Study of GSK961081 in Healthy Volunteer Subjects

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00887406
First received: April 23, 2009
Last updated: May 15, 2009
Last verified: May 2009
  Purpose

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.


Condition Intervention Phase
Healthy Subjects
Drug: GSK961081 50mcg SD
Drug: GSK961081 200mcg SD
Drug: GSK961081 300mcg SD
Drug: Placebo SD
Drug: GSK961081 300mcg RD
Drug: Placebo RD
Drug: GSK961081 100mcg RD
Drug: GSK961081 100mcg SD
Drug: GSK961081 15mcg SD
Drug: GSK961081 3mcg SD
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Study to Evaluate the Safety, Tolerability, Systemic Pharmacokinetic Profile and Pharmacodynamics of Single and Repeat Inhaled Doses of GSK961081 in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • General safety and tolerability (adverse events, clinical laboratory safety tests, cardiac monitoring, vital signs (including postural changes in blood pressure), 12-lead ECG parameters including QTc(b) and QTc(f), blood glucose and serum potassium). [ Time Frame: Pre and post-dose on Days 1, 4 and 7 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Maxiumum and weighted mean (over 0-8 hours post-dose) for systolic and diastolic blood pressure, heart rate, QTc(F), QTc(B), plasma glucose and serum potassium [ Time Frame: Days 1, 4 and 7 ] [ Designated as safety issue: No ]
  • specific airway conductance (sGaW) [ Time Frame: pre and post-dose on Days 1, 4 and 7 ] [ Designated as safety issue: No ]
  • forced expiratory volume in one second (FEV1) [ Time Frame: Pre and post-dose on Days 1, 4 and 7 ] [ Designated as safety issue: No ]

