Pulmonary Disease, Chronic ObstructivePhase 2NCT00515502

Safety Study Using GSK573719 And Tiotropium In Patients With Chronic Obstructive Pulmonary Disease

A Phase 2 study testing GSK573719 and Tiotropium in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 3 sites in Germany.

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

GSK573719 is a high-affinity specific muscarinic receptor (mAChR) antagonist which is being developed for once daily treatment of chronic obstructive pulmonary disease (COPD). The long duration of action of GSK573719 when administered via inhalation in animal models supports the potential for use as a once-daily… 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?: GSK573719 and Tiotropium
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 24 participants
Where: 3 sitesGermany
Study dates: 21 Jun 2007to 6 Nov 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

Caucasian male or female subjects aged 40-75 years inclusive. The need to recruit only Caucasian subjects is related to the need to rigorously exclude 2D6 poor metabolisers based on genotype.
Female subjects must be of non-childbearing potential.
An established clinical history of COPD (ATS/ERS definition).
'Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease characterised by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it also produces significant systemic consequences.'
Subject is a smoker or an ex-smoker with a smoking history of at least 10 pack years (1 pack year = 20 cigarettes smoked per day for 1 year or equivalent).
Subject has FEV1/FVC < 0.7 post-bronchodilator (salbutamol) dose.

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Subject has 40 ≥ FEV1 ≤ 80% of predicted normal for height, age and gender after inhalation of salbutamol dose.
Response to ipratropium bromide.
Subject is able and has given written informed consent to take part in the study.
Subject is available to complete all study measurements and procedures.
Subject's BMI is 18.0 - 32.0 kg/m2.
Subjects have a 24hr 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 of any organ system, which as judged by the Investigator, may affect the outcome of this study.
The subject has a positive pre-study drug screen. A minimum list of drugs that will be screened for include Amphetamines, Barbiturates, Cannabis, Cocaine and Opiates. The detection of drugs with a legitimate medical use would not be an exclusion to study participation.
The subject has a positive pre-study alcohol screen. The detection of alcohol would not be an exclusion at screening but would need to be negative pre-dose and during the study.
A suspected history of alcohol abuse within the six months previous to the screening visit.
The subject has tested positive for hepatitis C antibody, hepatitis B surface antigen or HIV (if determined by local SOP's).
Subject has received an investigational drug within 30 days of screening.

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The subject is currently taking medication which is known to be a CYP 2D6 inhibitor/substrate.
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, tiotropium bromide, atropine and any of its derivatives or lactose/milk protein.
Subject is unable to use the DISKUS™/HandiHaler devices correctly.
Subject has prostatic hypertrophy, bladder outlet obstruction, or narrow angle glaucoma.
Subjects with a 2D6 poor metaboliser genotype (Caucasian).
The subject has claustrophobia that may be aggravated by entering the plethysmography cabinet (American Association of Respiratory Care 2001 guidelines for body plethysmography)
Received antibiotic therapy for either a lower respiratory tract infection or for COPD exacerbation within the 4 weeks prior to Screening.
Respiratory criteria
Subject has a diagnosis of active tuberculosis, lung cancer, clinically overt bronchiectasis, allergic rhinitis, or asthma.
Subject has poorly controlled COPD, defined as either: acute worsening of COPD that is managed by the subject at home by treatment with corticosteroids in the 6 weeks prior to screening visit Or more than two exacerbations in the previous 6 months prior to screening that required a course of oral corticosteroids or antibiotics, or, for which the subject was hospitalised.
Subject has participated in a Pulmonary Rehabilitation Program within 4 weeks prior to screening visit or will enter a program during the study.
Subject has had a respiratory tract infection in the 4 weeks prior to the screening visit.
Cardiovascular criteria
Current congestive heart failure (greater than NYHA I), myocardial infarction (within 3-years of the screening date) or ischaemic heart disease requiring regular therapy (such as β blockers, long-acting nitrates, calcium antagonists or nicorandil). Aspirin, Clopidogrel and statins are allowed.
A history of clinically significant arrhythmia or clinically important 24hr Holter findings that, in the opinion of the investigator, would cause a safety concern for entry into the study.
A mean QTc(B) value at screening >450msec, the QTc(B) of all 3 screening ECGs are not within 10% of the mean, or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the T wave)
Mobitz type II or third degree heart block.
Risk factors for torsades de pointes (heart failure NYHA II-IV, chronic hypokalaemia, familial long QT syndrome).
Elevated resting blood pressure or a mean blood pressure equal to or higher than 150/95 mmHg at screening. A history of hypertension is acceptable provided control has been achieved for > 3 months prior to screening with diuretic only.
A mean heart rate outside the range 50-100 bpm at screening (from vital signs measurement).
Concurrent medication criteria
Subject requires treatment with inhaled cromolyn sodium or nedocromil, oral β2-agonists, nebulised β2-agonists, nebulised anticholinergics or leukotriene modifiers.
Subject is unable to abstain from xanthines (other than caffeine) 13-15 days prior to the first dose of study medication until completion of the study (last study-related procedure at the follow-up visit).
Subject is unable to abstain from short-acting inhaled bronchodilators from 6hrs prior to screening until after completion of screening, or, from 6hrs prior to the administration of study medication until after completion of any given treatment period (i.e. the last assessment in a dosing period).
Subject is unable to abstain from long-acting inhaled bronchodilators from 72hrs prior to the screening until after completion of all treatment periods (i.e. the last assessment in the final dosing period).
Subject has changed dose of inhaled corticosteroids within the last 4 weeks, or, will be unable to maintain a constant dose of inhaled corticosteroids during the study.
Subject is receiving treatment with long term or short-term oxygen therapy or requires nocturnal positive pressure ventilation (CPAP or NIPPV).
Subject is receiving treatment with beta-blockers, except eye drops, Diltiazem or Verapamil.
Subject is receiving co-medication with drugs which are commonly recognised to prolong the QTc interval (e.g. quinolones, amiodarone, disopyramide, quinidine, sotalol, chlorpromazine, haloperidol, ketoconazole, terfenadine, cisapride and terodiline).

