Pulmonary Disease, Chronic ObstructivePhase 2NCT00453479

A Dose Ascending, Study To Examine The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of GSK233705B.

A Phase 2 study testing GSK233705B in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 4 sites in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

GSK233705 is a high-affinity specific muscarinic receptor (mAChR) antagonist which is being developed for the treatment of chronic obstructive pulmonary disease. This is a randomised, double-blind, placebo-controlled, dose ascending, parallel group study to examine the safety, tolerability, pharmacokinetics and… Read more about this study

Who is it for?: Ages 40 to 75 years
Conditions the study is for: Pulmonary Disease, Chronic Obstructive
What is being tested?: GSK233705B
How many people: 23 participants
Where: 4 sitesNetherlands
Study dates: 28 Mar 2007to 11 Oct 2007
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Men or women who are between 40 and 75 years of age
Female subjects must be of non-childbearing
Subject diagnosed with COPD
Body Mass Index 18.0 - 32.0 kg/m2 (inclusive)
Subject is a smoker or an ex-smoker
Subject has post-bronchodilator (200µg salbutamol) FEV1 of = 40% to = 80% of predicted normal.

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Subject has FEV1/FVC < 0.7 post-bronchodilator (200µg salbutamol).
Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Subject is available to complete all study measurements and procedures.
Subjects have a 24hour holter recording that is within normal limits and does not demonstrate any clinically important abnormality that, in the opinion of the investigator, would make the subject unsuitable for participation in the study.

Who cannot join

Subjects who have a past or present disease, which as judged by the Investigator and the Medical Monitor, may affect the outcome of this study.
The subject has a positive pre-study alcohol screen.
The subject has a positive pre-study drug screen.
History of alcohol/drug abuse or dependence within 12 months of the study: Abuse
The subject has a positive pregnancy test.
A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening

Show all 13Show fewer

Subject has tested positive for HIV
The subject has participated in a clinical trial and has received a drug or a new chemical entity within 60 days or 5 half-lives
Exposure to more than three new chemical entities (NCE) within 10 months prior to the first dosing day or one NCE within 3 months prior to the first dosing day.
The subject has donated a unit (400ml) of blood within 60 days of screening, or, intends to donate during the study.
The subject has a known allergy or hypersensitivity to ipratropium bromide, atropine and any of its derivatives or milk protein/lactose.
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 physician responsible, contraindicates their participation
Subject has prostate hypertrophy or narrow angle glaucoma

Trial locations and contacts

4 sites in 1 country.

Netherlands4 sites

GSK Investigational Site
Eindhoven, 5623 EJ
GSK Investigational Site
Harderwijk, 3844 DG
GSK Investigational Site
Utrecht, 3584 CJ
GSK Investigational Site
Zuidlaren, 9471 GP

Other trials in Netherlands

About this study

Official title: A Randomised, Double-blind, Placebo-controlled, Dose Ascending, 2-cohort, Parallel Group Study to Examine the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Twice-daily Inhaled Doses of GSK233705B Formulated With the Excipient Magnesium Stearate in COPD Subjects for 7-days.

Conditions: Pulmonary Disease, Chronic Obstructive
Being tested: GSK233705B
Keywords: muscarinic receptor,, bronchodilators, Chronic obstructive pulmonary disease,
Medical subject headings: Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GSK233705BDrug