Enrollment: 46
Study Start Date: November 2005
Study Completion Date: October 2006
Primary Completion Date: October 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1, Period 2
GSK961081 3mcg, Placebo, GSK961081 15mcg, GSK961081 50mcg
Drug: GSK961081 50mcg SD
single dose delivered via solution for nebulisation
Other Name: GSK961081 50mcg SD
Drug: Placebo SD
single dose via nebuliser
Other Name: Placebo SD
Drug: GSK961081 15mcg SD
Single dose delivered via solution for nebulisation
Other Names:
  • GSK961081 100mcg SD
  • GSK961081 200mcg SD
  • GSK961081 300mcg SD
  • Placebo
  • GSK961081 3mcg SD
  • GSK961081 15mcg SD
  • GSK961081 50mcg SD
Drug: GSK961081 3mcg SD
single dose delivered via nebulsier
Other Name: GSK961081 3mcg SD
Experimental: Cohort 2, period 3
GSK961081 100mcg, GSK961081 200mcg, Placebo, GSK961081 300mcg
Drug: GSK961081 200mcg SD
single dose via nebuliser
Other Name: GSK961081 200mcg SD
Drug: GSK961081 300mcg SD
single dose via nebuliser
Other Name: GSK961081 300mcg SD
Drug: Placebo SD
single dose via nebuliser
Other Name: Placebo SD
Drug: GSK961081 100mcg SD
single dose delivered via solution for nebulisation
Other Name: GSK961081 100mcg SD
Experimental: Cohort 1, period 4
GSK961081 3mcg, GSK961081 15mcg, GSK961081 50mcg, Placebo
Drug: GSK961081 50mcg SD
single dose delivered via solution for nebulisation
Other Name: GSK961081 50mcg SD
Drug: Placebo SD
single dose via nebuliser
Other Name: Placebo SD
Drug: GSK961081 15mcg SD
Single dose delivered via solution for nebulisation
Other Names:
  • GSK961081 100mcg SD
  • GSK961081 200mcg SD
  • GSK961081 300mcg SD
  • Placebo
  • GSK961081 3mcg SD
  • GSK961081 15mcg SD
  • GSK961081 50mcg SD
Drug: GSK961081 3mcg SD
single dose delivered via nebulsier
Other Name: GSK961081 3mcg SD
Experimental: Cohort 2, period 4
GSK961081 100mcg, GSK961081 200mcg, GSK961081 300mcg, Placebo
Drug: GSK961081 200mcg SD
single dose via nebuliser
Other Name: GSK961081 200mcg SD
Drug: GSK961081 300mcg SD
single dose via nebuliser
Other Name: GSK961081 300mcg SD
Drug: Placebo SD
single dose via nebuliser
Other Name: Placebo SD
Drug: GSK961081 100mcg SD
single dose delivered via solution for nebulisation
Other Name: GSK961081 100mcg SD
Experimental: Cohort 1, period 3
GSK961081 3mcg, GSK961081 15mcg, Placebo, GSK961081 50mcg
Drug: GSK961081 50mcg SD
single dose delivered via solution for nebulisation
Other Name: GSK961081 50mcg SD
Drug: Placebo SD
single dose via nebuliser
Other Name: Placebo SD
Drug: GSK961081 15mcg SD
Single dose delivered via solution for nebulisation
Other Names:
  • GSK961081 100mcg SD
  • GSK961081 200mcg SD
  • GSK961081 300mcg SD
  • Placebo
  • GSK961081 3mcg SD
  • GSK961081 15mcg SD
  • GSK961081 50mcg SD
Drug: GSK961081 3mcg SD
single dose delivered via nebulsier
Other Name: GSK961081 3mcg SD
Experimental: Cohort 1, period 1
Placebo, GSK961081 3mcg, GSK961081 15mcg, GSK961081 50mcg
Drug: GSK961081 50mcg SD
single dose delivered via solution for nebulisation
Other Name: GSK961081 50mcg SD
Drug: Placebo SD
single dose via nebuliser
Other Name: Placebo SD
Drug: GSK961081 15mcg SD
Single dose delivered via solution for nebulisation
Other Names:
  • GSK961081 100mcg SD
  • GSK961081 200mcg SD
  • GSK961081 300mcg SD
  • Placebo
  • GSK961081 3mcg SD
  • GSK961081 15mcg SD
  • GSK961081 50mcg SD
Drug: GSK961081 3mcg SD
single dose delivered via nebulsier
Other Name: GSK961081 3mcg SD
Experimental: Cohort 2, period 1
Placebo, GSK961081 100mcg, GSK961081 200mcg, GSK961081 300mcg,
Drug: GSK961081 200mcg SD
single dose via nebuliser
Other Name: GSK961081 200mcg SD
Drug: GSK961081 300mcg SD
single dose via nebuliser
Other Name: GSK961081 300mcg SD
Drug: Placebo SD
single dose via nebuliser
Other Name: Placebo SD
Drug: GSK961081 100mcg SD
single dose delivered via solution for nebulisation
Other Name: GSK961081 100mcg SD
Experimental: Cohort 3
GSK961081 100mcg or Placebo
Drug: Placebo RD
repeat dose via nebuliser
Other Name: Placebo RD
Drug: GSK961081 100mcg RD
repeat dose via nebuliser
Other Name: GSK961081 100mcg SD
Experimental: Cohort 2, period 2
GSK961081 100mcg, Placebo, GSK961081 200mcg, GSK961081 300mcg
Drug: GSK961081 200mcg SD
single dose via nebuliser
Other Name: GSK961081 200mcg SD
Drug: GSK961081 300mcg SD
single dose via nebuliser
Other Name: GSK961081 300mcg SD
Drug: Placebo SD
single dose via nebuliser
Other Name: Placebo SD
Drug: GSK961081 100mcg SD
single dose delivered via solution for nebulisation
Other Name: GSK961081 100mcg SD
Experimental: Cohort 4
GSK961081 300mcg or Placebo
Drug: GSK961081 300mcg RD
repeat dose vai nebuliser
Other Name: GSK961081 300mcg RD
Drug: Placebo RD
repeat dose via nebuliser
Other Name: Placebo RD

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
  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: NCT00887406

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

No publications provided

Responsible Party: Study Director, GSK
ClinicalTrials.gov Identifier: NCT00887406     History of Changes
Other Study ID Numbers: 104865, MAB104865
Study First Received: April 23, 2009
Last Updated: May 15, 2009
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:
COPD
long-acting bronchodilator
first time in human study

ClinicalTrials.gov processed this record on July 29, 2014