Last updated: 07/02/2020 03:40:06

Linerixibat and obeticholic acid drug interaction study in healthy subjects

GSK study ID
206224
See study documents
Clinicaltrials.gov ID
NCT04053023
See results summary
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: An open-label, single sequence crossover, drug interaction study to investigate the effect of linerixibat (GSK2330672) on plasma concentrations of obeticholic acid and conjugates in healthy participants
Trial description: In participants with inadequate response/intolerance to ursodeoxycholic acid (UDCA) taking obeticholic acid (OCA) who experience pruritus (due to primary biliary cholangitis [PBC], OCA, or both) the addition of linerixibat to OCA therapy may be considered following marketing approval. It is therefore important to characterize any potential effect of linerixibat on the pharmacokinetics of OCA in humans at clinically relevant dosages. Accordingly, a drug-drug interaction (DDI) study with linerixibat (potential perpetrator) and OCA (potential victim) will be conducted to inform both future clinical trials with linerixibat and the potential concomitant administration of these drugs in a clinical setting. This is a single-center, one part (with optional second part) open-label, single sequence crossover, drug interaction study to investigate the effect of linerixibat on plasma concentrations of OCA and OCA conjugates in healthy participants. Approximately 19 participants will be enrolled in part A and further 19 participants in part B (if performed) in the study and will have a phone call follow-up till 7-14 days post-last linerixibat dose.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:

Part A- Area under the concentration-time curve from time 0 to time of the last quantifiable concentration (AUC[0-t]) of total-OCA at steady state

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part A- Area under the concentration-time curve from time 0 to 24 hour (AUC[0-24]) of total-OCA at steady state

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part A- Maximum observed concentration (Cmax) of total-OCA at steady state

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part A- Trough concentration (Ctrough) of total-OCA at steady state

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part B- AUC(0-t) of total-OCA at steady state

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part B- AUC(0-24) of total-OCA at steady state

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part B- Cmax of total-OCA at steady state

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part B- Ctrough of total-OCA at steady state

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Secondary outcomes:

Part A- Time to reach maximum observed plasma concentration (Tmax) of total-OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part A- AUC(0-t) of OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part A- AUC(0-24) of OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part A- Cmax of OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part A- Ctrough of OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part A- Tmax of OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part A- AUC(0-t) of tauro-OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part A- AUC(0-24) of tauro-OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part A- Cmax of tauro-OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part A- Ctrough of tauro-OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part A- Tmax of tauro-OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part A- AUC(0-t) of glyco-OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part A- AUC(0-24) of glyco-OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part A- Cmax of glyco-OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part A- Ctrough of glyco-OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part A- Tmax of glyco-OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part B- Tmax of total-OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part B- AUC(0-t) of OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part B- AUC(0-24) of OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part B- Cmax of OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part B- Ctrough of OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part B- Tmax of OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part B- AUC(0-t) of tauro-OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part B- AUC(0-24) of tauro-OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part B- Cmax of tauro-OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part B- Ctrough of tauro-OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part B- Tmax of tauro-OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part B- AUC(0-t) of glyco-OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part B- AUC(0-24) of glyco-OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part B- Cmax of glyco-OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part B- Ctrough of glyco-OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part B- Tmax of glyco-OCA

Timeframe: Pre-dose(Day 17), pre-dose,0.25,0.50,0.75,1,1.5,2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 18-Day 19),pre-dose(Day 35),pre-dose(Day 36),pre-dose,0.25,0.50,0.75,1,1.5, 2,3,4,5,6,7,8,9,10,11,12,14 and 24hours post-dose(Day 37-Day 38)

Part A- Number of subjects with Treatment-emergent adverse events and serious adverse events (SAEs)

Timeframe: Up to Day 52

Part B- Number of subjects with Treatment-emergent adverse events and SAEs

Timeframe: Up to Day 52

Part A- Number of subjects with abnormal 12-lead electrocardiogram (ECG) at Day -1

