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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00549744




Registration number
NCT00549744
Ethics application status
Date submitted
25/10/2007
Date registered
26/10/2007
Date last updated
26/06/2017

Titles & IDs
Public title
Clinical Endpoint Trial Investigating Once Daily and Bronchodilator Dosing
Scientific title
A Randomized, Double-blind, Double-dummy, Placebocontrolled,Three-period, Incomplete Block, Crossover Study, to a Investigate the Effect of 14 Days Repeat Inhaled Dosing With GSK256066 in Mild/Moderate Asthmatic Patients.
Secondary ID [1] 0 0
IPA107948
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from Baseline (pre-bronchodilator and pre-dose) forced expiratory volume at 1 second (FEV1) on Day 14
Timepoint [1] 0 0
Baseline (Day 1, pre-dose) and Day 14 of each treatment period
Secondary outcome [1] 0 0
Change from Baseline (pre-bronchodilator and pre-dose) FEV1 on Day 7 and at one h post-dose on Day 7 and Day 14
Timepoint [1] 0 0
Day 1 (Baseline, pre-dose), Day 7 and Day 14 of each treatment period
Secondary outcome [2] 0 0
Change from Baseline in FEV1 over 12 h post-dose on Day 1
Timepoint [2] 0 0
Baseline (Day 1, pre-dose) and Day 1 (0.5 h, 1 h, 2 h, 8 h and 12 h post-dose) of each treatment period
Secondary outcome [3] 0 0
Change from Baseline in FEV1 over 12 h post-dose on Day 14
Timepoint [3] 0 0
Baseline (Day 1, pre-dose) and Day 14 (0.5 h, 1 h, 2 h, 8 h and 12 h post-dose) of each treatment period
Secondary outcome [4] 0 0
Mean change from Baseline (pre-bronchodilator and pre-dose) Peak Expiratory Flow Rate (PEFR) averaged over the 14-day period
Timepoint [4] 0 0
Baseline (Screening, 7 days prior to Day 1 of Treatment period 1) and Day 1 to 14 of each treatment period
Secondary outcome [5] 0 0
Mean change from Baseline ratio of exhaled nitric oxide on Day 1, Day 7 and Day 14
Timepoint [5] 0 0
Baseline (Day 1 pre-dose), Day 7 and Day 14 of each treatment period
Secondary outcome [6] 0 0
Mean provocative concentration of methacholine resulting in a 20% reduction in FEV1 (PC20) on Day 15
Timepoint [6] 0 0
Day 15 of each treatment period
Secondary outcome [7] 0 0
Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC [0-t]) and to infinity (AUC [0-infinity]) of GSK256066 at Day 1 and Day 14
Timepoint [7] 0 0
Day 1 (pre-dose, 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h and 12 h) and Day 14 (pre-dose, 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h and 24 h)
Secondary outcome [8] 0 0
Maximum observed concentration (Cmax) of GSK256066 at Day 1 and 14
Timepoint [8] 0 0
Day 1 (pre-dose, 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h and 12 h) and Day 14 (pre-dose, 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h and 24 h)
Secondary outcome [9] 0 0
Time of occurrence of Cmax (Tmax) and time to apparent terminal elimination phase half-life (t1/2) of GSK256066 at Day 1 and Day 14
Timepoint [9] 0 0
Day 1 (pre-dose, 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h and 12 h) and Day 14 (pre-dose, 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h and 24 h)
Secondary outcome [10] 0 0
AUC (0-t) and AUC (0-infinity) of GSK614917 at Day 1 and Day 14
Timepoint [10] 0 0
Day 1 (pre-dose, 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h and 12 h) and Day 14 (pre-dose, 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h and 24 h)
Secondary outcome [11] 0 0
Cmax of GSK614917 at Day 1 and Day 14
Timepoint [11] 0 0
Day 1 (pre-dose, 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h and 12 h) and Day 14 (pre-dose, 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h and 24 h)
Secondary outcome [12] 0 0
Tmax and t1/2 of GSK614917 at Day 1 and Day 14
Timepoint [12] 0 0
Day 1 (pre-dose, 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h and 12 h) and Day 14 (pre-dose, 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h and 24 h)
Secondary outcome [13] 0 0
Number of participants with any adverse event (AE), serious adverse event (SAE) or death
Timepoint [13] 0 0
Up to Follow-up (18 weeks)
Secondary outcome [14] 0 0
Number of participants with abnormal both clinically non-significant (CNS) and clinically significant (CS) electrocardiograph (ECG) values
Timepoint [14] 0 0
Up to Day 14 of each treatment period
Secondary outcome [15] 0 0
Number of participants with hematology abnormalities of potential clinical importance (PCI) during the treatment period
Timepoint [15] 0 0
Up to Day 14 of each treatment period
Secondary outcome [16] 0 0
Number of participants with clinical chemistry abnormalities of PCI during the treatment period
Timepoint [16] 0 0
Up to Day 14 of each treatment period
Secondary outcome [17] 0 0
Number of participants with abnormal urinalysis results
Timepoint [17] 0 0
Up to Day 14 of each treatment period
Secondary outcome [18] 0 0
Number of participants with vital sign value of PCI during the treatment period
Timepoint [18] 0 0
Up to Day 14 of each treatment period
Secondary outcome [19] 0 0
Number of participants with troponin results
Timepoint [19] 0 0
Up to Day 14 of each treatment period
Secondary outcome [20] 0 0
Genetic variations of participants for relationship between genetic variants and or PK, tolerability and efficacy of GSK256066
Timepoint [20] 0 0
At any time post-Randomization
Secondary outcome [21] 0 0
Mean phosphodiesterase-4 (PDE4) values
Timepoint [21] 0 0
Day 7 of each treatment period
Secondary outcome [22] 0 0
Mean differential cell counts during sputum analysis
Timepoint [22] 0 0
Day 7 of each treatment period
Secondary outcome [23] 0 0
Biomarkers of sputum analysis
Timepoint [23] 0 0
Day 7 of each treatment period
Secondary outcome [24] 0 0
Mean interleukin-10 (IL-10), IL-13 and tumour necrosis factor alfa (TNFa) values
Timepoint [24] 0 0
Day 7 of each treatment period
Secondary outcome [25] 0 0
Anti inflammatory activity in sputum assessed by SNF1LK Cytospin on Day 7
Timepoint [25] 0 0
Day 7 of each treatment period
Secondary outcome [26] 0 0
Anti-inflammatory activity in sputum assessed by ratio of SNF1LK Cytospin on Day 7
Timepoint [26] 0 0
Day 7 of each treatment period

