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Linerixibat Long-term Safety and Tolerability Study

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.
 
ClinicalTrials.gov Identifier: NCT04167358
Recruitment Status : Recruiting
First Posted : November 18, 2019
Last Update Posted : September 10, 2020
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
This is an open-label, non-comparator, global, multi-center, long-term safety study for evaluating safety and tolerability of linerixibat in participants with cholestatic pruritus in primary biliary cholangitis (PBC) who participated in a prior eligible clinical trial with linerixibat. Participants will be administered with 90 milligrams (mg) linerixibat orally twice daily. The total daily dose will not exceed 180 mg total daily dose. The effect of linerixibat on measures of quality of life and health-related quality of life in the study population will also be assessed. The duration of the study will be approximately four years until study end and the total duration of study participation will vary by participant depending upon time of entry relative to study end in their respective country. Approximately 75 participants will be enrolled in this study.

Condition or disease Intervention/treatment Phase
Cholestasis Drug: Linerixibat Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This is a non-comparator single group study.
Masking: None (Open Label)
Masking Description: This is an open label non-comparator study.
Primary Purpose: Treatment
Official Title: Long-term Safety and Tolerability Study of Linerixibat for the Treatment of Cholestatic Pruritus in Participants With Primary Biliary Cholangitis
Actual Study Start Date : July 8, 2020
Estimated Primary Completion Date : December 9, 2024
Estimated Study Completion Date : December 9, 2024


Arm Intervention/treatment
Experimental: Participants receiving linerixibat
Participants will receive twice daily dose of 90 mg linerixibat from Day 1 to Month 48.
Drug: Linerixibat
Linerixibat will be available as tablets and administered orally. Participants will be administered with linerixibat with a dose level of 90 mg twice daily.




Primary Outcome Measures :
  1. Number of participants with non-serious adverse events (AEs) and Serious AEs (SAEs) [ Time Frame: Up to 49 months ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/ birth defect and other situations which involve medical or any other situation according to medical or scientific judgment.

  2. Number of participants with Severe AEs [ Time Frame: Up to 49 months ]
    An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.


Secondary Outcome Measures :
  1. Change from Baseline in domain scores of the PBC-40 over time [ Time Frame: Baseline and up to 48 months ]
    The PBC-40 is a participant-derived, disease specific health-related quality of life measure with data to support its validity in PBC. The PBC-40 measure is comprised of 40 questions, each scored on a scale of 1 to 5 (where 1 = least impact, 5 = greatest impact) grouped into six domains (symptoms, itch, fatigue, cognition, social, and emotional). The PBC-40 scale will be administered by appropriate site personnel, with a 7-day recall period, at the Baseline visit and at each study visit thereafter and at study end or study withdrawal.

  2. Change from Baseline in health-related quality of life (QoL) by the Euro Quality-5 dimension-3 level (EQ-5D-3L) scores over time [ Time Frame: Baseline and up to 48 months ]
    The EQ-5D-3L is a standardized instrument developed by the EuroQol Group as a measure of health-related quality of life that can be used in a wide range of health conditions and treatments. The EQ-5D consists of a descriptive system and the EQ Visual Analogue Scale (VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: 1=no problems, 2=some problems, and 3=extreme problems. The EQ-5D-3L will be administered by site personnel at the Baseline visit and at each study visit thereafter and at study end or study withdrawal.

  3. Change from Baseline in self-rated health by EQ VAS scores over time [ Time Frame: Baseline and up to 48 months ]
    The EQ-5D-3L is a standardized instrument developed by the EuroQol Group as a measure of health-related quality of life that can be used in a wide range of health conditions and treatments. The EQ-5D consists of a descriptive system and the EQ VAS. The EQ VAS records self-rated health on a vertical visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'.

  4. Change from Baseline in the Beck Depression Inventory (BDI-II) scores over time [ Time Frame: Baseline and up to 48 months ]
    The BDI-II is a 21-item questionnaire used to assess the intensity of depression in clinical and normal participants. Each item is scored from 0 (Normal) to 3 (Severe). The total score on the BDI-II ranges from 0-63, with higher scores reflecting higher levels of depression.

  5. Number of participants with clinically significant hematology parameters [ Time Frame: Up to 48 months ]
    Blood samples will be collected for the analysis of hematology parameters including platelet count, red blood cell (RBC) count, hemoglobin, hematocrit, percentage reticulocytes, mean corpuscular volume (MCV), mean corpuscular hemoglobin, coagulation time, neutrophils, lymphocytes, monocytes, eosinophils, basophils and Prothrombin Time/International Normalized Ratio.

  6. Number of participants with clinically significant clinical chemistry parameters [ Time Frame: Up to 48 months ]
    Blood samples will be collected for the analysis of clinical chemistry parameters including blood urea nitrogen (BUN), bicarbonate, creatinine, estimated glomerular filtration rate (eGRF), potassium, sodium, calcium, fasting glucose, total protein and albumin.

