Succinate Salt Version of GSK961081 for Healthy Volunteers

Study Overview
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Brief Summary
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Salt Bridging study for GSK961081

Official Title
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A Randomised, Double-blind, Dose Escalating Study in Healthy Volunteers to Assess the Safety, Tolerability, Extra Pulmonary Pharmacodynamics and Pharmacokinetics of Single Doses of GSK961081 (Succinate Salt)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: GSK961081
* Drug: GSK961081 matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult males or female aged between 18 and 50 years. Body mass index within the range 19-29.9 kilograms/metre2 Forced Expiratory Volume in 1 second (FEV1) >80% predicted and a FEV1/ Forced Vital Capacity (FVC) ratio > 0.7 Subjects 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: Who have a past or present disease, which as judged by the Investigator and medical monitor may affect the outcome of the study or the safety of the subject History of respiratory disease Significant abnormal 12 lead ECG, QTc(B) and QTc(F) value at screening >450msec on an individual ECG or a PR interval outside the range 120-210 msec Supine mean heart rate outside the range 40-90 beats per minute (bpm) at screening. Subject has donated a unit of blood within the 56 days or intends to donate within 56 days after completing the study 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. Subject has participated in a clinical study with a New Chemical Entity (NCE) within the past 3 months Infected with the Hepatitis B, Hepatitis C, or HIV virus Subject has a history of drug or other allergy, which, in the opinion of the Investigator, contraindicates their participation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

