- ICH GCP
- USA klinikai vizsgálatok nyilvántartása
- Klinikai vizsgálat NCT00555022
Effect of GSK1160724 In Healthy Volunteers
2017. szeptember 5. frissítette: GlaxoSmithKline
A Randomized Double-blind, Placebo-controlled, Crossover, Dose Escalation Study to Examine the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Single Inhaled Doses of GSK1160724 and Tiotropium Bromide
GSK1160724 is a potent mAChR antagonist, which is being developed for treatment of chronic obstructive pulmonary disease (COPD)
A tanulmány áttekintése
Állapot
Befejezve
Körülmények
Beavatkozás / kezelés
Tanulmány típusa
Beavatkozó
Beiratkozás (Tényleges)
21
Fázis
- 1. fázis
Kapcsolatok és helyek
Ez a rész a vizsgálatot végzők elérhetőségeit, valamint a vizsgálat lefolytatásának helyére vonatkozó információkat tartalmazza.
Tanulmányi helyek
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Middlesex
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Harrow, Middlesex, Egyesült Királyság, HA1 3UJ
- GSK Investigational Site
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Részvételi kritériumok
A kutatók olyan embereket keresnek, akik megfelelnek egy bizonyos leírásnak, az úgynevezett jogosultsági kritériumoknak. Néhány példa ezekre a kritériumokra a személy általános egészségi állapota vagy a korábbi kezelések.
Jogosultsági kritériumok
Tanulmányozható életkorok
18 év (Felnőtt)
Egészséges önkénteseket fogad
Igen
Tanulmányozható nemek
Összes
Leírás
Inclusion Criteria:
- Healthy male and female subjects. Female subjects must be of non-child bearing potential.
- Aged between 18-55 years inclusive
- Non-smokers
- Normal spirometry
- 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
- The subject is greater than or equal to 50kg with a body mass index within the range 19.0 to 29.9 kg/m2 inclusive
- Response to ipratropium bromide
Exclusion Criteria:
- Any clinically relevant and important abnormality identified at the screening medical assessment (physical examination/medical history), clinical laboratory tests, or ECG (12-lead or Holter)
- A history of breathing problems
- A mean QTc(B) value > 450ms, the QTc(B) of the 3 screening ECGs are not within 10% of the mean, a PR interval outside the range 90-210ms or an ECG that is not suitable for QT measurements at screening
- 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 inclusive at screening
- History of use of tobacco- or nicotine-containing products within 6 months of screening, and/or positive urine cotinine test results at screening
- Where participation in the study would result in donation of blood in excess of 500mL within a 56 day period at screening
- The subject is currently taking regular (or a course of) medication, whether prescribed or not, including herbal remedies such as St John's Wort etc.
The subject has taken:
- prescription medications for 14 days prior to first dose of study drug, or
- Over-the-counter (OTC) medications/preparations (including herbal remedies, etc.) excluding simple analgesics for 48 hours prior to first dose of study drug,unless it is judged by the Investigator not to compromise the subject's safety or influence the outcome of the study.
- The subject has participated in a study with a new molecular entity or any other trial within a period of 3 months prior first dose of study drug
- The subject has tested positive for hepatitis C antibody (third generation enzyme immunoassay), hepatitis B surface antigen or HIV antibodies (if tested according to site SOP's) at screening.
- The subject has tested positive for drugs-of-abuse at screening
- The subject has tested positive for urine alcohol (including ethanol) at screening The detection of alcohol would not be an exclusion at screening but would need to be negative pre-dose and during the study
- The subject is unable to use the DISKUS™ and/or HandiHaler inhaler devices correctly at screening
- The subject has a suspected history of alcohol abuse within the six months previous to the screening visit
- The subject has a known allergy or hypersensitivity to magnesium stearate, milk protein or the excipient lactose monohydrate, iodine, ipratropium bromide, tiotropium bromide, atropine and/or any of its derivatives
- The subject has a significant clinical history of prostatic hypertrophy or narrow angle glaucoma
- The subject has received an allogeneic bone marrow transplant
- The subject has claustrophobia that may be aggravated by entering the whole body plethysmography cabinet
Tanulási terv
Ez a rész a vizsgálati terv részleteit tartalmazza, beleértve a vizsgálat megtervezését és a vizsgálat mérését.
Hogyan készül a tanulmány?