  7. Number of participants with clinically significant liver parameters over time [ Time Frame: Up to 48 months ]
    Blood samples will be collected for the analysis of liver parameters including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphate (ALP), gamma glutamyl transferase (GGT), total and direct bilirubin.

  8. Number of participants with clinically significant lipid parameters over time [ Time Frame: Up to 48 months ]
    Blood samples will be collected for the analysis of lipid parameters including fasting total cholesterol, direct and indirect low density lipoprotein (LDL) cholesterol, indirect very low density lipoprotein (VLDL) cholesterol, triglycerides and direct high density lipoprotein (HDL) cholesterol.



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.


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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
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 in the participant's parent trial BAT117213 (NCT01899703) or 201000 (NCT02966834)
  • Participants with a diagnosis of PBC and a history of associated pruritus as evidenced by randomization into a prior eligible linerixibat clinical trial.
  • Participants must have completed the main treatment period in a prior eligible linerixibat clinical trial.
  • Male or female; Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Contraception by male participants or male partners of female participants is not required in this protocol.
  • A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:

    1. is not a woman of childbearing potential (WOCBP) or
    2. is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1 percent [%] per year), with low user dependency, as described during the intervention period and for at least 4 weeks, after the last dose of study intervention. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention;
    3. a WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention;
    4. if a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
    5. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
  • Capable of giving signed informed consent as described in 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 upper limit of normal (ULN). Total bilirubin >2x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%.
  • Screening ALT or AST >6x ULN.
  • Screening eGFR <45 milliliters per minute per 1.73 square meter (mL/min/1.73m^2) based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
  • History or presence of hepatic decompensation (e.g., variceal bleeds, encephalopathy or ascites).
  • Presence of actively replicating viral hepatitis B or C (HBV, HCV) infection and/or confirmed hepatocellular carcinoma or biliary cancer.
  • Recent or current clinically significant diarrhea in the Investigator's medical opinion.
  • Current symptomatic cholelithiasis or inflammatory gallbladder disease is exclusionary. Participants with history of cholecystectomy >=3 months before screening may be eligible for enrollment.
  • Current diagnosis or previous diagnosis of colorectal cancer.
  • 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.
  • Use of Obeticholic acid: within 8 weeks prior to the date of the screening visit and may not restart until after the end of the study or study withdrawal.
  • Administration of any other ileal bile acid transporter (IBAT) inhibitor in the 1 month prior to screening.
  • Current enrollment or participation in any other clinical study (except for 201000) involving an investigational study treatment within 8 weeks prior to the screening visit.
  • QT interval corrected (QTc) >480 millisecond (msec): A QTc >480 msec (12-lead electrocardiogram [ECG]) at screening is exclusionary.
  • 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 grams (g) of alcohol: a half-pint (~240 milliliter [mL]) of beer, 1 glass (125 mL) of wine or 1 measure (25 mL) of spirits.

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): NCT04167358


Contacts
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Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Locations
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United States, Florida
GSK Investigational Site Recruiting
Miami, Florida, United States, 33136
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Cynthia Levy         
United States, Michigan
GSK Investigational Site Recruiting
Novi, Michigan, United States, 48377
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Stuart Gordon         
United States, Washington
GSK Investigational Site Recruiting
Seattle, Washington, United States, 98105
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Kris V Kowdley         
Japan
GSK Investigational Site Recruiting
Chiba, Japan, 270-1694
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Tomomi Okubo         
GSK Investigational Site Recruiting
Fukui, Japan, 918-8503
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Kazuo Notsumata         
GSK Investigational Site Recruiting
Gunma, Japan, 371-8511
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Ken Sato         
GSK Investigational Site Recruiting
Kagawa, Japan, 760-8557
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Koichi Takaguchi         
GSK Investigational Site Recruiting
Nagasaki, Japan, 856-8562
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Atsumasa Komori         
GSK Investigational Site Recruiting
Osaka, Japan, 545-8586
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Sawako Uchida         
GSK Investigational Site Recruiting
Osaka, Japan, 591-8025
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Naoki Hiramatsu         
GSK Investigational Site Recruiting
Tokyo, Japan, 173-8606
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Atsushi Tanaka         
Poland
GSK Investigational Site Recruiting
Czestochowa, Poland, 42-217
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Krzysztof Janik         
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT04167358    
Other Study ID Numbers: 212358
First Posted: November 18, 2019    Key Record Dates
Last Update Posted: September 10, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: 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.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Linerixibat
Cholestasis
Cholestatic pruritus
Primary biliary cholangitis
Additional relevant MeSH terms:
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Cholestasis
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases