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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00674817




Registration number
NCT00674817
Ethics application status
Date submitted
24/04/2008
Date registered
8/05/2008

Titles & IDs
Public title
An Investigation Of The Interaction Of GSK961081 With Inhaled Beta-Agonist And Anti-Muscarinic Drugs.
Scientific title
A Randomized, Double-blind, Crossover Study to Investigate the Bronchodilatation Post-inhalation of GSK961081 Alone and With the Addition of Cumulative Doses of Short Acting Bronchodilators (Salbutamol and Ipratropium Bromide) in Patients With COPD
Secondary ID [1] 0 0
MAB110123
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Disease, Chronic Obstructive 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - 400 microgrammes GSK961081
Treatment: Drugs - 1200 microgrammes GSK961081

Experimental: 400 microgrammes GSK961081 and salbutamol - 400 microgrammes of GSK961081 single-dose (via DISKUS Metered Dry Powder Inhaler/ MDPI) followed by cumulative doses (3x 200 microgrammes at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.

Experimental: 1200 microgrammes GSK961081 and salbutamol - 1200 microgrammes of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 microgrammes at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.

Experimental: 400 microgrammes GSK961081 and ipratropium bromide - 400 microgrammes of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (20 microgrammes, 20 microgrammes and 40 microgrammes at 20 min intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing.

Experimental: 1200 microgrammes of GSK961081 and ipratropium bromide - 1200 microgrammes of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (20 microgrammes, 20 microgrammes and 40 microgrammes at 20 min intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing.

Placebo comparator: 400 microgrammes of GSK961081 and placebo - 400 microgrammes of GSK961081 single-dose (via DISKUS Metered Dry Powder Inhaler/ MDPI) followed by cumulative doses (3 doses at 20 min intervals, administered via spacer) of placebo at 1h, 12h and 24h of dosing.

Placebo comparator: 1200 microgrammes of GSK961081 and placebo - 1200 microgrammes of GSK961081 single-dose (via DISKUS Metered Dry Powder Inhaler/ MDPI) followed by cumulative doses (3 doses at 20 min intervals, administered via spacer) of placebo at 1h, 12h and 24h of dosing.


Treatment: Drugs: 400 microgrammes GSK961081
Inhaled GSK961081 administered via Dry Powder Inhaler.

