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PruritusPhase 1NCT05393076

Phase I Study of Linerixibat in Adults With Moderate Hepatic Impairment and Healthy Controls

A Phase 1 study testing Linerixibat in people with Pruritus, run by GlaxoSmithKline at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a phase 1, open-label, single-dose study in adults with moderate hepatic impairment (defined as Child-Pugh B cirrhosis) and matched healthy control participants with normal hepatic function. Read more about this study

Who is it for?
Ages 18 to 75 yearsHealthy volunteers can take part
Conditions the study is for
Pruritus
What is being tested?
Linerixibat
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
2 sitesUnited States
Study dates
19 Jul 2022to 6 Dec 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • All Participants:
  • Age: 18 to 75 years of age (inclusive).
  • Weight greater than (>) 45 kilograms (kg) and body mass index (BMI) 18.5 - 40 kg per square meter (kg/m^2) (inclusive).
  • Male and female- A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies; not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow contraceptive guidance during the treatment period and until at least 4 weeks after the last dose of study treatment.
  • Participant capable of giving signed informed consent.
  • Participants with Moderate Hepatic Impairment (Cohort 1):
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  • Moderate hepatic impairment (of any etiology) and clinically stable for at least 1 month prior to screening.
  • Child-Pugh score of 7-9.
  • Previous confirmation of liver cirrhosis confirmed by either- Liver biopsy, Imaging technique, or Noninvasive liver assessment consistent with cirrhosis.
  • Hepatic impairment needs to be chronic (>6 months), stable.
  • Matched Healthy Control Participants (Cohort 2):
  • Participants will be matched by age plus or minus (±)10 years to a corresponding participant in the hepatic impairment group. Age should remain between 18 and 75 years of age (inclusive).
  • Participants will be matched by total body weight ±15 percentage (%) to a corresponding participant in the hepatic impairment group.
  • Participants will be matched by gender and race to a corresponding participant in the hepatic impairment group.
  • Healthy participant as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and ECG.

Who cannot join

  • All Participants:
  • Participants are excluded from the study if any of the following medical conditions apply:
  • History of cholecystectomy, current symptomatic cholelithiasis or inflammatory gallbladder disease.
  • Significant history of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
  • Any clinically relevant abnormality identified at the screening medical assessment (physical examination/medical history review), clinical laboratory tests, or 12-lead ECG.
  • Current clinically significant diarrhea.
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  • History of gastrointestinal surgery with ileal resection or ileal bypass at any time.
  • Any malignancy within the past 5 years except for basal cell or squamous cell carcinoma of the skin disease for 3 years.
  • Participants with unstable cardiac function or participants with uncontrolled hypertension.
  • Any current medical or psychiatric condition, clinical or laboratory abnormality, or examination finding which may affect study compliance or investigational procedures or possible consequences of the study.
  • Administration of any other Ileal bile acid transport (IBAT) inhibitor (including linerixibat) in the 3 months prior to screening.
  • For healthy participants, past or intended use of over the counter or prescription medication, including vitamins and dietary or herbal supplements) within 7 days prior to the first dose of study medication.
  • Current enrolment in a clinical trial or recent participation in a clinical trial and has received an investigational product within the following time-period prior to study drug administration in the current study: 30 days.
  • Positive pregnancy test at screening or at Day -1 in women of childbearing potential.
  • Positive human immunodeficiency virus (HIV) antibody test.
  • Healthy control participant has corrected interval using the Fridericia's QT correction formula (QTcF) >450 millisecond (msec); or participant with hepatic impairment has a baseline QTcF >480 msec on ECG.
  • Regular use of known drugs of abuse or history of drug abuse or dependence within 6 months of the study.
  • Moderate (or greater) alcohol consumption defined as one standard drink per day for women and two drinks per day for men.
  • History of regular use of tobacco or nicotine-containing products.
  • Positive drug/alcohol screen at Screening or at Day -1.
  • Where participation in the study would result in donation of blood or blood products more than 500 milliliter (mL) within a 56-day period.
  • Unwillingness or inability to follow the procedures outlined in the protocol.
  • Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that contraindicates participation in the study.
  • Participants with Hepatic Impairment (Cohort 1):
  • History of gastric or oesophageal variceal bleeding within the past 6 months and for which varices have not been adequately treated medically or endoscopically.
  • Grade 3 ascites (large ascites with marked abdominal distension) refractory to medical therapy.
  • Refractory hepatic encephalopathy as judged by the investigator.
  • Child-Pugh score of 10 or higher or Child-Pugh score of 6 or lower.
  • Hepatopulmonary or hepatorenal syndrome and history of liver transplantation.
  • Evidence of active infection, including spontaneous bacterial peritonitis.
  • Confirmed hepatocellular carcinoma (HCC) or biliary cancer.
  • Alanine amino transferase (ALT) value >3 x upper limit of normal (ULN).
  • Platelet count less than (<) 50,000/microliter (μl).
  • Matched Healthy control participants (Cohort 2):
  • Current or chronic history of liver disease or known hepatic or biliary abnormalities and/or confirmed hepatocellular carcinoma or biliary cancer.
  • Screening ALT or aspartate aminotransferase (AST) above the upper limit of normal (ULN).
  • Elevated bilirubin above the ULN unless this is due to underlying Gilbert's syndrome.
  • Presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention.
  • Positive hepatitis C antibody ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • GSK Investigational Site

