An Extension Study to Evaluate the Long-Term Safety and D... | NCT02047318

ID	Type	Description	Link
2013-003832-54	EudraCT Number

Label	Type	Description	Intervention Names
LUM001 (Maralixibat)	Experimental	LUM001 also known as Maralixibat (MRX) administered orally up to twice each day	Drug: LUM001 (Maralixibat)

Name	Type	Description	Arm Group Labels	Other Names
LUM001 (Maralixibat)	Drug	Dosing of LUM001 also known as Maralixibat (MRX) with the objective of achieving optimal control of pruritus at a dose level that is tolerated by the participant and up to a maximum daily dose of 560 micrograms per kilogram (mcg/kg).

Measure	Description	Time Frame
Change From MRX Baseline to Week 48 in Fasting sBA Levels	The primary endpoint of this study was the mean change from MRX baseline to Week 48 in fasting sBA level.	MRX baseline to Week 48

Measure	Description	Time Frame
Change From MRX Baseline Over Time in Fasting sBA Levels	This secondary efficacy endpoint is the mean change from MRX baseline over time in fasting sBA levels. Results reported here are the long-term results.	MRX baseline to End of Treatment (maximum exposure was 336 weeks)
Change From MRX Baseline to Week 48 in Pruritus

Name	Affiliation	Role
Study Director	Mirum	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Birmingham Children's Hospital		Birmingham	West Midlands	B4 6NH	United Kingdom
Leeds Teaching Hospital NHS Trust

ID	Title	Description
FG000	LUM001 (Maralixibat)	LUM001 also known as Maralixibat (MRX) administered orally up to twice each day

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 8, 2019	Mar 2, 2021

ID	Title	Description
BG000	Core Study Period	In the lead-in Study LUM001-302, participants were randomized to receive either placebo or active drug (MRX). The last observation obtained before first dose of MRX (either for participants who received MRX in Study LUM001-302 or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302. The core study period of Study LUM001-303 was from Day 1 to Week 72. It encompassed: - a 4-week double-blind dose-escalation period - an 8-week dose-optimization period - a 60-week stable dosing period. Participants could consent to continued long-term follow-up. The furthest analysis timepoint reached by any participant was Week 336. All participants received MRX.

Units	Counts
Participants	BG00019

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From MRX Baseline to Week 48 in Fasting sBA Levels

The primary endpoint of this study was the mean change from MRX baseline to Week 48 in fasting sBA level.

Data collected from 19 participants at MRX baseline. Data collected at Week 48 from 17 of the 19 participants who contributed values at MRX baseline.

Since all participants escalated to MRX 280 ug/kg/day by Week 48, the summary is presented as a single arm.

Posted

Mean

Standard Deviation

μmol/L

MRX baseline to Week 48

ID	Title	Description
OG000	Core Study Period: MRX Baseline Values	These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.
OG001	Core Study Period: Week 48 Values	These are the Week 48 values for participants. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 48 in the same participants.

Units	Counts
Participants	OG00019 OG00117

Title

Denominators

Categories

Title	Measurements
	OG000261.96± 206.839 OG001128.32± 101.742

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	This analysis investigated whether a statistically significant change in sBA levels was observed when comparing MRX baseline to Week 48. The analysis was based on the safety population.	Student's t-test		0.0012	Data for this analysis were obtained from 19 participants at MRX baseline; 17 of those participants contributed Week 48 data.	Mean Difference (Net)	-94.4	Standard Deviation	98.915	2-Sided	95	-145.26	-43.55					Equivalence	The null hypothesis that the mean change was equal to zero was tested using the Student's t-test to determine if the mean change in sBA levels between MRX baseline and Week 48 was statistically significant.

Secondary

Change From MRX Baseline Over Time in Fasting sBA Levels

This secondary efficacy endpoint is the mean change from MRX baseline over time in fasting sBA levels. Results reported here are the long-term results.

Data collected from 19 participants at MRX baseline. Data collected at Week 252 from all 6 participants who contributed values at MRX baseline. Week 252 was chosen as this was the latest timepoint with more than 5 participants reporting data and was considered representative of values near the end of treatment. Since all participants escalated to MRX 280 ug/kg/day, the summary is presented as a single arm.

