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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02966834


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT02966834
Ethics application status
Date submitted
15/11/2016
Date registered
17/11/2016

Titles & IDs
Public title
Dose Response Study of GSK2330672 for the Treatment of Pruritus in Participants 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)
Secondary ID [1] 0 0
2016-002416-41
Secondary ID [2] 0 0
201000
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cholestasis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Infection 0 0 0 0
Other infectious diseases
Skin 0 0 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - GSK2330672

Placebo comparator: Placebo - Participants will receive matching placebo

Experimental: GSK2330672 20 mg once daily - Participants will receive GSK2330672 and matching placebo to maintain blind

Experimental: GSK2330672 90 mg once daily - Participants will receive GSK2330672 and matching placebo to maintain blind

Experimental: GSK2330672 180 mg once daily - Participants will receive GSK2330672 and matching placebo to maintain blind

Experimental: GSK2330672 40 mg twice daily - Participants will receive GSK2330672 and matching placebo to maintain blind

Experimental: GSK2330672 90 mg twice daily - Participants will receive GSK2330672 and matching placebo to maintain blind


Treatment: Drugs: Placebo
GSK2330672 matching placebo will be supplied as white film-coated tablets.

Treatment: Drugs: GSK2330672
GSK2330672 will be supplied in 2 dose strengths of 10 mg and 45 mg white film-coated tablets.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean Change From Baseline at Week 16 in the Mean Worst Daily Itch Score
Timepoint [1] 0 0
Baseline and Week 16
Secondary outcome [1] 0 0
Mean Change From Baseline at Week 16 in Primary Biliary Cholangitis-40 (PBC-40) Scale
Timepoint [1] 0 0
Baseline and at Week 16
Secondary outcome [2] 0 0
Mean Change From Baseline at Week 16 in Serum Alkaline Phosphatase (ALP) Concentrations, in Participants With High Risk of PBC Progression
Timepoint [2] 0 0
Baseline and at Week 16
Secondary outcome [3] 0 0
Number of Participants With Serum ALP Concentrations Less Than (<)1.67 Times ULN and Total Bilirubin Concentrations Less Than or Equal to (<=) ULN at Week 16
Timepoint [3] 0 0
At Week 16
Secondary outcome [4] 0 0
Mean Change From Baseline at Week 16 in Serum Alanine Aminotransferase (ALT) Among Those With a High Risk of PBC Progression
Timepoint [4] 0 0
Baseline and at Week 16
Secondary outcome [5] 0 0
Mean Change From Baseline at Week 16 in Serum Aspartate Aminotransferase (AST) Among Those With a High Risk of PBC Progression
Timepoint [5] 0 0
Baseline and at Week 16
Secondary outcome [6] 0 0
Mean Change From Baseline at Week 16 in Serum Gamma Glutamyl Transferase (GGT), Among Those With a High Risk of PBC Progression
Timepoint [6] 0 0
Baseline and at Week 16
Secondary outcome [7] 0 0
Mean Change From Baseline at Week 16 in Total Bilirubin Concentration, Among Those With a High Risk of PBC Progression
Timepoint [7] 0 0
Baseline and at Week 16
Secondary outcome [8] 0 0
Mean Change From Baseline at Week 16 in Albumin Concentration, Among Those With a High Risk of PBC Progression
Timepoint [8] 0 0
Baseline and at Week 16
Secondary outcome [9] 0 0
Mean Change From Baseline at Week 16 in Prothrombin International Normalized Ratio (INR), Among Those With a High Risk of PBC Progression
