Pulmonary Disease, Chronic ObstructivePhase 1NCT00783003
A Study to Assess the Safety and Pharmacokinetics of Inhaled Doses of GSK233705 and GW642444 in Healthy Subjects
A Phase 1 study testing GSK233705 and GW642444, GW642444 and GSK233705 in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 1 site in United Kingdom.
Trial summary
GW642444 and GSK233705 are in development for treatment of Chronic Obstructive Pulmonary Disease. Development of these two inhaled drugs as a combination therapy would have potential for improved patient benefit as they both work through different mechanisms and the combined bronchodilatory effect might be additive. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive
- What is being tested?
- GSK233705 and GW642444, GW642444 and GSK233705
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 10 Nov 2008to 6 Feb 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Japanese ethnic origin (defined as having been born in Japan with four ethnic Japanese grandparents and able to speak Japanese)
- Male or female between 18 and 65 years of age.
- Female subjects must be of non childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy or double oophorectomy or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol < 40 pg/ml (<140 pmol/L) or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
- Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until 90 days post-last dose.
- Body weight > 45 kg and body mass index within the range of 18-28 kg/m2 inclusive.
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- Average QTc(B) < 450 msec taken from triplicate assessments at screening.
- No clinically active and relevant abnormality on 12-lead ECG at screening or 24h Holter ECG.
- Normal spirometry (FEV1 ≥ 80% of predicted, FEV1/FVC ≥ 70%).
- Non-smokers (never smoked or not smoking for >6 months with <10 pack years history (Pack years = (cigarettes per day smoked/20) x number of years smoked))
- A signed and dated written informed consent is obtained from the subject
- The subject is capable of giving informed consent, which includes compliance with the requirements and restrictions listed in the consent form
- Available to complete the study
Who cannot join
- Any clinically important abnormality identified at the screening medical assessment (physical examination/medical history), clinical laboratory tests, or ECG (12-lead). 24hr Holter monitoring outside normal limits.
- A history of breathing problems (i.e. history of asthmatic symptomatology, unless asthma in childhood that has now resolved and no longer requires maintenance therapy which should not be an exclusion).
- A mean QTc(B) value at screening >450msec, or an ECG that is not suitable for QT measurements (e.g. LBBB or poorly defined termination of the T wave).
- A history of elevated resting blood pressure or a mean blood pressure higher than 140/90 mmHg at screening.
- A mean heart rate outside the range 40-90 bpm at screening.
- The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates and benzodiazepines. The detection of drugs with a legitimate medical use would not necessarily be an exclusion to study participation. The detection of alcohol would not be an exclusion at screening but would need to be negative pre-dose and during the study.
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- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- A positive test for HIV antibody (if determined by the local SOP's).
- History of high alcohol consumption within 3months of the study defined as: an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- Use of prescription or non-prescription drugs, (except for simple analgesics eg paracetamol), including vitamins, herbal and dietary supplements (including St John's Wort (Hypericum)) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Urinary cotinine levels indicative of smoking or history of regular use of tobacco- or nicotine-containing products prior to screening.
- The subject is unable to use the novel dry powder inhaler correctly.
- The subject has a known allergy or hypersensitivity to ipratropium bromide, Tiotropium, atropine and any of its derivatives.
- Any adverse reaction including immediate or delayed hypersensitivity to any β2 agonist or sympathomimetic drug,
- The subject has a known allergy or hypersensitivity to milk protein or the excipients lactose monohydrate and MgSt.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single Centre, Randomised, Placebo-controlled, Four-way Cross Over Study to Assess the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Single Inhaled Doses of GSK233705 and GW642444 as Monotherapies and in Combination in Healthy Japanese Subjects
GW642444 and GSK233705 are in development for treatment of Chronic Obstructive Pulmonary Disease. Development of these two inhaled drugs as a combination therapy would have potential for improved patient benefit as they both work through different mechanisms and the combined bronchodilatory effect might be additive. This study will look at the this combination, for the first time, in healthy Japanese subjects.
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Being tested
- GSK233705 and GW642444, GW642444, GSK233705, Placebo
- Keywords
- Tolerability, Muscarinic Receptor Antagonist, Anticholinergic, Safety, Anticholinergic, ß2 agonist, Pharmacokinetics
- 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.
GSK233705 and GW642444Drug
Inhaled Long acting muscarinic receptor antagonist (LAMA) and a inhaled Long acting Beta 2 agonist (LABA) both in development as treatment for Chronic Obstructive Pulmonary Disease, taken in combination.
GW642444Drug
Inhaled Long acting Beta 2 agonist (LABA)
GSK233705Drug
Inhaled Long acting muscarinic receptor antagonist (LAMA which is in development as a treatment for Chronic Obstructive Pulmonary Disease.
PlaceboDrug
Matching placebo.
| Study group | Role | What they receive |
|---|---|---|
| Long acting muscarinic receptor antagonist (LAMA) | Experimental | Inhaled Long acting muscarinic receptor antagonist (LAMA which is in development as a treatment for Chronic Obstructive Pulmonary Disease. Receives: Drug: GSK233705 |
| Long acting Beta 2 agonist (LABA) | Experimental | Inhaled Long Acting Beta 2 agonist (LABA) which is in development as a treatment for Chronic Obstructive Pulmonary Disease. Receives: Drug: GW642444 |
| LAMA with LABA | Experimental | Inhaled Long Acting Muscarinic receptor Antagonist (LAMA) and a inhaled Long Acting Beta 2 Agonist (LABA), both in development for treatment of Chronic Obstructive Pulmonary Disease and taken in combination. Receives: Drug: GSK233705 and GW642444 |
| Placebo | Placebo comparator | Matching placebo, no intervention. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heart rate
Measured: 24 hours
Systolic and diastolic blood pressure
Measured: 24 hours
12 lead ECG
Measured: 24 hours
Lung Function
Measured: 24 hours
Clinical laboratory safety tests
Measured: 24 hours
Adverse events
Measured: Duration of study
Secondary outcomes (3)
Plasma concentrations of GSK233705 and derived pharmacokinetic parameters.
