Download PDF

Clinical Trial Results:
Single (open-label) and repeat dose (randomized, placebo-controlled) trial to assess the safety, tolerability and pharmacokinetics of GB1211 (Gal-3 inhibitor) in participants with hepatic impairment (Child-Pugh B and Child-Pugh C).

Summary
EudraCT number	2021-001235-12
Trial protocol	BG
Global end of trial date	04 Jul 2022

Results information
Results version number	v1(current)
This version publication date	21 Sep 2023
First version publication date	21 Sep 2023
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

GULLIVER-2

ISRCTN number

US NCT number

NCT05009680

WHO universal trial number (UTN)

Sponsor organisation name

Galecto Biotech AB

Sponsor organisation address

Cobis Science Park Ole Maaloes Vej 3, Copenhagen, Denmark, DK-2200

Public contact

Chief Medical Officer , Galecto Biotech AB, Clinicaltrials@galecto.com

Scientific contact

Chief Medical Officer , Galecto Biotech AB, Clinicaltrials@galecto.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

20 Jun 2023

Is this the analysis of the primary completion data?

Yes

Primary completion date

04 Jul 2022

Global end of trial reached?

Yes

Global end of trial date

04 Jul 2022

Was the trial ended prematurely?

Main objective of the trial

Primary objective (Part 1, 2 and 3): To assess the effect of hepatic impairment on the safety, tolerability and pharmacokinetics of GB1211 in participants with moderate or severe hepatic impairment. Secondary objectives (Part 2): To assess the effect of GB1211 on hepatic function in participants with moderate hepatic impairment.

Protection of trial subjects

This study was conducted in accordance with the International Council on Harmonisation (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.

Background therapy

Evidence for comparator

Actual start date of recruitment

26 Aug 2021

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Bulgaria: 54

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Male or female subjects between 18 and 75 years with moderate hepatic impairment as defined by Child-Pugh B score, with severe hepatic impairment as defined by the Child-Pugh C score and healthy participants (controls).

Screening details

Demographics; Medical and surgical history; Inclusion and exclusion criteria; Physical examination; Recording body weight and height; Vital signs; 12-lead ECG; Safety laboratory; Serum pregnancy test; Alcohol breath test; Urine drug screen; Prior and Concomitant medication; AEs; SARS-CoV-2 antigen; Serology; (LiMAx test and FibroScan in Part 2).

Period 1 title

Baseline Period

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)

Arm description

Subjects with moderate hepatic impairment (Child-Pugh B) received single oral dose of 100 mg GB1211 (2 x 50 mg capsule) on Day 1.

Arm type

Experimental

Investigational medicinal product name

Test product

Investigational medicinal product code

Other name

GB1211

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Orally administered 100 mg GB1211 (2 x 50 mg, capsule), single dose.

Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)

Arm description

Healthy Subjects received single oral dose of 100 mg GB1211 (2 x 50 mg) on Day 1.

Arm type

Matching control

Investigational medicinal product name

Test product

Investigational medicinal product code

Other name

GB1211

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Orally administered 100 mg GB1211 (2 x 50 mg, capsule), single dose.

Part 2 GB1211 100 mg (2 x 50 mg)

Arm description

Subjects with moderate hepatic impairment (Child-Pugh B) received GB1211, 100 mg (2 x 50 mg capsules of GB1211), twice daily for 12 weeks.

Arm type

Experimental

Investigational medicinal product name

Test product

Investigational medicinal product code

Other name

GB1211

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Orally administered 100 mg GB1211 (2 x 50 mg, capsule), twice daily.

Part 2 Placebo (2 x 0 mg)

Arm description

Subjects with moderate hepatic impairment (Child-Pugh B) received Placebo (2 x 0 mg, capsule), twice daily for 12 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Orally administered Placebo (2 x 0 mg, capsule), twice daily.

Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)

Arm description

Subjects with severe hepatic impairment (Child-Pugh C) received single oral dose of 100 mg GB1211 (2 x 50 mg capsule) on Day 1.

Arm type

Experimental

Investigational medicinal product name

Test product

Investigational medicinal product code

Other name

GB1211

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Orally administered 100 mg GB1211 (2 x 50 mg, capsule), single dose.

Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)

Arm description

Healthy Subjects received single oral dose of 100 mg GB1211 (2 x 50 mg) on Day 1.

