The Safety and Tolerability of GW805858 in Healthy Volunteers and Mild Asthmatics

Study Overview
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Brief Summary
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This study will be the First Time in Human Study (FTIH) aiming to assess the safety and tolerability of GW805858 for both single and repeat dose. The study also aims to assess safety and tolerability in mild asthmatic subjects as well as healthy volunteers.

Official Title
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A Randomised, Single and Repeat Dose, Double-blind, Placebo Controlled Study to Assess the Safety and Tolerability of GW805858 in Healthy Volunteers and Mild Asthmatics

Conditions
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Asthma

Intervention / Treatment
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* Drug: GW805858
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women of non-child bearing potential, aged between 18 and 60 years of age inclusive. Body weight = 50 kg (110 lbs) for men and = 45 kg for women and Body Mass Index (BMI) within the range 19.0-30.0 kg/m2 inclusive. The subject is a current non-smoker who has not used any tobacco products in the last year. A signed and dated written informed consent is obtained for the subject. The subject is able to understand and comply with protocol requirements and timetables, instructions and protocol-stated restrictions. If asthmatic, the subject must be a clinically stable asthmatic. Exclusion Criteria: The subject has a history of allergy to ingredients within the inhaler. The subject has received an investigational drug or participated in any other research trial within 30 days, prior to the first dose of current study medication. The subject has used prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 14 days prior to the first dose of study medication. The subject has an average weekly alcohol intake of greater than 21 units if male or 14 units if female. The subject has any history of breathing problems (e.g. history of asthmatic symptoms). The subject is infected with the hepatitis B, hepatitis C, or HIV virus. The subject has had a respiratory tract infection or worsening of asthma within 4 weeks of the start of the study. The subject has a past or present disease, which as judged by the Investigator, may affect the outcome of this study. The subject has a history of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxia seizures. The subject has taken inhaled, nasal or dermal steroids within 4 weeks or oral steroids within 8 weeks of the start of the study. The subject is unable to abstain from other drugs that may interfere with the conduct of the study. The subject has ongoing rhinitis that requires treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subjects receiving treatment sequence 1: Part 1<br>Eligible subjects will receive placebo followed by GW805858 with a starting dose of 150 micrograms administered using Metered Dose Inhaler (MDI). | Drug: GW805858<br>* GW805858 MDI will be given with dose of 150 micrograms per metered actuation and 120 actuations per inhaler. GW805858 MDI comprises a solution of GW805858 in a liquefied hydrofluoroalkane propellant (1,1,1,2-tetrafluoroethane) which is contained in an aluminium alloy can, internally coated with a specified fluoropolymer, fitted with a metering valve.<br>Drug: Placebo<br>* Placebo MDI will be given to the subjects.<br>|
| Experimental: Subjects receiving treatment sequence 2: Part 1<br>Eligible subjects will receive GW805858 with a starting dose of 150 micrograms followed by placebo administered using MDI. | Drug: GW805858<br>* GW805858 MDI will be given with dose of 150 micrograms per metered actuation and 120 actuations per inhaler. GW805858 MDI comprises a solution of GW805858 in a liquefied hydrofluoroalkane propellant (1,1,1,2-tetrafluoroethane) which is contained in an aluminium alloy can, internally coated with a specified fluoropolymer, fitted with a metering valve.<br>Drug: Placebo<br>* Placebo MDI will be given to the subjects.<br>|
| Experimental: Subjects receiving treatment sequence 1: Part 2<br>Eligible subjects will receive placebo followed by GW805858 with a starting dose of 150 micrograms administered using MDI. | Drug: GW805858<br>* GW805858 MDI will be given with dose of 150 micrograms per metered actuation and 120 actuations per inhaler. GW805858 MDI comprises a solution of GW805858 in a liquefied hydrofluoroalkane propellant (1,1,1,2-tetrafluoroethane) which is contained in an aluminium alloy can, internally coated with a specified fluoropolymer, fitted with a metering valve.<br>Drug: Placebo<br>* Placebo MDI will be given to the subjects.<br>|
| Experimental: Subjects receiving treatment sequence 2: Part 2<br>Eligible subjects will receive GW805858 with a starting dose of 150 micrograms followed by placebo administered using MDI. | Drug: GW805858<br>* GW805858 MDI will be given with dose of 150 micrograms per metered actuation and 120 actuations per inhaler. GW805858 MDI comprises a solution of GW805858 in a liquefied hydrofluoroalkane propellant (1,1,1,2-tetrafluoroethane) which is contained in an aluminium alloy can, internally coated with a specified fluoropolymer, fitted with a metering valve.<br>Drug: Placebo<br>* Placebo MDI will be given to the subjects.<br>|
| Experimental: Subjects receiving GW805858: Part 3<br>Eligible subjects will receive GW805858 1200 micrograms twice daily administered using MDI. | Drug: GW805858<br>* GW805858 MDI will be given with dose of 150 micrograms per metered actuation and 120 actuations per inhaler. GW805858 MDI comprises a solution of GW805858 in a liquefied hydrofluoroalkane propellant (1,1,1,2-tetrafluoroethane) which is contained in an aluminium alloy can, internally coated with a specified fluoropolymer, fitted with a metering valve.<br>|
| Experimental: Subjects receiving placebo: Part 3<br>Eligible subjects will receive placebo administered using MDI. | Drug: Placebo<br>* Placebo MDI will be given to the subjects.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability parameters will be compared between active and placebo treatment groups using summary statistics. No formal statistical analyses of the safety and tolerability data will be performed. |  | Up to 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Derived GW805858 and GW288967 PK parameters will be compared between active and placebo treatment groups using summary statistics. |  | Pre-dose, 5,20,30,45,60,90 minutes, 2,3,4,6,8,10,12,12.5,13,14, 24 hours Post-dose on Days 1 and 28. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GW805858, MDI, asthma, surfactant