Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Linerixibat tablet
Linerixibat · 7 trials · 2 indications
Itch Scores were assessed using a NRS twice daily, ranging from 0 to 10, where 0 represents no itching and 10 the worst imaginable itching. The worst daily itch score was defined as the worst of the two scores recorded daily. The weekly itch score was defined as the average of the worst daily itch scores in one week. The monthly itch score was defined as the worst weekly itch score for the month (4 weeks). Higher monthly itch scores indicate worse itching. Baseline is the worst weekly itch score in the 28 days prior to randomization (Day 1). Change from Baseline is defined as the post dose value minus baseline value. Least-squares (LS) means and the corresponding 95% confidence intervals are reported by taking average of LS means of change from baseline in monthly itch scores obtained over 24 weeks using equal weighting for all time points. Analyzed using Mixed Model Repeated Measures (MMRM) method.
AEs and SAEs will be collected.
AEs and SAEs will be collected.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Not applicable (NA) indicates geometric coefficient of variation could not be calculated as a single participant was analyzed.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Hepatic clearance was calculated as total plasma IV clearance minus renal clearance.
Blood samples were collected at indicated time points for PK analysis. Absolute bioavailability is the amount of drug from a formulation that reaches the systemic circulation relative to an IV dose. It is expressed as percentage bioavailability, which is calculated by ratio of AUC(oral)/Dose(oral) with AUC(IV)/Dose(IV) multiplied by 100.
Blood samples were collected from participants at indicated time points. Fh was expressed as percentage and was calculated as: 1 minus hepatic extraction ratio multiplied by 100. Hepatic extraction ratio=hepatic blood clearance (milliliters per minute)/hepatic blood flow (milliliters per minute).
Blood samples were collected from participants at indicated time points. Fa was expressed as percentage which was calculated as ratio of oral bioavailability and Fh multiplied by 100.
Urine samples were collected at indicated time points and total radioactivity measurement was done using Liquid Scintillation counting (LSC). Percentage of radioactive dose excreted in urine was calculated as (amount excreted in urine divided by administered radioactivity dose) multiplied by 100.
Urine samples were collected at indicated time points and total radioactivity measurement was done using LSC. Percentage of radioactive dose excreted in urine was calculated as (amount excreted in urine divided by administered radioactivity dose) multiplied by 100.
Feces samples were collected at indicated time points and total radioactivity measurement was done using LSC. Percentage of radioactive dose excreted was calculated as (amount excreted in feces homogenate divided by administered radioactivity dose) multiplied by 100.
Feces samples were collected at indicated time points and total radioactivity measurement was done using LSC. Percentage of radioactive dose excreted was calculated as (amount excreted in feces homogenate divided by administered radioactivity dose) multiplied by 100.
| Arm | Type | Description |
|---|---|---|
| Linerixibat | EXPERIMENTAL | Participants with cholestatic pruritus associated with primary biliary cholangitis (PBC) who completed the LLSAT study will receive linerixibat. |
| Part A: Linerixibat 40 milligrams (mg) | EXPERIMENTAL | Participants were randomized to receive linerixibat 40 mg tablet orally twice a day (BID) in Part A (up to Week 24). |
| Part A: Placebo | EXPERIMENTAL | Participants were randomized to receive Placebo orally twice a day (BID) in Part A (up to Week 24). |
| Part B: Placebo in Part A and Part B | PLACEBO_COMPARATOR | Participants who were randomized to receive Placebo (up to Week 24) orally twice a day (BID) in Part A, continued to receive Placebo (from Week 24 to Week 32) orally twice a day (BID) in Part B. |
| Part B: Placebo in Part A and Linerixibat 40 mg in Part B | EXPERIMENTAL | Participants who were randomized to receive Placebo (up to Week 24) orally twice a day (BID) in Part A, switched to receive linerixibat 40 mg tablet orally twice a day (BID) (from Week 24 to Week 32) in Part B. |
| Part B: Linerixibat 40 mg in Part A and Placebo in Part B | EXPERIMENTAL | Participants who were randomized to receive linerixibat 40 mg tablet orally BID (up to Week 24) in Part A, switched to receive Placebo (from Week 24 to Week 32) orally twice a day (BID) in Part B. |
| Part B: Linerixibat 40 mg in Part A and Part B | EXPERIMENTAL | Participants who were randomized to receive linerixibat 40 mg tablet orally twice a day (BID) (up to Week 24) in Part A, continued to receive linerixibat 40 mg twice a day (BID) (from Week 24 to Week 32) in Part B. |
| Participants receiving linerixibat | EXPERIMENTAL | Participants who previously participated in the Phase 2 studies (BAT117213 and 201000 GLIMMER \[Group 1\]) and Phase 3 study (212620 GLISTEN \[Group 2\]), will receive linerixibat. |
