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A Study to Investigate the Pharmacology of a Dual Pharmacophore in Healthy Volunteers

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00687700
First Posted: June 2, 2008
Last Update Posted: August 11, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose
Study will investigate the pharmacodynamics of a dual pharmacophore in which a combination of GSK961081 and Propanolol is used to give a total effect of bronchodilation.

Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive Drug: GSK961081 Drug: GSK961081 matching placebo Drug: Propranolol Drug: Propranolol matching placebo Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Primary Purpose: Treatment
Official Title: A Study to Investigate the Relative Pharmacological Activity of Aninhaled B2-agonist/Anticholinergic Dual Pharmacophore Inhealthy Volunteers

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • To assess the bronchodilation of single doses of GSK961081 over 24 hours following ß blockade with the ß antagonist propranolol as measured by sGaw in healthy subjects. [ Time Frame: Up to 32 hours ]

Secondary Outcome Measures:
  • Assess safety of GSK961081 after single doses of it with&without ß blockade with propranolol as measured by specific indicators [ Time Frame: Up to 71 days ]
  • Adverse events, clinical laboratory safety tests, FEV1, vital signs, 12-lead ECG parameters, blood glucose and serum potassium. [ Time Frame: Up to 71 days ]
  • Propranolol and GSK961081blood levels to derive pharmacokinetics [ Time Frame: Up to 32 hours ]
  • Assess systemic pharmacokinetics of GSK961081 and propranolol after single doses of both [ Time Frame: Up to 32 hours ]

Enrollment: 23
Actual Study Start Date: March 10, 2008
Study Completion Date: May 27, 2008
Primary Completion Date: May 27, 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: All subjects
Eligible subjects will receive GSK961081 (400 micrograms or 1200 micrograms), GSK961081 matching placebo, propranolol (80 milligrams) and propranolol matching placebo in five treatment sessions through ten different crossover treatment sequences. There will be a washout period between treatment sessions of 7 to 14 days.
Drug: GSK961081
GSK961081 multidose dry powder inhaler (Diskus inhaler) will be available with dosing strengths of 400 micrograms and 1200 micrograms administered once daily in the morning.
Drug: GSK961081 matching placebo
GSK961081 matching placebo multidose dry powder inhaler (Diskus inhaler) will be available to be administered once daily in the morning.
Drug: Propranolol
Propranolol over encapsulated tablet will be available with dosing strengths of 40 milligrams administered orally with 240 milliliters of water.
Drug: Propranolol matching placebo
Propranolol matching placebo over encapsulated tablet will be available to be administered orally with 240 milliliters of water.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes 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 19-29.9 kg/m2.
  • FEV1 ≥ 80% predicted and a FEV1/ Forced Vital Capacity (FVC) ratio ≥ 0.7
  • Signed and dated written informed consent is obtained from the subject
  • The subject is able to understand and comply with the protocol requirements, instructions and protocol-stated restrictions.
  • The subject has an increase in sGAW of ≥15% over pre-dose baseline within 2 h of administration of 400 µg salbutamol by MDI inhaler at screening or in the 3 months before screening.
  • The subject has an increase in sGAW of ≥25% over pre-dose baseline within 2 h following 80 µg ipratropium bromide at screening or in the 3 months before screening.
  • 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 ≥ 10 pack years.

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 respiratory disease (i.e. history of asthmatic symptoms).
  • Clinically significant abnormal 12 lead ECG at
  • A subject in whom ipratropium bromide, salbutamol or propranolol are contraindicated.
  • 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 45-90 beats per minute (bpm) at screening.
  • The subject has donated a unit of blood within the 56 days or intends to donate within 56 days after completing the study.
  • The subject is currently taking regular (or course of) medication whether prescribed or not (with the exception of contraceptives, 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 medical monitor the medication will not interfere with the study procedures or compromise subject safety.
  • The subject has participated in a clinical study with a New Chemical Entity (NCE) within the past 3 months.
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • 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 history of regular alcohol consumption exceeding weekly intake of alcohol greater than 28 units for males, or an average daily intake of greater than 4 units.
  • Are unable to use the inhaler correctly.
  • The subject has a history of drug or other allergy, which, in the opinion of the Investigator, contraindicates their participation.
  • The subject has had a lower respiratory tract infection within 4 weeks of study start.
  • Subject is unable to perform the sGAW measurements
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00687700


Locations
United Kingdom
GSK Investigational Site
Harrow, Middlesex, United Kingdom, HA1 3UJ
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Study Data/Documents: Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: MAB110553
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: MAB110553
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: MAB110553
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: MAB110553
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: MAB110553
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: MAB110553
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: MAB110553
For additional information about this study please refer to the GSK Clinical Study Register

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00687700     History of Changes
Other Study ID Numbers: MAB110553
First Submitted: May 28, 2008
First Posted: June 2, 2008
Last Update Posted: August 11, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
URL: http://

Keywords provided by GlaxoSmithKline:
propranolol
B2-agonist,
B-antagonist,

Additional relevant MeSH terms:
Lung Diseases
Chronic Disease
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes
Lung Diseases, Obstructive
Propranolol
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents
Vasodilator Agents