Arm type

Matching control

Investigational medicinal product name

Test product

Investigational medicinal product code

Other name

GB1211

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Orally administered 100 mg GB1211 (2 x 50 mg, capsule), single dose.

Number of subjects in period 1	Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)	Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)	Part 2 GB1211 100 mg (2 x 50 mg)	Part 2 Placebo (2 x 0 mg)	Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)	Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)
Started	6	6	15	15	6	6
Completed	6	6	13	15	6	6
Not completed	0	0	2	0	0	0
Adverse event, serious fatal	-	-	1	-	-	-
Withdrawal of informed consent	-	-	1	-	-	-

Period 2 title

PART 2

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Blinding implementation details

Part 2 of this study was a double-blinded trial. During the clinical phase of the trial, neither the subjects nor the site personnel involved in the study assessments were aware of the identity of the treatments administered (GB1211 or Placebo). Blinding was ensured by the Interactive Web-based Response System (IWRS) and was to be broken by a PI only for specific subjects where there was a reason to do.

Are arms mutually exclusive

Yes

Part 2 GB1211 100 mg (2 x 50 mg)

Arm description

Subjects with moderate hepatic impairment (Child-Pugh B) received GB1211, 100 mg (2 x 50 mg capsules of GB1211), twice daily for 12 weeks.

Arm type

Experimental

Investigational medicinal product name

Test product

Investigational medicinal product code

Other name

GB1211

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Orally administered 100 mg GB1211 (2 x 50 mg, capsule), twice daily.

Part 2 Placebo (2 x 0 mg)

Arm description

Subjects with moderate hepatic impairment (Child-Pugh B) received Placebo (2 x 0 mg, capsule), twice daily for 12 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Orally administered Placebo (2 x 0 mg, capsule), twice daily.

Number of subjects in period 2 ^[1]	Part 2 GB1211 100 mg (2 x 50 mg)	Part 2 Placebo (2 x 0 mg)
Started	15	15
Completed	13	15
Not completed	2	0
Adverse event, serious fatal	1	-
Withdrawal of informed consent	1	-

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Period 1 and period 2 had different enrolled population.

Period 3 title

PART 1

Is this the baseline period?

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)

Arm description

Subjects with moderate hepatic impairment (Child-Pugh B) received single oral dose of 100 mg GB1211 (2 x 50 mg capsule) on Day 1.

Arm type

Experimental

Investigational medicinal product name

Test product

Investigational medicinal product code

Other name

GB1211

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Orally administered 100 mg GB1211 (2 x 50 mg, capsule), single dose.

Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)

Arm description

Healthy Subjects received single oral dose of 100 mg GB1211 (2 x 50 mg) on Day 1.

Arm type

Matching control

Investigational medicinal product name

Test product

Investigational medicinal product code

Other name

GB1211

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Orally administered 100 mg GB1211 (2 x 50 mg, capsule), single dose.

Number of subjects in period 3 ^[2]	Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)	Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)
Started	6	6
Completed	6	6

Notes
[2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Period 2 and period 3 had different enrolled population.

Period 4 title

PART 3

Is this the baseline period?

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)

Arm description

Subjects with severe hepatic impairment (Child-Pugh C) received single oral dose of 100 mg GB1211 (2 x 50 mg capsule) on Day 1.

Arm type

Experimental

Investigational medicinal product name

Test product

Investigational medicinal product code

Other name

GB1211

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Orally administered 100 mg GB1211 (2 x 50 mg, capsule), single dose.

Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)

Arm description

Healthy Subjects received single oral dose of 100 mg GB1211 (2 x 50 mg) on Day 1.

Arm type

Matching control

Investigational medicinal product name

Test product

Investigational medicinal product code

Other name

GB1211

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Orally administered 100 mg GB1211 (2 x 50 mg, capsule), single dose.

Number of subjects in period 4	Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)	Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)
Started	6	6
Completed	6	6

Baseline characteristics

Top of page

Reporting group title

Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)

Reporting group description

Subjects with moderate hepatic impairment (Child-Pugh B) received single oral dose of 100 mg GB1211 (2 x 50 mg capsule) on Day 1.

Reporting group title

Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)

Reporting group description

Healthy Subjects received single oral dose of 100 mg GB1211 (2 x 50 mg) on Day 1.

