Pulmonary Disease, Chronic ObstructivePhase 2NCT00674817
An Investigation Of The Interaction Of GSK961081 With Inhaled Beta-Agonist And Anti-Muscarinic Drugs.
A Phase 2 study testing 400 microgrammes GSK961081 and 1200 microgrammes GSK961081 in people with Pulmonary Disease, Chronic Obstructive, run by Theravance Biopharma at 4 sites in 3 countries.
Trial summary
GSK961081 is a potent dual pharmacophore that demonstrates both antimuscarinic and beta-agonist pharmacology in preclinical studies, both pharmacologies being of long duration. If reproduced in man, GSK961081 has the potential to deliver a medicine that can be given 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?
- 400 microgrammes GSK961081 and 1200 microgrammes GSK961081
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 4 sitesin 3 countries
- Study dates
- 1 Apr 2008to 19 Oct 2008
- 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
- 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
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
Thailand2 sites
GSK Investigational Site
Chiang Mai, 50200
GSK Investigational Site
Khon Kaen, 40002
About this study
Official 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
GSK961081 is a potent dual pharmacophore that demonstrates both antimuscarinic and beta-agonist pharmacology in preclinical studies, both pharmacologies being of long duration. If reproduced in man, GSK961081 has the potential to deliver a medicine that can be given once daily. The bronchodilatation after inhalation of single doses of GSK961081 alone and in the presence of the short acting beta agonist salbutamol and the short acting muscarinic antagonist, ipratropium bromide will be measured in this study. Any residual bronchodilatation post-inhalation of GSK961081 and demonstrated by addition of salbutamol or ipratropium bromide may provide an indirect assessment of the beta-agonist and antimuscarinic components of GSK961081
Read the detailed description
GSK961081 is a potent dual pharmacophore that demonstrates both antimuscarinic and beta-agonist pharmacology in preclinical studies, both pharmacologies being of long duration. If reproduced in man, GSK961081 has the potential to deliver a medicine that can be given once daily. The bronchodilatation after inhalation of single doses of GSK961081 alone and in the presence of the short acting beta agonist salbutamol and the short acting muscarinic antagonist, ipratropium bromide will be measured in this study. Any residual bronchodilatation post-inhalation of GSK961081 and demonstrated by addition of salbutamol or ipratropium bromide may provide an indirect assessment of the beta-agonist and antimuscarinic components of GSK961081
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Being tested
- 400 microgrammes GSK961081, 1200 microgrammes GSK961081
- Keywords
- salbutamol,, Chronic Obstructive Pulmonary Disease (COPD), GSK961081 muscarinic receptor antagonist,, COPD, ipratropium bromide,, Asthma, ß2-adrenergic agonist,
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
400 microgrammes GSK961081Drug
Inhaled GSK961081 administered via Dry Powder Inhaler.
1200 microgrammes GSK961081Drug
Inhaled GSK961081 adminisntered via dry powder inhaler.
| Study group | Role | What they receive |
|---|---|---|
| 400 microgrammes GSK961081 and salbutamol | Experimental | 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. Receives: Drug: 400 microgrammes GSK961081 |
| 1200 microgrammes GSK961081 and salbutamol | Experimental | 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. Receives: Drug: 400 microgrammes GSK961081; Drug: 1200 microgrammes GSK961081 |
| 400 microgrammes GSK961081 and ipratropium bromide | Experimental | 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. Receives: Drug: 1200 microgrammes GSK961081 |
| 1200 microgrammes of GSK961081 and ipratropium bromide | Experimental | 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. Receives: Drug: 400 microgrammes GSK961081; Drug: 1200 microgrammes GSK961081 |
| 400 microgrammes of GSK961081 and placebo | Placebo comparator | 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. Receives: Drug: 1200 microgrammes GSK961081 |
| 1200 microgrammes of GSK961081 and placebo | Placebo comparator | 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. Receives: Drug: 400 microgrammes GSK961081 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second as measured by spirometry. Adjusted mean has been presented as least square (LS) mean.
