Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Linerixibat · 5 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 |
|---|---|---|
| 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 |
| 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 | Participants will receive linerixibat. |
| Placebo | DRUG | Participants will receive placebo. |
| 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: * Male and female participants must be between 18 to 80 years of age inclusive, at the time of signing the informed consent. * Participants who have documented PBC. * Participants who have moderate to severe itch. Exclusion Criteria: * Total bilirubin \>2.0 times Upper Limit o...
Linerixibat is an investigational small molecule being developed for pruritus (itching) associated with cholestasis, including pruritus in primary biliary cholangitis (PBC). It is currently in Phase 3 clinical development and is not yet approved by regulatory authorities.
Linerixibat is being developed by GSK plc, a global biopharma company listed on the New York Stock Exchange under the ticker symbol GSK. The company is conducting clinical trials to evaluate the drug's safety and efficacy for pruritus in cholestatic conditions.
Linerixibat is in Phase 3 clinical development. It is an investigational drug, meaning it has not been approved by regulatory agencies such as the FDA. Its safety and efficacy are still being evaluated in clinical trials.
Linerixibat has been studied in several trials. A Phase 3 long-term safety study (NCT04167358) is active but not recruiting. The GLISTEN study (NCT04950127), a Phase 3 efficacy trial in PBC pruritus, is completed. Two Phase 1 studies (NCT05393076 and NCT05435170) in healthy volunteers are also completed.
Linerixibat is a small molecule that targets the ileal bile acid transporter (IBAT). By inhibiting this transporter, it reduces bile acid reabsorption in the gut, which may lower systemic bile acid levels and alleviate pruritus associated with cholestasis.
Linerixibat is a distinct investigational compound developed by GSK. It is not known to be the same as any other marketed drug. Its mechanism of IBAT inhibition differentiates it from other pruritus treatments, though no alternative names for Linerixibat have been reported.