A Randomised, Double-blind, Placebo-controlled, Two-part Study to Evaluate the Pharmacokinetics, Safety and Tolerability, and Preliminary Efficacy of Two Dose Levels of Golexanolone in Subjects With Primary Biliary Cholangitis (PBC), Fatigue, and Cognitive Dysfunction
The present phase 1b/2 randomised, double-blind, placebo-controlled, two-part study is designed to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of two dose levels of golexanolone compared with placebo among subjects with a history of non-cirrhotic or Child-Pugh class A cirrhotic Primary Biliary Cholangitis (PBC) with clinically significant fatigue and cognitive symptoms on stable background standard of care (SoC) PBC medication. The objectives of this research study are to assess the safety and tolerability as well the pharmacokinetic (PK) characteristics of golexanolone administered 40 mg BID for 5 days in the target population (part A) and to assess the safety and tolerability, the effects of golexanolone on health-related quality of life (HRQoL), including fatigue, day-time sleepiness and cognitive function as well as Investigator's overall impression of treatment effect of 28 days twice per day (BID) treatment with two dose levels of golexanolone versus placebo (part B).
• 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-40 fatigue domain score of ≥29 at screening
• Clinically significant cognitive symptoms, defined for the purposes of this study as a 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 at screening and a negative urine dip-stick pregnancy test at baseline, prior to first dose of IMP
• WOCBP must be willing to use a contraceptive method with a failure rate of \< 1% and agree to continue use of this method for the duration of the study and thereafter for 1 month after the last dosing of the IMP
• Females of non-childbearing potential must have documented tubal ligation or hysterectomy; or be post-menopausal
• Fertile male subjects must be willing to use condom and assure that their female partner 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