Tervezési részletek
- Elsődleges cél: Kezelés
- Kiosztás: Véletlenszerűsített
- Beavatkozó modell: Crossover kiosztás
Fegyverek és beavatkozások
Résztvevő csoport / kar |
Beavatkozás / kezelés |
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Kísérleti: All subjects
Eligible subjects will receive one of the following treatment in cohort I and cohort II in five different treatment periods; Placebo, GSK1160724 (10 micrograms, 50 micrograms or 125 micrograms) and tiotropium bromide
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Az alanyok placebót kapnak.
GSK1160724 will be available with dosing strengths of 10, 50 and 125 micrograms/blister for inhalation using the DISKUS inhaler.
Tiotropium bromide capsules will be supplied with a dose of 18 micrograms administered via a HandiHaler device.
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Mit mér a tanulmány?
Elsődleges eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
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Number of subjects with adverse events (AEs)
Időkeret: Up to Week 24
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An AE is any untoward medical occurrence in a clinical study subjects, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.
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Up to Week 24
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Number of subjects with abnormal values for blood pressure
Időkeret: Up to Week 24
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Systolic and diastolic blood pressure will be measured in a semi-recumbent position after 5 minutes rest.
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Up to Week 24
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Number of subjects with abnormal values for heart rate
Időkeret: Up to Week 24
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Heart rate will be measured in a semi-recumbent position after 5 minutes rest.
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Up to Week 24
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Number of subjects with abnormal electrocardiogram (ECG) findings
Időkeret: Up to Week 24
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Triplicate 12-lead ECGs will be measured in a semi-recumbent position after 5 minutes rest at each time point using ECG machine.
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Up to Week 24
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Number of subjects with abnormal findings after holter monitoring
Időkeret: Up to 24 hour
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Holter monitoring will be conducted at 24 hour.
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Up to 24 hour
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Forced expiratory volume in 1 second (FEV1)
Időkeret: Up to Week 24
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Lung function will be measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second.
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Up to Week 24
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Forced vital capacity (FVC)
Időkeret: Up to Week 24
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Lung function will be measured by FVC, defined as the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.
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Up to Week 24
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Number of subjects having abnormal hematology laboratory parameters
Időkeret: Up to Week 24
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Hematology parameters will be assessed as a measure of safety.
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Up to Week 24
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Number of subjects with abnormal clinical chemistry parameters
Időkeret: Up to Week 24
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Clinical parameters will be assessed as a measure of safety.
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Up to Week 24
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Number of subjects with abnormal values for urinalysis
Időkeret: Up to Week 24
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Urinalysis will be performed as a measure of safety.
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Up to Week 24
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Maximum value for resting heart rate over 0-4 hour
Időkeret: Up to 4 hours
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Maximum value for heart rate over 0-4 hour will be determined.
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Up to 4 hours
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Maximum value for resting blood pressure over 0-4 hour
Időkeret: Up to 4 hours
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Maximum value for resting systolic and diastolic blood pressure over 0-4 hour will be determined.
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Up to 4 hours
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Maximum value for resting ECG over 0-4 hour
Időkeret: Up to 4 hours
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Maximum value for resting ECG over 0-4 hour will be determined.
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Up to 4 hours
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Weighted mean of resting heart rate over 0-4 hour
Időkeret: Up to 4 hours
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Weighted mean for resting heart rate over 0-4 hour will be determined.
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Up to 4 hours
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Weighted mean of resting blood pressure over 0-4 hour
Időkeret: Up to 4 hours
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Weighted mean for resting systolic and diastolic blood pressure over 0-4 hour will be determined.
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Up to 4 hours
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Weighted mean of resting ECG over 0-4 hour
Időkeret: Up to 4 hours
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Weighted mean for resting resting ECG over 0-4 hour will be determined.
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Up to 4 hours
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Másodlagos eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
---|---|---|
Plasma concentrations of GSK1160724
Időkeret: Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Plasma samples will be collected at the indicated time points to measure the concentration of GSK1160724.
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Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Plasma concentrations of GSK1762245
Időkeret: Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Plasma samples will be collected at the indicated time points to measure the concentration of the active metabolite GSK1762245.
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Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Urine concentrations of GSK1160724
Időkeret: 0-2 hours, 2-8 hours, 8-12 hours and 12-24 hours
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Urine samples will be collected at the indicated time points to measure the concentration of GSK1160724.
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0-2 hours, 2-8 hours, 8-12 hours and 12-24 hours
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Urine concentrations of GSK1762245
Időkeret: 0-2 hours, 2-8 hours, 8-12 hours and 12-24 hours
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Urine samples will be collected at the indicated time points to measure the concentration of the active metabolite GSK1762245.
