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

Inclusion Criteria:

• Male and female subjects age ≥ 18 years

• Diagnosis of PBC based on the presence of ≥2 of 3 key disease characteristics

• Clinically significant fatigue defined for the purposes of this study as a PBC-40fatigue domain score of ≥29 at screening

• Clinically significant cognitive symptoms, defined for the purposes of this study asa PBC-40 cognitive domain ≥16 at screening

• Stable PBC SoC therapy (if any),for at least 3 months prior to randomisation

• For all women of childbearing potential (WOCBP) a negative pregnancy test atscreening and a negative urine dip-stick pregnancy test at baseline, prior to firstdose of IMP

• WOCBP must be willing to use a contraceptive method with a failure rate of < 1% andagree to continue use of this method for the duration of the study and thereafterfor 1 month after the last dosing of the IMP

• Females of non-childbearing potential must have documented tubal ligation orhysterectomy; or be post-menopausal

• Fertile male subjects must be willing to use condom and assure that their femalepartner will use contraceptive methods with a failure rate of < 1%

• Willing and able to give informed consent

• The subject should be judged by the Investigator to be lucid and oriented to person,place, time, and situation when giving the informed consent

Exclusion Criteria:

• Child-Pugh class B or C cirrhosis

• Clinical evidence of hepatic decompensation (e.g. current or prior HE, ascites, orvariceal 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), orhepatitis B (serum hepatitis B surface antigen positive)

• Prolonged QTcF (>500 ms), or any clinically significant abnormality in the restingECG, as judged by the Investigator (at screening)

• Concomitant disease characterised by chronic fatigue and/or cognitive impairment

• Clinically significant bowel disease, including obstruction, active inflammatorybowel 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 requiringimmunosuppressive drugs

• Clinical diagnosis of autoimmune hepatitis overlap

• The presence, as judged by the Investigator, of clinically significant concomitantillness which would jeopardise safe participation in the study and /or theinterpretation of study findings

• Regular use of prescribed or over the counter (OTC) medications known to causefatigue or cognitive dysfunction

• Use of prohibited medications within 14 days prior to randomisation

• Anticipated change in PBC medication and/or significant medical or surgicalintervention within the duration of the study

• Regular (more than 1 week per month) alcohol consumption in excess of 14 units perweek

• Administration of another new chemical entity or has participated in any otherclinical study that included drug treatment with the last administration within 3months 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 applicabledose level

• History of severe allergy/hypersensitivity or on-going allergy/hypersensitivity, asjudged by the Investigator