| Treatment sequence AB | EXPERIMENTAL | Participants will receive linerixibat in fed state (Treatment A) in period 1 followed by linerixibat in fasted state (Treatment B) in period 2. The washout period will be of at least 7 days. |
| Treatment sequence BA | EXPERIMENTAL | Participants will receive linerixibat in fasted state (Treatment B) in period 1 followed by linerixibat in fed state (Treatment A) in period 2. The washout period will be of at least 7 days. |
| Cohort 1 (Moderate hepatic impairment participants) | EXPERIMENTAL | Eligible participants to receive single dose of linerixibat. |
| Cohort 2 (Matched healthy control participants) | EXPERIMENTAL | Eligible participants to receive single dose of linerixibat |
| Treatment Arm 1 | EXPERIMENTAL | Participants will receive OCA at dose level 1, 4 hours after the linerixibat administration |
| Treatment Arm 2 | EXPERIMENTAL | Participants will receive OCA at dose level 2 along with linerixibat |
| Treatment Arm 3 | EXPERIMENTAL | Participants will receive OCA at dose level 1 along with linerixibat |
| Treatment Arm 4 | EXPERIMENTAL | Participants will receive OCA at dose level 2, 4 hours after the linerixibat administration |
| Linerixibat + [14C]-linerixibat | EXPERIMENTAL | Subjects will receive a single oral dose of linerixibat 90 milligram (mg) (2\*45 mg) tablets concomitantly with \[14C\]-linerixibat 100 microgram (approximately 9.25 kilobecquerel; 250 nano curie) IV infusion for 3 hours, after an overnight fast that continues for 2 hours after the oral dose/start of IV infusion, small standard high-fat meal will be given on Day 1 in treatment Period 1; followed by a single oral dose of \[14C\]-linerixibat 90 mg (approximately 4.96 megabecquerel; 134.1 micro curie) solution on Day 1 in treatment Period 2. A wash out period of at least 13 days will be maintained between oral doses of treatment periods. |
| Name | Type | Description |
|---|---|---|
| Linerixibat | DRUG | Linerixibat will be administered. |
| Placebo | DRUG | Participants will receive placebo. |
| Obeticholic acid | DRUG | OCA will be administered |
| Linerixibat tablet | DRUG | Linerixibat will be available as white to slightly colored film-coated round tablet to be administered as two tablets taken in the fasted state in the morning with 240 milliliter (mL) of room temperature water. |
| [14C]-linerixibat intravenous infusion | DRUG | \[14C\]-linerixibat will be available as clear, colorless solution free from visible particulates to be administered 25 mL IV over 3 hours immediately after the oral dose. |
| Linerixibat oral solution | DRUG | Linerixibat will be available as clear, colorless solution free from visible particulates to be administered 60 mL solution in the fasted state in the morning. |
Inclusion Criteria: * Participants with a diagnosis of PBC and a history of associated pruritus as evidenced by randomization into an eligible linerixibat clinical study prior to LLSAT (GLIMMER or GLISTEN) * Participants must have completed the main treatment period in LLSAT * A Female participant ...
Linerixibat is an investigational oral medicine being developed for cholestasis and pruritus, the itching associated with cholestatic liver disease. It is a small molecule in Phase 3 development and has not been approved for any indication. GSK plc is running clinical studies in adults with pruritus, including a Phase 3 extension study in Japan.
Linerixibat targets SLC10A2, also known as the ileal bile acid transporter, and acts as an inhibitor of that transporter. By inhibiting SLC10A2 in the ileum, the drug is designed to reduce bile acid reabsorption, which is the proposed mechanism behind its development for cholestatic pruritus. It is a small molecule.
Linerixibat is developed by GSK plc, which trades under the ticker GSK. GSK is the sponsor of the clinical program, which includes Phase 3 and Phase 1 studies of the linerixibat tablet in pruritus and cholestasis. The asset is identified in chemical databases by the ChEMBL ID CHEMBL2387408.
Linerixibat is in Phase 3 clinical development and is investigational. It has not been approved by the FDA or any other regulator for cholestasis or pruritus. The program includes one active Phase 3 study, the J-LINX Japan linerixibat extension study, plus completed Phase 1 studies.
The active trial is NCT07860710, the J-LINX Japan LINerixibat eXtension Study, a Phase 3 study in pruritus with 40 planned participants that is not yet recruiting. Completed studies include NCT05435170, a Phase 1 food effect study, NCT05393076, a Phase 1 study in moderate hepatic impairment, and NCT05133830, a Phase 1 drug interaction study with obeticholic acid.
Yes. Linerixibat tablet is the oral tablet formulation of linerixibat, the same active drug developed by GSK plc. Clinical studies in the program, including the Phase 1 food effect study NCT05435170, were conducted with linerixibat tablets. Searches for either name refer to the same investigational small molecule.