Last updated: 11/07/2018 04:26:03
A study to assess the safety and pharmacokinetics of inhaled doses of GSK233705 and GW642444 in healthy subjects
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
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
Trial description: 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.
Primary purpose:
Other
Trial design:
Crossover Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Heart rate
Timeframe: 24 hours
Systolic and diastolic blood pressure
Timeframe: 24 hours
12 lead ECG
Timeframe: 24 hours
Lung Function
Timeframe: 24 hours
Clinical laboratory safety tests
Timeframe: 24 hours
Adverse events
Timeframe: Duration of study
Secondary outcomes:
Plasma concentrations of GSK233705 and derived pharmacokinetic parameters.
Timeframe: 24 hours
Plasma concentrations of GW642444 and derived pharmacokinetic parameters.
Timeframe: 24 hours
Weighted mean and minimum value potassium
Timeframe: 0 to 4 hours post dose
Interventions:
Enrollment:
16
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Mehta R, Preece A, Newlands A, Blowers J, Cahn A. Safety, pharmacodynamics (PD) and pharmacokinetics (PK) of darotropium (DARO) and vilanterol (VI) in healthy subjects: two phase 1 studies. European Respiratory Journal. 2013;42(Suppl. 57):125-6s.
Medical condition
Pulmonary Disease, Chronic Obstructive
Product
darotropium bromide, vilanterol
Collaborators
Not applicable
Study date(s)
November 2008 to February 2009
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18 - 65 years
Accepts healthy volunteers
Yes
- 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)
- 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).
Inclusion and exclusion criteria
Inclusion criteria:
- 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. -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
Exclusion criteria:
- 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. -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 location(s)
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Study complete
Actual primary completion date
Not applicable
Actual study completion date
2009-06-02
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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Additional information
Results for study 112146 can be found on the GSK Clinical Study Register.
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