Measured: Baseline (pre-dose on Day 1), 1h, 12h, and 24h on Day 1
Secondary outcomes (22)
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.
FVC is defined as the amount of air that can be forcibly exhaled from the lungs after a maximum inspiration as measured by spirometry. Adjusted mean has been presented as least square (LS) mean.
Measured: Baseline (Pre-dose on Day 1), 1h, 12h, and 24h on Day 1
Number of Participants With Adverse Events and Serious Adverse Events
An adverse event (AE) is any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious AE (SAE) is 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, or is a congenital anomaly/birth defect.
Measured: Upto 82 days
Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)
The normal ranges of laboratory parameters were hemoglobin: 130-167 grams per deciliter (g/dL), platelets: 173-383 Giga per liter (GI/L), lymphocytes: 20.1-44.5 %, glucose: 3.8857-6.106 millimoles per liter (mmol/L), creatinine: 44.2-132.6 micromoles per liter (uM/L) , aspartate transaminases (AST): 12-32 international units per liter (IU/L), total bilirubin (TB): 4.275-25.65 uM/L and potassium: 3.4-4.7 mmol/L, respectively. Laboratory values recorded outside the normal range were considered of potential clinical concern (PCC).
Measured: Up to 42 days
Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours
Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was analyzed. Change from baseline is the difference in the blood pressure at the indicated time point minus the Baseline value.
Measured: Up to 27 hours post Day 1 dosing
Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours
Heart rate was considered as a measure of vital sign. Change from baseline is the difference in the blood pressure at the indicated time point minus the Baseline value.
Measured: Up to 27 hours post Day 1 dosing
Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings
Analysis QTc interval of ECG was performed by Bazett's formula (QTc B) and Fridericia's correction (QTc F). Number of participants with abnormal ECG findings were recorded. Any participant with QTc(B) or QTc(F) >500 milliseconds (msec) or uncorrected QT >600 msec (machine or manual over read) was withdrawn from the study. Participants that had right bundle branch block with QTc(B) or QTc(F) >530 msec were also withdrawn from the study.
Measured: From dosing until 24h post-dose.
Maximum Change From Baseline (Pre-dose on Day 1) in QTc (F) in Supine Position From 0 to 4 Hours After Dosing
Analysis of QT (F) interval during ECG (taken in supine position) was performed using Fridericia's method. Change from baseline is the value at indicated time point minus the value at Baseline. Adjusted means are considered as least square (LS) mean values while presenting the data.
Measured: From dosing until 4 hours (0-4h)
Maximum Change From Baseline (Pre-dose on Day 1) in QTc (F) in Supine Position From 0 to 27 Hours After Dosing
Analysis of Q T (F) interval during ECG (taken in supine position) was performed using Fridericia's method. Change from baseline is the value at indicated time point minus the value at Baseline. Adjusted means are considered as LS mean values while presenting the data .
Measured: From dosing until 27 hours (0-27h)
Weighted Mean Change From Baseline (Pre-dose on Day 1) in QTc(F) in Supine Position From 0 to 4 Hours
Analysis of QT(F) interval during ECG (taken in supine position) was performed using Fridericia's method. Change from baseline is the value at indicated time point minus the value at Baseline. Weighted means are considered as LS mean values while presenting the data.
Measured: From dosing until 4 hours (0-4h)
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
Analysis of QT (B) interval during ECG (taken in supine position) was performed using Bazett's method. Change from baseline is the value at indicated time point minus the value at Baseline. Weighted means are considered as LS mean values while presenting the data .
Measured: From dosing until 4 hours (0-4h) and 27 hours (0-27h)
Weighted Mean Change From Baseline (Pre-dose on Day 1) in QTc(B) in Supine Position From 0 to 4 Hours
Analysis of QT (B) interval during ECG (taken in supine position) was performed using Bazett's method. Change from baseline is the value at indicated time point minus the value at Baseline. Weighted means are considered as LS mean values while presenting the data.
Measured: From dosing until 4 hours (0-4h)
Maximum Change From Baseline (Pre-dose on Day 1) in Supine Heart Rate From 0 to 4 Hours and From 0 to 27 Hours.
