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

This study is currently recruiting participants.
Verified by GlaxoSmithKline, May 2008

Sponsors and Collaborators: GlaxoSmithKline
Parexel Northwick Park
Information provided by: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00687700
  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
Healthy Volunteers
Drug: GSK961081
Drug: Propanolol
Phase I

ChemIDplus related topics:   Propranolol    Dexpropranolol    Propranolol hydrochloride   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Pharmacodynamics Study
Official Title:   A Study to Investigate the Relative Pharmacological Activity of an Inhaled B2-Agonist/Anticholinergic Dual Pharmacophore in Healthy Volunteers

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.

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

Estimated Enrollment:   23
Study Start Date:   February 2008
Estimated Study Completion Date:   May 2008
Estimated Primary Completion Date:   May 2008 (Final data collection date for primary outcome measure)

  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 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00687700

Locations
United Kingdom, London
GSK Clinical Trials Call Center     Recruiting
      Harrow, London, United Kingdom, HA1 3UJ
      Contact: GSK Clinical Trials Call Centre     1-877-379-3718        

Sponsors and Collaborators
GlaxoSmithKline
Parexel Northwick Park

Investigators
Study Director:     GSK Clinical Trials, MD MSc FFPM     GlaxoSmithKline    
  More Information


Study ID Numbers:   MAB110553
First Received:   May 28, 2008
Last Updated:   May 30, 2008
ClinicalTrials.gov Identifier:   NCT00687700
Health Authority:   United Kingdom: Research Ethics Committee

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

Study placed in the following topic categories:
Propranolol
Healthy

Additional relevant MeSH terms:
Vasodilator Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents
Therapeutic Uses
Physiological Effects of Drugs
Adrenergic beta-Antagonists
Adrenergic Antagonists
Cardiovascular Agents
Anti-Arrhythmia Agents
Antihypertensive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 15, 2008




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