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: Sequence 1<br>In session 1, subjects will receive 300 microgram GSK961081 succinate followed by placebo in session 2. The subjects will receive 1500 micrograms of GSK961081 succinate in session 3 and 1500 micrograms of GSK961081 edisylate in session 4. | Drug: GSK961081<br>* GSK961081 edisylate and succinate will be administered as capsules via DISKUS inhaler formulated with lactose as a vehicle to make 12.5 milligrams. GSK961081 succinate will be given in a dose-ascending manner with a starting dose of 300 micrograms. The dose of GSK961081 edisylate is 1500 micrograms.<br>Drug: GSK961081 matching placebo<br>* GSK961081 matching placebo formulated with lactose only as a vehicle to 12.5 milligrams will be administered via the DISKUS inhaler.<br>|
| Experimental: Sequence 2<br>In session 1, subjects will receive 300 microgram GSK961081 succinate followed by 1500 micrograms of GSK961081 edisylate in session 2. The subjects will receive 1500 micrograms of GSK961081 succinate in session 3 and placebo in session 4. | Drug: GSK961081<br>* GSK961081 edisylate and succinate will be administered as capsules via DISKUS inhaler formulated with lactose as a vehicle to make 12.5 milligrams. GSK961081 succinate will be given in a dose-ascending manner with a starting dose of 300 micrograms. The dose of GSK961081 edisylate is 1500 micrograms.<br>Drug: GSK961081 matching placebo<br>* GSK961081 matching placebo formulated with lactose only as a vehicle to 12.5 milligrams will be administered via the DISKUS inhaler.<br>|
| Experimental: Sequence 3<br>In session 1, subjects will receive 300 microgram GSK961081 succinate followed by placebo in session 2. The subjects will receive 1500 micrograms of GSK961081edisylate in session 3 and an additional dose of GSK961081 succinate in session 4. | Drug: GSK961081<br>* GSK961081 edisylate and succinate will be administered as capsules via DISKUS inhaler formulated with lactose as a vehicle to make 12.5 milligrams. GSK961081 succinate will be given in a dose-ascending manner with a starting dose of 300 micrograms. The dose of GSK961081 edisylate is 1500 micrograms.<br>Drug: GSK961081 matching placebo<br>* GSK961081 matching placebo formulated with lactose only as a vehicle to 12.5 milligrams will be administered via the DISKUS inhaler.<br>|
| Experimental: Sequence 4<br>In session 1, subjects will receive 300 microgram GSK961081 succinate followed by 1500 micrograms of GSK961081 edisylate in session 2. The subjects will receive placebo in session 3 and an additional dose of GSK961081 succinate in session 4. | Drug: GSK961081<br>* GSK961081 edisylate and succinate will be administered as capsules via DISKUS inhaler formulated with lactose as a vehicle to make 12.5 milligrams. GSK961081 succinate will be given in a dose-ascending manner with a starting dose of 300 micrograms. The dose of GSK961081 edisylate is 1500 micrograms.<br>Drug: GSK961081 matching placebo<br>* GSK961081 matching placebo formulated with lactose only as a vehicle to 12.5 milligrams will be administered via the DISKUS inhaler.<br>|
| Experimental: Sequence 5<br>In session 1, subjects will receive 1500 micrograms of GSK961081 edisylate followed by 900 microgram GSK961081 succinate in session 2. The subjects will receive 1500 micrograms of GSK961081 succinate in session 3 and placebo in session 4. | Drug: GSK961081<br>* GSK961081 edisylate and succinate will be administered as capsules via DISKUS inhaler formulated with lactose as a vehicle to make 12.5 milligrams. GSK961081 succinate will be given in a dose-ascending manner with a starting dose of 300 micrograms. The dose of GSK961081 edisylate is 1500 micrograms.<br>Drug: GSK961081 matching placebo<br>* GSK961081 matching placebo formulated with lactose only as a vehicle to 12.5 milligrams will be administered via the DISKUS inhaler.<br>|
| Experimental: Sequence 6<br>In session 1, subjects will receive placebo followed by 900 micrograms of GSK961081 succinate in session 2. The subjects will receive 1500 micrograms of GSK961081 succinate in session 3 and 1500 micrograms of GSK961081 edisylate in session 4. | Drug: GSK961081<br>* GSK961081 edisylate and succinate will be administered as capsules via DISKUS inhaler formulated with lactose as a vehicle to make 12.5 milligrams. GSK961081 succinate will be given in a dose-ascending manner with a starting dose of 300 micrograms. The dose of GSK961081 edisylate is 1500 micrograms.<br>Drug: GSK961081 matching placebo<br>* GSK961081 matching placebo formulated with lactose only as a vehicle to 12.5 milligrams will be administered via the DISKUS inhaler.<br>|
| Experimental: Sequence 7<br>In session 1, subjects will receive 1500 micrograms of GSK961081 edisylate followed by 900 microgram GSK961081 succinate in session 2. The subjects will receive placebo in session 3 and an additional dose of GSK961081 succinate in session 4. | Drug: GSK961081<br>* GSK961081 edisylate and succinate will be administered as capsules via DISKUS inhaler formulated with lactose as a vehicle to make 12.5 milligrams. GSK961081 succinate will be given in a dose-ascending manner with a starting dose of 300 micrograms. The dose of GSK961081 edisylate is 1500 micrograms.<br>Drug: GSK961081 matching placebo<br>* GSK961081 matching placebo formulated with lactose only as a vehicle to 12.5 milligrams will be administered via the DISKUS inhaler.<br>|
| Experimental: Sequence 8<br>In session 1, subjects will receive placebo followed by 900 microgram GSK961081 succinate in session 2. The subjects will receive 1500 micrograms of GSK961081 edisylate in session 3 and an additional dose of GSK961081 succinate in session 4. | Drug: GSK961081<br>* GSK961081 edisylate and succinate will be administered as capsules via DISKUS inhaler formulated with lactose as a vehicle to make 12.5 milligrams. GSK961081 succinate will be given in a dose-ascending manner with a starting dose of 300 micrograms. The dose of GSK961081 edisylate is 1500 micrograms.<br>Drug: GSK961081 matching placebo<br>* GSK961081 matching placebo formulated with lactose only as a vehicle to 12.5 milligrams will be administered via the DISKUS inhaler.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 at intervals |  | during the 10 week study | 
| Cardiac monitoring at intervals |  | during the 10 week study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentrations of GSK961081 at intervals |  | during the 10 week study | 
| PK parameters at intervals |  | during the 10week study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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succinate, anti-muscarinic, b-agonist