Timeframe: Day -1

Part A- Number of subjects with abnormal 12-lead ECG at Day 17

Timeframe: Day 17

Part A- Number of subjects with abnormal 12-lead ECG at Day 38

Timeframe: Day 38

Part B- Number of subjects with abnormal 12-lead ECG at Day -1

Timeframe: Day -1

Part B- Number of subjects with abnormal 12-lead ECG at Day 17

Timeframe: Day 17

Part B- Number of subjects with abnormal 12-lead ECG at Day 38

Timeframe: Day 38

Part A- Number of subjects with abnormal systolic blood pressure (SBP) and diastolic blood pressure (DBP) at Day -1

Timeframe: Day -1

Part A- Number of subjects with abnormal SBP and DBP at Day 1

Timeframe: Day 1

Part A- Number of subjects with abnormal SBP and DBP at Day 17

Timeframe: Day 17

Part A- Number of subjects with abnormal SBP and DBP at Day 38

Timeframe: Day 38

Part B- Number of subjects with abnormal SBP and DBP at Day -1

Timeframe: Day -1

Part B- Number of subjects with abnormal SBP and DBP at Day 1

Timeframe: Day 1

Part B- Number of subjects with abnormal SBP and DBP at Day 17

Timeframe: Day 17

Part B- Number of subjects with abnormal SBP and DBP at Day 38

Timeframe: Day 38

Part A- Number of subjects with abnormal heart rate at Day -1

Timeframe: Day -1

Part A- Number of subjects with abnormal heart rate at Day 1

Timeframe: Day 1

Part A- Number of subjects with abnormal heart rate at Day 17

Timeframe: Day 17

Part A- Number of subjects with abnormal heart rate at Day 38

Timeframe: Day 38

Part B- Number of subjects with abnormal heart rate at Day -1

Timeframe: Day -1

Part B- Number of subjects with abnormal heart rate at Day 1

Timeframe: Day 1

Part B- Number of subjects with abnormal heart rate at Day 17

Timeframe: Day 17

Part B- Number of subjects with abnormal heart rate at Day 38

Timeframe: Day 38

Part A- Number of subjects with abnormal respiratory rate at Day -1

Timeframe: Day -1

Part A- Number of subjects with abnormal respiratory rate at Day 1

Timeframe: Day 1

Part A- Number of subjects with abnormal respiratory rate at Day 17

Timeframe: Day 17

Part A- Number of subjects with abnormal respiratory rate at Day 38

Timeframe: Day 38

Part B- Number of subjects with abnormal respiratory rate at Day -1

Timeframe: Day -1

Part B- Number of subjects with abnormal respiratory rate at Day 1

Timeframe: Day 1

Part B- Number of subjects with abnormal respiratory rate at Day 17

Timeframe: Day 17

Part B- Number of subjects with abnormal respiratory rate at Day 38

Timeframe: Day 38

Part A- Number of subjects with abnormal temperature at Day -1

Timeframe: Day -1

Part A- Number of subjects with abnormal temperature at Day 1

Timeframe: Day 1

Part A- Number of subjects with abnormal temperature at Day 17

Timeframe: Day 17

Part A- Number of subjects with abnormal temperature at Day 38

Timeframe: Day 38

Part B- Number of subjects with abnormal temperature at Day -1

Timeframe: Day -1

Part B- Number of subjects with abnormal temperature at Day 1

Timeframe: Day 1

Part B- Number of subjects with abnormal temperature at Day 17

Timeframe: Day 17

Part B- Number of subjects with abnormal temperature at Day 38

Timeframe: Day 38

Part A- Number of subjects with abnormal hematology parameters at Day -1

Timeframe: Day -1

Part A- Number of subjects with abnormal hematology parameters at Day 17

Timeframe: Day 17

Part A- Number of subjects with abnormal hematology parameters at Day 38

Timeframe: Day 38

Part B- Number of subjects with abnormal hematology parameters at Day -1

Timeframe: Day -1

Part B- Number of subjects with abnormal hematology parameters at Day 17

Timeframe: Day 17

Part B- Number of subjects with abnormal hematology parameters at Day 38

Timeframe: Day 38