Reporting group title

Part 2 GB1211 100 mg (2 x 50 mg)

Reporting group description

Subjects with moderate hepatic impairment (Child-Pugh B) received GB1211, 100 mg (2 x 50 mg capsules of GB1211), twice daily for 12 weeks.

Reporting group title

Part 2 Placebo (2 x 0 mg)

Reporting group description

Subjects with moderate hepatic impairment (Child-Pugh B) received Placebo (2 x 0 mg, capsule), twice daily for 12 weeks.

Reporting group title

Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)

Reporting group description

Subjects with severe hepatic impairment (Child-Pugh C) received single oral dose of 100 mg GB1211 (2 x 50 mg capsule) on Day 1.

Reporting group title

Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)

Reporting group description

Healthy Subjects received single oral dose of 100 mg GB1211 (2 x 50 mg) on Day 1.

Reporting group values	Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)	Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)	Part 2 GB1211 100 mg (2 x 50 mg)	Part 2 Placebo (2 x 0 mg)	Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)	Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)	Total
Number of subjects	6	6	15	15	6	6	54
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0
Adults (18-64 years)	5	6	11	13	6	5	46
From 65-84 years	1	0	4	2	0	1	8
85 years and over	0	0	0	0	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	56.67 ± 8.04	51.50 ± 7.42	58.07 ± 6.33	52.53 ± 6.81	58.33 ± 4.63	57.00 ± 7.64	-
Gender categorical
Units: Subjects
Female	2	2	5	5	2	2	18
Male	4	4	10	10	4	4	36
Race
Units: Subjects
White	6	6	15	15	6	6	54
Height
Units: cm
arithmetic mean (standard deviation)	170.17 ± 7.81	167.67 ± 5.57	168.80 ± 9.32	174.13 ± 7.61	168.17 ± 7.14	174.83 ± 10.09	-
Weight
Units: kg
arithmetic mean (standard deviation)	64.12 ± 11.62	65.23 ± 12.74	87.12 ± 20.92	76.33 ± 18.76	79.00 ± 17.15	86.90 ± 21.66	-
BMI
Units: (kg/m2)
arithmetic mean (standard deviation)	22.22 ± 4.69	23.37 ± 5.45	30.51 ± 6.68	25.06 ± 5.60	27.93 ± 6.05	28.13 ± 5.00	-

End points

Top of page

Reporting group title

Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)

Reporting group description

Subjects with moderate hepatic impairment (Child-Pugh B) received single oral dose of 100 mg GB1211 (2 x 50 mg capsule) on Day 1.

Reporting group title

Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)

Reporting group description

Healthy Subjects received single oral dose of 100 mg GB1211 (2 x 50 mg) on Day 1.

Reporting group title

Part 2 GB1211 100 mg (2 x 50 mg)

Reporting group description

Subjects with moderate hepatic impairment (Child-Pugh B) received GB1211, 100 mg (2 x 50 mg capsules of GB1211), twice daily for 12 weeks.

Reporting group title

Part 2 Placebo (2 x 0 mg)

Reporting group description

Subjects with moderate hepatic impairment (Child-Pugh B) received Placebo (2 x 0 mg, capsule), twice daily for 12 weeks.

Reporting group title

Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)

Reporting group description

Subjects with severe hepatic impairment (Child-Pugh C) received single oral dose of 100 mg GB1211 (2 x 50 mg capsule) on Day 1.

Reporting group title

Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)

Reporting group description

Healthy Subjects received single oral dose of 100 mg GB1211 (2 x 50 mg) on Day 1.

Reporting group title

Part 2 GB1211 100 mg (2 x 50 mg)

Reporting group description

Subjects with moderate hepatic impairment (Child-Pugh B) received GB1211, 100 mg (2 x 50 mg capsules of GB1211), twice daily for 12 weeks.

Reporting group title

Part 2 Placebo (2 x 0 mg)

Reporting group description

Subjects with moderate hepatic impairment (Child-Pugh B) received Placebo (2 x 0 mg, capsule), twice daily for 12 weeks.

Reporting group title

Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)

Reporting group description

Subjects with moderate hepatic impairment (Child-Pugh B) received single oral dose of 100 mg GB1211 (2 x 50 mg capsule) on Day 1.

Reporting group title

Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)

Reporting group description

Healthy Subjects received single oral dose of 100 mg GB1211 (2 x 50 mg) on Day 1.