Treatment: Drugs: 1200 microgrammes GSK961081
Inhaled GSK961081 adminisntered via dry powder inhaler.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximal Change in Forced Expiratory Volume in One Second (FEV1) From Baseline (Pre-dose on Day 1) in Combination With Short Acting Bronchodialator (Salbutamol or Ipratropium Bromide) at 1h,12h and 24h.
Timepoint [1] 0 0
Baseline (pre-dose on Day 1), 1h, 12h, and 24h on Day 1
Secondary outcome [1] 0 0
Maximal Change in Forced Vital Capacity (FVC) in One Second From Pre-dose in Combination With Short Acting Bronchodialator (Salbutamol or Ipratropium Bromide) at 1h, 12h and 24h.
Timepoint [1] 0 0
Baseline (Pre-dose on Day 1), 1h, 12h, and 24h on Day 1
Secondary outcome [2] 0 0
Number of Participants With Adverse Events and Serious Adverse Events
Timepoint [2] 0 0
Upto 82 days
Secondary outcome [3] 0 0
Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)
Timepoint [3] 0 0
Up to 42 days
Secondary outcome [4] 0 0
Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours
Timepoint [4] 0 0
Up to 27 hours post Day 1 dosing
Secondary outcome [5] 0 0
Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours
Timepoint [5] 0 0
Up to 27 hours post Day 1 dosing
Secondary outcome [6] 0 0
Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings
Timepoint [6] 0 0
From dosing until 24h post-dose.
Secondary outcome [7] 0 0
Maximum Change From Baseline (Pre-dose on Day 1) in QTc (F) in Supine Position From 0 to 4 Hours After Dosing
Timepoint [7] 0 0
From dosing until 4 hours (0-4h)
Secondary outcome [8] 0 0
Maximum Change From Baseline (Pre-dose on Day 1) in QTc (F) in Supine Position From 0 to 27 Hours After Dosing
Timepoint [8] 0 0
From dosing until 27 hours (0-27h)
Secondary outcome [9] 0 0
Weighted Mean Change From Baseline (Pre-dose on Day 1) in QTc(F) in Supine Position From 0 to 4 Hours
Timepoint [9] 0 0
From dosing until 4 hours (0-4h)
Secondary outcome [10] 0 0
Maximum Change From Baseline (Pre-dose on Day 1) in QTc(B) in Supine Position From 0 to 4 Hours and 0 to 27 Hours
Timepoint [10] 0 0
From dosing until 4 hours (0-4h) and 27 hours (0-27h)
Secondary outcome [11] 0 0
Weighted Mean Change From Baseline (Pre-dose on Day 1) in QTc(B) in Supine Position From 0 to 4 Hours
Timepoint [11] 0 0
From dosing until 4 hours (0-4h)
Secondary outcome [12] 0 0
Maximum Change From Baseline (Pre-dose on Day 1) in Supine Heart Rate From 0 to 4 Hours and From 0 to 27 Hours.
Timepoint [12] 0 0
From dosing until 4 hours (0-4h) and until 27 hours (0-27 h)
Secondary outcome [13] 0 0
Weighted Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate in Supine Position From 0 to 4 Hours
Timepoint [13] 0 0
From dosing until 4 hours (0-4h)
Secondary outcome [14] 0 0
Maximum Change From Baseline (Pre-dose on Day 1) in Supine Systolic Blood Pressure (SBP) Over 4 and 27 Hours and Weighted Mean Change From Baseline in Supine SBP Over 4 Hours
Timepoint [14] 0 0
0-4h and 0-27h for maximum change and 0-4 h for weighted mean change
Secondary outcome [15] 0 0
Minimum Change From Baseline (Pre-dose on Day 1) in Supine Diastolic Blood Pressure (DBP) Over 4 and 27 Hours and Weighted Mean Change From Baseline in Supine DBP Over 4 Hours
Timepoint [15] 0 0
0-4h and 0-27h for maximum change and 0-4 h for weighted mean change
Secondary outcome [16] 0 0
Maximum Change From Baseline (Pre-dose on Day 1) in Glucose Over 4 and 27 Hours and Weighted Mean Change From Baseline in Glucose Over 4 Hours
Timepoint [16] 0 0
0-4h and 0-27h for maximum change and 0-4 h for weighted mean change
Secondary outcome [17] 0 0
Minimum Change From Baseline (Pre-dose on Day 1) in Potassium Over 4 and 27 Hours and Weighted Mean Change From Baseline in Potassium Over 4 Hours
Timepoint [17] 0 0
0-4h and 0-27h for maximum change and 0-4 h for weighted mean change
Secondary outcome [18] 0 0
Time to Maximum Change From Baseline (Pre-dose on Day 1) for QTc(B), QTc(F), Heart Rate, Systolic BP, Glucose in Supine Position and Time to Minimum Change From Baseline for Potassium and Diastolic BP in Supine Position
Timepoint [18] 0 0
From dosing until 4 hours (0-4h)
Secondary outcome [19] 0 0
Area Under Plasma Concentration Time Curve (AUC) of GSK961081 to the Last Quantifiable Concentration
Timepoint [19] 0 0
Up to 82 days
Secondary outcome [20] 0 0
Maximum Plasma Concentration (Cmax) of GSK961081 Over Period Determined Directly From the Concentration-time Data
Timepoint [20] 0 0
Up to 82 days
Secondary outcome [21] 0 0
Time to Maximum Plasma Concentration (Tmax) of GSK961081 Over Period Determined Directly From the Concentration-time Data
Timepoint [21] 0 0
Up to 82 days
Secondary outcome [22] 0 0
Time to Last Quantifiable Plasma Concentration (Tlast) of GSK961081 Over Period Determined Directly From the Concentration-time Data
Timepoint [22] 0 0
Up to 82 days