Trial locations and contacts

3 sites in 1 country.

Germany3 sites

GSK Investigational Site
Berlin, 14050
GSK Investigational Site
Hamburg, 22291
GSK Investigational Site
Hanover, Lower Saxony, 30625

Other trials in Germany

About this study

Official title: A Randomised, Double Blind, Placebo-controlled, Double Dummy, 4-way Cross-over, Dose Ascending Study to Assess the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Single Inhaled Doses of GSK573719 (250, 500 and 1000 μg) and Tiotropium Bromide (18 μg) Via DPI in COPD Patients.

Read the detailed description

A randomised, double blind, placebo-controlled, double dummy, 4-way cross-over, dose ascending study to assess the safety, tolerability, pharmacodynamics and pharmacokinetics of single inhaled doses of GSK573719 (3 escalating mcg doses will be used) and tiotropium bromide (18µg) via DPI in COPD patients

Conditions: Pulmonary Disease, Chronic Obstructive
Being tested: GSK573719, Tiotropium
Keywords: chronic obstructive pulmonary disease,, GSK573719,, muscarinic receptor antagonist
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.

GSK573719Drug
250 micrograms (μg) per blister, administered via dry powder inhaler, dose-ascending study doses began at 250 ug, then 500 ug, and 1000 μg
TiotropiumDrug
strips of five capsules, each containing 18 μg administered via dry powder inhaler

Study groups in NCT00515502
Study group	Role	What they receive
Seq 1: UMEC 250 µg, UMEC 500 µg, Tiotropium 18 µg, placebo	Active comparator	Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: umeclidinium bromide (UMEC) 250 micrograms (µg), UMEC 500 µg, Tiotropium 18 µg and placebo. Treatment periods were seperated by a washout period of at least 14 days. Receives: Drug: GSK573719; Drug: Tiotropium
Seq 2: UMEC 250 µg, UMEC 500 µg, UMEC 1000 µg, placebo	Active comparator	Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: UMEC 250 µg, UMEC 500 µg, UMEC 1000 µg and placebo. Treatment periods were seperated by a washout period of at least 14 days. Receives: Drug: GSK573719
Seq 3: UMEC 250 µg, placebo, UMEC 500 µg, UMEC 1000 µg	Active comparator	Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: UMEC 250 µg, placebo, UMEC 500 µg and UMEC 1000 µg. Treatment periods were seperated by a washout period of at least 14 days. Receives: Drug: GSK573719
Seq 4: UMEC 250 µg, UMEC 500 µg, placebo, UMEC 1000 µg	Active comparator	Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: UMEC 250 µg, UMEC 500 µg, placebo and UMEC 1000 µg. Treatment periods were seperated by a washout period of at least 14 days. Receives: Drug: GSK573719
Seq 5: Placebo, UMEC 250 µg, UMEC 500 µg, UMEC 1000 µg	Active comparator	Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: Placebo, UMEC 250 µg, UMEC 500 µg and UMEC 1000 µg. Treatment periods were seperated by a washout period of at least 14 days. Receives: Drug: GSK573719
Seq 6: UMEC 250 µg, placebo, Tiotropium 18 µg, UMEC 500 µg	Active comparator	Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: UMEC 250 µg, placebo, Tiotropium 18 µg and UMEC 500 µg. Treatment periods were seperated by a washout period of at least 14 days. Receives: Drug: GSK573719; Drug: Tiotropium
Seq 7: Placebo, Tiotropium 18 µg, UMEC 250 µg, UMEC 500 µg	Active comparator	Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: Placebo, Tiotropium 18 µg, UMEC 250 µg and UMEC 500 µg. Treatment periods were seperated by a washout period of at least 14 days. Receives: Drug: GSK573719; Drug: Tiotropium
Seq 8: Tiotropium 18 µg, placebo, UMEC 250 µg, UMEC 500 µg	Active comparator	Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: Tiotropium 18 µg, placebo, UMEC 250 µg and UMEC 500 µg. Treatment periods were seperated by a washout period of at least 14 days. Receives: Drug: GSK573719; Drug: Tiotropium
Seq 9: Tiotropium 18 µg, UMEC 250 µg, UMEC 500 µg, placebo	Active comparator	Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: Tiotropium 18 µg, UMEC 250 µg, UMEC 500 µg and placebo. Treatment periods were seperated by a washout period of at least 14 days. Receives: Drug: GSK573719; Drug: Tiotropium
Seq 10: Tiotropium 18 µg, UMEC 250 µg, placebo, UMEC 500 µg	Active comparator	Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: Tiotropium 18 µg, UMEC 250 µg, placebo and UMEC 500 µg. Treatment periods were seperated by a washout period of at least 14 days. Receives: Drug: GSK573719; Drug: Tiotropium
Seq 11: Placebo, UMEC 250 µg, Tiotropium 18 µg, UMEC 500 µg	Active comparator	Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: Placebo, UMEC 250 µg, Tiotropium 18 µg and UMEC 500 µg. Treatment periods were seperated by a washout period of at least 14 days. Receives: Drug: GSK573719; Drug: Tiotropium
Seq 12: UMEC 250 µg, placebo, UMEC 500 µg, Tiotropium 18 µg	Active comparator	Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: UMEC 250 µg, placebo, UMEC 500 µg and Tiotropium 18 µg. Treatment periods were seperated by a washout period of at least 14 days. Receives: Drug: GSK573719; Drug: Tiotropium

