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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 12 December 2020
Main ID:  NCT02966834
Date of registration: 15/11/2016
Prospective Registration: Yes
Primary sponsor: GlaxoSmithKline
Public title: Dose Response Study of GSK2330672 for the Treatment of Pruritus in Patients With Primary Biliary Cholangitis
Scientific title: 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)
Date of first enrolment: January 11, 2017
Target sample size: 147
Recruitment status: Completed
URL:  https://clinicaltrials.gov/show/NCT02966834
Study type:  Interventional
Study design:  Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).  
Phase:  Phase 2
Countries of recruitment
Australia Canada France Germany Italy Japan Poland Spain
United Kingdom United States
Contacts
Name:     GSK Clinical Trials
Address: 
Telephone:
Email:
Affiliation:  GlaxoSmithKline
Key inclusion & exclusion criteria

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.



Age minimum: 18 Years
Age maximum: 80 Years
Gender: All
Health Condition(s) or Problem(s) studied
Cholestasis
Intervention(s)
Drug: GSK2330672
Drug: Placebo
Primary Outcome(s)
Mean change from Baseline at Week 16 in the Mean Worst Daily Itch Score [Time Frame: Baseline and Week 16]
Secondary Outcome(s)
Electrocardiogram (ECG) assessment as a measure of safety [Time Frame: Up to Week 20]
Mean number of days with Worst Daily Itch Score at least 2-points lower than the Baseline Mean Daily Score [Time Frame: Baseline to Week 16]
Mean number of days with Worst Daily Itch Score at least 30% lower than the Baseline Mean Worst Daily Itch Score [Time Frame: Baseline to Week 16]
Number of participants with at least a 30% reduction from Baseline in the Mean Worst Daily Itch Score at Week 16 [Time Frame: Baseline and Week 16]
Change from Baseline in the Mean Daily Sleep Score at Week 16 [Time Frame: Baseline and Week 16]
Gastrointestinal Symptom Rating Scale (GSRS) assessment [Time Frame: Up to Week 20]
Change from Baseline in the 5-D Itch Scale at Week 16 [Time Frame: Baseline and Week 16]
Mean change from Baseline at Week 16 in albumin concentration, among those with a high risk of PBC progression [Time Frame: Baseline and Week 16]
Mean change from Baseline at Week 16 in PBC-40 scale [Time Frame: Baseline and Week 16]
Mean change from Baseline at Week 16 in serum alkaline phosphatase (ALP) concentrations, in participants with high risk of PBC progression [Time Frame: Baseline and Week 16]
Mean change from Baseline at Week 16 in prothrombin time/international normalised ratio (PT/INR), among those with a high risk of PBC progression [Time Frame: Baseline and Week 16]
Mean change from Baseline at Week 16 in serum gamma glutamyl transferase (GGT), among those with a high risk of PBC progression [Time Frame: Baseline and Week 16]
Number of participants with serum ALP concentrations <1.67xULN and total bilirubin concentrations = [Time Frame: Week 16]
Mean change from Baseline at Week 16 in serum 7-alpha hydroxy-4-cholesten-3-one (C4) [Time Frame: Baseline and Week 16]
Number of participants with abnormal clinical chemistry parameters, as a measure of safety [Time Frame: Up to Week 20]
Number of subjects with abnormal hematology laboratory parameters, as a measure of safety [Time Frame: Up to Week 20]
Mean change from Baseline at Week 16 in total bilirubin concentration, among those with a high risk of PBC progression [Time Frame: Baseline and Week 16]
Mean change from Baseline at Week 16 in serum alanine aminotransferase (ALT)among those with a high risk of PBC progression [Time Frame: Baseline and Week 16]
Blood pressure assessment as a measure of safety [Time Frame: Up to Week 20]
Mean number of days with Worst Daily Itch Score of <4 [Time Frame: Baseline to Week 16]
Number of participants with at least a 2-point reduction from Baseline in the Mean Worst Daily Itch Score at Week 16 [Time Frame: Baseline and Week 16]
Number of participants with any adverse event (AE) or serious adverse event (SAE) [Time Frame: Up to Week 20]
Measurement of heart rate as a measure of safety [Time Frame: Up to Week 20]
Change from Baseline in the Mean Daily Fatigue Score at Week 16 [Time Frame: Baseline and Week 16]
Mean change from Baseline at Week 16 in serum aspartate aminotransferase (AST) among those with a high risk of PBC progression [Time Frame: Baseline and Week 16]
Mean change from Baseline at Week 16 in serum total bile acid concentration [Time Frame: Baseline and Week 16]
Number of participants with Mean Worst Daily Itch Score of <4 at Week 16 [Time Frame: Week 16]
Plasma concentration of GSK2330672 after sparse sampling [Time Frame: Week 8 and Week 12 (Between 1 and 3 hours post-dose, and between 5 and 8 hours post-dose)]
Secondary ID(s)
201000
2016-002416-41
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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