Eligibility
Key inclusion criteria
* Subject is male or female (of non-child bearing potential) = 40 years of age and = 75 years of age.
* Non- child bearing potential is defined as physiologically incapable of becoming pregnant, including females who are post-menopausal (more than 2 years without menses with appropriate clinical history i.e. age, history of vasomotor symptoms-estradiol and FSH levels may be checked if indicated) and females who are surgically sterile (hysterectomy, tubal ligation or bilateral oophorectomy).
* Subject diagnosed with COPD in accordance with ATS/ERS guidelines (as per protocol).
* Subject is a smoker or an ex-smoker with a 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)
* Subject has FEV1 < 80 % of predicted normal for height, age, gender after inhalation of salbutamol
* Response to ipatropium bromide defined as:
* Either an increase in FEV1 of > 12 % and > 150 mL within 2 hours following inhalation of 80 µg ipratopium bromide (Atrovent MDI via spacer) at the screening visit
* Or: a documented increase in FEV1 of >12 % and > 150 mL within 2 hours following inhalation of 80 µg ipratopium bromide within 6 months of screening and an increase in FEV1 of > 6 % and > 100 mL within 2h following inhalation of 80 µg ipratopium bromide (Atrovent MDI via spacer) at the screening visit (in order to allow for potential fluctuations in the response to ipratropium bromide in patients known to be responders to ipratropium bromide)
* Response to salbutamol defined as:
* Either an increase in FEV1 of > 12 % and > 150 mL within 2 hours following inhalation of 400 µg salbutamol MDI (via spacer) at the screening visit
* Or: a documented increase in FEV1 of >12 % and > 150 mL within 2 hours following inhalation of 400 µg salbutamol MDI within 6 months of screening and an increase in FEV1 of > 6 % and >100 mL within 2h following inhalation of 400 µg salbutamol MDI (via spacer) at the screening visit (in order to allow for potential fluctuations in the response to salbutamol in patients known to be responders to salbutamol)
* Body mass index (BMI) within the range 18-35 kg/m2
* Subject is able and willing to give written informed consent to take part in the study.
* Subject is available to complete all study assessments
Minimum age
40 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Subjects who have a past or present disease, which as judged by the Investigator and medical monitor may affect the outcome of the study or the safety of the subject
* Subjects with clinically relevant findings on laboratory safety tests. Subjects with laboratory values outside the reference range may be include in the study if the Investigator and medical monitor agree that these findings would not put the subject at risk or interfere with the objectives of the study
* Women who are pregnant or lactating
* An unwillingness of subjects to abstain from sexual intercourse with pregnant or lactating women; or an unwillingness of the subject to use a condom/spermicide in addition to having their female partner use another form of contraception such as IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants or tubal ligation if the woman could become pregnant from the time of the first dose study medication until 90 days post-dose
* The subject has a positive urine drugs of abuse screen. A minimum list of drugs that will be screened for include amphetamines, barbituates, cocaine, opiates, cannabinoids and benzodiazepines.
* A history, or suspected history, of alcohol abuse within the 6 months before the screening visit.
* A positive test for hepatitis C antibody, hepatitis B surface antigen, or HIV.
* The subject has participated in a clinical study with another New Chemical Entity within the past 2 months or participated in a clinical study with any other drug during the previous month.
* The subject has donated a unit of blood within the 56 days of dosing or intends to donate within 56 days after completing the study.
* Subject has an FEV1 < 40 % of predicted for age, height and gender after inhalation of salbutamol.
* The subject has a diagnosis of active tuberculosis, lung cancer, sarcoidosis, bronchiectasis, lung fibrosis, pulmonary hypertension or with a primary diagnosis of asthma
* The subject has a known allergy or hypersensitivity to ipratropium bromide, salbutamol, or lactose
* A subject in whom ipratropium bromide or salbutamol is contraindicated
* Subjects with lung volume reduction surgery within 12 months of screening
* Poorly controlled COPD defined as:
* Either: acute worsening of COPD that is managed by the subject at home by treatment with increased corticosteroids or antibiotics in the 6 weeks before screening
* Or: more than 2 exacerbations in the previous 12 months before screening that required a course of oral steroids or antibiotics, and/or required hospitalisation
* Subject has had a respiratory tract infection in the 4 weeks before screening
* Subject requires treatment with inhaled cromolyn sodium, theophyline, oral ß2- agonists, nebulised anticholinergics or leukotriene antagonists
* Subject is unable to abstain from long acting ß2-agonist from 72 hours before screening and throughout the dosing period
* Subject is unable to abstain from tiotropium bromide from 28 days before screening and throughout the dosing period
* Subject is predicted to be unable to abstain from short acting inhaled ß2-agonists or short acting antimuscarinics for 6 hours before screening and for 6 hours before dosing with GSK961081 until all post-dose lung function tests have been completed for a given study day.
* Subject has received oral corticosteroids within the 6 weeks before screening
* Subject is receiving > 1000 µg FP (or equivalent) a day of inhaled corticosteroid or has changed dose within the 6 weeks before screening or is predicted not to be able to maintain a constant dose during the study
* Subject is receiving oxygen therapy or nocturnal positive pressure treatment
* Medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the study investigator would prevent use of an inhaled anticholinergic
* The subject is unable to use the dosing devices (MDPI/ MDI/ spacer) correctly.
* Subject with carcinoma that has not been in complete remission for at least 5 years (with the exception of carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma if the subject is considered cured)
* A history of congestive heart failure, coronary insufficiency or cardiac arrhythmia or a finding on screening 24h Holter monitor that would contraindicate the subject's participation in the study
* 12- lead ECG abnormality which is either clinically significant or may interfere with QTc measurement or QTc > 450 msec or PR interval outside the range 120 to 220 msec.
* A supine mean heart rate outside the range 40-90 bpm at screening.
* Persistently elevated supine blood pressure higher than 160/95 at screening.
* Subject is receiving a high-dose diuretic and/ or ß2-adrenergic antagonist
* Subject has a serum potassium level below the reference range at screening.
* Inability to understand the protocol requirements, instructions and study-related restrictions; the nature, scope and possible consequences of the study.
* Unlikely to complete the study; e.g., uncooperative attitude, inability to return for follow-up visits.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Wellington
Country [2] 0 0
Thailand
State/province [2] 0 0
Chiangmai
Country [3] 0 0
Thailand
State/province [3] 0 0
Khon Kaen
Country [4] 0 0
United Kingdom
State/province [4] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Theravance Biopharma
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
GlaxoSmithKline
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.