705 100 mcg / GW642444 25 mcg via DPI once daily for 28 days.
Change From Baseline in Weighted Mean Pulse Rate Over (0-4 Hours) at Day 28.	-3.8 Beat per minute (bpm) Standard Error 1.78	-4.8 Beat per minute (bpm) Standard Error 1.32

SECONDARY outcome

Timeframe: On-treatment; from treatment start until one day after treatment stop (Up to Day 29)

Population: ITT Population.

AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Eligible participants received oral inhalation of matching Placebo via DPI once daily for 28 days.	GSK233705/GW642444 n=40 Participants Eligible participants received oral inhalation of GSK233705 100 mcg / GW642444 25 mcg via DPI once daily for 28 days.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AE	8 Participants	10 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any SAE	0 Participants	0 Participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

GSK233705/GW642444

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=21 participants at risk Eligible participants received oral inhalation of matching Placebo via DPI once daily for 28 days.	GSK233705/GW642444 n=40 participants at risk Eligible participants received oral inhalation of GSK233705 100 mcg / GW642444 25 mcg via DPI once daily for 28 days.
Infections and infestations Gastroenteritis	0.00% 0/21 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.	2.5% 1/40 • Number of events 1 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.
Infections and infestations Influenza	4.8% 1/21 • Number of events 1 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.	0.00% 0/40 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.
Infections and infestations Sinusitis	4.8% 1/21 • Number of events 1 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.	0.00% 0/40 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.
Infections and infestations Upper respiratory tract infection	0.00% 0/21 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.	2.5% 1/40 • Number of events 1 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.
Infections and infestations Viral infection	0.00% 0/21 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.	2.5% 1/40 • Number of events 1 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.
Respiratory, thoracic and mediastinal disorders Dry throat	0.00% 0/21 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.	5.0% 2/40 • Number of events 2 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.
Respiratory, thoracic and mediastinal disorders Cough	4.8% 1/21 • Number of events 1 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.	0.00% 0/40 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.
Respiratory, thoracic and mediastinal disorders Postnasal drip	4.8% 1/21 • Number of events 1 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.	0.00% 0/40 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.
Respiratory, thoracic and mediastinal disorders Productive cough	4.8% 1/21 • Number of events 1 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.	0.00% 0/40 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.
Nervous system disorders Dysgeusia	4.8% 1/21 • Number of events 1 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.	5.0% 2/40 • Number of events 2 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.
Gastrointestinal disorders Diarrhoea	4.8% 1/21 • Number of events 1 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.	2.5% 1/40 • Number of events 1 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.
Gastrointestinal disorders Dry mouth	0.00% 0/21 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.	2.5% 1/40 • Number of events 1 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.
General disorders Chest pain	4.8% 1/21 • Number of events 1 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.	0.00% 0/40 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.
General disorders Oedema peripheral	4.8% 1/21 • Number of events 1 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.	0.00% 0/40 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.
Injury, poisoning and procedural complications Joint sprain	4.8% 1/21 • Number of events 1 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.	0.00% 0/40 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.
Injury, poisoning and procedural complications Muscle injury	0.00% 0/21 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.	2.5% 1/40 • Number of events 1 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.
Investigations Blood glucose increased	4.8% 1/21 • Number of events 1 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.	0.00% 0/40 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.
Investigations Gamma-glutamyltransferase increased	0.00% 0/21 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.	2.5% 1/40 • Number of events 1 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/21 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.	2.5% 1/40 • Number of events 1 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.
Musculoskeletal and connective tissue disorders Joint stiffness	0.00% 0/21 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.	2.5% 1/40 • Number of events 1 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/21 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.	2.5% 1/40 • Number of events 1 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.
Vascular disorders Venous thrombosis limb	0.00% 0/21 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.	2.5% 1/40 • Number of events 1 • On-treatment; from treatment start until one day after treatment stop (Up to Day 29) Intent to treat population was used to collect the AEs. There were no on-treatment SAEs reported in the study. Only on-treatment SAEs and nSAEs are presented.