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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

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

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
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
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.

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Number of subjects with adverse events (AEs)
Zeitfenster: Up to Week 24
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.
Up to Week 24
Number of subjects with abnormal values for blood pressure
Zeitfenster: Up to Week 24
Systolic and diastolic blood pressure will be measured in a semi-recumbent position after 5 minutes rest.
Up to Week 24
Number of subjects with abnormal values for heart rate
Zeitfenster: Up to Week 24
Heart rate will be measured in a semi-recumbent position after 5 minutes rest.
Up to Week 24
Number of subjects with abnormal electrocardiogram (ECG) findings
Zeitfenster: Up to Week 24
Triplicate 12-lead ECGs will be measured in a semi-recumbent position after 5 minutes rest at each time point using ECG machine.
Up to Week 24
Number of subjects with abnormal findings after holter monitoring
Zeitfenster: Up to 24 hour
Holter monitoring will be conducted at 24 hour.
Up to 24 hour
Forced expiratory volume in 1 second (FEV1)
Zeitfenster: Up to Week 24
Lung function will be measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second.
Up to Week 24
Forced vital capacity (FVC)
Zeitfenster: Up to Week 24
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.
Up to Week 24
Number of subjects having abnormal hematology laboratory parameters
Zeitfenster: Up to Week 24
Hematology parameters will be assessed as a measure of safety.
Up to Week 24
Number of subjects with abnormal clinical chemistry parameters
Zeitfenster: Up to Week 24
Clinical parameters will be assessed as a measure of safety.
Up to Week 24
Number of subjects with abnormal values for urinalysis
Zeitfenster: Up to Week 24
Urinalysis will be performed as a measure of safety.
Up to Week 24
Maximum value for resting heart rate over 0-4 hour
Zeitfenster: Up to 4 hours
Maximum value for heart rate over 0-4 hour will be determined.
Up to 4 hours
Maximum value for resting blood pressure over 0-4 hour
Zeitfenster: Up to 4 hours
Maximum value for resting systolic and diastolic blood pressure over 0-4 hour will be determined.
Up to 4 hours
Maximum value for resting ECG over 0-4 hour
Zeitfenster: Up to 4 hours
Maximum value for resting ECG over 0-4 hour will be determined.
Up to 4 hours
Weighted mean of resting heart rate over 0-4 hour
Zeitfenster: Up to 4 hours
Weighted mean for resting heart rate over 0-4 hour will be determined.
Up to 4 hours
Weighted mean of resting blood pressure over 0-4 hour
Zeitfenster: Up to 4 hours
Weighted mean for resting systolic and diastolic blood pressure over 0-4 hour will be determined.
Up to 4 hours
Weighted mean of resting ECG over 0-4 hour
Zeitfenster: Up to 4 hours
Weighted mean for resting resting ECG over 0-4 hour will be determined.
Up to 4 hours

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
Plasma samples will be collected at the indicated time points to measure the concentration of GSK1160724.
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
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
Plasma samples will be collected at the indicated time points to measure the concentration of the active metabolite GSK1762245.
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
Urine concentrations of GSK1160724
Zeitfenster: 0-2 hours, 2-8 hours, 8-12 hours and 12-24 hours
Urine samples will be collected at the indicated time points to measure the concentration of GSK1160724.
0-2 hours, 2-8 hours, 8-12 hours and 12-24 hours
Urine concentrations of GSK1762245
Zeitfenster: 0-2 hours, 2-8 hours, 8-12 hours and 12-24 hours
Urine samples will be collected at the indicated time points to measure the concentration of the active metabolite GSK1762245.
0-2 hours, 2-8 hours, 8-12 hours and 12-24 hours
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
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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
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
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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
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
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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
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
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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
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
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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
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
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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
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
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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
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
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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
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
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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
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
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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
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
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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
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
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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
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
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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
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
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
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
Serial specific airway conductance (sGaw) response over 24 hours post-dose of GSK1160724 and tiotropium bromide
Zeitfenster: Up to 24 hours
The sGaw response will be assessed by whole body plethysmograph at the indicated timepoints.
Up to 24 hours
FEV1 over 24 hours post-dose of GSK1160724 and tiotropium bromide
Zeitfenster: Up to 24 hours
The sGaw response will be assessed by whole body plethysmograph at the indicated timepoints.
Up to 24 hours
FVC over 24 hours post-dose of GSK1160724 and tiotropium bromide
Zeitfenster: Up to 24 hours
The sGaw response will be assessed by whole body plethysmograph at the indicated timepoints.
Up to 24 hours
Serial sGaw measurements over 48 hours of GSK1160724 and tiotropium bromide
Zeitfenster: Up to 48 hours
The sGaw is a measure of the change in specific airway conductance. It will be assessed by whole body plethysmograph at the indicated timepoints.
Up to 48 hours

Mitarbeiter und Ermittler

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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

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