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.
Measured: Up to follow-up (approximately 45 days)
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Blood pressure was measured subsequent to 12 lead electrocardiogram (ECG). Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on Baseline (triplicate), 15, 30 minutes, 1.5, 4, 8 and 24 hours on Day 1 and 7.
Measured: Up to Day 7 (24 hours post-dose)
Summary of Mean Heart Rate
Heart rate was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on Baseline (triplicate), 15, 30 minutes, 1.5, 4, 8 and 24 hours on Day 1 and 7.
Measured: Up to Day 7 (24 hour post dose)
Maximum Value of SBP and DBP (0-4 Hour) for the Morning Dose
Blood pressure was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean.
Measured: Up to Day 7 (0-4 hour)
Maximum Value of Heart Rate (0-4 Hour) for the Morning Dose
Heart rate was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean.
Measured: Up to Day 7 (0-4 hour)
Weighted Mean of SBP and DBP (0-4 Hour) for the Morning Dose
Blood pressure was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean.
Measured: Up to Day 7 (0-4 hour)
Weighted Mean of Heart Rate (0-4 Hour) for the Morning Dose
Heart rate was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean.
Measured: Up to Day 7 (0-4 hour)
Number of Participants With Abnormal 12-lead ECG Findings
Single measurements were taken at all time points. The pre-dose values were classed as Baseline. Data for number of participants with normal, abnormal not clinically significant and abnormal clinically significant is presented. It was assessed on Baseline (triplicate), 15, 30 minutes, 1.5, 4, 8 and 24 hours on Day 1 and 7.
Measured: Up to Day 7 (24 hour post dose)
Maximum Value (0-4 Hour) for the Morning Dose of ECG Parameters Corrected According to Fredericia's Formula (QTcF) and Corrected According to Bazett's Formula (QTc B)
Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean.
Measured: Up to Day 7 (0-4 hour)
Weighted Mean (0-4 h) for the Morning Dose of ECG Parameters QTcF and QTc B
Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean.
Measured: Up to Day 7 (0-4 hour)
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC)
It was assessed on 1, 2, 4, 9, 12 and 24 hours on Days 1 and 7. Also on Day 7, it was measured on 0 hour (Baseline). At all time points 3 measurements were taken and formal statistical analysis was carried out on the derived maximum readings. Data for adjusted mean is presented as least square mean.
Measured: Up to Day 7 (24-hour post dose)
Number of Participants Who Used Rescue Medication
Inhaled salbutamol was used as a rescue medication. Participants were required to keep a diary of their rescue medication (total number of salbutamol doses taken) over the entire 7-day treatment period. Diaries were reviewed by the Investigator when participants were admitted to the unit on Days 1, 2, 7 and 8.
Measured: Up to Day 7
Number of Participants With Abnormalities in Chemistry Data of Clinical Concern
Clinical chemistry parameters included urea, potassium, aspartate aminotransferase (AST), total bilirubin, creatinine, creatine kinase, chloride, alanine aminotransferase (ALT), uric acid, glucose, gamma glutamyltransferase (GGT), albumin, sodium, phosphorus inorganic, calcium, alkaline phosphatase (ALP) and total protein. It was assessed on Day 1 (pre-dose, 24 hours) and Day 7 (pre-dose, 24 hours). Data for parameters with above and below the potential clinical concern (PCI) is provided.
Measured: Up to Day 7
Number of Participants With Abnormalities in Hematology Data of Clinical Concern
Hematology parameters included platelet count, red blood cell (RBC) count, mean corpuscular volume (MCV), total neutrophils, white blood cell (WBC) count (absolute), mean corpuscular hemoglobin (MCH), lymphocytes, mean corpuscular hemoglobin concentration (MCHC), monocytes, hemoglobin, eosinophils, hematocrit and basophils. It was assessed on Day 1 (pre-dose, 24 hours) and Day 7 (pre-dose, 24 hours). Data for parameters with above and below the PCI is provided.
Measured: Up to Day 7
Summary of Microscopy Data for Participants With Abnormal Urinalysis Dipstick Results
Urinalysis parameters included protein, blood, ketones, glucose, bilirubin, urobilinogen, leukocyte esterase, specific gravity, nitrites and pH. Sediment microscopy was performed only on urine samples showing an abnormality on the dipstick. Microscopy was performed for: WBC, RBC, hyaline casts, granular casts and cellular casts. It was assessed on Day 1 (pre-dose, 24 hours) and Day 7 (pre-dose, 24 hours).
Measured: Up to Day 7 (pre dose)
Summary of Mean (0-24 Hour) and Maximum (0-24 Hour) Heart Rate Measured Using 24 Hour Using Holter ECG Data
Holter monitors were switched on immediately prior to dosing (up to 15mins pre-dose) so as to capture Holter ECG data from the 24 hour period following dosing. It was assessed on Day 1 and 7.
Measured: Up to Day 7

Secondary outcomes (9)