What is being measured

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

Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE)
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An 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, is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, or is an event of possible drug-induced liver injury. Refer to the general AE/SAE module for a list of AEs and SAEs.
Measured: From Day 1 of Treatment Period 1until Follow-up (up to 10 weeks)
Maximum (0-4 Hours) Heart Rate on Day 1 of Each Treatment Period
Resting heart rate was measured at pre-dose and 15 minutes (min), 45min, 1.5 hour (h) 4 h, 8 h, and 24 h post-dose of each treatment period and the maximum value for heart rate (0-4hours) was derived at rest. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Measured: Day 1 of each treatment period (up to Study Day 46)
Weighted Mean (0-4 Hours) Heart Rate at Day 1 of Each Treatment Period
Resting heart rate was measured at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the weighted mean value for heart rate (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Measured: Day 1 of each treatment period (up to Study Day 46)
Maximum (0-4 Hours) Systolic Blood Pressure at Day 1 of Each Treatment Period
Resting systolic blood pressure was measured at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the maximum value for systolic blood pressure (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Measured: Day 1 of each treatment period (up to Study Day 46)
Weighted Mean (0-4 Hours) Systolic Blood Pressure at Day 1 of Each Treatment Period
Resting systolic blood pressure was measured at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the weighted mean value for systolic blood pressure (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Measured: Day 1 of each treatment period (up to Study Day 46)
Maximum (0-4 Hours) Diastolic Blood Pressure at Day 1 of Each Treatment Period
Resting diastolic blood pressure was measured at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the maximum value for diastolic blood pressure (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Measured: Day 1 of each treatment period (up to Study Day 46)
Weighted Mean (0-4 Hours) Diastolic Blood Pressure at Day 1 of Each Treatment Period
Resting diastolic blood pressure was measured at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the weighted mean value for diastolic blood pressure (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Measured: Day 1 of each treatment period (up to Study Day 46)
Maximum (0-4 Hours) QTcB at Day 1 of Each Treatment Period
Twelve-lead ECGs (electrocardiograms) were performed to measure QT interval corrected according to Bazzet's formula (QTcB) at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the maximum value for QTcB (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Measured: Day 1 of each treatment period (up to Study Day 46)
Weighted Mean (0-4 Hours) QTcB at Day 1 of Each Treatment Period
Twelve-lead ECGs were performed to measure QTcB at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the weighted mean value for QTcB (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Measured: Day 1 of each treatment period (up to Study Day 46)
Maximum (0-4 Hours) QTcF at Day 1 of Each Treatment Period
Twelve-lead ECGs were performed to measure QT interval corrected according to Fredericia's formula (QTcF) at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the maximum value for QTcF (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Measured: Day 1 of each treatment period (up to Study Day 46)
Weighted Mean (0-4 Hours) QTcF at Day 1 of Each Treatment Period
Twelve-lead ECGs were performed to measure QTcF at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the weighted mean value for QTcF (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Measured: Day 1 of each treatment period (up to Study Day 46)
Maximum (0-24 Hours) Heart Rate as Measured From Holter Monitoring at Day 1 of Each Treatment Period
Twenty-four hour Holter monitoring was conducted to measure heart rate for the 24-hour period following dosing at each treatment period and the maximum value for heart rate (0-24 hours) was derived. Analysis was performed using a mixed model of period and treatment group fitted as fixed effects and participant as a random effect.
Measured: Day 1 of each treatment period (up to Study Day 46)
Mean (0-24 Hours) Heart Rate as Measured From Holter Monitoring at Day 1 of Each Treatment Period
Twenty-four-hour Holter monitoring was conducted to measure heart rate for the 24-h period following dosing of each treatment period and the mean value for heart rate (0-24 hours) was derived. Analysis was performed using a mixed model of period and treatment group fitted as fixed effects and participant as a random effect.
Measured: Day 1 of each treatment period (up to Study Day 46)
Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils Values at the Indicated Time Points on Day 1 of Each Treatment Period
Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, and total neutrophils at pre-dose and 24 hour (h) post-dose of each treatment period.
Measured: Day 1 of each treatment period (up to Study Day 46)
Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points on Day 1 of Each Treatment Period
Blood samples were collected for the measurement of hemoglobin, MCHC, albumin and total protein at pre-dose and 24 hour (h) post-dose of each treatment period.
Measured: Day 1 of each treatment period (up to Study Day 46)
Hematocrit Values at the Indicated Time Points on Day 1 of Each Treatment Period
Blood samples were collected for the measurement of hematocrit at pre-dose and 24 hour (h) post-dose of each treatment period.
Measured: Day 1 of each treatment period (up to Study Day 46)
Mean Corpuscle Hemoglobin Values at the Indicated Time Points on Day 1 of Each Treatment Period
Blood samples were collected for the measurement of the mean corpuscle hemoglobin at pre-dose and 24 hour (h) post-dose of each treatment period.
Measured: Day 1 of each treatment period (up to Study Day 46)
Mean Corpuscle Volume Values at the Indicated Time Points on Day 1 of Each Treatment Period
Blood samples were collected for the measurement of the mean corpuscle volume at pre-dose and 24 hour (h) post-dose of each treatment period.
Measured: Day 1 of each treatment period (up to Study Day 46)
Red Blood Cells Count Values at the Indicated Time Points on Day 1 of Each Treatment Period
Blood samples were collected for the measurement of the red blood cells count at pre-dose and 24 hour (h) post-dose of each treatment period.
Measured: Day 1 of each treatment period (up to Study Day 46)
Platelets Count and White Blood Cells (WBC) Count Values at the Indicated Time Points on Day 1 of Each Treatment Period
Blood samples were collected for the measurement of platelets count and WBC count at pre-dose and 24 hour (h) post-dose of each treatment period.
Measured: Day 1 of each treatment period (up to Study Day 46)
Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Phosphokinase (CPK), and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points on Day 1 of Each Treatment Period
Blood samples were collected for the measurement of ALP, ALT, AST, CPK, and GGT at pre-dose and 24 hour (h) post-dose of each treatment period.
Measured: Day 1 of each treatment period (up to Study Day 46)
Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points on Day 1 of Each Treatment Period
Blood samples were collected for the measurement of total bilirubin, creatinine, and uric acid at pre-dose and 24 hour (h) post-dose of each treatment period.
Measured: Day 1 of each treatment period (up to Study Day 46)
Calcium, Bicarbonate, Chloride, Glucose, Inorganic Phosphorus (IP), Potassium, Sodium, and Urea Values at the Indicated Time Points on Day 1 of Each Treatment Period
Blood samples were collected for the measurement of the calcium, bicarbonate, chloride, glucose, IP, potassium, sodium, and urea at pre-dose and 24 hour (h) post-dose of each treatment period.
Measured: Day 1 of each treatment period (up to Study Day 46)
Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points on Day 1 of Each Treatment Period
FEV1 and FVC are measures of lung function. FEV1 is defined as the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. FEV1 and FVC measurements were taken at pre-dose and 1 hour (h), 2 h, 6 h, 9 h, 12 h and 24 h post-dose of each treatment period.
Measured: Day 1 of each treatment period (up to Study Day 46)

