Study of GSK961081 in Healthy Volunteer Subjects

NCT ID: NCT00887406

Last Updated: 2021-10-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-07
• Study Completion Date: 2006-10-04

Brief Summary

GSK961081 is a new long-acting bronchodilator being developed for the treatment of chronic obstructive pulmonary disease (COPD). This study is the first clinical study in humans. The purpose of this study is to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of GSK961081 in healthy male subjects.

Conditions

Pulmonary Disease, Chronic Obstructive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Cohort 1, Period 2

GSK961081 3mcg, Placebo, GSK961081 15mcg, GSK961081 50mcg

Group Type: EXPERIMENTAL

GSK961081 15mcg SD

Intervention Type: DRUG

Single dose delivered via solution for nebulisation

GSK961081 3mcg SD

Intervention Type: DRUG

single dose delivered via nebulsier

GSK961081 50mcg SD

Intervention Type: DRUG

single dose delivered via solution for nebulisation

Placebo SD

Intervention Type: DRUG

single dose via nebuliser

Cohort 1, period 1

Placebo, GSK961081 3mcg, GSK961081 15mcg, GSK961081 50mcg

Group Type: EXPERIMENTAL

GSK961081 15mcg SD

Intervention Type: DRUG

Single dose delivered via solution for nebulisation

GSK961081 3mcg SD

Intervention Type: DRUG

single dose delivered via nebulsier

GSK961081 50mcg SD

Intervention Type: DRUG

single dose delivered via solution for nebulisation

Placebo SD

Intervention Type: DRUG

single dose via nebuliser

Cohort 1, period 3

GSK961081 3mcg, GSK961081 15mcg, Placebo, GSK961081 50mcg

Group Type: EXPERIMENTAL

GSK961081 15mcg SD

Intervention Type: DRUG

Single dose delivered via solution for nebulisation

GSK961081 3mcg SD

Intervention Type: DRUG

single dose delivered via nebulsier

GSK961081 50mcg SD

Intervention Type: DRUG

single dose delivered via solution for nebulisation

Placebo SD

Intervention Type: DRUG

single dose via nebuliser

Cohort 1, period 4

GSK961081 3mcg, GSK961081 15mcg, GSK961081 50mcg, Placebo

Group Type: EXPERIMENTAL

GSK961081 15mcg SD

Intervention Type: DRUG

Single dose delivered via solution for nebulisation

GSK961081 3mcg SD

Intervention Type: DRUG

single dose delivered via nebulsier

GSK961081 50mcg SD

Intervention Type: DRUG

single dose delivered via solution for nebulisation

Placebo SD

Intervention Type: DRUG

single dose via nebuliser

Cohort 2, period 1

Placebo, GSK961081 100mcg, GSK961081 200mcg, GSK961081 300mcg,

Group Type: EXPERIMENTAL

Placebo SD

Intervention Type: DRUG

single dose via nebuliser

GSK961081 100mcg SD

Intervention Type: DRUG

single dose delivered via solution for nebulisation

GSK961081 200mcg SD

Intervention Type: DRUG

single dose via nebuliser

GSK961081 300mcg SD

Intervention Type: DRUG

single dose via nebuliser

Cohort 2, period 2

GSK961081 100mcg, Placebo, GSK961081 200mcg, GSK961081 300mcg

Group Type: EXPERIMENTAL

Placebo SD

Intervention Type: DRUG

single dose via nebuliser

GSK961081 100mcg SD

Intervention Type: DRUG

single dose delivered via solution for nebulisation

GSK961081 200mcg SD

Intervention Type: DRUG

single dose via nebuliser

GSK961081 300mcg SD

Intervention Type: DRUG

single dose via nebuliser

Cohort 2, period 3

GSK961081 100mcg, GSK961081 200mcg, Placebo, GSK961081 300mcg

Group Type: EXPERIMENTAL

Placebo SD

Intervention Type: DRUG

single dose via nebuliser

GSK961081 100mcg SD

Intervention Type: DRUG

single dose delivered via solution for nebulisation

GSK961081 200mcg SD

Intervention Type: DRUG

single dose via nebuliser

GSK961081 300mcg SD

Intervention Type: DRUG

single dose via nebuliser

Cohort 2, period 4

GSK961081 100mcg, GSK961081 200mcg, GSK961081 300mcg, Placebo

Group Type: EXPERIMENTAL

Placebo SD

Intervention Type: DRUG

single dose via nebuliser

GSK961081 100mcg SD

Intervention Type: DRUG

single dose delivered via solution for nebulisation

GSK961081 200mcg SD

Intervention Type: DRUG

single dose via nebuliser

GSK961081 300mcg SD

Intervention Type: DRUG

single dose via nebuliser

Cohort 3

GSK961081 100mcg or Placebo

Group Type: EXPERIMENTAL

GSK961081 100mcg RD

Intervention Type: DRUG

repeat dose via nebuliser

Placebo RD

Intervention Type: DRUG

repeat dose via nebuliser

Cohort 4

GSK961081 300mcg or Placebo

Group Type: EXPERIMENTAL

GSK961081 300mcg RD

Intervention Type: DRUG

repeat dose vai nebuliser

Placebo RD

Intervention Type: DRUG

repeat dose via nebuliser

Interventions

GSK961081 15mcg SD

Single dose delivered via solution for nebulisation

Intervention Type: DRUG

GSK961081 3mcg SD

single dose delivered via nebulsier

Intervention Type: DRUG

GSK961081 50mcg SD

single dose delivered via solution for nebulisation

Intervention Type: DRUG

Placebo SD

single dose via nebuliser

Intervention Type: DRUG

GSK961081 100mcg SD

single dose delivered via solution for nebulisation

Intervention Type: DRUG

GSK961081 200mcg SD

single dose via nebuliser

Intervention Type: DRUG

GSK961081 300mcg SD

single dose via nebuliser

