- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT00555022
Effect of GSK1160724 In Healthy Volunteers
5. September 2017 aktualisiert von: 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)
Studienübersicht
Status
Abgeschlossen
Bedingungen
Intervention / Behandlung
Studientyp
Interventionell
Einschreibung (Tatsächlich)
21
Phase
- Phase 1
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienorte
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Middlesex
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Harrow, Middlesex, Vereinigtes Königreich, HA1 3UJ
- GSK Investigational Site
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Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
18 Jahre bis 55 Jahre (Erwachsene)
Akzeptiert gesunde Freiwillige
Ja
Studienberechtigte Geschlechter
Alle
Beschreibung
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
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Crossover-Aufgabe
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
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Experimental: 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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Die Probanden erhalten ein Placebo.
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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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Number of subjects with adverse events (AEs)
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Plasma concentrations of GSK1160724
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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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Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Sponsor
Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn (Tatsächlich)
12. Dezember 2007
Primärer Abschluss (Tatsächlich)
7. April 2008
Studienabschluss (Tatsächlich)
7. April 2008
Studienanmeldedaten
Zuerst eingereicht
6. November 2007
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
6. November 2007
Zuerst gepostet (Schätzen)
7. November 2007
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
8. September 2017
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
5. September 2017
Zuletzt verifiziert
1. September 2017
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Erkrankungen der Atemwege
- Lungenkrankheit
- Lungenerkrankungen, obstruktive
- Lungenerkrankung, chronisch obstruktiv
- Physiologische Wirkungen von Arzneimitteln
- Neurotransmitter-Agenten
- Molekulare Mechanismen der pharmakologischen Wirkung
- Parasympatholytika
- Autonome Agenten
- Agenten des peripheren Nervensystems
- Cholinerge Antagonisten
- Cholinerge Wirkstoffe
- Antikonvulsiva
- Bronchodilatatoren
- Anti-Asthmatiker
- Atemwegsmittel
- Tiotropiumbromid
- Bromide
Andere Studien-ID-Nummern
- AC5108696
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .
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