A Healthy Volunteer Study With Inhaled GSK573719 and Placebo

A Single Centre, Randomized, Double-blind, Dose Ascending, Placebo-controlled Study, in Two Parts, to Evaluate the Safety, Tolerability and Pharmacokinetics of Escalating Single and Repeat Inhaled Doses of GSK573719 and Placebo Formulated With the Excipient Magnesium Stearate, in Healthy Subjects and in a Healthy Population of Cytochrome P450 Isoenzyme 2D6 Poor Metabolisers.

This study is to look at a new formulation of GSK573719 to see if it is safe and tolerated in healthy volunteers

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: 100mcg; Drug: 500mcg; Drug: 1000mcg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium, 2060
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy.
• Male or female 18 to 65 years of age inclusive.
• Non-childbearing women or women of child bearing potential who agree to use contraception
• Subject has had their CYP2D6 genotype confirmed and can be included in either of the following parts:
• Part 1: may include extensive, intermediate and ultra-rapid metabolizers
• Part 2: includes only poor (no enzyme activity) metabolizers, with previously confirmed phenotype
• Body Mass Index within the range 18 - 30 kg/m2 (inclusive).
• Capable of giving written informed consent
• Normal ECG;
• Normal lung function.
• 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))
• A signed and dated written informed consent is obtained from the subject
• The subject is capable of giving informed consent
• Available to complete the study

Exclusion Criteria:

• Any clinically important abnormality identified at the screening medical assessment (physical examination/medical history), clinical laboratory tests, or ECG (12-lead). 24hr Holter monitoring outside normal limits.
• A history of breathing problems (i.e. history of asthmatic symptomatology).
• Abnormal ECG.
• Abnormal blood pressure.
• Abnormal heart rate
• The subject has a positive pre-study drug/alcohol screen.
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within three months of screening.
• A positive test for HIV antibody (if determined by the local SOPs).
• History of high alcohol consumption within three months of the study
• The subject has participated in a clinical trial and has received an IP within the following time period prior to the first dosing day in the current study: 30 days, five half-lives or twice the duration of the biological effect of the IP (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, (except for simple analgesics e.g. paracetamol), including vitamins, herbal and dietary supplements (including St John's Wort) within seven days (or 14 days if the drug is a potential enzyme inducer) or five half-lives (whichever is longer) prior to the first dose of study medication
• 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 500mL within a 56 day period.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Urinary cotinine levels indicative of smoking or history of regular use of tobacco- or nicotine-containing products prior to screening.
• The subject is unable to use the novel dry powder inhaler correctly.
• The subject has a known allergy or hypersensitivity to milk protein or the excipients magnesium stearate and lactose monohydrate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active; 100mcg 719	Drug: 100mcg; 100mcg '719
Experimental: Active 2; 500mcg '719	Drug: 500mcg; 500mcg '719
Experimental: Active 3; 1000mcg '719	Drug: 1000mcg; 1000mcg '719
Placebo Comparator: Placebo; Placebo '719	Drug: Placebo; Placebo '719

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
General safety and tolerability endpoints: Adverse Events (AE), HR, BP, 12- lead ECG and lung function (FEV1) and clinical laboratory safety tests	Various

Secondary Outcome Measures

Outcome Measure	Time Frame
Blood and urine levels of study drug	various

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Cahn A, Mehta R, Preece A, Blowers J, Donald A. Safety, tolerability and pharmacokinetics and pharmacodynamics of inhaled once-daily umeclidinium in healthy adults deficient in CYP2D6 activity: a double-blind, randomized clinical trial. Clin Drug Investig. 2013 Sep;33(9):653-64. doi: 10.1007/s40261-013-0109-6.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2008
• Primary Completion (Actual): October 16, 2008
• Study Completion (Actual): October 16, 2008

Study Registration Dates

• First Submitted: December 4, 2008
• First Submitted That Met QC Criteria: December 4, 2008
• First Posted (Estimate): December 5, 2008

Study Record Updates

• Last Update Posted (Actual): July 21, 2017
• Last Update Submitted That Met QC Criteria: July 18, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Healthy volunteers; New formulation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 110106

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Study Data/Documents

1. Annotated Case Report Form
   Information identifier: 110106
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: 110106
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: 110106
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Individual Participant Data Set
   Information identifier: 110106
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Informed Consent Form
   Information identifier: 110106
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: 110106
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Clinical Study Report
   Information identifier: 110106
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register