Posted

Mean

Standard Deviation

μmol/L

MRX baseline to End of Treatment (maximum exposure was 336 weeks)

ID	Title	Description
OG000	Core Study Period: MRX Baseline Value	These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.
OG001	Week 252 Values	Week 252 values for participants continuing in the study. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 252 in the same participants.

Secondary

Change From MRX Baseline to Week 48 in Pruritus

This secondary efficacy endpoint is the change from MRX baseline to Week 48 in pruritus as measured by ItchRO(Obs) weekly average morning severity score. ItchRO scores range from 0 to 4; the higher score indicates increasing itch severity (0 = none; 4 = very severe).

Values were collected from 19 participants at MRX baseline. Data collected at Week 48 from 17 of the 19 participants who contributed values at MRX baseline.

Since all participants escalated to MRX 280 ug/kg/day by Week 48, the summary is presented as a single arm.

Posted

Mean

Standard Deviation

scores on a scale

MRX baseline to Week 48

ID	Title	Description
OG000	Core Study Period: MRX Baseline Value	These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.
OG001	Core Study Period: Week 48 Values	These are the Week 48 values for participants. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 48 in the same participants.

Secondary

Change From MRX Baseline Over Time in Pruritus

This secondary efficacy endpoint is the change from MRX baseline over time in pruritus as measured by ItchRO(Obs) weekly average morning severity score. ItchRO scores range from 0 to 4; the higher score indicates increasing itch severity (0 = none; 4 = very severe). Results reported here are the long-term results.

Data collected from 19 participants at MRX baseline Data collected at Week 278 from all 6 participants who contributed values at MRX baseline. Week 278 was chosen as this was the latest timepoint with more than 5 participants reporting data and was considered representative of values near the end of treatment. Since all participants escalated to MRX 280 ug/kg/day, the summary is presented as a single arm.

Posted

Mean

Standard Deviation

scores on a scale

MRX baseline to End of Treatment (maximum exposure was 336 weeks)

ID	Title	Description
OG000	Core Study Period: MRX Baseline Value	These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.
OG001

Secondary

Change From MRX Baseline to Week 48 in Clinician Xanthoma Severity Score

This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in clinician xanthoma severity scores. It is based on a 0-4 scale to rate the number of lesions present and the degree to which the participant's lesions interfere or limit his or her activities. Clinician xanthoma severity scores range from 0 to 4, with a xanthoma score of zero representing no evidence of xanthomatosis and a score of 4 representing xanthoma so severe that it is disabling. Clinician xanthoma severity scores were not assessed in Study LUM001-302 so mean clinician xanthoma severity score at MRX baseline was calculated from the 5 participants who were assigned to placebo in Study LUM001-302, and analysis of change from MRX baseline is not presented.

Mean MRX baseline scores were calculated from the 5 participants assigned placebo in LUM001-302 who had a baseline value in study LUM001-303. Those assigned to MRX within study LUM001-302 did not have this data collected at baseline.

Mean MRX Week 48 scores were calculated from 17 participants. Since all participants escalated to MRX 280 ug/kg/day by Week 48, the summary is presented as a single arm.

Posted

Mean

Standard Deviation

scores on a scale

MRX baseline to Week 48

ID	Title	Description
OG000	Core Study Period: MRX Baseline Values	These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.

Secondary

Change From MRX Baseline Over Time in Clinician Xanthoma Severity Score

This secondary efficacy endpoint is the mean change from MRX baseline over time (with Week 252 chosen as the end point, as the last analysis visit with at least 6 participants) in clinician xanthoma severity scores. It is based on a 0-4 scale to rate the number of lesions present and the degree to which the lesions interfere or limit activities. Clinician xanthoma severity scores range from 0 to 4, with a score of zero representing no evidence of xanthomatosis and a score of 4 representing xanthoma so severe that it is disabling. Clinician xanthoma severity scores were not assessed in Study LUM001-302 so mean clinician xanthoma severity score at MRX baseline was calculated from the 5 participants assigned to placebo in Study LUM001-302, and analysis of change from MRX baseline is not presented. Results reported here are the long-term results.

