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Trial record 1 of 9 for:    gsk2330672
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Dose Response Study of GSK2330672 for the Treatment of Pruritus in Patients With Primary Biliary Cholangitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02966834
Recruitment Status : Active, not recruiting
First Posted : November 17, 2016
Last Update Posted : February 5, 2020
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE November 15, 2016
First Posted Date  ICMJE November 17, 2016
Last Update Posted Date February 5, 2020
Actual Study Start Date  ICMJE January 11, 2017
Estimated Primary Completion Date April 20, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 15, 2016)
Mean change from Baseline at Week 16 in the Mean Worst Daily Itch Score [ Time Frame: Baseline and Week 16 ]
Participant's itch severity is recorded on an electronic diary (eDiary) each morning and evening using a 0 to 10 numerical rating scale (NRS). The Worst Daily Itch Score is averaged over the 7 days preceding Baseline and over the 7 days preceding Week 16.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02966834 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 15, 2016)
  • Mean change from Baseline at Week 16 in PBC-40 scale [ Time Frame: Baseline and Week 16 ]
    The PBC-40 is a disease specific health related quality of life measure.
  • 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 ]
    Criteria for high risk of PBC progression is defined as serum ALP concentrations >=1.67x upper limit of normal range (ULN) and/or total bilirubin concentrations >ULN at Day 1.
  • Number of participants with serum ALP concentrations <1.67xULN and total bilirubin concentrations =<ULN at Week 16, among those with a high risk of PBC progression [ Time Frame: Week 16 ]
    Criteria for high risk of PBC progression is defined as serum ALP concentrations >=1.67xULN and/or total bilirubin concentrations >ULN at Day 1
  • 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 ]
    Criteria for high risk of PBC progression is defined as serum ALP concentrations >=1.67xULN and/or total bilirubin concentrations >ULN at Day 1
  • 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 ]
    Criteria for high risk of PBC progression is defined as serum ALP concentrations >=1.67xULN and/or total bilirubin concentrations >ULN at Day 1
  • 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 ]
    Criteria for high risk of PBC progression is defined as serum ALP concentrations >=1.67xULN and/or total bilirubin concentrations >ULN at Day 1
  • 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 ]
    Criteria for high risk of PBC progression is defined as serum ALP concentrations >=1.67xULN and/or total bilirubin concentrations >ULN at Day 1
  • 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 ]
    Criteria for high risk of PBC progression is defined as serum ALP concentrations >=1.67xULN and/or total bilirubin concentrations >ULN at Day 1
  • 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 ]
    Criteria for high risk of PBC progression is defined as serum ALP concentrations >=1.67xULN and/or total bilirubin concentrations >ULN at Day 1
  • Number of participants with any adverse event (AE) or serious adverse event (SAE) [ Time Frame: Up to Week 20 ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. Any untoward event resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persisting disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.
  • Number of participants with abnormal clinical chemistry parameters, as a measure of safety [ Time Frame: Up to Week 20 ]
    Blood samples will be collected to measure blood urea nitrogen, creatinine, estimated glomerular filtration rate (eGFR-chronic kidney disease epidemiology collaboration [CKD-EPI]), glucose (fasting), total cholesterol (fasting), potassium, sodium, calcium, direct low density lipoprotein (LDL) cholesterol (fasting), triglycerides (fasting), AST, ALT, ALP, GGT, total bilirubin, direct bilirubin, total protein, and albumin
  • Number of subjects with abnormal hematology laboratory parameters, as a measure of safety [ Time Frame: Up to Week 20 ]
    Blood samples will be collected to measure platelet count, red blood cell (RBC) count, hemoglobin, hematocrit, percent reticulocytes, mean cell volume (MCV), mean corpuscular hemoglobin (MCH), white blood cell (WBC) count, neutrophils, lymphocytes, monocytes, eosinophils, and basophils
  • Electrocardiogram (ECG) assessment as a measure of safety [ Time Frame: Up to Week 20 ]
    Single 12-lead ECG will be obtained to measure PR, QRS, QT, and Corrected QT interval
  • Blood pressure assessment as a measure of safety [ Time Frame: Up to Week 20 ]
    Systolic and diastolic blood pressure will be measured after 5 minutes rest in a quiet setting without distractions
  • Measurement of heart rate as a measure of safety [ Time Frame: Up to Week 20 ]
    Pulse rate will be measured after 5 minutes rest in a quiet setting without distractions
  • Gastrointestinal Symptom Rating Scale (GSRS) assessment [ Time Frame: Up to Week 20 ]
    The GSRS is a validated scale that will be used to assess gastrointestinal symptoms experienced by participants
  • Number of participants with Mean Worst Daily Itch Score of <4 at Week 16 [ Time Frame: Week 16 ]
    Participant's itch severity is recorded on an eDiary each morning and evening using a 0 to 10 NRS.