Timepoint [9] 0 0
Baseline and at Week 16
Secondary outcome [10] 0 0
Mean Change From Baseline at Week 16 in Prothrombin Time, Among Those With a High Risk of PBC Progression
Timepoint [10] 0 0
Baseline and at Week 16
Secondary outcome [11] 0 0
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) -Main Study Period
Timepoint [11] 0 0
Up to 12 weeks
Secondary outcome [12] 0 0
Number of Participants With Non-SAEs and SAEs -Final Study Period
Timepoint [12] 0 0
Up to 4 weeks
Secondary outcome [13] 0 0
Number of Participants With Non-SAEs and SAEs - Follow-up Period
Timepoint [13] 0 0
Up to 4 weeks
Secondary outcome [14] 0 0
Number of Participants With Clinical Chemistry Data of Potential Clinical Importance
Timepoint [14] 0 0
At Weeks 8, 12, 16 and 20
Secondary outcome [15] 0 0
Number of Participants With Hematology Data of Potential Clinical Importance
Timepoint [15] 0 0
At Weeks 8, 12, 16 and 20
Secondary outcome [16] 0 0
Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Parameters
Timepoint [16] 0 0
At Weeks 8, 12, 16 and 20
Secondary outcome [17] 0 0
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Timepoint [17] 0 0
Baseline and Week 20
Secondary outcome [18] 0 0
Change From Baseline in Pulse Rate
Timepoint [18] 0 0
Baseline and Week 20
Secondary outcome [19] 0 0
Change From Baseline in Gastrointestinal Symptom Rating Scale (GSRS) Assessment
Timepoint [19] 0 0
Baseline and Week 20
Secondary outcome [20] 0 0
Number of Participants With Mean Worst Daily Itch Score of <4 at Week 16
Timepoint [20] 0 0
At Week 16
Secondary outcome [21] 0 0
Number of Participants With Improvement of >= 30 Percent (%) in the Mean Worst Daily Itch Score at Week 16 From Baseline
Timepoint [21] 0 0
Baseline and At Week 16
Secondary outcome [22] 0 0
Number of Participants With Improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 From Baseline
Timepoint [22] 0 0
Baseline and At Week 16
Secondary outcome [23] 0 0
Percentage of Responder Days With Worst Daily Itch Score of <4
Timepoint [23] 0 0
Up to Week 16
Secondary outcome [24] 0 0
Percentage of Responder Days With Improvement of >= 30% in the Mean Worst Daily Itch Score at Week 16 From Baseline
Timepoint [24] 0 0
Baseline and at Week 16
Secondary outcome [25] 0 0
Percentage of Responder Days With Improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 From Baseline
Timepoint [25] 0 0
Baseline and at Week 16
Secondary outcome [26] 0 0
Change From Baseline in the Mean Daily Sleep Score at Week 16
Timepoint [26] 0 0
Baseline and at Week 16
Secondary outcome [27] 0 0
Change From Baseline in the Mean Daily Fatigue Score at Week 16
Timepoint [27] 0 0
Baseline and at Week 16
Secondary outcome [28] 0 0
Change From Baseline in the Five-Dimensional (5-D) Itch Scale at Week 16
Timepoint [28] 0 0
Baseline and at Week 16
Secondary outcome [29] 0 0
Mean Change From Baseline at Week 16 in Serum Total Bile Acid Concentration
Timepoint [29] 0 0
Baseline and at Week 16
Secondary outcome [30] 0 0
Mean Change From Baseline at Week 16 in Serum 7-alpha Hydroxy-4-cholesten-3-one (C4)
Timepoint [30] 0 0
Baseline and at Week 16
Secondary outcome [31] 0 0
Plasma Concentration of GSK2330672 After Sparse Sampling
Timepoint [31] 0 0
At Week 4 (between 1 and 3 hours post-dose) and At Weeks 8, 12 and 16 (between 1 and 3 hours post-dose, and between 5 and 8 hours post-dose)

Eligibility
Key inclusion 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.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