Plasma Concentrations of GSK233705
Blood samples were collected at indicated time points. 12 hour pharmacokinetic (PK) sampling was before evening dose.
Measured: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose
Urine Concentrations of GSK233705
Urine GSK233705 pharmacokinetic excretion rate-time data is presented. Urine samples were collected throughout study and consolidated data is presented as 0-12 hours and 12-24 hours. 12 hour pharmacokinetic sampling was before evening dose.
Measured: Day 1 and 7 throughout 24 hours
Derived Plasma PK Parameters-area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC0-tau)
Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning samples.
Measured: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose
Derived Plasma PK Parameters-area Under Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-t)
Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning sample as adjusted geometric mean.
Measured: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose
Derived PK Plasma Parameters-area Under Concentration-maximum Observed Plasma Concentration (Cmax)
Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning and evening samples as adjusted geometric mean.
Measured: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose
Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last)
Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning and evening samples.
Measured: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose
Derived Urine Pharmacokinetic (PK) Parameters-area Under the Plasma Concentration-amount of Drug Excreted Unchanged in Urine (Ae)
Urine GSK233705 pharmacokinetic excretion rate-time data is presented. Urine samples were collected throughout study and consolidated data presented as AM dose and PM dose. 12 hour pharmacokinetic sampling was before evening dose.
Measured: Day 1 and 7 throughout 24 hours
Derived Urine PK Parameters-area Under Concentration-fraction of Dose Excreted Unchanged in Urine (Fe)
Urine GSK233705 pharmacokinetic excretion rate-time data is presented. Urine samples were collected throughout study and consolidated data presented as 0-12 hours and 12-24 hours. 12 hour pharmacokinetic sampling was before evening dose.
Measured: Day 1 and 7 throughout 24 hours
Derived Urine PK Parameters-area Under Concentration-renal Clearance (Clr)
Urine GSK233705 pharmacokinetic excretion rate-time data is presented. Urine samples were collected throughout study. 12 hour pharmacokinetic sampling was before evening dose.
Measured: Day 1 and 7 throughout 24 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Mar 200711 Oct 2007

First posted29 Mar 2007 (estimated)
Study start28 Mar 2007
Primary completion11 Oct 2007
Study completion11 Oct 2007

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Parallel groups
Enrolment: 23 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00453479
Sponsor's protocol ID: AC2108378
Status last verified: Jul 2017
First submitted: 27 Mar 2007
Last updated: 12 Mar 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Publications

This study has not been published in the scientific literature.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Pulmonary Disease, Chronic Obstructive trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomised, Double-blind, Placebo-controlled, Dose Ascending, 2-cohort, Parallel Group Study to Examine the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Twice-daily Inhaled Doses of GSK233705B Formulated With the Excipient Magnesium Stearate in COPD Subjects for 7-days.
ClinicalTrials.gov ID: NCT00453479
Acronym / sponsor ID: AC2108378
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: muscarinic receptor,, bronchodilators, Chronic obstructive pulmonary disease,
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 23 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 28 Mar 2007 (actual)
Primary completion: 11 Oct 2007 (actual)
Study completion: 11 Oct 2007 (actual)
First posted: 29 Mar 2007 (estimated)
Results: Posted 8 Feb 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Parallel groups

Who may qualify

Ages: 40 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

Men or women who are between 40 and 75 years of age
Female subjects must be of non-childbearing
Subject diagnosed with COPD
Body Mass Index 18.0 - 32.0 kg/m2 (inclusive)
Subject is a smoker or an ex-smoker

Key exclusion criteria (13 listed)

Subjects who have a past or present disease, which as judged by the Investigator and the Medical Monitor, may affect the outcome of this study.
The subject has a positive pre-study alcohol screen.
The subject has a positive pre-study drug screen.
History of alcohol/drug abuse or dependence within 12 months of the study: Abuse
The subject has a positive pregnancy test.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GSK233705B	Drug	–