Intervention Type: DRUG

GSK961081 100mcg RD

repeat dose via nebuliser

Intervention Type: DRUG

GSK961081 300mcg RD

repeat dose vai nebuliser

Intervention Type: DRUG

Placebo RD

repeat dose via nebuliser

Intervention Type: DRUG

Other Intervention Names

Placebo; GSK961081 200mcg SD; GSK961081 50mcg SD; GSK961081 300mcg SD; GSK961081 100mcg SD; GSK961081 3mcg SD; GSK961081 100mcg SD

Eligibility Criteria

Inclusion Criteria

• Healthy adult males aged between 18 and 50 years.
• Body mass index within the range 18.5-29.9 kilograms/meter2 (kg/m2).
• Forced Expiratory Volume in 1 second (FEV1) <80% predicted and a FEV1/ Forced Vital Capacity (FVC) ratio <0.7
• Response to Salbutamol defined as: an increase in sGAW of >15% over pre-dose baseline within 2 h following administration of 400 mcg Salbutamol by MDI inhaler OR: a documented increase in sGAW of >15% over pre-dose baseline within 2 h following administration of 400 mcg Salbutamol by MDI inhaler within 6 months of screening.
• Response to Ipratropium bromide defined as: an increase in sGaw of >25% over pre-dose baseline within 2 h following 80 mcg Ipratropium bromide; OR: a documented increase in sGaw of >25% over pre-dose baseline 2 h following administration of 80 mcg Ipratropium bromide within 6 months of screening.
• A signed and dated written informed consent is obtained for the subject
• The subject is able to understand and comply with the protocol requirements, instructions and protocol-stated restrictions.
• Subjects who are current non-smokers who have not used any tobacco products in the 6-month period preceding the screening visit and have a pack history of > or = 10 pack years.

[number of pack years = (number of cigarettes per day/20) x number of years smoked]

Exclusion Criteria

• Any clinically relevant 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 (i.e. history of asthmatic symptoms). Screening lung function tests (FEV1, FVC and sGaw) will be performed to confirm normal lung function parameters.
• A mean QTc(B) and QTc(F) value at screening >430msec, the 3 screening ECGs are not within 10% of the mean, a PR interval outside the range 120-210msec or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the T wave).
• A supine blood pressure that is persistently higher than 140/90 millimetres of mercury (mmHg) at screening.
• A supine mean heart rate outside the range 40-90 beats per minute (bpm) at screening.
• The subject has donated a unit of blood within the 90 days or intends to donate within 90 days after completing the study.
• A history of claustrophobia such that they may not tolerate plethysmography measurements.
• The subject is currently taking regular (or course of) medication whether prescribed or not, including vitamins and herbal remedies such as St John's Wort.
• The subject has used 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 (which ever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and Sponsor the medication will not interfere with the study procedures or compromise subject safety.
• The subject has participated in a clinical study with another New Chemical Entity (NCE) within the past 112 days or a clinical study with any other drug during the previous 84 days.
• The subject is infected with the Hepatitis B, Hepatitis C, or HIV virus.
• The subject has a positive pre-study urine cotinine/ breath carbon monoxide test, urine drug/urine alcohol screen. A minimum list of drugs that will be screened for include Amphetamines, Barbituates, Cocaine, Opiates, Cannabinoids and Benzodiazepines.
• A history of regular alcohol consumption exceeding weekly intake of alcohol greater than 28 units, or an average daily intake of greater than 4 units.
• Are unable to use the Prodose AAD nebuliser device correctly.
• An unwillingness of subjects to abstain from sexual intercourse with pregnant or lactating women; or an unwillingness of the subject to use a condom/spermicide in addition to having their female partner use another form of contraception such as IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants or tubal ligation if the woman could become pregnant from the time of the first dose study medication until 90 days post-dose.
• The subject has a history of drug or other allergy, which, in the opinion of the responsible physician, contraindicates their participation.
• The subject has a history of hypersensitivity to Salbutamol or Ipratropium bromide, and for those subjects in cohorts III and IV, hypersensitivity to a beta-blocker.
• The subject has had a lower respiratory tract infection within 4 weeks of study start

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Theravance Biopharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

London, , United Kingdom

Countries

United Kingdom

Study Documents

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

https://www.clinicalstudydatarequest.com

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

Other Identifiers

104865

Identifier Type: -

Identifier Source: org_study_id