Secondary outcomes (9)

Area Under Concentration-time Curve From Time 0 to 2 Hours [AUC(0-2)] and Area Under Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration [AUC(0-t)] of UMEC
Blood samples were collected to determine the plasma concentrations of UMEC from pre-dose up to 24 hour post-dose of each treatment period to derive the AUC(0-2) and AUC(0-t). Blood samples for PK analysis of UMEC were obtained on Day 1at pre-dose and 5 minutes (min), 15 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, and 24 h post UMEC dose administration.
Measured: Day 1 of each treatment period (up to Study Day 46)
Maximum Observed Plasma Concentration (Cmax) of UMEC
Blood samples were collected to determine the plasma concentrations of UMEC from pre-dose up to 24 hour post-dose of each treatment period to derive the Cmax. Blood samples for PK analysis of UMEC were obtained on Day 1at pre-dose and 5 minutes (min), 15 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, and 24 h post UMEC dose administration.
Measured: Day 1 of each treatment period (up to Study Day 46)
Time of Maximum Observed Plasma Concentration (Tmax), Last Time Point Where the Concentration is Above the Limit of Quantification (Tlast), and Plasma Half-life (t1/2) of UMEC
Blood samples were collected to determine the plasma concentrations of UMEC from pre-dose up to 24 hour post-dose of each treatment period to derive tmax, tlast and t1/2. Blood samples for PK analysis of UMEC were obtained on Day 1at pre-dose and 5 minutes (min), 15 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, and 24 h post UMEC dose administration.
Measured: Day 1 of each treatment period (up to Study Day 46)
Amount of Drug Excreted Unchanged in Urine From Time Zero to: 2h [Ae(0-2)] , 8h [Ae(0-8)], 12h [Ae(0-12)], 24h [Ae(0-24)], and 48h [Ae(0-48)]; and Area Under the Excretion Rate Curve From Time Zero to: 18h [AUER(0-18)] and 36h [AUER(0-36)] for UMEC
Urine samples were collected to determine the urine concentrations of UMEC from 0 min up to 48 hours post-dose of each treatment period to derive Ae(0-2), Ae(0-8), Ae(0-12), Ae(0-24), Ae(0-48), AUER(0-18) and AUER(0-36). Urine samples for PK analysis of UMEC were obtained on Day 1; a single sample was collected at each of the following timepoints: 0-2 h, 2-8 h, 8-12 h, 12-24 h and 24-48 h post UMEC dose administration.
Measured: Day 1 of each treatment period (up to Study Day 46)
Renal Clearance (CLr) of UMEC Following Dose Administration on Day 1
The CLr is defined as the apparent total clearance of the drug from plasma after oral administration. Blood samples for PK analysis of UMEC were obtained on Day 1at pre-dose and 5 minutes (min), 15 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, and 24 h post UMEC dose administration.
Measured: Day 1 of each treatment period (up to Study Day 46)
Half-life for Renal Excretion of UMEC on Day 1
The terminal half-life (t1/2) of UMEC is defined as the time required for the urine concentration of UMEC to reach half of its original concentration. Urine samples for PK analysis of UMEC were obtained on Day 1; a single sample was collected at each of the following timepoints: 0-2 h, 2-8 h, 8-12 h, 12-24 h and 24-48 h post UMEC dose administration.
Measured: Day 1 of each treatment period (up to Study Day 46)
Fraction of Dose Excreted Unchanged in Urine From Time Zero to: 24 Hours [Fe(0-24)] and 48 Hours [Fe(0-48)] for UMEC
Urine samples were collected to determine the urine concentrations of UMEC from 0 min up to 48 hours post-dose of each treatment period to derive Fe(0-24) and Fe(0-48). Urine samples for PK analysis of UMEC were obtained on Day 1; a single sample was collected at each of the following timepoints: 0-2 h, 2-8 h, 8-12 h, 12-24 h and 24-48 h post UMEC dose administration.
Measured: Day 1 of each treatment period (up to Study Day 46)
Mean Serial FEV1over 24 Hours After Dosing on Day 1 of Each Treatment Period
Serial spirometry assessments were conducted on Day 1 of each treatment period over the course of 24 hours and were taken at 1 hour (h), 2 h, 6 h, 9 h, 12 h and 24 h post-dose. The maximum of the 3 FEV1 measurements for each participant, treatment period and timepoint were used in the calculation of the mean for each treatment group at each timepoint.
Measured: Day 1 of each treatment period (up to Study Day 46)
Mean Serial Specific Airway Resistance (sGaw) Over 24 Hours After Dosing on Day 1 of Each Treatment Period
sGaw is the specific airways resistance (mid) which was assessed by whole body plethysmography. Values used were the mean of the 3 readings recorded at each timepoint. sGaw measurements were taken at 2 hour (h), 6 h, 12 h and 24 h post-dose of each treatment period. 1/kPa.s=1(the inverses)/kPa (kilopascal).s (second)
Measured: Day 1 of each treatment period (up to Study Day 46)

