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Table 1 Eligibility criteria

From: BAT117213: Ileal bile acid transporter (IBAT) inhibition as a treatment for pruritus in primary biliary cirrhosis: study protocol for a randomised controlled trial

A subject will be eligible for inclusion in this study only if all of the following criteria apply:
1. Male or female aged between 18 and 75 years of age inclusive, at the time of signing the informed consent.
2. Proven or likely PBC, as demonstrated by the patient presenting with at least 2 of the following:
• History of sustained increased AP levels first recognized at least 6 months prior to Day 1
• Positive AMA titer (>1:40 titer on immunofluorescence or M2 positive by ELISA) or PBC-specific antinuclear antibodies (antinuclear dot and nuclear rim positive)
• Liver biopsy consistent with PBC.
3. Screening AP value < 10 × ULN.
4. Subjects should be on stable doses of UDCA for >8 weeks at time of screening. Subjects not taking UDCA due to intolerance may be enrolled into this study following agreement by the GSK medical monitor.
5. Symptoms of pruritus as follows (one of the following):
• PBC patients with severe symptoms of pruritus that significantly impact daily life and have proven refractory after at least one previous therapy has been discontinued due to inadequate clinical response, poor tolerability or adverse events. Temporary response to cooling, 1 % menthol in aqueous cream, nasobiliary drainage or MARS therapy is still compatible with refractory itch.
• PBC patients with unresolved symptoms with use of a single antipruritic agent who can tolerate washout of current therapy for the duration of the trial.
• PBC patients seeking treatment for pruritus that is newly diagnosed or previously untreated.
6. A female subject is eligible to participate if she is not pregnant, as confirmed by a negative serum human chorionic gonadotropin (hCG) test or at least one of the following conditions applies:
• Non-reproductive potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea
• Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods along with either a second form of highly effective contraception or barrier protection (condoms with spermicide) if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
• Reproductive potential and agrees to follow one of the specified contraception options for the specified duration of time.
7. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Main exclusion criteria:
1. Screening total bilirubin >1.5x ULN. Isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 %.
2. Screening ALT or AST >4x ULN.
3. Screening serum creatinine >2.5 mg/dL (221 umol/L).
4. History or presence of hepatic decompensation (e.g., variceal bleeds, encephalopathy, or poorly controlled ascites).
5. History or presence of other concomitant liver diseases including hepatitis due to hepatitis B or C virus (HCV, HBV) infection, primary sclerosing cholangitis (PSC), alcoholic liver disease, definite autoimmune hepatitis or biopsy proven non-alcoholic steatohepatitis (NASH).
6. Administration of the following drugs at any time during the 3 months prior to screening for the study: colchicine, methotrexate, azathioprine, or systemic corticosteroids.
7. Current or chronic history of inflammatory bowel disease, chronic diarrhoea, Crohn’s disease or diarrhoea related to malabsorption syndromes.
8. Faecal occult blood positive test at screening.
9. Based on averaged QTc values of triplicate ECGs obtained at least 5 min apart:
• QTc ≥ 450 msec; or
• QTc ≥ 480 msec in subjects with Bundle Branch Block.
10. History of sensitivity to heparin or heparin-induced thrombocytopenia.
11. History of sensitivity to any of the study medications, 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.
12. 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.
13. A positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
14. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
15. The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
16. Exposure to more than four new chemical entities within 12 months prior to the first dosing day.