A Two-part Study to Investigate the Effects in Adults of Two Doses of Golexanolone in Patients With Primary Biliary Cholangitis (PBC) With Fatigue and Cognitive Dysfunction

Exclusion Criteria

• •Child-Pugh class B or C cirrhosis
• •Clinical evidence of hepatic decompensation (e.g. current or prior HE, ascites, or variceal bleeding)
• •History of hepatocellular carcinoma
• •Bilirubin \>1.5 x ULN
• •Glomerular filtration rate (GFR) \<35 mL/min/1.73m2
• •Low Haemoglobin (HB), i.e. subjects with moderate/severe anaemia
• •Low S-B12 or low P-folate
• •Evidence of biliary obstruction
• •Any positive result on screening for human immunodeficiency virus (HIV), or hepatitis B (serum hepatitis B surface antigen positive)
• •Prolonged QTcF (\>500 ms), or any clinically significant abnormality in the resting ECG, as judged by the Investigator (at screening)
• •Concomitant disease characterised by chronic fatigue and/or cognitive impairment
• •Clinically significant bowel disease, including obstruction, active inflammatory bowel disease, or malabsorption
• •Clinically significant sleep apnoea
• •An uncontrolled thyroid disorder
• •Subjects with a history of or currently active immune disorders (i.e. uncontrolled) other that PBC (including autoimmune disease) and/or diseases requiring immunosuppressive drugs
• •Clinical diagnosis of autoimmune hepatitis overlap
• •The presence, as judged by the Investigator, of clinically significant concomitant illness which would jeopardise safe participation in the study and /or the interpretation of study findings
• •Regular use of prescribed or over the counter (OTC) medications known to cause fatigue or cognitive dysfunction
• •Use of prohibited medications within 14 days prior to randomisation
• •Anticipated change in PBC medication and/or significant medical or surgical intervention within the duration of the study
• •Regular (more than 1 week per month) alcohol consumption in excess of 14 units per week
• •Administration of another new chemical entity or has participated in any other clinical study that included drug treatment with the last administration within 3 months prior to administration of IMP in this study
• •Females who are pregnant, nursing or actively trying to conceive a child
• •Expected inability to swallow the required number of IMP capsules at the applicable dose level
• •History of severe allergy/hypersensitivity or on-going allergy/hypersensitivity, as judged by the Investigator