Heart rate was measured in supine position. Change from baseline is the value at indicated time point minus the value at Baseline. Adjusted means are considered as LS mean values while presenting the data.
Measured: From dosing until 4 hours (0-4h) and until 27 hours (0-27 h)
Weighted Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate in Supine Position From 0 to 4 Hours
Heart rate was recorded in supine position. Change from baseline is the value at indicated time point minus the value at Baseline. Weighted means are considered as LS mean values while presenting the data.
Measured: From dosing until 4 hours (0-4h)
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
Systolic blood pressure (SBP) values were recorded in supine position. Change from baseline is the value at indicated time point minus the value at Baseline. Adjusted or maximum change/ (MC) and weighted mean change (WMC) are considered as LS mean change values while presenting the data.
Measured: 0-4h and 0-27h for maximum change and 0-4 h for weighted mean change
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
Diastolic blood pressure (DBP) values were recorded in supine position. Change from baseline is the value at indicated time point minus the value at Baseline. Adjusted or maximum change/(MC) and weighted mean change (WMC) are considered as LS mean change values while presenting the data .
Measured: 0-4h and 0-27h for maximum change and 0-4 h for weighted mean change
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
Maximum change (MC) from Baseline (BL) and weighted mean change (WMC) from baseline in glucose (GLU) were analyzed. Change from Baseline is the value at indicated time point minus the value at Baseline. Weighted means are considered as LS mean values while presenting the data.
Measured: 0-4h and 0-27h for maximum change and 0-4 h for weighted mean change
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
Maximum change (MC) from Baseline (BL) and weighted mean change (WMC) from baseline in potassium (K) were analyzed. Change from Baseline is the value at indicated time point minus the value at Baseline. Weighted means are considered as LS mean values while presenting the data.
Measured: 0-4h and 0-27h for maximum change and 0-4 h for weighted mean change
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
Analysis of QT (B) or QTc (F) interval during ECG (taken in supine position) was performed using Bazett's method and Fridericia's method, respectively. Heart rate, BP, potassium, and glucose were measured in supine body position. Change from baseline is the value at indicated time point minus the value at Baseline. Weighted means are considered as LS mean values while presenting the data.
Measured: From dosing until 4 hours (0-4h)
Area Under Plasma Concentration Time Curve (AUC) of GSK961081 to the Last Quantifiable Concentration
AUC(0-t) is the area under plasma concentration time curve of GSK961081 to the last quantifiable concentration. This parameter was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. A large proportion of AUC(0-t) and Cmax values were reported as not countable (NC) at the GSK961081 400 micrograms (ug) dose level, therefore only limited summaries were calculated. Logarithmic transformed values are presented. AUC(0-t) imputed with 1/2 lowest observed AUC(0-t), where lowest AUC(0-t) was 56.46 hour picograms per milliliter (h*pg/mL).
Measured: Up to 82 days
Maximum Plasma Concentration (Cmax) of GSK961081 Over Period Determined Directly From the Concentration-time Data
Cmax is the Maximum observed concentration of GSK961081 determined directly from the concentration-time data. A large proportion of Cmax values were reported as not countable (NC ) at the GSK961081 400 micrograms (ug) dose level, therefore only limited summaries were calculated. Logarithmic transformed values are presented. Cmax was imputed with 1/2 lowest limit of quantification (LLQ), where LLQ was 25 picograms per milliliter (pg/mL).
Measured: Up to 82 days
Time to Maximum Plasma Concentration (Tmax) of GSK961081 Over Period Determined Directly From the Concentration-time Data
Tmax is the time to maximum plasma concentration of GSK961081 over period determined directly from the concentration-time data
Measured: Up to 82 days
Time to Last Quantifiable Plasma Concentration (Tlast) of GSK961081 Over Period Determined Directly From the Concentration-time Data
Tlast is the time to last quantifiable plasma concentration of GSK961081 over period determined directly from the concentration-time data
Measured: Up to 82 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2008 (estimated)
- Study start1 Apr 2008
- Primary completion1 Oct 2008
- Study completion19 Oct 2008
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.
