GSK573719 IV Enabling Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01110018
First received: April 15, 2010
Last updated: August 23, 2012
Last verified: February 2011
  Purpose

A single-centre, open-label, sequential, cross-over study to examine the safety, tolerability and pharmacokinetics of 3 ascending single intravenous doses, a single 1000μg oral dose and a single 1000μg inhaled dose of GSK573719 in healthy male volunteers.


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: GSK573719 (SOLUTION)
Drug: GSK573719 (INHALATION POWDER)
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single-centre, Open-label, Sequential, Cross-over Study to Examine the Safety, Tolerability and Pharmacokinetics of 3 Ascending Single Intravenous Doses, a Single 1000μg Oral Dose and a Single 1000μg Inhaled Dose of GSK573719 in Healthy Male Volunteers.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Safety and tolerability of GSK573719 [ Time Frame: Study duration (5 weeks) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • IV dose plasma PK parameters: AUC(0-∞) (if calculable), AUC(0-t), and Cmax, tlast, CL, Vss, MRT, λz and t½ [ Time Frame: Pre-dose to 24h post-dose (48h post-dose in IV dose 3) ] [ Designated as safety issue: No ]
  • Oral and Inhaled dose plasma PK parameters: AUC(0-∞) (if calculable), AUC(0-t) and Cmax, tmax, tlast, F, λz and t½, if calculable. [ Time Frame: Pre-dose to 24h post-dose ]
  • Urine PK parameters for all routes of administration: CLr, t½, Ae(0-2), Ae(0-4) , Ae(0-8) , Ae(0-12) , Ae(0-24) , Ae(0-36), Ae(0-48), fe, F , AUER(0-18), AUER(0-36) if available, AUER(0-∞). [ Time Frame: 0-48h post-dose ]

Enrollment: 10
Study Start Date: April 2010
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Period 1
20μg intravenous infusion administered over 30 minutes
Drug: GSK573719 (SOLUTION)
20μg /mL solution for IV and Oral dosing
Active Comparator: Period 2
1000μg Oral dose
Drug: GSK573719 (SOLUTION)
20μg /mL solution for IV and Oral dosing
Active Comparator: Period 3
50μg Intravenous infusion administered over 30 minutes
Drug: GSK573719 (SOLUTION)
20μg /mL solution for IV and Oral dosing
Active Comparator: Period 4
1000μg Inhaled dose
Drug: GSK573719 (INHALATION POWDER)
500μg inhalation powder delivered via Novel Dry Powder Inhaler. GSK573719 1000μg per dose (2x 500μg strips in device).
Active Comparator: Period 5
100μg Intravenous infusion administered over 30 minutes
Drug: GSK573719 (SOLUTION)
20μg /mL solution for IV and Oral dosing

Detailed Description:

GSK573719 is a high-affinity, specific, reversible muscarinic receptor (mAChR) antagonist which is being developed for the treatment of Chronic Obstructive Pulmonary Disease (COPD). The long duration of action of GSK573719, when administered via inhalation to humans, supports the potential for use as a long acting bronchodilator for COPD.

This will be an open-label, single dose, dose-ascending study in healthy male subjects to establish well tolerated intravenous (IV) dose of GSK573719 to be administered in a subsequent definitive human radiolabel metabolic study. The pharmacokinetics and the bioavailability of a single oral and a single inhaled dose of GSK573719 will also be evaluated.

Blood and urine samples for pharmacokinetic analysis will be taken at regular intervals up to 48 hours after dosing. Safety will be assessed by measurement of heart rate, blood pressure, ECG, lead II monitoring and twenty four hour Holter monitoring, safety laboratory data and review of adverse events.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Healthy as determined by a responsible and experienced 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.
  • Male between 18 and 65 years of age inclusive, at the time of signing the informed consent.
  • 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 follow up.
  • Body Mass Index within the range 18-30 kg/m2 (inclusive).
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  • Average QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.
  • 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)

Exclusion Criteria:

  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • A positive pre-study drug/alcohol screen.
  • A positive test for HIV antibody.
  • History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >21 units for males. One unit is equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.
  • 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, 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 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.
  • Subject is mentally or legally incapacitated.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01110018

Locations
United Kingdom
GSK Investigational Site
London, United Kingdom, NW10 7EW
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01110018     History of Changes
Other Study ID Numbers: 112008
Study First Received: April 15, 2010
Last Updated: August 23, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:
Tolerability
COPD
Safety
Muscarinic receptor (mAChR) antagonist
GSK573719
Healthy subjects
Pharmacokinetics
IV study

Additional relevant MeSH terms:
Lung Diseases
Chronic Disease
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes
Lung Diseases, Obstructive

ClinicalTrials.gov processed this record on September 30, 2014