Measured: 24 hours
Plasma concentrations of GW642444 and derived pharmacokinetic parameters.
Measured: 24 hours
Weighted mean and minimum value potassium
Measured: 0 to 4 hours post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2008 (estimated)
- Study start10 Nov 2008
- Primary completion6 Feb 2009
- Study completion6 Feb 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00783003
- Sponsor's protocol ID
- 112146
- Status last verified
- Jul 2017
- First submitted
- 30 Oct 2008
- Last updated
- 18 Jul 2017
- Results posted
- No
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Centre, Randomised, Placebo-controlled, Four-way Cross Over Study to Assess the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Single Inhaled Doses of GSK233705 and GW642444 as Monotherapies and in Combination in Healthy Japanese Subjects
- ClinicalTrials.gov ID
- NCT00783003
- Acronym / sponsor ID
- 112146
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Keywords
- Tolerability, Muscarinic Receptor Antagonist, Anticholinergic, Safety, Anticholinergic, ß2 agonist, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 10 Nov 2008 (actual)
- Primary completion
- 6 Feb 2009 (actual)
- Study completion
- 6 Feb 2009 (actual)
- First posted
- 31 Oct 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
GW642444 and GSK233705 are in development for treatment of Chronic Obstructive Pulmonary Disease. Development of these two inhaled drugs as a combination therapy would have potential for improved patient benefit as they both work through different mechanisms and the combined bronchodilatory effect might be additive. This study will look at the this combination, for the first time, in healthy Japanese subjects.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Long acting muscarinic receptor antagonist (LAMA) | Experimental | Drug: GSK233705Inhaled Long acting muscarinic receptor antagonist (LAMA which is in development as a treatment for Chronic Obstructive Pulmonary Disease. |
| Long acting Beta 2 agonist (LABA) | Experimental | Drug: GW642444Inhaled Long Acting Beta 2 agonist (LABA) which is in development as a treatment for Chronic Obstructive Pulmonary Disease. |
| LAMA with LABA | Experimental | Drug: GSK233705 and GW642444Inhaled Long Acting Muscarinic receptor Antagonist (LAMA) and a inhaled Long Acting Beta 2 Agonist (LABA), both in development for treatment of Chronic Obstructive Pulmonary Disease and taken in combination. |
| Placebo | Placebo comparator | Drug: PlaceboMatching placebo, no intervention. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Healthy as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Japanese ethnic origin (defined as having been born in Japan with four ethnic Japanese grandparents and able to speak Japanese)
- Male or female between 18 and 65 years of age.
- Female subjects must be of non childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy or double oophorectomy or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol < 40 pg/ml (<140 pmol/L) or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
- Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until 90 days post-last dose.
Key exclusion criteria (20 listed)
- Any clinically important abnormality identified at the screening medical assessment (physical examination/medical history), clinical laboratory tests, or ECG (12-lead). 24hr Holter monitoring outside normal limits.
- A history of breathing problems (i.e. history of asthmatic symptomatology, unless asthma in childhood that has now resolved and no longer requires maintenance therapy which should not be an exclusion).
- A mean QTc(B) value at screening >450msec, or an ECG that is not suitable for QT measurements (e.g. LBBB or poorly defined termination of the T wave).
- A history of elevated resting blood pressure or a mean blood pressure higher than 140/90 mmHg at screening.
- A mean heart rate outside the range 40-90 bpm at screening.
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 |
|---|---|---|
| GSK233705 and GW642444Inhaled Long acting muscarinic receptor antagonist (LAMA) and a inhaled Long acting Beta 2 agonist (LABA) both in development as treatment for Chronic Obstructive Pulmonary Disease, taken in combination. | Drug | LAMA with LABA |
| GW642444Inhaled Long acting Beta 2 agonist (LABA) | Drug | Long acting Beta 2 agonist (LABA) |
| GSK233705Inhaled Long acting muscarinic receptor antagonist (LAMA which is in development as a treatment for Chronic Obstructive Pulmonary Disease. | Drug | Long acting muscarinic receptor antagonist (LAMA) |
| PlaceboMatching placebo. | Drug | Placebo |
Primary outcome
Heart rate
Time frame: 24 hours
Systolic and diastolic blood pressure
Time frame: 24 hours
12 lead ECG
Time frame: 24 hours
Lung Function
Time frame: 24 hours
Clinical laboratory safety tests
Time frame: 24 hours
Adverse events
Time frame: Duration of study
3 secondary outcomes
Plasma concentrations of GSK233705 and derived pharmacokinetic parameters.
Time frame: 24 hours
Plasma concentrations of GW642444 and derived pharmacokinetic parameters.
Time frame: 24 hours
Weighted mean and minimum value potassium
Time frame: 0 to 4 hours post dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2017.
- Results for study 112146 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
- 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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK233705 and GW642444, GW642444 and GSK233705 in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 1 site in United Kingdom.
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 13 inclusion and 20 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 18 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Heart rate (time frame: 24 hours). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Jul 2017.