Dose Response Study of GSK2330672 for the Treatment of Pruritus in Participants 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 percent (%).
* Screening ALT or AST \>6x ULN.
* Screening eGFR \<45 milliliter (mL)/minute/1.73 square meter (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 virus (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 Inhibitor of the Human Ileal Bile Acid Transporter (IBAT) 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 GlaxoSmithKline (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 (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 measure (25 mL) of spirits.