Timeline

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

21 Jun 20076 Nov 2007

First posted13 Aug 2007 (estimated)
Study start21 Jun 2007
Primary completion6 Nov 2007
Study completion6 Nov 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: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00515502
Sponsor's protocol ID: AC4108123
Status last verified: Aug 2017
First submitted: 9 Aug 2007
Last updated: 22 Aug 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: 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

Tal-Singer R, Cahn A, Mehta R, Preece A, Crater G, Kelleher D, Pouliquen IJ. Initial assessment of single and repeat doses of inhaled umeclidinium in patients with chronic obstructive pulmonary disease: two randomised studies. Eur J Pharmacol. 2013 Feb 15;701(1-3):40-8. doi: 10.1016/j.ejphar.2012.12.019. Epub 2012 Dec 28.
PubMed 23276660

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?
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Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Pulmonary Disease, Chronic Obstructive trials

Study at a glance

From the registry record, last updated by the sponsor on 22 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomised, Double Blind, Placebo-controlled, Double Dummy, 4-way Cross-over, Dose Ascending Study to Assess the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Single Inhaled Doses of GSK573719 (250, 500 and 1000 μg) and Tiotropium Bromide (18 μg) Via DPI in COPD Patients.
ClinicalTrials.gov ID: NCT00515502
Acronym / sponsor ID: AC4108123
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: chronic obstructive pulmonary disease,, GSK573719,, muscarinic receptor antagonist
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 24 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 21 Jun 2007 (actual)
Primary completion: 6 Nov 2007 (actual)
Study completion: 6 Nov 2007 (actual)
First posted: 13 Aug 2007 (estimated)
Results: Posted 24 Apr 2014

Clinical summary

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 12

Arm	Type	Receives
Seq 1: UMEC 250 µg, UMEC 500 µg, Tiotropium 18 µg, placebo	Active comparator	Drug: GSK573719, Drug: TiotropiumParticipants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: umeclidinium bromide (UMEC) 250 micrograms (µg), UMEC 500 µg, Tiotropium 18 µg and placebo. Treatment periods were seperated by a washout period of at least 14 days.
Seq 2: UMEC 250 µg, UMEC 500 µg, UMEC 1000 µg, placebo	Active comparator	Drug: GSK573719Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: UMEC 250 µg, UMEC 500 µg, UMEC 1000 µg and placebo. Treatment periods were seperated by a washout period of at least 14 days.
Seq 3: UMEC 250 µg, placebo, UMEC 500 µg, UMEC 1000 µg	Active comparator	Drug: GSK573719Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: UMEC 250 µg, placebo, UMEC 500 µg and UMEC 1000 µg. Treatment periods were seperated by a washout period of at least 14 days.
Seq 4: UMEC 250 µg, UMEC 500 µg, placebo, UMEC 1000 µg	Active comparator	Drug: GSK573719Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: UMEC 250 µg, UMEC 500 µg, placebo and UMEC 1000 µg. Treatment periods were seperated by a washout period of at least 14 days.
Seq 5: Placebo, UMEC 250 µg, UMEC 500 µg, UMEC 1000 µg	Active comparator	Drug: GSK573719Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: Placebo, UMEC 250 µg, UMEC 500 µg and UMEC 1000 µg. Treatment periods were seperated by a washout period of at least 14 days.
Seq 6: UMEC 250 µg, placebo, Tiotropium 18 µg, UMEC 500 µg	Active comparator	Drug: GSK573719, Drug: TiotropiumParticipants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: UMEC 250 µg, placebo, Tiotropium 18 µg and UMEC 500 µg. Treatment periods were seperated by a washout period of at least 14 days.
Seq 7: Placebo, Tiotropium 18 µg, UMEC 250 µg, UMEC 500 µg	Active comparator	Drug: GSK573719, Drug: TiotropiumParticipants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: Placebo, Tiotropium 18 µg, UMEC 250 µg and UMEC 500 µg. Treatment periods were seperated by a washout period of at least 14 days.
Seq 8: Tiotropium 18 µg, placebo, UMEC 250 µg, UMEC 500 µg	Active comparator	Drug: GSK573719, Drug: TiotropiumParticipants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: Tiotropium 18 µg, placebo, UMEC 250 µg and UMEC 500 µg. Treatment periods were seperated by a washout period of at least 14 days.
Seq 9: Tiotropium 18 µg, UMEC 250 µg, UMEC 500 µg, placebo	Active comparator	Drug: GSK573719, Drug: TiotropiumParticipants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: Tiotropium 18 µg, UMEC 250 µg, UMEC 500 µg and placebo. Treatment periods were seperated by a washout period of at least 14 days.
Seq 10: Tiotropium 18 µg, UMEC 250 µg, placebo, UMEC 500 µg	Active comparator	Drug: GSK573719, Drug: TiotropiumParticipants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: Tiotropium 18 µg, UMEC 250 µg, placebo and UMEC 500 µg. Treatment periods were seperated by a washout period of at least 14 days.
Seq 11: Placebo, UMEC 250 µg, Tiotropium 18 µg, UMEC 500 µg	Active comparator	Drug: GSK573719, Drug: TiotropiumParticipants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: Placebo, UMEC 250 µg, Tiotropium 18 µg and UMEC 500 µg. Treatment periods were seperated by a washout period of at least 14 days.
Seq 12: UMEC 250 µg, placebo, UMEC 500 µg, Tiotropium 18 µg	Active comparator	Drug: GSK573719, Drug: TiotropiumParticipants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: UMEC 250 µg, placebo, UMEC 500 µg and Tiotropium 18 µg. Treatment periods were seperated by a washout period of at least 14 days.

