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

NCT00687700 | Completed Phase 1

• 1 other identifier: MAB110553
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

propranolol; B2-agonist,; B-antagonist,

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 32 hours

Secondary Outcomes (4)

• Assess safety of GSK961081 after single doses of it with&without ß blockade with propranolol as measured by specific indicators

  Up to 71 days

• Adverse events, clinical laboratory safety tests, FEV1, vital signs, 12-lead ECG parameters, blood glucose and serum potassium.

  Up to 71 days

• Propranolol and GSK961081blood levels to derive pharmacokinetics

  Up to 32 hours

• Assess systemic pharmacokinetics of GSK961081 and propranolol after single doses of both

  Up to 32 hours

Study Arms (1)

All subjects

EXPERIMENTAL

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; Drug: GSK961081 matching placebo; Drug: Propranolol; Drug: Propranolol matching placebo

Interventions

GSK961081 DRUG

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.

All subjects

GSK961081 matching placebo DRUG

GSK961081 matching placebo multidose dry powder inhaler (Diskus inhaler) will be available to be administered once daily in the morning.

All subjects

Propranolol DRUG

Propranolol over encapsulated tablet will be available with dosing strengths of 40 milligrams administered orally with 240 milliliters of water.

All subjects

Propranolol matching placebo DRUG

Propranolol matching placebo over encapsulated tablet will be available to be administered orally with 240 milliliters of water.

All subjects

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Theravance Biopharma: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

GSK Investigational Site

Harrow, Middlesex, HA1 3UJ, United Kingdom

Location

Related Links

• Results for study MAB110553 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

batefenterol; Propranolol

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2008
• First Posted: June 2, 2008
• Study Start: March 10, 2008
• Primary Completion: May 27, 2008
• Study Completion: May 27, 2008
• Last Updated: October 6, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)