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0-2 hours, 2-8 hours, 8-12 hours and 12-24 hours
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Maximum observed concentration (Cmax) of GSK1160724
Időkeret: Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Cmax of GSK1762245
Időkeret: Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Time to Cmax (Tmax) of GSK1160724
Időkeret: Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Tmax of GSK1762245
Időkeret: Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Time to last observed plasma concentration (Tlast) of GSK1160724
Időkeret: Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Tlast of GSK1762245
Időkeret: Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Area under the plasma concentration time curve from time 0 to last time of quantifiable concentration (AUC [0-T]) of GSK1160724
Időkeret: Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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AUC (0-T) of GSK1762245
Időkeret: Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Area under the plasma concentration time curve from time 0 to infinity (AUC [0-infinity]) of GSK1160724
Időkeret: Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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AUC (0-infinity) of GSK1762245
Időkeret: Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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The terminal phase elimination rate constant (Lambda z) of GSK1160724
Időkeret: Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Lambda z of GSK1762245
Időkeret: Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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The Terminal phase half life (T1/2) of GSK1160724
Időkeret: Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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T1/2 of GSK1762245
Időkeret: Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
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Serial specific airway conductance (sGaw) response over 24 hours post-dose of GSK1160724 and tiotropium bromide
Időkeret: Up to 24 hours
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The sGaw response will be assessed by whole body plethysmograph at the indicated timepoints.
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Up to 24 hours
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FEV1 over 24 hours post-dose of GSK1160724 and tiotropium bromide
Időkeret: Up to 24 hours
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The sGaw response will be assessed by whole body plethysmograph at the indicated timepoints.
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Up to 24 hours
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FVC over 24 hours post-dose of GSK1160724 and tiotropium bromide
Időkeret: Up to 24 hours
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The sGaw response will be assessed by whole body plethysmograph at the indicated timepoints.
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Up to 24 hours
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Serial sGaw measurements over 48 hours of GSK1160724 and tiotropium bromide
Időkeret: Up to 48 hours
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The sGaw is a measure of the change in specific airway conductance.
It will be assessed by whole body plethysmograph at the indicated timepoints.
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Up to 48 hours
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Együttműködők és nyomozók
Itt találhatja meg a tanulmányban érintett személyeket és szervezeteket.
Szponzor
Tanulmányi rekorddátumok
Ezek a dátumok nyomon követik a ClinicalTrials.gov webhelyre benyújtott vizsgálati rekordok és összefoglaló eredmények benyújtásának folyamatát. A vizsgálati feljegyzéseket és a jelentett eredményeket a Nemzeti Orvostudományi Könyvtár (NLM) felülvizsgálja, hogy megbizonyosodjon arról, hogy megfelelnek-e az adott minőség-ellenőrzési szabványoknak, mielőtt közzéteszik őket a nyilvános weboldalon.
Tanulmány főbb dátumok
Tanulmány kezdete (Tényleges)
2007. december 12.
Elsődleges befejezés (Tényleges)
2008. április 7.
A tanulmány befejezése (Tényleges)
2008. április 7.
Tanulmányi regisztráció dátumai
Először benyújtva
2007. november 6.
Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak
2007. november 6.
Első közzététel (Becslés)
2007. november 7.
Tanulmányi rekordok frissítései
Utolsó frissítés közzétéve (Tényleges)
2017. szeptember 8.
Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak
2017. szeptember 5.
Utolsó ellenőrzés
2017. szeptember 1.
Több információ
A tanulmányhoz kapcsolódó kifejezések
További vonatkozó MeSH feltételek
- Légúti betegségek
- Tüdőbetegségek
- Tüdőbetegségek, obstruktív
- Tüdőbetegség, krónikus obstruktív
- A gyógyszerek élettani hatásai
- Neurotranszmitter szerek
- A farmakológiai hatás molekuláris mechanizmusai
- Paraszimpatolitikumok
- Autonóm ügynökök
- Perifériás idegrendszeri szerek
- Kolinerg antagonisták
- Kolinerg szerek
- Antikonvulzív szerek
- Hörgőtágító szerek
- Asztmaellenes szerek
- Légzőrendszeri szerek
- Tiotropium-bromid
- Bromidok
Egyéb vizsgálati azonosító számok
- AC5108696
Ezt az információt közvetlenül a clinicaltrials.gov webhelyről szereztük be, változtatás nélkül. Ha bármilyen kérése van vizsgálati adatainak módosítására, eltávolítására vagy frissítésére, kérjük, írjon a következő címre: register@clinicaltrials.gov. Amint a változás bevezetésre kerül a clinicaltrials.gov oldalon, ez a webhelyünkön is automatikusan frissül. .