Dose Response Study of GSK2330672 for the Treatment of Pruritus in Patients With Primary Biliary Cholangitis

Inclusion Criteria

- Participant must be 18 to 80 years of age inclusive, at the time of signing the
informed consent.

- Participants who have proven PBC, as demonstrated by having at least 2 of the
following: History of sustained increased ALP levels >ULN first recognized at least 6
months prior to the Screening Visit (Sustained ALP elevations at the time of Screening
is not required, recognizing that the ALP may have decreased after institution of
ursodeoxycholic acid (UDCA) therapy as described in inclusion number 4). Documented
positive anti-mitochondrial antibody (AMA) titer (>1:40 titer on immunofluorescence or
M2 positive by enzyme-linked immunosorbent assay) or PBC-specific antinuclear
antibodies (antinuclear dot and/or nuclear rim positive). Liver biopsy (at any time in
the past) consistent with PBC.

- Participants must rate their itch severity as being >=4 on a 0 to 10 point scale for
the majority of time (at least half the days, as recalled by the participant) during
the 8 weeks prior to the Screening Visit. Periods of low itch or no itch are
acceptable as long as the worst daily itch score is >=4 on the majority of days.

- Participants who are currently taking UDCA should be on stable doses of UDCA for >8
weeks at time of screening. Participants not taking UDCA due to intolerance may be
enrolled 8 weeks after their last dose of UDCA. No changes or discontinuation is
permitted until completion of the Main Study Period.

- Male and/or female: Female participants- A female participant is eligible to
participate if she is not pregnant, not breastfeeding, and at least one of the
following conditions applies: Not a woman of childbearing potential (WOCBP) or a WOCBP
who agrees to follow the contraceptive guidance during the treatment period and until
at least 4 weeks after the last dose of study treatment.

- Capable of giving signed informed consent, which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in this
protocol.

Exclusion Criteria

- Screening total bilirubin >2x ULN. Total bilirubin >2x ULN is acceptable if bilirubin
is fractionated and direct bilirubin <35%.

- Screening ALT or AST >6x ULN.

- Screening eGFR <45 milliliter (mL)/minute/1.73 meter squared (m^2) based on the
CKD-EPI.

- History or presence of hepatic decompensation (e.g., variceal bleeds, encephalopathy
or ascites).

- Presence of actively replicating viral hepatitis due to hepatitis B or C (HBV, HCV)
infection, and/or confirmed hepatocellular carcinoma or biliary cancer. Other hepatic
conditions ( e.g., primary sclerosing cholangitis [PSC], alcoholic liver disease,
autoimmune hepatitis, non-alcoholic steatohepatitis [NASH] ) are permitted if PBC is
the dominant liver injury in the investigator's opinion.

- Current diarrhea.

- Current symptomatic cholelithiasis or inflammatory gall bladder disease. Participants
with history of cholecystectomy >=3 months before screening may be eligible for
enrolment.

- Any current medical condition (e.g. psychiatric disorder, senility or dementia), which
may affect the participant's ability to comply with the protocol specified procedures.

- Initiation or increase in dose of colchicine, methotrexate, azathioprine, or systemic
corticosteroids in the 2 months prior to screening. If a change in dose in any of
these medications is anticipated during the course of the study, the participant
should be excluded.

- Initiation or increase in dose of bezafibrate or fenofibrate at any time during the 3
months prior to screening. Participants may join the study on stable doses of these
medications, but no change or discontinuation is permitted until completion of the
Main Study Period.

- Initiation or increase in dose of any of the following in the 8 weeks prior to
screening: rifampicin, naltrexone, naloxone, nalfurafine, or sertraline. Participants
may join the study on stable or decreased doses of these medications, but no change in
dose is permitted until completion of the Main Study Period.

- Bile acid binding resin use: a participant must discontinue use of cholestyramine,
colesevelam, colestipol or colestimide prior to the start of the Initial Study Period
(no later than Day-2). Note: these drugs may be administered after completion of the
Main Study Period, if clinically indicated.

- Obeticholic acid use: a participant must discontinue use of obeticholic acid at least
8 weeks prior to the start of the Initial Study Period and may not restart until after
the end of the study.

- Administration of any other IBAT inhibitor in the 3 months prior to screening.

- Current enrolment or participation within the 8 weeks before start of the Initial
Study Period, in any other clinical study involving an investigational study
treatment.

- QT interval corrected for heart rate QTc >480 millisecond (msec).

- History of sensitivity to the study treatment or components thereof or a history of
drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor,
contraindicates their participation in the study.

- History of regular alcohol consumption within 6 months of the study defined as an
average weekly intake of >21 units for males or >14 units for females. One unit is
equivalent to 8 gram of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of
wine or 1 measure (25 mL) of spirits.