Part A- Number of subjects with abnormal clinical chemistry parameters at Day -1

Timeframe: Day -1

Part A- Number of subjects with abnormal clinical chemistry parameters at Day 17

Timeframe: Day 17

Part A- Number of subjects with abnormal clinical chemistry parameters at Day 38

Timeframe: Day 38

Part B- Number of subjects with abnormal clinical chemistry parameters at Day -1

Timeframe: Day -1

Part B- Number of subjects with abnormal clinical chemistry parameters at Day 17

Timeframe: Day 17

Part B- Number of subjects with abnormal clinical chemistry parameters at Day 38

Timeframe: Day 38

Part A- Number of subjects with abnormal microscopy parameters at Day -1

Timeframe: Day -1

Part A- Number of subjects with abnormal microscopy parameters at Day 17

Timeframe: Day 17

Part A- Number of subjects with abnormal microscopy parameters at Day 38

Timeframe: Day 38

Part B- Number of subjects with abnormal microscopy parameters at Day -1

Timeframe: Day -1

Part B- Number of subjects with abnormal microscopy parameters at Day 17

Timeframe: Day 17

Part B- Number of subjects with abnormal microscopy parameters at Day 38

Timeframe: Day 38

Part A- AUC(0-t) of linerixibat at Day 1 (i.e., study Day 20)

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose

Part A- Area under the concentration-time curve from time 0 to 12 hour (AUC[0-12]) of linerixibat at Day 1 (i.e., study Day 20)

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose

Part A- Cmax of linerixibat at Day 1 (i.e., study Day 20)

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose

Part A- Tmax of linerixibat at Day 1 (i.e., study Day 20)

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose

Part A- AUC(0-t) of linerixibat at Day 14 (i.e., study Day 33)

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose

Part A- AUC(0-12) of linerixibat at Day 14 (i.e., study Day 33)

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose

Part A- Cmax of linerixibat at Day 14 (i.e., study Day 33)

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose

Part A- Tmax of linerixibat at Day 14 (i.e., study Day 33)

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose

Part B- AUC(0-t) of linerixibat at Day 1 (i.e., study Day 20)

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18 and 24 hours post-dose

Part B- AUC(0-12) of linerixibat at Day 1 (i.e., study Day 20)

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18 and 24 hours post-dose

Part B- Cmax of linerixibat at Day 1 (i.e., study Day 20)

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18 and 24 hours post-dose

Part B- Tmax of linerixibat at Day 1 (i.e., study Day 20)

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18 and 24 hours post-dose

Part B- AUC(0-t) of linerixibat at Day 14 (i.e., study Day 33)

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18 and 24 hours post-dose

Part B- AUC(0-12) of linerixibat at Day 14 (i.e., study Day 33)

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18 and 24 hours post-dose

Part B- Cmax of linerixibat at Day 14 (i.e., study Day 33)

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18 and 24 hours post-dose

Part B- Tmax of linerixibat at Day 14 (i.e., study Day 33)

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18 and 24 hours post-dose

Interventions:
  • Drug: GSK2330672 (linerixibat)
  • Drug: Obeticholic acid
    • Enrollment:
    19
    Primary completion date:
    2019-25-11
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Not applicable
    Medical condition
    Cholestasis
    Product
    Not applicable
    Collaborators
    Not applicable
    Study date(s)
    August 2019 to November 2019
    Type
    Interventional
    Phase
    1