Mean MRX baseline scores were calculated from the 5 participants assigned placebo in LUM001-302.Mean Week 252 scores were calculated from 6 participants. Week 252 was chosen as this was the latest timepoint with more than 5 participants reporting data and was considered representative of values near the end of treatment. Since all participants escalated to MRX 280 ug/kg/day, the summary is presented as a single arm.

Posted

Mean

Standard Deviation

scores on a scale

MRX baseline to End of Treatment (maximum exposure was 336 weeks)

ID	Title	Description
OG000	Core Study Period: MRX Baseline Value	These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.

Secondary

Secondary: Change From MRX Baseline to Week 48 in Alkaline Phosphatase

This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in ALP.

Data collected from 19 participants at MRX baseline. [Data collected at Week 48 from 17 of the 19 participants who contributed values at MRX baseline. Since all participants escalated to MRX 280 ug/kg/day by Week 48, the summary is presented as a single arm.](streamdown:incomplete-link)

Posted

Mean

Standard Deviation

U/L

MRX baseline to Week 48

ID	Title	Description
OG000	Core Study Period: MRX Baseline Value	These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.
OG001	Core Study Period: Week 48 Values	These are the Week 48 values for participants. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 48 in the same participants.

Secondary

Change From MRX Baseline Over Time in Alkaline Phosphatase

This secondary efficacy endpoint is the mean change from MRX baseline over time in ALP. Results reported here are the long-term results.

Data collected from 19 participants at MRX baseline. Data collected at Week 252 from 6 participants who contributed values at MRX baseline. Week 252 was chosen as this was the latest timepoint with more than 5 participants reporting data and was considered representative of values near the end of treatment. Since all participants escalated to MRX 280 ug/kg/day, the summary is presented as a single arm.

Posted

Mean

Standard Deviation

U/L

MRX baseline to end of treatment (maximum exposure was 336 weeks)

ID	Title	Description
OG000	Core Study Period: MRX Baseline Value	These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.
OG001	Week 252 Values	Week 252 values for participants continuing in the study. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 252 in the same participants.

Secondary

Change From MRX Baseline to Week 48 in Alanine Aminotransferase

This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in ALT.

Data collected from 19 participants at MRX baseline. Data collected at Week 48 from 17 of the 19 participants who contributed values at MRX baseline. Since all participants escalated to MRX 280 ug/kg/day by Week 48, the summary is presented as a single arm.

Posted

Mean

Standard Deviation

U/L

MRX baseline to Week 48

ID	Title	Description
OG000	Core Study Period: MRX Baseline Value	These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.
OG001	Core Study Period: Week 48 Values	These are the Week 48 values for participants. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 48 in the same participants.

Secondary

Change From MRX Baseline Over Time in Alanine Aminotransferase

This secondary efficacy endpoint is the mean change from MRX baseline over time in ALT levels. Results reported here are the long-term results.

Posted

Mean

Standard Deviation

U/L

MRX baseline to End of Treatment (maximum exposure was 336 weeks)

ID	Title	Description
OG000	Core Study Period: MRX Baseline Value	These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.
OG001	Week 252 Values	Week 252 values for participants continuing in the study. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 252 in the same participants.

Secondary

Change From MRX Baseline to Week 48 in Aspartate Aminotransferase

This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in AST levels.

Posted

Mean

Standard Deviation

U/L

MRX baseline to Week 48

ID	Title	Description
OG000	Core Study Period: MRX Baseline Values	These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.
OG001	Core Study Period: Week 48 Values	These are the Week 48 values for participants. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 48 in the same participants.

Secondary

Change From MRX Baseline Over Time in Aspartate Aminotransferase

This secondary efficacy endpoint is the mean change from MRX baseline over time in AST levels. Results reported here are the long-term results.