Eligibility
Key inclusion criteria
* Subjects with clinically stable persistent mild/moderate asthma within the 4 weeks preceding the screening visit, with the exclusion of other significant pulmonary diseases (e.g. chronic bronchitis, emphysema, bronchiectasis, cystic fibrosis or bronchopulmonary dysplasia)
* Subjects with a screening pre-bronchodilator FEV1 70% predicted (having abstained from bronchodilators for the required period). Predicted values are based on the NHanes normal ranges
* During the screening visit, subjects must demonstrate the presence of reversible airway disease, defined as an increase in FEV1 of 12.0% over the max of the three screening measures and an absolute change of 150 mL within 30 minutes following a single 400 mg salbutamol dose
* Male and females who are aged between 18 and 65 years of age.A female is eligible to enter and participate in the study if she is of:

1. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who is post menopausal. For the purposes of this study, post menopausal is defined as 1 year without menses (FSH/LH will be also tested to confirm menopausal status); or
2. Child bearing potential, has a negative pregnancy test (urine) at screening and pre-dose Day 1, and agrees to one of the following acceptable contraceptive methods when used consistently and correctly (i.e., in accordance with the approved product label and the instructions of a physician for the duration of the study - screening visit to follow-up contact):

Complete abstinence from intercourse from the screening visit, throughout the trial and for 7 (~5 half-lives of GSK256066) days after the completion of the trial; or Male partner was sterile prior to the female subject's entry into the study, or Implants of levonorgestrel inserted for at least 1 month prior to the study medication administration but not beyond the third successive year following insertion; or Injectable progestogen administered for at least 1 month prior to the study medication administration and administered for 1 month following study completion; or Oral contraceptive (combined or progestogen only) administered for a least one monthly cycle prior to study medication administration; or The contraceptive transdermal patch, Ortho Evra (if the subject is less than 89kg); or Double-barrier method - spermicide plus a mechanical barrier (e.g., spermicide plus a male condom or a spermicide and female diaphragm.

Recent data now shows that certain double-barrier methods have a failure rate below 1% [Trussell, 2003]. Specifically, these are a spermicide plus a mechanical barrier (e.g., spermicide plus a male condom or a female diaphragm). This provides validated confirmation of the failure rate of the double-barrier method. Thus this method now meets the stated criterion for acceptable contraception in the EMEA guidelines [CPMP/ICH/285/95, 2000]; or Condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; or An intrauterine device (IUD) or intrauterine system (IUS), inserted by a qualified physician, with published data showing that the highest expected failure rate is less than 1% per year; (not all IUDs meet this criterion) Acceptable IUDs: Tcu-380A (Paragard), TCU-380 Slimline (Gyne T Slimline), Tcu-220C, MULTILOAD-250 (MLCu-250) and 375, NOVA T and CUNOVAT (Novagard), Levonorgesterol (LNG-20) Intra-uterine System (Mirena/Levonova), and FlexiGard 330/CuFix PP330 (Gynefix). The device must be inserted at least 2 weeks prior to the Screen visit, and remain throughout the study and through the follow-up phase of the study or Any other methods with published data showing that the highest expected failure rate is less than 1% per year.