Who may qualify

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

Key inclusion criteria (12 listed)

Caucasian male or female subjects aged 40-75 years inclusive. The need to recruit only Caucasian subjects is related to the need to rigorously exclude 2D6 poor metabolisers based on genotype.
Female subjects must be of non-childbearing potential.
An established clinical history of COPD (ATS/ERS definition).
'Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease characterised by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it also produces significant systemic consequences.'
Subject is a smoker or an ex-smoker with a smoking history of at least 10 pack years (1 pack year = 20 cigarettes smoked per day for 1 year or equivalent).

Key exclusion criteria (36 listed)

Subjects who have a past or present disease of any organ system, which as judged by the Investigator, may affect the outcome of this study.
The subject has a positive pre-study drug screen. A minimum list of drugs that will be screened for include Amphetamines, Barbiturates, Cannabis, Cocaine and Opiates. The detection of drugs with a legitimate medical use would not be an exclusion to study participation.
The subject has a positive pre-study alcohol screen. The detection of alcohol would not be an exclusion at screening but would need to be negative pre-dose and during the study.
A suspected history of alcohol abuse within the six months previous to the screening visit.
The subject has tested positive for hepatitis C antibody, hepatitis B surface antigen or HIV (if determined by local SOP's).

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
GSK573719250 micrograms (μg) per blister, administered via dry powder inhaler, dose-ascending study doses began at 250 ug, then 500 ug, and 1000 μg	Drug	Seq 10: Tiotropium 18 µg, UMEC 250 µg, placebo, UMEC 500 µg, Seq 11: Placebo, UMEC 250 µg, Tiotropium 18 µg, UMEC 500 µg, Seq 12: UMEC 250 µg, placebo, UMEC 500 µg, Tiotropium 18 µg, Seq 1: UMEC 250 µg, UMEC 500 µg, Tiotropium 18 µg, placebo, Seq 2: UMEC 250 µg, UMEC 500 µg, UMEC 1000 µg, placebo, Seq 3: UMEC 250 µg, placebo, UMEC 500 µg, UMEC 1000 µg, Seq 4: UMEC 250 µg, UMEC 500 µg, placebo, UMEC 1000 µg, Seq 5: Placebo, UMEC 250 µg, UMEC 500 µg, UMEC 1000 µg, Seq 6: UMEC 250 µg, placebo, Tiotropium 18 µg, UMEC 500 µg, Seq 7: Placebo, Tiotropium 18 µg, UMEC 250 µg, UMEC 500 µg, Seq 8: Tiotropium 18 µg, placebo, UMEC 250 µg, UMEC 500 µg, Seq 9: Tiotropium 18 µg, UMEC 250 µg, UMEC 500 µg, placebo
Tiotropiumstrips of five capsules, each containing 18 μg administered via dry powder inhaler	Drug	Seq 10: Tiotropium 18 µg, UMEC 250 µg, placebo, UMEC 500 µg, Seq 11: Placebo, UMEC 250 µg, Tiotropium 18 µg, UMEC 500 µg, Seq 12: UMEC 250 µg, placebo, UMEC 500 µg, Tiotropium 18 µg, Seq 1: UMEC 250 µg, UMEC 500 µg, Tiotropium 18 µg, placebo, Seq 6: UMEC 250 µg, placebo, Tiotropium 18 µg, UMEC 500 µg, Seq 7: Placebo, Tiotropium 18 µg, UMEC 250 µg, UMEC 500 µg, Seq 8: Tiotropium 18 µg, placebo, UMEC 250 µg, UMEC 500 µg, Seq 9: Tiotropium 18 µg, UMEC 250 µg, UMEC 500 µg, placebo