Posted

Mean

Standard Deviation

U/L

MRX baseline to End of treatment (maximum exposure was 336 weeks)

ID	Title	Description
OG000	Core Study Period: MRX Baseline Value	These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.
OG001	Week 252 Values	Week 252 values for participants continuing in the study. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 252 in the same participants.

Secondary

Change From MRX Baseline to Week 48 in Gamma Glutamyltransferase

This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in GGT.

Posted

Mean

Standard Deviation

U/L

MRX baseline to Week 48

ID	Title	Description
OG000	Core Study Period: MRX Baseline Value	These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.
OG001	Core Study Period: Week 48 Values	These are the Week 48 values for participants. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 48 in the same participants.

Secondary

Change From MRX Baseline Over Time in Gamma Glutamyltransferase

This secondary efficacy endpoint is the mean change from MRX baseline over time in GGT. Results reported here are the long-term results.

Posted

Mean

Standard Deviation

U/L

MRX baseline to End of Treatment (maximum exposure was 336 weeks)

ID	Title	Description
OG000	Core Study Period: MRX Baseline Value	These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.
OG001	Week 252 Values	Week 252 values for participants continuing in the study. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 252 in the same participants.

Secondary

Change From MRX Baseline to Week 48 in Total and Direct Bilirubin

This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in total bilirubin and direct bilirubin.

Posted

Mean

Standard Deviation

mg/dL

MRX baseline to Week 48

ID	Title	Description
OG000	Core Study Period: MRX Baseline Value	These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.
OG001	Core Study Period: Week 48 Values	These are the Week 48 values for participants. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 48 in the same participants.

Secondary

Change From MRX Baseline Over Time in Total and Direct Bilirubin

This secondary efficacy endpoint is the mean change from MRX baseline over time in total bilirubin and direct bilirubin. Results reported here are the long-term results.

Posted

Mean

Standard Deviation

mg/dL

MRX baseline to End of Treatment (maximum exposure was 336 weeks)

ID	Title	Description
OG000	Core Study Period: MRX Baseline Value	These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.
OG001	Week 252 Values	Week 252 values for participants continuing in the study. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 252 in the same participants.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	14 Microgram Per Kilogram Per Day (mcg/kg/Day)	Participants received LUM001 (also known as Maralixibat or MRX) as an oral solution once daily based on participant's weight. Participants who received placebo in the predecessor study LUM001-302 had their dose escalated starting at 14 microgram per kilogram per day (mcg/kg/day) for one week. This reporting group includes the period of time that participants received 14 mcg/kg/day.	6	0	6	3	6
EG001	35 Microgram Per Kilogram Per Day (mcg/kg/Day)	Participants received LUM001 (also known as Maralixibat or MRX) as an oral solution once daily based on participant's weight. Participants who received placebo in the predecessor study LUM001-302 had their dose escalated from 14 to 35 for one week. This reporting group includes the period of time that participants received 35 mcg/kg/day.	10	0	10	6	10
EG002	70 Microgram Per Kilogram Per Day (mcg/kg/Day)	Participants received LUM001 (also known as Maralixibat or MRX) as an oral solution once daily based on participant's weight. Participants who received placebo in the predecessor study LUM001-302 had their dose escalated from 35 to 70 microgram per kilogram per day (mcg/kg/day) for one week. This reporting group includes the period of time that participants received 70 mcg/kg/day.	10	1	10	3	10
EG003	140 Microgram Per Kilogram Per Day (mcg/kg/Day)	Participants received LUM001 (also known as Maralixibat or MRX) as an oral solution once daily based on participant's weight. Participants who received placebo in the predecessor study LUM001-302 had their dose escalated from 70 to 140 microgram per kilogram per day (mcg/kg/day) for one week. This reporting group includes the period of time that participants received 140 mcg/kg/day.	13	0	13	10	13
EG004	280 Microgram Per Kilogram Per Day (mcg/kg/Day)	Participants received LUM001 (also known as Maralixibat or MRX) as an oral solution once daily based on participant's weight. Participants who received placebo in the predecessor study LUM001-302 had their dose escalated from 140 to 280 microgram per kilogram per day (mcg/kg/day) for 8-week dose optimization period and during the stable dosing period for up to 124 weeks. Participants who received MRX in the predecessor study LUM001-302 started on their dose from Week 13 of that study (280 mcg/kg/day or highest tolerated dose). This reporting group includes the period of time that participants received 280 mcg/kg/day.	19	6	19	18	19
EG005	420 Microgram Per Kilogram Per Day (mcg/kg/Day)	Participants received LUM001 (also known as Maralixibat or MRX) as an oral solution once daily based on participant's weight. Based on efficacy and safety assessments, participants could receive BID dosing after week 136, starting at 420 microgram per kilogram per day (mcg/kg/day) for 4-week dose escalation period. This reporting group includes the period of time that participants received 420 mcg/kg/day.	5	0	5	3	5
EG006	560 Microgram Per Kilogram Per Day (mcg/kg/Day)	Participants received LUM001 (also known as Maralixibat or MRX) as an oral solution once daily based on participant's weight. Participants on BID dosing could have their dose escalated from 480 to 560 microgram per kilogram per day (mcg/kg/day) for the remainder of the study. This reporting group includes the period of time that participants received 560 mcg/kg/day.	5	1	5	5	5
EG007	LUM001 MRX Treatment	Participants received LUM001 (also known as Maralixibat or MRX) as an oral solution once daily based on participant's weight. Participants who received placebo in the predecessor study LUM001-302 had their dose escalated from 14, 35, 70, and 140 microgram per kilogram per day (mcg/kg/day) for 4-week dose escalation period. Participants who received maralixibat during study LUM001-302, underwent a mock dose escalation and remained on the dose received at the end of study LUM001-302. During 8-weeks of dose optimization period, drug was adjusted in titrated manner up to 280 mcg/kg/day or highest tolerated dose and dosing was continued to complete the stable dosing and safety monitoring periods for up to 136 weeks of cumulative MRX exposure in this study at this dose level. In the long-term extension, participants could receive BID dosing up to 560 mcg/kg/day for the remainder of the study for up to 336 weeks of cumulative MRX exposure in this study. This reporting group includes all doses of MRX.	19	6	19	18	19

