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This study will be the first to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics following single dose of 10 milligrams (mg) to 180 mg of GSK2330672 in Japanese healthy subjects. This is a double-blind, randomized, placebo-controlled, dose-escalating and incomplete block crossover study to be conducted in 16 Japanese healthy subjects. Study will be conducted in four periods; subjects will receive either placebo or GSK2330672 (10 mg, 30 mg, 90 mg or 180 mg based on randomization) in each treatment period. Each period will be separated by washout period (at least 6 days from dosing). Total duration of study for each subject will be approximately 5 weeks from the first dosing to follow up visit.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence 1: GSK2230672 10mg, 30mg, 90mg, and Placebo | Experimental | Subjects will receive GSK2230672 10 mg in period 1, GSK2230672 30 mg in Period 2, GSK2230672 90 mg in Period 3 and placebo in period 4. |
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| Sequence 2:GSK2230672 10mg, 30mg, Placebo, and GSK2230672 90mg | Experimental | Subjects will receive GSK2230672 10 mg in period 1, GSK2230672 30 mg in Period 2, placebo in period 3, and GSK2230672 90 mg in period 4. |
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| Sequence 3:GSK2230672 10mg, Placebo, GSK2230672 90mg and 180mg | Experimental | Subjects will receive GSK2230672 10 mg in period 1, placebo in Period 2, GSK2230672 90 mg in Period 3 and GSK2230672 180 mg in period 4. |
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| Sequence 4: Placebo, GSK2230672 30mg, 90mg and 180mg | Experimental | Subjects will receive placebo in period 1, GSK2230672 30 mg in Period 2, GSK2230672 90 mg in Period 3 and GSK2230672 180 mg in period 4. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK2230672 | Drug | It will be supplied as white to slightly colored, round, film coated tablet for oral administration containing 10 mg or 45 mg of GSK2330672. |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects with Adverse events (AE) | Maximum of 5 weeks | |
| Safety as assessed by blood pressure | Systolic and diastolic blood pressure will be measured on Day -1, post dose 2 hours (hrs), 12.5 hrs, 24.5 hrs and at 48 hrs in each period and at follow-up. | Maximum of 5 weeks |
| Safety as assessed by heart rate | Heart rate will be measured on Day -1, post dose 2 hrs, 12.5 hrs, 24.5 hrs and at 48 hrs in each period and at follow-up. | Maximum of 5 weeks |
| Safety as assessed by body temperature | Body temperature will be measured on Day -1, post dose 2 hrs, 12.5 hrs, 24.5 hrs and at 48 hrs in each period and at follow-up. | Maximum of 5 weeks |
| Safety as assessed by clinical chemistry parameters | Blood sample will be collected on Day -1, at 48 hrs in each period and at follow-up | Maximum of 5 weeks |
| Safety as assessed by haematology | Blood sample will be collected on Day -1, at 48 hrs in each period and at follow-up | Maximum of 5 weeks |
| Safety as assessed by urinalysis | Sample will be collected on Day -1, at 48 hrs in each period and at follow-up | Maximum of 5 weeks |
| Safety as assessed by fecal occult blood |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma concentration of GSK2330672 | Blood samples will be collected predose and post dose at 0.5 hrs, 2 hr, 3.5 hr, 5 hr on Day 1 of each period |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Tokyo | 192-0071 | Japan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38780109 | Derived | Karatza E, Swift B, Carreno F, Mukherjee S, Casillas L, Lennie J, Fettiplace J, McLaughlin MM, Kremer AE. Serum bile acid change correlates with improvement in pruritus in patients with primary biliary cholangitis receiving linerixibat. Liver Int. 2024 Sep;44(9):2293-2302. doi: 10.1111/liv.15982. Epub 2024 May 23. |
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| ID | Term |
|---|---|
| D002779 | Cholestasis |
| ID | Term |
|---|---|
| D001649 | Bile Duct Diseases |
| D001660 | Biliary Tract Diseases |
| D004066 | Digestive System Diseases |
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| Placebo | Drug | It will be supplied as placebo tablets (with no GSK2230672) visually matching to GSK2230672 |
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Fecal occult blood testing will be conducted on Screening (2 samples during Screening period) and each dosing period (anytime from dosing to next dose). |
| Maximum of 5 weeks |
| Safety as assessed by Electrocardiogram (ECG) | Electrocardiogram will be measured on Day -1, post dose 2 hrs, 12.5 hrs, 24.5 hrs and at 48 hrs in each period and at follow-up. | Maximum of 5 weeks |