Reporting group title

Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)

Reporting group description

Subjects with severe hepatic impairment (Child-Pugh C) received single oral dose of 100 mg GB1211 (2 x 50 mg capsule) on Day 1.

Reporting group title

Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)

Reporting group description

Healthy Subjects received single oral dose of 100 mg GB1211 (2 x 50 mg) on Day 1.

Subject analysis set title

Safety Population

Subject analysis set type

Safety analysis

Subject analysis set description

The safety population included all participants who received at least 1 dose of study treatment (GB1211 or placebo). The safety population was used for summaries of safety and other (such as disposition, concomitant medications, etc.) variables and for all safety analyses. The participants in the safety population were analyzed according to the treatment they have received.

Subject analysis set title

PK Population

Subject analysis set type

Per protocol

Subject analysis set description

The PK population in Part 2 included all participants who received GB1211 and had enough quantifiable PK samples to estimate the PK profiles on at least one out of Days 1 and 21 and who had no important protocol deviations affecting the PK parameters. The PK population was used for the descriptive summaries and statistical analyses of the PK concentrations and parameters.

Subject analysis set title

mITT Population

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

The mITT population included all participants who were randomized and received study treatment (GB1211 or placebo) for the 12-week planned dosing period. The participants in the mITT population were analyzed according to the treatment to which they were randomized. Note: this population was defined post hoc.

Subject analysis set title

Per Protocol (PP) Population

Subject analysis set type

Per protocol

Subject analysis set description

The PP population included all participants who were randomized, received at least 1 dose of study treatment (GB1211 or placebo) and who had no important protocol deviations. Each participant in the PP population was analyzed according to the treatment they had received.

Primary: Part 2 AUC(0-τ),ss (total GB1211)

Top of page

End point title

Part 2 AUC(0-τ),ss (total GB1211) ^[1]

End point description

Area under the total plasma concentration versus time curve during a dosage interval tau at steady state.

End point type

Primary

End point timeframe

From time 0 to dosage interval tau at steady state.

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	11
Units: (h.ng/mL)
arithmetic mean (standard deviation)	15494.72 ± 10708.99

No statistical analyses for this end point

Primary: Part 2 AUC(0-τ) (total GB1211)

Top of page

End point title

Part 2 AUC(0-τ) (total GB1211) ^[2]

End point description

Area under the total plasma concentration versus time curve during a dosage interval tau.

End point type

Primary

End point timeframe

From time 0 to dosage interval tau.

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	15
Units: h.ng/mL
arithmetic mean (standard deviation)	4259.38 ± 2211.40

No statistical analyses for this end point

Primary: Part 2 Cmax,ss (total GB1211)

Top of page

End point title

Part 2 Cmax,ss (total GB1211) ^[3]

End point description

Maximum measured total plasma drug concentration at steady-state (on Day 21).

End point type

Primary

End point timeframe

From time zero to t at steady-state (on Day 21).

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	11
Units: ng/mL
arithmetic mean (standard deviation)	1910.91 ± 1078.13

No statistical analyses for this end point

Primary: Part 2 Cmax (total GB1211)

Top of page

End point title

Part 2 Cmax (total GB1211) ^[4]

End point description

Maximum measured total plasma drug concentration.

End point type

Primary

End point timeframe

From time zero to t.

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	15
Units: ng/mL
arithmetic mean (standard deviation)	636.86 ± 334.89

No statistical analyses for this end point

Primary: Part 2 Cmin,ss (total GB1211)

Top of page

End point title

Part 2 Cmin,ss (total GB1211) ^[5]

End point description

Minimum measured total plasma drug concentration at steady-state (on Day 21).

End point type

Primary

End point timeframe

From time zero to t at steady-state (on Day 21).

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	11
Units: ng/mL
arithmetic mean (standard deviation)	813.30 ± 586.74

No statistical analyses for this end point

Primary: Part 2 Cav,ss (total GB1211)

Top of page

End point title

Part 2 Cav,ss (total GB1211) ^[6]

End point description

Average total plasma concentration at steady-state (on Day 21).

End point type

Primary

End point timeframe

At steady-state.

Notes
[6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	11
Units: ng/mL
arithmetic mean (standard deviation)	1291.23 ± 892.42

No statistical analyses for this end point

Primary: Part 2 CLss/F (total GB1211)

Top of page

End point title

Part 2 CLss/F (total GB1211) ^[7]

End point description

Apparent oral clearance at steady-state.