Primary outcome

Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Time frame: Up to follow-up (approximately 45 days)
An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Time frame: Up to Day 7 (24 hours post-dose)
Blood pressure was measured subsequent to 12 lead electrocardiogram (ECG). Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on Baseline (triplicate), 15, 30 minutes, 1.5, 4, 8 and 24 hours on Day 1 and 7.
Summary of Mean Heart Rate
Time frame: Up to Day 7 (24 hour post dose)
Heart rate was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on Baseline (triplicate), 15, 30 minutes, 1.5, 4, 8 and 24 hours on Day 1 and 7.
Maximum Value of SBP and DBP (0-4 Hour) for the Morning Dose
Time frame: Up to Day 7 (0-4 hour)
Blood pressure was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean.
Maximum Value of Heart Rate (0-4 Hour) for the Morning Dose
Time frame: Up to Day 7 (0-4 hour)
Heart rate was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean.
Weighted Mean of SBP and DBP (0-4 Hour) for the Morning Dose
Time frame: Up to Day 7 (0-4 hour)
Blood pressure was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean.
Weighted Mean of Heart Rate (0-4 Hour) for the Morning Dose
Time frame: Up to Day 7 (0-4 hour)
Heart rate was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean.
Number of Participants With Abnormal 12-lead ECG Findings
Time frame: Up to Day 7 (24 hour post dose)
Single measurements were taken at all time points. The pre-dose values were classed as Baseline. Data for number of participants with normal, abnormal not clinically significant and abnormal clinically significant is presented. It was assessed on Baseline (triplicate), 15, 30 minutes, 1.5, 4, 8 and 24 hours on Day 1 and 7.
Maximum Value (0-4 Hour) for the Morning Dose of ECG Parameters Corrected According to Fredericia's Formula (QTcF) and Corrected According to Bazett's Formula (QTc B)
Time frame: Up to Day 7 (0-4 hour)
Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean.
Weighted Mean (0-4 h) for the Morning Dose of ECG Parameters QTcF and QTc B
Time frame: Up to Day 7 (0-4 hour)
Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean.
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC)
Time frame: Up to Day 7 (24-hour post dose)
It was assessed on 1, 2, 4, 9, 12 and 24 hours on Days 1 and 7. Also on Day 7, it was measured on 0 hour (Baseline). At all time points 3 measurements were taken and formal statistical analysis was carried out on the derived maximum readings. Data for adjusted mean is presented as least square mean.
Number of Participants Who Used Rescue Medication
Time frame: Up to Day 7
Inhaled salbutamol was used as a rescue medication. Participants were required to keep a diary of their rescue medication (total number of salbutamol doses taken) over the entire 7-day treatment period. Diaries were reviewed by the Investigator when participants were admitted to the unit on Days 1, 2, 7 and 8.
Number of Participants With Abnormalities in Chemistry Data of Clinical Concern
Time frame: Up to Day 7
Clinical chemistry parameters included urea, potassium, aspartate aminotransferase (AST), total bilirubin, creatinine, creatine kinase, chloride, alanine aminotransferase (ALT), uric acid, glucose, gamma glutamyltransferase (GGT), albumin, sodium, phosphorus inorganic, calcium, alkaline phosphatase (ALP) and total protein. It was assessed on Day 1 (pre-dose, 24 hours) and Day 7 (pre-dose, 24 hours). Data for parameters with above and below the potential clinical concern (PCI) is provided.
Number of Participants With Abnormalities in Hematology Data of Clinical Concern
Time frame: Up to Day 7
Hematology parameters included platelet count, red blood cell (RBC) count, mean corpuscular volume (MCV), total neutrophils, white blood cell (WBC) count (absolute), mean corpuscular hemoglobin (MCH), lymphocytes, mean corpuscular hemoglobin concentration (MCHC), monocytes, hemoglobin, eosinophils, hematocrit and basophils. It was assessed on Day 1 (pre-dose, 24 hours) and Day 7 (pre-dose, 24 hours). Data for parameters with above and below the PCI is provided.
Summary of Microscopy Data for Participants With Abnormal Urinalysis Dipstick Results
Time frame: Up to Day 7 (pre dose)
Urinalysis parameters included protein, blood, ketones, glucose, bilirubin, urobilinogen, leukocyte esterase, specific gravity, nitrites and pH. Sediment microscopy was performed only on urine samples showing an abnormality on the dipstick. Microscopy was performed for: WBC, RBC, hyaline casts, granular casts and cellular casts. It was assessed on Day 1 (pre-dose, 24 hours) and Day 7 (pre-dose, 24 hours).
Summary of Mean (0-24 Hour) and Maximum (0-24 Hour) Heart Rate Measured Using 24 Hour Using Holter ECG Data
Time frame: Up to Day 7
Holter monitors were switched on immediately prior to dosing (up to 15mins pre-dose) so as to capture Holter ECG data from the 24 hour period following dosing. It was assessed on Day 1 and 7.

9 secondary outcomes

Plasma Concentrations of GSK233705
Time frame: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose
Urine Concentrations of GSK233705
Time frame: Day 1 and 7 throughout 24 hours
Derived Plasma PK Parameters-area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC0-tau)
Time frame: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose
Derived Plasma PK Parameters-area Under Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-t)
Time frame: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose
Derived PK Plasma Parameters-area Under Concentration-maximum Observed Plasma Concentration (Cmax)
Time frame: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose
Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last)
Time frame: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose
Derived Urine Pharmacokinetic (PK) Parameters-area Under the Plasma Concentration-amount of Drug Excreted Unchanged in Urine (Ae)
Time frame: Day 1 and 7 throughout 24 hours
Derived Urine PK Parameters-area Under Concentration-fraction of Dose Excreted Unchanged in Urine (Fe)
Time frame: Day 1 and 7 throughout 24 hours
Derived Urine PK Parameters-area Under Concentration-renal Clearance (Clr)
Time frame: Day 1 and 7 throughout 24 hours

Results and safety

Results posted to the registry on 8 Feb 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	6	6
GSK233705 50 µg Twice Daily	9	9
GSK233705 100 µg Twice Daily	8	8

Primary outcome: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)

Time frame: Up to follow-up (approximately 45 days). Count of participants. Unit: Participants

Measure	Placebo n = 6	GSK233705 50 µg Twice Daily n = 9	GSK233705 100 µg Twice Daily n = 8
Any AE	4	4	4
Any SAE	0	0	0

Population analysed: All subject population included all available data on participants who had received at least one dose of study medication (including placebo).