Primary outcome

Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE)
Time frame: From Day 1 of Treatment Period 1until Follow-up (up to 10 weeks)
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An 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, is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, or is an event of possible drug-induced liver injury. Refer to the general AE/SAE module for a list of AEs and SAEs.
Maximum (0-4 Hours) Heart Rate on Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)
Resting heart rate was measured at pre-dose and 15 minutes (min), 45min, 1.5 hour (h) 4 h, 8 h, and 24 h post-dose of each treatment period and the maximum value for heart rate (0-4hours) was derived at rest. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Weighted Mean (0-4 Hours) Heart Rate at Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)
Resting heart rate was measured at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the weighted mean value for heart rate (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Maximum (0-4 Hours) Systolic Blood Pressure at Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)
Resting systolic blood pressure was measured at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the maximum value for systolic blood pressure (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Weighted Mean (0-4 Hours) Systolic Blood Pressure at Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)
Resting systolic blood pressure was measured at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the weighted mean value for systolic blood pressure (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Maximum (0-4 Hours) Diastolic Blood Pressure at Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)
Resting diastolic blood pressure was measured at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the maximum value for diastolic blood pressure (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Weighted Mean (0-4 Hours) Diastolic Blood Pressure at Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)
Resting diastolic blood pressure was measured at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the weighted mean value for diastolic blood pressure (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Maximum (0-4 Hours) QTcB at Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)
Twelve-lead ECGs (electrocardiograms) were performed to measure QT interval corrected according to Bazzet's formula (QTcB) at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the maximum value for QTcB (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Weighted Mean (0-4 Hours) QTcB at Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)
Twelve-lead ECGs were performed to measure QTcB at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the weighted mean value for QTcB (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Maximum (0-4 Hours) QTcF at Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)
Twelve-lead ECGs were performed to measure QT interval corrected according to Fredericia's formula (QTcF) at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the maximum value for QTcF (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Weighted Mean (0-4 Hours) QTcF at Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)
Twelve-lead ECGs were performed to measure QTcF at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the weighted mean value for QTcF (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Maximum (0-24 Hours) Heart Rate as Measured From Holter Monitoring at Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)
Twenty-four hour Holter monitoring was conducted to measure heart rate for the 24-hour period following dosing at each treatment period and the maximum value for heart rate (0-24 hours) was derived. Analysis was performed using a mixed model of period and treatment group fitted as fixed effects and participant as a random effect.
Mean (0-24 Hours) Heart Rate as Measured From Holter Monitoring at Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)
Twenty-four-hour Holter monitoring was conducted to measure heart rate for the 24-h period following dosing of each treatment period and the mean value for heart rate (0-24 hours) was derived. Analysis was performed using a mixed model of period and treatment group fitted as fixed effects and participant as a random effect.
Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils Values at the Indicated Time Points on Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)
Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, and total neutrophils at pre-dose and 24 hour (h) post-dose of each treatment period.
Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points on Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)
Blood samples were collected for the measurement of hemoglobin, MCHC, albumin and total protein at pre-dose and 24 hour (h) post-dose of each treatment period.
Hematocrit Values at the Indicated Time Points on Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)
Blood samples were collected for the measurement of hematocrit at pre-dose and 24 hour (h) post-dose of each treatment period.
Mean Corpuscle Hemoglobin Values at the Indicated Time Points on Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)
Blood samples were collected for the measurement of the mean corpuscle hemoglobin at pre-dose and 24 hour (h) post-dose of each treatment period.
Mean Corpuscle Volume Values at the Indicated Time Points on Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)
Blood samples were collected for the measurement of the mean corpuscle volume at pre-dose and 24 hour (h) post-dose of each treatment period.
Red Blood Cells Count Values at the Indicated Time Points on Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)
Blood samples were collected for the measurement of the red blood cells count at pre-dose and 24 hour (h) post-dose of each treatment period.
Platelets Count and White Blood Cells (WBC) Count Values at the Indicated Time Points on Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)
Blood samples were collected for the measurement of platelets count and WBC count at pre-dose and 24 hour (h) post-dose of each treatment period.
Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Phosphokinase (CPK), and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points on Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)
Blood samples were collected for the measurement of ALP, ALT, AST, CPK, and GGT at pre-dose and 24 hour (h) post-dose of each treatment period.
Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points on Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)
Blood samples were collected for the measurement of total bilirubin, creatinine, and uric acid at pre-dose and 24 hour (h) post-dose of each treatment period.
Calcium, Bicarbonate, Chloride, Glucose, Inorganic Phosphorus (IP), Potassium, Sodium, and Urea Values at the Indicated Time Points on Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)
Blood samples were collected for the measurement of the calcium, bicarbonate, chloride, glucose, IP, potassium, sodium, and urea at pre-dose and 24 hour (h) post-dose of each treatment period.
Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points on Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)
FEV1 and FVC are measures of lung function. FEV1 is defined as the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. FEV1 and FVC measurements were taken at pre-dose and 1 hour (h), 2 h, 6 h, 9 h, 12 h and 24 h post-dose of each treatment period.

9 secondary outcomes

Area Under Concentration-time Curve From Time 0 to 2 Hours [AUC(0-2)] and Area Under Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration [AUC(0-t)] of UMEC
Time frame: Day 1 of each treatment period (up to Study Day 46)
Maximum Observed Plasma Concentration (Cmax) of UMEC
Time frame: Day 1 of each treatment period (up to Study Day 46)
Time of Maximum Observed Plasma Concentration (Tmax), Last Time Point Where the Concentration is Above the Limit of Quantification (Tlast), and Plasma Half-life (t1/2) of UMEC
Time frame: Day 1 of each treatment period (up to Study Day 46)
Amount of Drug Excreted Unchanged in Urine From Time Zero to: 2h [Ae(0-2)] , 8h [Ae(0-8)], 12h [Ae(0-12)], 24h [Ae(0-24)], and 48h [Ae(0-48)]; and Area Under the Excretion Rate Curve From Time Zero to: 18h [AUER(0-18)] and 36h [AUER(0-36)] for UMEC
Time frame: Day 1 of each treatment period (up to Study Day 46)
Renal Clearance (CLr) of UMEC Following Dose Administration on Day 1
Time frame: Day 1 of each treatment period (up to Study Day 46)
Half-life for Renal Excretion of UMEC on Day 1
Time frame: Day 1 of each treatment period (up to Study Day 46)
Fraction of Dose Excreted Unchanged in Urine From Time Zero to: 24 Hours [Fe(0-24)] and 48 Hours [Fe(0-48)] for UMEC
Time frame: Day 1 of each treatment period (up to Study Day 46)
Mean Serial FEV1over 24 Hours After Dosing on Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)
Mean Serial Specific Airway Resistance (sGaw) Over 24 Hours After Dosing on Day 1 of Each Treatment Period
Time frame: Day 1 of each treatment period (up to Study Day 46)