- 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Theravance Biopharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00674817
- Sponsor's protocol ID
- MAB110123
- Status last verified
- Sep 2021
- First submitted
- 24 Apr 2008
- Last updated
- 20 Oct 2021
- 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
Norris V, Ambery C. Bronchodilation and safety of supratherapeutic doses of salbutamol or ipratropium bromide added to single dose GSK961081 in patients with moderate to severe COPD. Pulm Pharmacol Ther. 2013 Oct;26(5):574-80. doi: 10.1016/j.pupt.2013.03.009. Epub 2013 Mar 21.
PubMed 23524017
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT00674817
- Acronym / sponsor ID
- MAB110123
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Keywords
- salbutamol,, Chronic Obstructive Pulmonary Disease (COPD), GSK961081 muscarinic receptor antagonist,, COPD, ipratropium bromide,, Asthma, ß2-adrenergic agonist,
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Theravance BiopharmaIndustry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Study start
- 1 Apr 2008
- Primary completion
- 1 Oct 2008 (actual)
- Study completion
- 19 Oct 2008 (actual)
- First posted
- 8 May 2008 (estimated)
- Results
- Posted 27 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
GSK961081 is a potent dual pharmacophore that demonstrates both antimuscarinic and beta-agonist pharmacology in preclinical studies, both pharmacologies being of long duration. If reproduced in man, GSK961081 has the potential to deliver a medicine that can be given once daily. The bronchodilatation after inhalation of single doses of GSK961081 alone and in the presence of the short acting beta agonist salbutamol and the short acting muscarinic antagonist, ipratropium bromide will be measured in this study. Any residual bronchodilatation post-inhalation of GSK961081 and demonstrated by addition of salbutamol or ipratropium bromide may provide an indirect assessment of the beta-agonist and antimuscarinic components of GSK961081
Detailed description
GSK961081 is a potent dual pharmacophore that demonstrates both antimuscarinic and beta-agonist pharmacology in preclinical studies, both pharmacologies being of long duration. If reproduced in man, GSK961081 has the potential to deliver a medicine that can be given once daily. The bronchodilatation after inhalation of single doses of GSK961081 alone and in the presence of the short acting beta agonist salbutamol and the short acting muscarinic antagonist, ipratropium bromide will be measured in this study. Any residual bronchodilatation post-inhalation of GSK961081 and demonstrated by addition of salbutamol or ipratropium bromide may provide an indirect assessment of the beta-agonist and antimuscarinic components of GSK961081
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| 400 microgrammes GSK961081 and salbutamol | Experimental | Drug: 400 microgrammes GSK961081400 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. |
| 1200 microgrammes GSK961081 and salbutamol | Experimental | Drug: 400 microgrammes GSK961081, Drug: 1200 microgrammes GSK9610811200 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. |
| 400 microgrammes GSK961081 and ipratropium bromide | Experimental | Drug: 1200 microgrammes GSK961081400 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. |
| 1200 microgrammes of GSK961081 and ipratropium bromide | Experimental | Drug: 400 microgrammes GSK961081, Drug: 1200 microgrammes GSK9610811200 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. |
| 400 microgrammes of GSK961081 and placebo | Placebo comparator | Drug: 1200 microgrammes GSK961081400 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. |
| 1200 microgrammes of GSK961081 and placebo | Placebo comparator | Drug: 400 microgrammes GSK9610811200 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. |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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)
Key exclusion criteria (36 listed)
- 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.
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 |
|---|---|---|
| 400 microgrammes GSK961081Inhaled GSK961081 administered via Dry Powder Inhaler. | Drug | 1200 microgrammes GSK961081 and salbutamol, 1200 microgrammes of GSK961081 and ipratropium bromide, 1200 microgrammes of GSK961081 and placebo, 400 microgrammes GSK961081 and salbutamol |
| 1200 microgrammes GSK961081Inhaled GSK961081 adminisntered via dry powder inhaler. | Drug | 1200 microgrammes GSK961081 and salbutamol, 1200 microgrammes of GSK961081 and ipratropium bromide, 400 microgrammes GSK961081 and ipratropium bromide, 400 microgrammes of GSK961081 and placebo |
Primary outcome
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.
