First Time in Human Study of GSK1223249 in Amyotrophic Lateral Sclerosis

Exclusion Criteria

• •Patients with other neuromuscular disorders (in addition to their ALS diagnosis), unless the investigator determines that such additional disorder will not affect safety or other measures in this study.
• •Patients with evidence of dementia or psychiatric illness which, in the investigator's opinion, is likely to prevent them from a full understanding of and/or compliance with the study requirements and procedures.
• •Patients with abnormalities detected during the screening evaluations which, in the investigator's medical judgement, are sufficiently significant to exclude them from participation in the study.
• •Patients who have participated in a clinical trial involving receipt of a biopharmaceutical product within 6 months prior to the first dosing day.
• •Exposure to more than four new investigational products within 12 months prior to the first dosing day.
• •The subject has a positive drugs of abuse test at the screening or pre dose visit. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates and benzodiazepines. Subjects who are on any of these drugs by prescription for medical reasons may be considered by the investigator for inclusion if they fulfil other entry criteria.
• •The subject has a positive alcohol test at the pre-dose visit. History of regular excessive alcohol consumption within 6 months of the study defined as:
• •For European sites: an average weekly intake of \> 28 units for males or \>21 units for females. One unit is equivalent to 8g of alcohol: a half-pint (\~240mL) of beer, 1 glass (125mL) of wine or 1 (25mL) measure of spirits.
• •For North American sites: an average weekly intake of \>21 drinks for males or \>14 drinks for women. One drink is equivalent to 12 g alcohol: 12 ounces (360mL) of beer, 5 ounces (150mL) of wine or 1.5 ounces (45mL) of 80 proof distilled spirits.
• •History of sensitivity to GSK1223249, or components thereof, or a history of drugs or other allergies that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
• •Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
• •Females of childbearing potential, pregnant females as determined by positive serum or urine beta hCG test at screening or prior to dosing, or lactating females.
• •Patients who have received any type of vaccination in the last 3 weeks before study drug administration.
• •Unwillingness or inability to follow the procedures outlined in the protocol
• •Subjects who will undergo muscle biopsies (cohorts 3-optional 5, 6, 7 and 8 will not be eligible for inclusion, if any of the following criteria apply:
• •Patients with wasted deltoids (MRC score ≤ 2) and patients with normal deltoids (MRC score 5).
• •Patients who cannot achieve normal coagulation in the peri-operative period and those who may otherwise be at higher risk of bleeding complications