End point type

Primary

End point timeframe

From time 0 to dosage interval tau at steady-state.

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	11
Units: L/h
arithmetic mean (standard deviation)	9.11 ± 5.30

No statistical analyses for this end point

Primary: Part 2 CL/F (total GB1211)

Top of page

End point title

Part 2 CL/F (total GB1211) ^[8]

End point description

Apparent oral clearance.

End point type

Primary

End point timeframe

From time 0 to dosage interval tau.

Notes
[8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	1
Units: L/h
median (full range (min-max))	12.80 (12.80 to 12.80)

No statistical analyses for this end point

Primary: Part 2 Vzss/F (total GB1211)

Top of page

End point title

Part 2 Vzss/F (total GB1211) ^[9]

End point description

Apparent volume of distribution at steady-state.

End point type

Primary

End point timeframe

From time 0 to dosage interval τ at steady state.

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	4
Units: litre(s)
arithmetic mean (standard deviation)	108.38 ± 52.26

No statistical analyses for this end point

Primary: Part 2 Vz/F (total GB1211)

Top of page

End point title

Part 2 Vz/F (total GB1211) ^[10]

End point description

Apparent volume of distribution.

End point type

Primary

End point timeframe

From time 0 to dosage interval tau.

Notes
[10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	1
Units: litre(s)
median (full range (min-max))	382.75 (382.75 to 382.75)

No statistical analyses for this end point

Primary: Part 2 tmax,ss (total GB1211)

Top of page

End point title

Part 2 tmax,ss (total GB1211) ^[11]

End point description

Time to reach maximum total plasma concentration at steady-state (on Day 21).

End point type

Primary

End point timeframe

Time to maximum observed plasma concentration at steady-state (on Day 21).

Notes
[11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	11
Units: hour
median (full range (min-max))	2.02 (1.00 to 12.00)

No statistical analyses for this end point

Primary: Part 2 tmax (total GB1211)

Top of page

End point title

Part 2 tmax (total GB1211) ^[12]

End point description

Time to reach maximum total plasma concentration after drug administration.

End point type

Primary

End point timeframe

Time to maximum observed plasma concentration.

Notes
[12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	15
Units: hour
median (full range (min-max))	4.00 (1.00 to 11.97)

No statistical analyses for this end point

Primary: Part 2 t1/2,ss (total GB1211)

Top of page

End point title

Part 2 t1/2,ss (total GB1211) ^[13]

End point description

Terminal elimination half-life at steady-state.

End point type

Primary

End point timeframe

Time until quantity reduce to half of its initial value at steady-state.

Notes
[13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	4
Units: hour
arithmetic mean (standard deviation)	9.37 ± 4.67

No statistical analyses for this end point

Primary: Part 2 t1/2 (total GB1211)

Top of page

End point title

Part 2 t1/2 (total GB1211) ^[14]

End point description

Terminal elimination half-life.

End point type

Primary

End point timeframe

Time until quantity reduce to half of its initial value.

Notes
[14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	1
Units: hour
median (full range (min-max))	20.72 (20.72 to 20.72)

No statistical analyses for this end point

Primary: Part 2 PTF (total GB1211)

Top of page

End point title

Part 2 PTF (total GB1211) ^[15]

End point description

Peak-trough fluctuation.

End point type

Primary

End point timeframe

At steady-state.

Notes
[15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	11
Units: percent
arithmetic mean (standard deviation)	101.17 ± 58.36

No statistical analyses for this end point

Primary: Part 2 RAC(Cmax) (total GB1211)

Top of page

End point title

Part 2 RAC(Cmax) (total GB1211) ^[16]

End point description

Accumulation ratio calculated on Day 21 using Cmax,ss.

End point type

Primary

End point timeframe

From time 0 to the end of steady-state.

Notes
[16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	11
Units: NA
arithmetic mean (standard deviation)	2.97 ± 1.03

No statistical analyses for this end point

Primary: Part 2 RAC(AUC) (total GB1211)

Top of page

End point title

Part 2 RAC(AUC) (total GB1211) ^[17]

End point description

Accumulation ratio calculated on Day 21 using AUC(0-τ),ss.

End point type

Primary

End point timeframe

From time 0 to the end of steady-state.