* Body weight of 50 kg and Body mass index within range of 19-31 kg/m2 inclusive
* Subjects who are current non-smokers, who have not used any inhaled tobacco products (snuff is permitted) in the 12 month period preceding the screening visit and who have a pack history of £ 10 pack years
* No significant abnormality on 12-lead ECG at screening, including the following requirements:

Ventricular rate = 40 beats per minute PR interval = 200 ms Q waves < 30 ms (up to 50 ms permitted in lead III only) QRS interval to be = 60 ms and = 110 ms QTc interval < 450msec (QTcB or QTcF; machine or manual reading) based on a single ECG value, or an average from three ECGs obtained over a brief recording period

* Able to provide written informed consent
* The subject is able to understand and comply with the protocol requirements, instructions and protocol-stated restrictions
* Demonstrated ability to use the inhaler device in a satisfactory and repeatable manner
Minimum age
18 Years
Maximum age
65 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
* As a result of medical interview, physical examination or screening investigations, the principle investigator or delegate physician deems the subject unsuitable for the study. Subjects must not have a systolic blood pressure above 145 mmHg or a diastolic pressure above 85 mmHg unless the Investigator confirms that it is satisfactory for their age
* The subject has been treated for or diagnosed with depression within six months of screening or has a history of significant psychiatric illness
* Past or present disease, which as judged by the investigator, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease*, haematological disease, neurological disease, endocrine disease or pulmonary disease (including but not confined to chronic bronchitis, emphysema, bronchiectasis or pulmonary fibrosis)
* Subjects will require normal serum creatinine clearance values at screening [calculated from serum creatinine by a predicting equation using Cockcroft-Gualt formula]. If the creatinine clearance value is greater than the upper limit of normal as determined by the local laboratory reference range, the Investigator will determine whether this is a clinically significant finding that would preclude participation
* Subject has a history of atrial arrhythmia or ventricular arrhythmia
* Pregnant or nursing females
* Women of childbearing potential who are unwilling or unable to use an appropriate method of contraception from at least two weeks prior to the first dose of study medication; and to continue until the final pregnancy test has been performed (not less than 150 hours after treatment
* Subjects with a history of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with either respiratory arrest or hypoxic seizures
* Asthma exacerbations requiring treatment with oral corticosteroids: any exacerbations within 3 months of the screening visit or two or more exacerbations within 6 months of the screening visit or admittance to hospital for an asthma exacerbation within 1 year of the screening visit
* Subjects who have suffered an upper or lower respiratory tract infection within 4 weeks of the screening visit
* 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 physician responsible, contraindicates their participation
* Subjects who are unable to washout the following protocol defined prohibited medications within the defined times at screening:

Oral corticosteroids Inhaled, intranasal and topical steroids Long acting beta agonists Short acting beta agonists

* The subject has taken prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is the longer) prior to the first dose of study medication, unless in the opinion of the Investigator and Sponsor the medication will not interfere with the study procedures or compromise subject safety
* History of alcohol/drug abuse or dependence within 12 months of the study
* Abuse of alcohol 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). 1 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 a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication
* Exposure to more than four new chemical entities within 12 months prior to the first dosing day
* Donation of blood in excess of 500 mL within a 56 day period prior to dosing
* A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
* The subject has tested positive for HIV antibodies (if tested according to site SOPs)
* The subject has a positive pre-study urine drug/ urine alcohol screen. A minimum list of drugs that will be screened for include Amphetamines, Barbiturates, Cocaine, Opiates, Cannabinoids and Benzodiazepines

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?



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
16/11/2007
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/08/2008
Sample size
Target
Accrual to date
Final
78
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
South Africa
State/province [2] 0 0
Eastern Cape
Country [3] 0 0
South Africa
State/province [3] 0 0
Bloemfontein

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Subjects will attend the unit for out-patient visits on Day 1, Day 7, Day 14 and Day 15 of each treatment period. The washout period between each treatment period will be a minimum of 10 days and maximum of 28 days. Subjects will participate in 3 treatment periods.
Trial website
https://clinicaltrials.gov/study/NCT00549744
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00549744