GSK573719 IV Enabling Study
Primary Purpose
Pulmonary Disease, Chronic Obstructive
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
GSK573719 (SOLUTION)
GSK573719 (INHALATION POWDER)
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Disease, Chronic Obstructive focused on measuring Tolerability, COPD, Safety, Muscarinic receptor (mAChR) antagonist, GSK573719, Healthy subjects, Pharmacokinetics, IV study
Eligibility 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.
Sites / Locations
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Arm Label
Period 1
Period 2
Period 3
Period 4
Period 5
Arm Description
20μg intravenous infusion administered over 30 minutes
1000μg Oral dose
50μg Intravenous infusion administered over 30 minutes
1000μg Inhaled dose
100μg Intravenous infusion administered over 30 minutes
Outcomes
Primary Outcome Measures
Safety and tolerability of GSK573719
Secondary Outcome Measures
IV dose plasma PK parameters: AUC(0-∞) (if calculable), AUC(0-t), and Cmax, tlast, CL, Vss, MRT, λz and t½
Oral and Inhaled dose plasma PK parameters: AUC(0-∞) (if calculable), AUC(0-t) and Cmax, tmax, tlast, F, λz and t½, if calculable.
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-∞).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01110018
Brief Title
GSK573719 IV Enabling Study
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.
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
April 28, 2010 (Actual)
Primary Completion Date
June 9, 2010 (Actual)
Study Completion Date
June 9, 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Disease, Chronic Obstructive
Keywords
Tolerability, COPD, Safety, Muscarinic receptor (mAChR) antagonist, GSK573719, Healthy subjects, Pharmacokinetics, IV study
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Period 1
Arm Type
Active Comparator
Arm Description
20μg intravenous infusion administered over 30 minutes
Arm Title
Period 2
Arm Type
Active Comparator
Arm Description
1000μg Oral dose
Arm Title
Period 3
Arm Type
Active Comparator
Arm Description
50μg Intravenous infusion administered over 30 minutes
Arm Title
Period 4
Arm Type
Active Comparator
Arm Description
1000μg Inhaled dose
Arm Title
Period 5
Arm Type
Active Comparator
Arm Description
100μg Intravenous infusion administered over 30 minutes
Intervention Type
Drug
Intervention Name(s)
GSK573719 (SOLUTION)
Intervention Description
20μg /mL solution for IV and Oral dosing
Intervention Type
Drug
Intervention Name(s)
GSK573719 (INHALATION POWDER)
Intervention Description
500μg inhalation powder delivered via Novel Dry Powder Inhaler. GSK573719 1000μg per dose (2x 500μg strips in device).
Primary Outcome Measure Information:
Title
Safety and tolerability of GSK573719
Time Frame
Study duration (5 weeks)
Secondary Outcome Measure Information:
Title
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)
Title
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
Title
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
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
London
ZIP/Postal Code
NW10 7EW
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Links:
URL
https://www.clinicalstudydatarequest.com
Description
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Available IPD and Supporting Information:
Available IPD/Information Type
Statistical Analysis Plan
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112008
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112008
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Annotated Case Report Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112008
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112008
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Informed Consent Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112008
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Clinical Study Report
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112008
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Dataset Specification
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112008
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Learn more about this trial
GSK573719 IV Enabling Study
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