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG0030 events0 affected13 at risk EG0040 events0 affected19 at risk EG0051 events1 affected5 at risk EG0060 events0 affected5 at risk EG0071 events1 affected19 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Ear pain	Ear and labyrinth disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Ear pruritus	Ear and labyrinth disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA v.22.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0012 events2 affected10 at risk EG0021 events1 affected10 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Abnormal faeces	Gastrointestinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Chapped lips	Gastrointestinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Dental caries	Gastrointestinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA v.22.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected10 at risk EG0021 events1 affected10 at risk EG003
Faeces discoloured	Gastrointestinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Frequent bowel movements	Gastrointestinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Gingival bleeding	Gastrointestinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Haematochezia	Gastrointestinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Inguinal hernia	Gastrointestinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected10 at risk EG0020 events0 affected10 at risk EG003
Lip haemorrhage	Gastrointestinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Malabsorption	Gastrointestinal disorders	MedDRA v.22.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Melaena	Gastrointestinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Mouth haemorrhage	Gastrointestinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Teething	Gastrointestinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Chest pain	General disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Fatigue	General disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Feeling abnormal	General disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Feeling hot	General disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Influenza like illness	General disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Pyrexia	General disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Biliary tract disorder	Hepatobiliary disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Hepatic lesion	Hepatobiliary disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Jaundice	Hepatobiliary disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Seasonal allergy	Immune system disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Clostridium difficile infection	Infections and infestations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Ear infection	Infections and infestations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Epstein-Barr virus infection	Infections and infestations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Gastrointestinal infection	Infections and infestations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Hepatitis infectious mononucleosis	Infections and infestations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Impetigo	Infections and infestations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Oral herpes	Infections and infestations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Otitis media	Infections and infestations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Tonsillitis	Infections and infestations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Varicella	Infections and infestations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected10 at risk EG0020 events0 affected10 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Anaemia postoperative	Injury, poisoning and procedural complications	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Clavicle fracture	Injury, poisoning and procedural complications	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Concussion	Injury, poisoning and procedural complications	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Drain site complication	Injury, poisoning and procedural complications	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Hand fracture	Injury, poisoning and procedural complications	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Head injury	Injury, poisoning and procedural complications	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Joint injury	Injury, poisoning and procedural complications	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Limb crushing injury	Injury, poisoning and procedural complications	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Limb injury	Injury, poisoning and procedural complications	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Post procedural fever	Injury, poisoning and procedural complications	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0021 events1 affected10 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Scratch	Injury, poisoning and procedural complications	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Skin abrasion	Injury, poisoning and procedural complications	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Stoma site erythema	Injury, poisoning and procedural complications	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Stoma site pain	Injury, poisoning and procedural complications	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Stress fracture	Injury, poisoning and procedural complications	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Vaccination complication	Injury, poisoning and procedural complications	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Wound haemorrhage	Injury, poisoning and procedural complications	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Bilirubin urine present	Investigations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Blood bilirubin increased	Investigations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Blood parathyroid hormone increased	Investigations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Body temperature increased	Investigations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
International normalised ratio increased	Investigations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected10 at risk EG0020 events0 affected10 at risk EG003
Intracardiac pressure increased	Investigations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Urobilinogen urine increased	Investigations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Vitamin D decreased	Investigations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Vitamin E decreased	Investigations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Vitamin D deficiency	Metabolism and nutrition disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Bone metabolism disorder	Musculoskeletal and connective tissue disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Disturbance in attention	Nervous system disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Dizziness	Nervous system disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Headache	Nervous system disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Lethargy	Nervous system disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Poor quality sleep	Nervous system disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Seizure	Nervous system disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Somnolence	Nervous system disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Taste disorder	Nervous system disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected10 at risk EG0020 events0 affected10 at risk EG003
Device occlusion	Product Issues	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Breath holding	Psychiatric disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Enuresis	Psychiatric disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Restlessness	Psychiatric disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Sleep disorder	Psychiatric disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Urinary incontinence	Renal and urinary disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Amenorrhoea	Reproductive system and breast disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Fibrinous bronchitis	Respiratory, thoracic and mediastinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0021 events1 affected10 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Sneezing	Respiratory, thoracic and mediastinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Acne	Skin and subcutaneous tissue disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected10 at risk EG0020 events0 affected10 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Skin discolouration	Skin and subcutaneous tissue disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Xanthelasma	Skin and subcutaneous tissue disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Hypertension	Vascular disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Hypotension	Vascular disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Thrombosis	Vascular disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003