Primary outcome: Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Time frame: Up to Day 7 (24 hours post-dose). Mean (Standard Deviation). Unit: Millimeters of mercury

Measure	Placebo n = 6	GSK233705 50 µg Twice Daily n = 9	GSK233705 100 µg Twice Daily n = 8
SBP, Day 1, Baseline	129.2 (15.37)	127.7 (9.03)	129.6 (11.78)
SBP, Day 1, 15 minutes	130.0 (12.84)	130.0 (8.99)	130.6 (16.04)
SBP, Day 1, 30 minutes	126.0 (14.24)	123.7 (10.85)	128.4 (9.32)
SBP, Day 1, 1.5 hour	131.2 (16.17)	124.1 (13.01)	133.5 (18.47)
SBP, Day 1, 4 hour	126.2 (17.52)	124.8 (9.90)	132.1 (12.96)
SBP, Day 1, 8 hour	132.8 (14.26)	121.1 (9.44)	124.0 (13.03)
SBP, Day 1, 24 hour	131.5 (13.49)	123.1 (7.64)	129.6 (16.10)
SBP, Day 7, Baseline	124.6 (15.25)	122.7 (11.94)	123.9 (9.21)

Population analysed: All subject population was used.

Primary outcome: Summary of Mean Heart Rate

Time frame: Up to Day 7 (24 hour post dose). Mean (Standard Deviation). Unit: Beats per minute

Measure	Placebo n = 6	GSK233705 50 µg Twice Daily n = 9	GSK233705 100 µg Twice Daily n = 8
Day 1, Baseline	65.7 (7.07)	66.7 (9.68)	71.5 (8.50)
Day 1, 15 minutes	62.2 (8.06)	65.1 (8.07)	70.4 (10.57)
Day 1, 30 minutes	61.2 (5.78)	64.9 (8.57)	66.6 (7.42)
Day 1, 1.5 hour	64.7 (9.52)	62.7 (9.63)	64.9 (6.29)
Day 1, 4 hour	63.2 (6.31)	66.6 (14.57)	64.0 (8.37)
Day 1, 8 hour	65.7 (5.75)	68.1 (11.12)	66.9 (6.01)
Day 1, 24 hour	62.3 (10.25)	68.1 (13.13)	65.5 (8.45)
Day 7, Baseline	63.6 (4.62)	67.0 (8.20)	67.8 (8.30)

Population analysed: All subject population was used.

Primary outcome: Maximum Value of SBP and DBP (0-4 Hour) for the Morning Dose

Time frame: Up to Day 7 (0-4 hour). Least squares mean (95% Confidence Interval). Unit: Millimeters of mercury

Measure	Placebo n = 6	GSK233705 50 µg Twice Daily n = 9	GSK233705 100 µg Twice Daily n = 8
SBP, Day 1	132.52 (123.46 to 141.58)	131.56 (124.15 to 138.97)	138.73 (130.88 to 146.59)
SBP, Day 7	132.43 (125.61 to 139.26)	128.33 (122.75 to 133.92)	127.67 (121.76 to 133.59)
DBP, Day 1	81.21 (77.72 to 84.71)	81.80 (79.00 to 84.60)	82.19 (79.17 to 85.22)
DBP, Day 7	86.14 (82.24 to 90.03)	79.50 (76.38 to 82.62)	75.33 (71.96 to 78.70)

Placebo vs GSK233705 50 µg Twice Daily: Mean Difference (Net): -0.97 (95% CI -12.68 to 10.75)
Placebo vs GSK233705 50 µg Twice Daily: Mean Difference (Net): -4.10 (95% CI -12.92 to 4.72)
Placebo vs GSK233705 100 µg Twice Daily: Mean Difference (Net): 6.21 (95% CI -5.78 to 18.19)

Population analysed: All subject population

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: All AE and SAE were reported until he or she has completed the study (including any follow-up period). This included 28 days of screening and 17 days of treatment and follow-up (approximately 45).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 6 (0%)	4 of 6 (66.7%)	0 of 6
GSK233705 50 µg Twice Daily	0 of 9 (0%)	4 of 9 (44.4%)	0 of 9
GSK233705 100 µg Twice Daily	0 of 8 (0%)	4 of 8 (50%)	0 of 8

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
BackgroundThis study has not been published in the scientific literature.
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GSK233705B in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 4 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) (time frame: Up to follow-up (approximately 45 days)). The study lists 16 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00453479, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2018.