Time frame: Baseline (pre-dose on Day 1), 1h, 12h, and 24h on Day 1
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second as measured by spirometry. Adjusted mean has been presented as least square (LS) mean.
22 secondary outcomes
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.
Time frame: Baseline (Pre-dose on Day 1), 1h, 12h, and 24h on Day 1
Number of Participants With Adverse Events and Serious Adverse Events
Time frame: Upto 82 days
Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)
Time frame: Up to 42 days
Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours
Time frame: Up to 27 hours post Day 1 dosing
Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours
Time frame: Up to 27 hours post Day 1 dosing
Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings
Time frame: From dosing until 24h post-dose.
Maximum Change From Baseline (Pre-dose on Day 1) in QTc (F) in Supine Position From 0 to 4 Hours After Dosing
Time frame: From dosing until 4 hours (0-4h)
Maximum Change From Baseline (Pre-dose on Day 1) in QTc (F) in Supine Position From 0 to 27 Hours After Dosing
Time frame: From dosing until 27 hours (0-27h)
Weighted Mean Change From Baseline (Pre-dose on Day 1) in QTc(F) in Supine Position From 0 to 4 Hours
Time frame: From dosing until 4 hours (0-4h)
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
Time frame: From dosing until 4 hours (0-4h) and 27 hours (0-27h)
Weighted Mean Change From Baseline (Pre-dose on Day 1) in QTc(B) in Supine Position From 0 to 4 Hours
Time frame: From dosing until 4 hours (0-4h)
Maximum Change From Baseline (Pre-dose on Day 1) in Supine Heart Rate From 0 to 4 Hours and From 0 to 27 Hours.
Time frame: From dosing until 4 hours (0-4h) and until 27 hours (0-27 h)
Weighted Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate in Supine Position From 0 to 4 Hours
Time frame: From dosing until 4 hours (0-4h)
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
Time frame: 0-4h and 0-27h for maximum change and 0-4 h for weighted mean change
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
Time frame: 0-4h and 0-27h for maximum change and 0-4 h for weighted mean change
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
Time frame: 0-4h and 0-27h for maximum change and 0-4 h for weighted mean change
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
Time frame: 0-4h and 0-27h for maximum change and 0-4 h for weighted mean change
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
Time frame: From dosing until 4 hours (0-4h)
Area Under Plasma Concentration Time Curve (AUC) of GSK961081 to the Last Quantifiable Concentration
Time frame: Up to 82 days
Maximum Plasma Concentration (Cmax) of GSK961081 Over Period Determined Directly From the Concentration-time Data
Time frame: Up to 82 days
Time to Maximum Plasma Concentration (Tmax) of GSK961081 Over Period Determined Directly From the Concentration-time Data
Time frame: Up to 82 days
Time to Last Quantifiable Plasma Concentration (Tlast) of GSK961081 Over Period Determined Directly From the Concentration-time Data
Time frame: Up to 82 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23524017Norris V, Ambery C. Bronchodilation and safety of supratherapeutic doses of salbutamol or ipratropium bromide added to single dose GSK961081 in patients with moderate to severe COPD. Pulm Pharmacol Ther. 2013 Oct;26(5):574-80. doi: 10.1016/j.pupt.2013.03.009. Epub 2013 Mar 21.
- 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 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 400 microgrammes GSK961081 and 1200 microgrammes GSK961081 in people with Pulmonary Disease, Chronic Obstructive, run by Theravance Biopharma at 4 sites in 3 countries.
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 15 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 20 Oct 2021. 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 Thailand, New Zealand, United Kingdom. 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. Some participants in this study may receive a placebo. 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 27 Mar 2017). 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?
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. (time frame: Baseline (pre-dose on Day 1), 1h, 12h, and 24h on Day 1). 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 NCT00674817, 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 20 Oct 2021.