  • 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 ]
    Participant's itch severity is recorded on an eDiary each morning and evening using a 0 to 10 NRS.
  • 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 ]
    Participant's itch severity is recorded on an eDiary each morning and evening using a 0 to 10 NRS.
  • Mean number of days with Worst Daily Itch Score of <4 [ Time Frame: Baseline to Week 16 ]
    Participant's itch severity is recorded on an eDiary each morning and evening using a 0 to 10 NRS.
  • 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 ]
    Participant's itch severity is recorded on an eDiary each morning and evening using a 0 to 10 NRS.
  • 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 ]
    Participant's itch severity is recorded on an eDiary each morning and evening using a 0 to 10 NRS.
  • Change from Baseline in the Mean Daily Sleep Score at Week 16 [ Time Frame: Baseline and Week 16 ]
    Participant's quality of sleep will be recorded on an eDiary each morning using a 0 to 10 NRS. The Daily Sleep Score is averaged over the 7 days preceding Baseline and over the 7 days preceding Week 16
  • Change from Baseline in the Mean Daily Fatigue Score at Week 16 [ Time Frame: Baseline and Week 16 ]
    Participant's fatigue level will be recorded on an eDiary each evening using a 0 to 10 NRS. The Daily Fatigue Score is averaged over the 7 days preceding Baseline and over the 7 days preceding Week 16
  • Change from Baseline in the 5-D Itch Scale at Week 16 [ Time Frame: Baseline and Week 16 ]
    5-D Itch Scale is measurement of participant's itch.
  • Mean change from Baseline at Week 16 in serum total bile acid concentration [ Time Frame: Baseline and Week 16 ]
    Blood samples will be collected for evaluating total bile acid concentration as a biomarker of PBC
  • Mean change from Baseline at Week 16 in serum 7-alpha hydroxy-4-cholesten-3-one (C4) [ Time Frame: Baseline and Week 16 ]
    Blood samples will be collected for evaluating C4 concentration as a marker of bile acid synthesis
  • 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) ]
    Blood samples will be collected for measurement of plasma GSK2330672 concentration
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose Response Study of GSK2330672 for the Treatment of Pruritus in Patients With Primary Biliary Cholangitis
Official Title  ICMJE 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)
Brief Summary This study is being conducted to evaluate the efficacy, safety and tolerability of GSK2330672 administration for the treatment of pruritus (itch) in participants with primary biliary cholangitis (PBC). Participants will be treated with either placebo or one of the 4 dose regimens of GSK2330672 (20 milligram [mg], 90 mg or 180 mg taken once daily or 90 mg twice daily). Subjects on GSK2330672 will also receive placebo tablets to maintain blinding. The total duration of a subject's participation will be up to 45 days of screening and 24 weeks of study including follow-up.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Cholestasis
Intervention  ICMJE
  • Drug: Placebo
    GSK2330672 matching placebo will be supplied as white film-coated tablets.
  • Drug: GSK2330672
    GSK2330672 will be supplied in 2 dose strengths of 10 mg and 45 mg white film-coated tablets.
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Subjects will receive matching placebo
    Intervention: Drug: Placebo
  • Experimental: GSK2330672 20 mg once daily
    Subjects will receive GSK2330672 and matching placebo to maintain blind
    Interventions:
    • Drug: Placebo
    • Drug: GSK2330672
  • Experimental: GSK2330672 90 mg once daily
    Subjects will receive GSK2330672 and matching placebo to maintain blind
    Interventions:
    • Drug: Placebo
    • Drug: GSK2330672
  • Experimental: GSK2330672 180 mg once daily
    Subjects will receive GSK2330672 and matching placebo to maintain blind
    Interventions:
    • Drug: Placebo
    • Drug: GSK2330672
  • Experimental: GSK2330672 90 mg twice daily
    Subjects will receive GSK2330672 and matching placebo to maintain blind
    Interventions:
    • Drug: Placebo
    • Drug: GSK2330672
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: October 11, 2018)
140
Original Estimated Enrollment  ICMJE
 (submitted: November 15, 2016)
120
Estimated Study Completion Date  ICMJE April 20, 2020
Estimated Primary Completion Date April 20, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   France,   Germany,   Italy,   Japan,   Poland,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02966834
Other Study ID Numbers  ICMJE 201000
2016-002416-41 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP