Clinical trial NCT00687700: A Study to Investigate the Pharmacology of a Dual Pharmacophore in Healthy Volunteers
Official title: A Study to Investigate the Relative Pharmacological Activity of Aninhaled B2-agonist/Anticholinergic Dual Pharmacophore Inhealthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: propranolol
B2-agonist,
B-antagonist,
Lead sponsor: Theravance Biopharma
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2008-06-02
Enrollment: 23
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: 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.
timeFrame: Up to 32 hours
Secondary outcomes:
measure: Assess safety of GSK961081 after single doses of it with&without ß blockade with propranolol as measured by specific indicators
timeFrame: Up to 71 days
measure: Adverse events, clinical laboratory safety tests, FEV1, vital signs, 12-lead ECG parameters, blood glucose and serum potassium.
timeFrame: Up to 71 days
measure: Propranolol and GSK961081blood levels to derive pharmacokinetics
timeFrame: Up to 32 hours
measure: Assess systemic pharmacokinetics of GSK961081 and propranolol after single doses of both
timeFrame: Up to 32 hours
Other outcomes:
Locations:
city: Harrow
country: United Kingdom
facility: GSK Investigational Site
state: Middlesex
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: