Last updated: 11/05/2022 12:24:00
Linerixibat and obeticholic acid drug interaction study in healthy adult participants
GSK study ID
213688
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A two-part, phase 1, open-label, randomized, parallel-arm, fixed sequence, drug-drug interaction study to investigate the effect of linerixibat on plasma concentrations of obeticholic acid and conjugates in healthy adult participants
Trial description: This study aims to investigate the effect of linerixibat on plasma concentrations of obeticholic acid (OCA) and its conjugates in healthy adult participants to inform the potential for drug interaction with coadministration of linerixibat and OCA.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Average trough concentration (Ctrough) in plasma for total-OCA at steady state
Timeframe: Days 35 to 38
Secondary outcomes:
Area under the concentration curve from time 0 to t (AUC0-t) for OCA, tauro-OCA, glyco-OCA and total-OCA at steady state
Timeframe: At Day 18 and Day 37
AUC from time 0 to 24 hour (AUC0-24) for OCA, tauro-OCA, glyco-OCA and total-OCA at steady state
Timeframe: Up to 24 hours on Day 18 and Day 37
Maximum observed plasma concentration (Cmax) for OCA, tauro-OCA, glyco-OCA and total-OCA at steady state
Timeframe: At Day 18 and Day 37
Average trough concentration (Ctrough) in plasma for OCA, tauro-OCA, glyco-OCA and total-OCA at steady state
Timeframe: Days 17 to 19 and Days 35 to 38
Time to maximum concentration (Tmax) for OCA, tauro-OCA, glyco-OCA and total-OCA
Timeframe: At Day 18 and Day 37
Ctrough of total OCA over Days 17 to 19 and Days 35 to 38
Timeframe: Days 17 to 19 and Days 35 to 38
Number of participants with adverse events
Timeframe: Up to Day 52
Interventions:
Drug: Obeticholic acid
Drug: Linerixibat
Enrollment:
52
Observational study model:
Not applicable
Primary completion date:
2022-31-05
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Pruritus
Product
Not applicable
Collaborators
Not applicable
Study date(s)
November 2021 to May 2022
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18 - 50 Years
Accepts healthy volunteers
Yes
- Overtly healthy male or female participants 18 to 50 years of age inclusive, at the time of signing the informed consent
- Body weight greater than (>) 50 kilogram (kg) and body mass index (BMI) within the range 18.5 – 32 kilogram per meter square (kg/m^2) (inclusive)
- Any active dermatologic disorder leading to or with the potential to cause itching or a recent history of unexplained clinically significant itching locally or generally within the prior 3 months
- Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) and/or confirmed hepatocellular carcinoma or biliary cancer
Inclusion and exclusion criteria
Inclusion criteria:
- Overtly healthy male or female participants 18 to 50 years of age inclusive, at the time of signing the informed consent
- Body weight greater than (>) 50 kilogram (kg) and body mass index (BMI) within the range 18.5 – 32 kilogram per meter square (kg/m^2) (inclusive)
- Capable of giving signed informed consent as the protocol.
Exclusion criteria:
- Any active dermatologic disorder leading to or with the potential to cause itching or a recent history of unexplained clinically significant itching locally or generally within the prior 3 months
- Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) and/or confirmed hepatocellular carcinoma or biliary cancer
- History of gall bladder removal
- Current symptomatic gallstones or inflammatory gall bladder disease
- Significant history of or current disorders that can significantly alter the absorption, metabolism, or elimination of drugs
- Current clinically significant diarrhea
- 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 epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years
- Administration of any other ileal bile acid transport (IBAT) inhibitor (including linerixibat) or Ocaliva in the 3 months prior to screening
- Past or intended use of over-the-counter or prescription medication, including vitamins and dietary or herbal supplements) within 7 days (or 14 days if the drug is a potential enzyme inhibitor) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless approved by the Investigator in conjunction with GSK
- Current enrolment in a clinical trial or recent participation in a clinical trial and has received an investigational product within 30 days before the first dose in the current study
- Exposure to more than 4 new chemical entities within 12 months before the first dose in the current study
- Screening alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5x upper limit of normal (ULN)
- Bilirubin >1.5xULN (isolated bilirubin >1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin lesser than (<)35%
- Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test or positive hepatitis C riboneucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention
- Positive pregnancy test at screening or at Day -1
- Positive human immunodeficiency virus (HIV) antibody test
- QT interval corrected (QTc) >450 millisecond (msec)
- Regular use of known drugs of abuse or history of drug abuse or dependence within 6 months of the study
- Participants with moderate (or greater) alcohol consumption
- History of or regular use of tobacco- or nicotine-containing products in the 3 months prior to screening.
- Female participants unable or unwilling to comply with specific contraception restrictions as detailed in the protocol
- Where participation in the study would result in donation of blood or blood products in excess of 500 milliliter (mL) within a 56-day period
- Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates participation in the study.
Trial location(s)
Location
GSK Investigational Site
Baltimore, Maryland, United States, 21225
Status
Study Complete
Study documents
No study documents available.
Results overview
Study Results yet to be posted
Recruitment status
Completed
Actual primary completion date
2022-31-05
Actual study completion date
2022-31-05
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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