ID	Term
D002780	Cholestasis, Intrahepatic
D002779	Cholestasis
D001649	Bile Duct Diseases
D001660	Biliary Tract Diseases
D004066	Digestive System Diseases
D008107	Liver Diseases
D006330	Heart Defects, Congenital
D018376	Cardiovascular Abnormalities
D002318	Cardiovascular Diseases
D000015	Abnormalities, Multiple
D000013	Congenital Abnormalities
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D030342	Genetic Diseases, Inborn

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Bradycardia	Cardiac disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG0030 events0 affected13 at risk EG0040 events0 affected19 at risk EG0050 events0 affected5 at risk EG0061 events1 affected5 at risk EG0071 events1 affected19 at risk
Pericardial effusion	Cardiac disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Right ventricular failure	Cardiac disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Ear haemorrhage	Ear and labyrinth disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Pyrexia	General disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Gastrointestinal infection	Infections and infestations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Forearm fracture	Injury, poisoning and procedural complications	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Humerus fracture	Injury, poisoning and procedural complications	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Gastrointestinal stoma output decreased	Investigations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
International normalised ratio increased	Investigations	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Fibrinous bronchitis	Respiratory, thoracic and mediastinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0021 events1 affected10 at risk EG003
Medical device change	Surgical and medical procedures	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003
Hypotension	Vascular disorders	MedDRA v.22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected10 at risk EG0020 events0 affected10 at risk EG003