SHS_610050 KOWK CGSK 16217
A Randomized, Double-blind, Multi-dose, Placebo-controlled Study to Evaluate the Efficacy, Safety and Tolerability of GSK2330672 Administration for the Treatment of Pruritus in Patients With Primary Biliary Cholangitis
A Randomized, Double-blind, Multi-dose, Placebo-controlled Study to Evaluate the Efficacy, Safety and Tolerability of GSK2330672 Administration for the Treatment of Pruritus in Patients With Primary Biliary Cholangitis (GLIMMER: GSK2330672 triaL of Ibat Inhibition With Multidose Measurement for Evaluation of Response).
• 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 (Note: 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 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 during the 8 weeks prior to the Screening Visit.
• 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.
• 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.
• Screening total bilirubin >1.5x ULN. Isolated bilirubin >1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%.
• Screening ALT or AST >4x 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).
• History or presence of other concomitant liver diseases including hepatitis due to hepatitis B or C virus (HBV, HCV) infection, primary sclerosing cholangitis (PSC), alcoholic liver disease, definite autoimmune hepatitis, biopsy proven nonalcoholic steatohepatitis (NASH) or confirmed hepatocellular carcinoma.
• Current symptomatic inflammatory bowel disease, chronic diarrhea, Crohn's disease or diarrhea related to malabsorption syndromes.
• Current symptomatic cholelithiasis or inflammatory gall bladder disease.
• Administration of the following drugs at any time during the 3 months prior to screening for the study or planned administration during the study: colchicine, methotrexate, azathioprine, or systemic corticosteroids.
• 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
• Obeticholic acid use: a participant must discontinue use of obeticholic acid at least 8 weeks prior to the start of the Initial Study Period
• 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.
Kris Kowdley, M.D.
Glaxo Smith Kline (GSK)