* Screening total bilirubin >2x ULN. Total bilirubin >2x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent (%).
* Screening ALT or AST >6x ULN.
* Screening eGFR <45 milliliter (mL)/minute/1.73 square meter (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 virus (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 Inhibitor of the Human Ileal Bile Acid Transporter (IBAT) 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 GlaxoSmithKline (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 (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 measure (25 mL) of spirits.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/01/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/04/2020
Sample size
Target
Accrual to date
Final
147
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Camperdown
Recruitment hospital [2] 0 0
GSK Investigational Site - Herston
Recruitment hospital [3] 0 0
GSK Investigational Site - Prahran
Recruitment hospital [4] 0 0
GSK Investigational Site - Nedlands
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
3181 - Prahran
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Washington
Country [10] 0 0
Canada
State/province [10] 0 0
Alberta
Country [11] 0 0
Canada
State/province [11] 0 0
Manitoba
Country [12] 0 0
Canada
State/province [12] 0 0
Ontario
Country [13] 0 0
Canada
State/province [13] 0 0
Quebec
Country [14] 0 0
France
State/province [14] 0 0
Clermont-Ferrand
Country [15] 0 0
France
State/province [15] 0 0
Grenoble Cedex 9
Country [16] 0 0
France
State/province [16] 0 0
Lille cedex
Country [17] 0 0
France
State/province [17] 0 0
Paris cedex 12
Country [18] 0 0
France
State/province [18] 0 0
Pessac cedex
Country [19] 0 0
Germany
State/province [19] 0 0
Bayern
Country [20] 0 0
Germany
State/province [20] 0 0
Saarland
Country [21] 0 0
Germany
State/province [21] 0 0
Hamburg
Country [22] 0 0
Italy
State/province [22] 0 0
Emilia-Romagna
Country [23] 0 0
Italy
State/province [23] 0 0
Lombardia
Country [24] 0 0
Italy
State/province [24] 0 0
Toscana
Country [25] 0 0
Italy
State/province [25] 0 0
Veneto
Country [26] 0 0
Japan
State/province [26] 0 0
Chiba
Country [27] 0 0
Japan
State/province [27] 0 0
Fukui
Country [28] 0 0
Japan
State/province [28] 0 0
Gunma
Country [29] 0 0
Japan
State/province [29] 0 0
Hiroshima
Country [30] 0 0
Japan
State/province [30] 0 0
Hokkaido
Country [31] 0 0
Japan
State/province [31] 0 0
Kagawa
Country [32] 0 0
Japan
State/province [32] 0 0
Kanagawa
Country [33] 0 0
Japan
State/province [33] 0 0
Nagasaki
Country [34] 0 0
Japan
State/province [34] 0 0
Osaka
Country [35] 0 0
Japan
State/province [35] 0 0
Tokyo
Country [36] 0 0
Poland
State/province [36] 0 0
Czestochowa
Country [37] 0 0
Poland
State/province [37] 0 0
Katowice
Country [38] 0 0
Poland
State/province [38] 0 0
Myslowice
Country [39] 0 0
Poland
State/province [39] 0 0
Warszawa
Country [40] 0 0
Poland
State/province [40] 0 0
Wroclaw
Country [41] 0 0
Spain
State/province [41] 0 0
Barcelona
Country [42] 0 0
Spain
State/province [42] 0 0
Madrid
Country [43] 0 0
Spain
State/province [43] 0 0
Sevilla
Country [44] 0 0
Spain
State/province [44] 0 0
Valencia
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Basingstoke
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Edgbaston
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Glasgow
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Liverpool.
Country [49] 0 0
United Kingdom
State/province [49] 0 0
London
Country [50] 0 0
United Kingdom
State/province [50] 0 0
Manchester
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Middlesbrough
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Newcastle-upon-Tyne
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Nottingham
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Plymouth
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
IPD for this study will be made available via the Clinical Study Data Request site.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
Available to whom?
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://clinicalstudydatarequest.com


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02966834

Additional trial details provided through ANZCTR
Accrual to date
Recruiting in Australia
Recruitment state(s)
NSW,QLD,WA
Funding & Sponsors
Primary sponsor
Commercial sector/Industry
Primary sponsor name
GlaxoSmithKline
Primary sponsor address
Primary sponsor country
Ethics approval
Ethics application status
Approved
 
Public notes
Investigators:
Richard Skoien, Royal Brisbane and Women's Hospital, Queensland, Herston, Australia, 4029
Simone Strasser, Royal Prince Alfred Hospital, New South Wales, Camperdown, Australia, 2050
George Garas, Sir Charles Gairdner Hospital, Western Australia, Nedlands, Australia, 6009

Contacts
Principal investigator
Title 69 0
Name 69 0
Address 69 0
Country 69 0
Phone 69 0
Fax 69 0
Email 69 0
Contact person for public queries
Title 70 0
Name 70 0
Address 70 0
Country 70 0
Phone 70 0
Fax 70 0
Email 70 0
GSKClinicalSupportHD@gsk.com
Contact person for scientific queries
Title 71 0
Name 71 0
Address 71 0
Country 71 0
Phone 71 0
Fax 71 0
Email 71 0
GSKClinicalSupportHD@gsk.com