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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00687700
First received: May 28, 2008
Last updated: May 31, 2012
Last verified: February 2011
  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
Healthy Subjects
Drug: GSK961081
Drug: Propanolol
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
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.

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: March 2008
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: GSK961081 Drug: Propanolol
    Other Names:
    • Propanolol
    • GSK961081
  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
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: 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

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00687700     History of Changes
Other Study ID Numbers: MAB110553
Study First Received: May 28, 2008
Last Updated: May 31, 2012
Health Authority: United Kingdom: Research Ethics Committee

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

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

ClinicalTrials.gov processed this record on November 25, 2014