    Participation criteria

    Sex
    Female & Male
    Age
    18 - 80 Years
    Accepts healthy volunteers
    Yes
    • Between 18 and 80 years of age inclusive, at the time of signing the informed consent.
    • Healthy, as determined by the investigator or medically qualified designee, based on a medical evaluation including medical history, physical examination, vital signs, laboratory tests, and ECG. A participant with a clinical abnormality or laboratory parameter (i.e., outside the reference range for the population being studied), which is not specifically listed in the eligibility criteria, may be included only if the investigator agrees in consultation with the GlaxoSmithKline (GSK) medical monitor and documents in the source documentation that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures or outcomes.
    • Any active dermatologic disorder leading to or with the potential to cause pruritus 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:
    • Between 18 and 80 years of age inclusive, at the time of signing the informed consent.
    • Healthy, as determined by the investigator or medically qualified designee, based on a medical evaluation including medical history, physical examination, vital signs, laboratory tests, and ECG. A participant with a clinical abnormality or laboratory parameter (i.e., outside the reference range for the population being studied), which is not specifically listed in the eligibility criteria, may be included only if the investigator agrees in consultation with the GlaxoSmithKline (GSK) medical monitor and documents in the source documentation that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures or outcomes.
    • Body weight > 50 kilogram (kg) and body mass index (BMI) within the range 18.5 to 32 kg per square meter (inclusive).
    • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol.
    • Male and female- A female participant is eligible to participate if she is not pregnant not 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. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
    Exclusion criteria:
    • Any active dermatologic disorder leading to or with the potential to cause pruritus 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
    • Participants with a history of cholecystectomy
    • Current symptomatic cholelithiasis or inflammatory gall bladder disease
    • Significant history of or current 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) clinical laboratory tests, or 12-lead ECG
    • Current episode, recent history (within 1 month of screening visit), or chronic history of clinically significant diarrhea
    • Lymphoma, leukaemia, or 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
    • Any current medical condition (e.g. psychiatric disorder, senility, dementia, or other condition), clinical or laboratory abnormality, or examination finding that the investigator considers would put the participant at unacceptable risk, which may affect study compliance or prevent understanding of the aims or investigational procedures or possible consequences of the study
    • Regular use of known drugs of abuse or history of drug abuse or dependence within 6 months of the study
    • Regular alcohol consumption within 6 months prior to the study defined as an average weekly intake of >14 units for females and >21 units for males. One unit is equivalent to 8 gram of alcohol: a glass (approximately [~] 240 milliliter [mL]) of beer, 1 small glass (~100 mL) of wine or 1 (~25 mL) measure of spirits
    • History of or regular use of tobacco- or nicotine-containing products (confirmed by smokerlyzer test) in the 3 months prior to screening.
    • Administration of any IBAT inhibitor (including linerixibat) or OCA 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 medical monitor.
    • Current enrollment in a clinical trial, recent participation in a clinical trial and has received an investigational product within 30 days (or 5 half-lives of previous trial intervention, whichever is longer) 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 ALT or AST >1.5 times the upper limit of normal (ULN)
    • Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
    • Presence of Hepatitis B surface antigen (HBsAg) at screening or positive Hepatitis C antibody test result at screening or within 3 months of the screening visit
    • Positive serum pregnancy test at screening or positive urine pregnancy test at admission in WOCBP only
    • Positive human immunodeficiency virus (HIV) antibody test
    • QTc >450 millisecond (msec) on ECG performed at screening.
    • Positive pre-study drug/alcohol screen or positive drug/alcohol screen at any time during the study.
    • Female participants unable or unwilling to comply with specific contraception restrictions.
    • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56-day period.
    • Unwillingness or inability to follow the procedures outlined in the protocol for the expected duration of study participation.
    • Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.

    Trial location(s)

    Location
    Status
    Contact us
    Contact us
    Location
    GSK Investigational Site
    Cambridge, United Kingdom, CB2 0GG
    Status
    Study Complete
    Contact us

    Study documents

    Protocol
    Available language(s): English
    Download document(s)
    Statistical analysis plan
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Study complete
    Actual primary completion date
    2019-25-11
    Actual study completion date
    2019-25-11

    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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