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Trial record 1 of 7 for:    GSK2330672
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Dose Response Study of GSK2330672 for the Treatment of Pruritus in Patients With Primary Biliary Cholangitis

This study is currently recruiting participants.
Verified November 2017 by GlaxoSmithKline
Sponsor:
ClinicalTrials.gov Identifier:
NCT02966834
First Posted: November 17, 2016
Last Update Posted: November 22, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose
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.

Condition Intervention Phase
Cholestasis Drug: Placebo Drug: GSK2330672 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official 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)

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 haemoglobin (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


Estimated Enrollment: 118
Actual Study Start Date: January 11, 2017
Estimated Study Completion Date: August 9, 2019
Estimated Primary Completion Date: August 9, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Subjects will receive matching placebo
Drug: Placebo
GSK2330672 matching placebo will be supplied as white film-coated tablets.
Experimental: GSK2330672 20 mg once daily
Subjects will receive GSK2330672 and matching placebo to maintain blind
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.
Experimental: GSK2330672 90 mg once daily
Subjects will receive GSK2330672 and matching placebo to maintain blind
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.
Experimental: GSK2330672 180 mg once daily
Subjects will receive GSK2330672 and matching placebo to maintain blind
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.
Experimental: GSK2330672 90 mg twice daily
Subjects will receive GSK2330672 and matching placebo to maintain blind
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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 (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.
  • 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 >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. 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.
  • 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.
  • 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.
  • 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 >450 millisecond (msec) or QTc >480 msec in participants with bundle branch block
  • 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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02966834


Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

  Show 52 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02966834     History of Changes
Other Study ID Numbers: 201000
First Submitted: November 15, 2016
First Posted: November 17, 2016
Last Update Posted: November 22, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:
PBC
itch
GSK2330672
GLIMMER
primary biliary cholangitis
pruritus

Additional relevant MeSH terms:
Pruritus
Cholangitis
Cholestasis
Liver Cirrhosis, Biliary
Skin Diseases
Skin Manifestations
Signs and Symptoms
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Cholestasis, Intrahepatic
Liver Diseases
Liver Cirrhosis