Results and safety

Results posted to the registry on 24 Apr 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Seq 1: UMEC 250 µg, UMEC 500 µg, Tiotropium 18 µg, Placebo	1	1
Seq 2: UMEC 250 µg, UMEC 500 µg, UMEC 1000 µg, Placebo	4	4
Seq 3: UMEC 250 µg, Placebo, UMEC 500 µg, UMEC 1000 µg	4	4
Seq 4: UMEC 250 µg, UMEC 500 µg, Placebo, UMEC 1000 µg	3	3
Seq 5: Placebo, UMEC 250 µg, UMEC 500 µg, UMEC 1000 µg	3	3
Seq 6: UMEC 250 µg, Placebo, Tiotropium 18 µg, UMEC 500 µg	1	1
Seq 7: Placebo, Tiotropium 18 µg, UMEC 250 µg, UMEC 500 µg	2	1
Seq 8: Tiotropium 18 µg, Placebo, UMEC 250 µg, UMEC 500 µg	1	1
Seq 9: Tiotropium 18 µg, UMEC 250 µg, UMEC 500 µg, Placebo	1	0
Seq 10: Tiotropium 18 µg, UMEC 250 µg, Placebo, UMEC 500 µg	2	2
Seq 11: Placebo, UMEC 250 µg, Tiotropium 18 µg, UMEC 500 µg	1	1
Seq 12: UMEC 250 µg, Placebo, UMEC 500 µg, Tiotropium 18 µg	1	0

Primary outcome: Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE)

Time frame: From Day 1 of Treatment Period 1until Follow-up (up to 10 weeks). Number. Unit: Participants

Measure	Placebo n = 21	UMEC 250 µg n = 22	UMEC 500 µg n = 21	UMEC 1000 µg n = 13	Tiotropium 18 µg n = 8
Any AE	6	9	8	4	3
Any SAE	0	0	0	0	0

Population analysed: All Subjects Population: all participants who received at least one dose of study medication.

Primary outcome: Maximum (0-4 Hours) Heart Rate on Day 1 of Each Treatment Period

Time frame: Day 1 of each treatment period (up to Study Day 46). Least squares mean (Standard Error). Unit: Beats per minute (bpm)

Measure	Placebo n = 21	UMEC 250 µg n = 22	UMEC 500 µg n = 21	UMEC 1000 µg n = 13	Tiotropium 18 µg n = 8
Value	69.1 (1.01)	68.7 (1.14)	69.5 (1.04)	71.2 (1.54)	66.4 (1.69)

Placebo vs UMEC 250 µg: Mean Difference (Final Values): -0.4 (95% CI -3.0 to 2.2), Mixed Models Analysis
Placebo vs UMEC 500 µg: Mean Difference (Final Values): 0.4 (95% CI -2.1 to 2.9), Mixed Models Analysis
Placebo vs UMEC 1000 µg: Mean Difference (Final Values): 2.1 (95% CI -1.4 to 5.7), Mixed Models Analysis

Population analysed: All Subjects Population. All participants with \>=1 post-Baseline assessment and non-missing covariate data are included in the analysis. The number of participants represents participants who provided data at Day 1.

Primary outcome: Weighted Mean (0-4 Hours) Heart Rate at Day 1 of Each Treatment Period

Time frame: Day 1 of each treatment period (up to Study Day 46). Least squares mean (Standard Error). Unit: Beats per minute (bpm)

Measure	Placebo n = 21	UMEC 250 µg n = 22	UMEC 500 µg n = 21	UMEC 1000 µg n = 13	Tiotropium 18 µg n = 8
Value	64.66 (0.882)	63.88 (0.953)	65.69 (0.894)	66.61 (1.177)	62.93 (1.275)

Placebo vs UMEC 250 µg: Mean Difference (Final Values): -0.78 (95% CI -2.47 to 0.92), Mixed Models Analysis
Placebo vs UMEC 500 µg: Mean Difference (Final Values): 1.04 (95% CI -0.57 to 2.64), Mixed Models Analysis
Placebo vs UMEC 1000 µg: Mean Difference (Final Values): 1.95 (95% CI -0.35 to 4.26), Mixed Models Analysis

Primary outcome: Maximum (0-4 Hours) Systolic Blood Pressure at Day 1 of Each Treatment Period

Time frame: Day 1 of each treatment period (up to Study Day 46). Least squares mean (Standard Error). Unit: Millimeters of mercury (mmHg)

Measure	Placebo n = 21	UMEC 250 µg n = 22	UMEC 500 µg n = 21	UMEC 1000 µg n = 13	Tiotropium 18 µg n = 8
Value	129.7 (1.59)	129.0 (1.84)	126.2 (1.65)	133.0 (2.41)	131.0 (2.78)

Placebo vs UMEC 250 µg: Mean Difference (Final Values): -0.8 (95% CI -5.0 to 3.4), Mixed Models Analysis
Placebo vs UMEC 500 µg: Mean Difference (Final Values): -3.5 (95% CI -7.6 to 0.6), Mixed Models Analysis
Placebo vs UMEC 1000 µg: Mean Difference (Final Values): 3.3 (95% CI -2.2 to 8.7), Mixed Models Analysis

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 21 (0%)	6 of 21 (28.6%)	Not reported
UMEC 250 µg	0 of 22 (0%)	9 of 22 (40.9%)	Not reported
UMEC 500 µg	0 of 21 (0%)	8 of 21 (38.1%)	Not reported
UMEC 1000 µg	0 of 13 (0%)	4 of 13 (30.8%)	Not reported
Tiotropium 18 µg	0 of 8 (0%)	3 of 8 (37.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 23276660Tal-Singer R, Cahn A, Mehta R, Preece A, Crater G, Kelleher D, Pouliquen IJ. Initial assessment of single and repeat doses of inhaled umeclidinium in patients with chronic obstructive pulmonary disease: two randomised studies. Eur J Pharmacol. 2013 Feb 15;701(1-3):40-8. doi: 10.1016/j.ejphar.2012.12.019. Epub 2012 Dec 28.
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

3 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 GSK573719 and Tiotropium in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 3 sites in Germany.

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 12 inclusion and 36 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 22 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Germany. 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 24 Apr 2014). 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 Any Adverse Event (AE) or Any Serious Adverse Event (SAE) (time frame: From Day 1 of Treatment Period 1until Follow-up (up to 10 weeks)). The study lists 24 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 NCT00515502, 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 22 Aug 2017.