    Orlando, Florida, 32809

  • GSK Investigational Site

    San Antonio, Texas, 78215

Other trials in United States

About this study

Official title: A Phase 1, Open-label, Single-dose Study to Evaluate the Pharmacokinetics and Safety of Linerixibat in Adults With Moderate Hepatic Impairment and Healthy Matched Control Participants

This is a phase 1, open-label, single-dose study in adults with moderate hepatic impairment (defined as Child-Pugh B cirrhosis) and matched healthy control participants with normal hepatic function. All participants in both cohorts (moderate hepatic impairment and matched healthy controls) will receive a single dose of the study drug, linerixibat. The purpose of this study is to assess the effect of hepatic impairment on the pharmacokinetics (PK) and safety of linerixibat.

Conditions
Pruritus
Being tested
Linerixibat
Keywords
Linerixibat, Pruritus, GSK2330672, Pharmacokinetics, Primary biliary cholangitis, Hepatic impairment, Liver Cirrhosis
Medical subject headings
Pruritus, Liver Cirrhosis, Biliary, Liver Cirrhosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LinerixibatDrug

    Linerixibat dose and administration as per study intervention.

Study groups in NCT05393076
Study groupRoleWhat they receive
Cohort 1 (Moderate hepatic impairment participants)ExperimentalEligible participants to receive single dose of linerixibat.
Receives: Drug: Linerixibat
Cohort 2 (Matched healthy control participants)ExperimentalEligible participants to receive single dose of linerixibat
Receives: Drug: Linerixibat

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Plasma area under the concentration-time curve from time zero (pre-dose) to the time of the last quantifiable concentration [AUC(0-t)] following a single dose of linerixibat

    Measured: Up to Day 3

  2. Maximum observed concentration (Cmax) following a single dose of linerixibat

    Measured: Up to Day 3

Secondary outcomes (9)

  1. Number of participants with adverse events (AEs) and serious adverse events (SAEs)

    AEs and SAEs will be collected

    Measured: Up to Day 14

  2. Number of participants with clinically significant change from baseline in electrocardiogram (ECG)

    Measured: Baseline (Day -1) and up to Day 3

  3. Number of participants with clinically significant change from baseline in vital signs

    Measured: Baseline (Day -1) and up to Day 3

  4. Number of participants with clinically significant change from baseline in clinical laboratory tests

    Blood samples will be collected for the assessment of clinical laboratory tests

    Measured: Baseline (Day -1) and up to Day 3

  5. Plasma area under the concentration-time curve from time zero (pre-dose) to 24 hours [AUC (0- 24)] following a single dose of linerixibat

    Measured: Up to Day 3

  6. Apparent terminal phase half-life (t1/2) of linerixibat

    Measured: Up to Day 3

  7. Apparent clearance (CL/F) of linerixibat

    Measured: Up to Day 3

  8. Time to Cmax (tmax) of linerixibat

    Measured: Up to Day 3

  9. Apparent terminal phase volume of distribution (Vz/F) of linerixibat

    Measured: Up to Day 3

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 May 2022
  2. Study start19 Jul 2022
  3. Primary completion6 Dec 2022
  4. Study completion6 Dec 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
This phase 1 study is an open-label, non-randomized, single-dose linerixibat study with 2 cohorts (moderate hepatic impairment and matched healthy control participants).
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05393076
Sponsor's protocol ID
214899
Status last verified
Jan 2023
First submitted
23 May 2022
Last updated
18 Jan 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Linerixibat in people with Pruritus, run by GlaxoSmithKline at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Plasma area under the concentration-time curve from time zero (pre-dose) to the time of the last quantifiable concentration [AUC(0-t)] following a single dose of linerixibat (time frame: Up to Day 3). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05393076.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2023.

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