Notes
[17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	11
Units: NA
arithmetic mean (standard deviation)	3.19 ± 1.10

No statistical analyses for this end point

Primary: Part 2 AUC(0-τ),ss (unbound GB1211)

Top of page

End point title

Part 2 AUC(0-τ),ss (unbound GB1211) ^[18]

End point description

Area under the unbound plasma concentration versus time curve during a dosage interval tau at steady state.

End point type

Primary

End point timeframe

From time 0 to dosage interval tau at steady state.

Notes
[18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	11
Units: h.ng/mL
arithmetic mean (standard deviation)	854.54 ± 500.65

No statistical analyses for this end point

Primary: Part 2 AUC(0-τ) (unbound GB1211)

Top of page

End point title

Part 2 AUC(0-τ) (unbound GB1211) ^[19]

End point description

Area under the unbound plasma concentration versus time curve during a dosage interval tau.

End point type

Primary

End point timeframe

From time 0 to dosage interval tau.

Notes
[19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	15
Units: h.ng/mL
arithmetic mean (standard deviation)	251.63 ± 132.94

No statistical analyses for this end point

Primary: Part 2 Cmax,ss (unbound GB1211)

Top of page

End point title

Part 2 Cmax,ss (unbound GB1211) ^[20]

End point description

Maximum measured unbound plasma drug concentration at steady-state (on Day 21).

End point type

Primary

End point timeframe

From time zero to t at steady-state (on Day 21).

Notes
[20] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	11
Units: ng/mL
arithmetic mean (standard deviation)	89.11 ± 48.44

No statistical analyses for this end point

Primary: Part 2 Cmax (unbound GB1211)

Top of page

End point title

Part 2 Cmax (unbound GB1211) ^[21]

End point description

Maximum measured unbound plasma drug concentration.

End point type

Primary

End point timeframe

From time zero to t.

Notes
[21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	15
Units: ng/mL
arithmetic mean (standard deviation)	28.62 ± 13.53

No statistical analyses for this end point

Primary: Part 2 Cmin,ss (unbound GB1211)

Top of page

End point title

Part 2 Cmin,ss (unbound GB1211) ^[22]

End point description

Minimum measured unbound plasma drug concentration at steady-state (on Day 21).

End point type

Primary

End point timeframe

From time zero to t at steady-state (on Day 21).

Notes
[22] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	11
Units: ng/mL
arithmetic mean (standard deviation)	48.98 ± 29.72

No statistical analyses for this end point

Primary: Part 2 Cav,ss (unbound GB1211)

Top of page

End point title

Part 2 Cav,ss (unbound GB1211) ^[23]

End point description

Average unound plasma concentration at steady-state (on Day 21).

End point type

Primary

End point timeframe

At steady-state.

Notes
[23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	11
Units: ng/mL
arithmetic mean (standard deviation)	71.21 ± 41.72

No statistical analyses for this end point

Primary: Part 2 tmax,ss (unbound GB1211)

Top of page

End point title

Part 2 tmax,ss (unbound GB1211) ^[24]

End point description

Time to reach maximum unbound plasma concentration at steady-state (on Day 21).

End point type

Primary

End point timeframe

Time to maximum observed plasma concentration at steady-state (on Day 21).

Notes
[24] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	10
Units: hour
median (full range (min-max))	3.00 (2.92 to 3.05)

No statistical analyses for this end point

Primary: Part 2 tmax (unbound GB1211)

Top of page

End point title

Part 2 tmax (unbound GB1211) ^[25]

End point description

Time to reach maximum unbound plasma concentration after drug administration.

End point type

Primary

End point timeframe

Time to maximum observed plasma concentration.

Notes
[25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	15
Units: hour
median (full range (min-max))	3.00 (3.00 to 12.00)

No statistical analyses for this end point

Primary: Part 2 Aeτ

Top of page

End point title

Part 2 Aeτ ^[26]

End point description

Cumulative urinary excretion of the unchanged drug from administration during a dosage interval tau after single dosing.

End point type

Primary

End point timeframe

During a dosage interval tau after single dosing.

Notes
[26] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	11
Units: mg
arithmetic mean (standard deviation)	4.91 ± 3.34

No statistical analyses for this end point

Primary: Part 2 Fe

Top of page

End point title

Part 2 Fe ^[27]

End point description

Fraction excreted into urine as unchanged drug after single dosing.

End point type

Primary

End point timeframe

From administration after single dosing.

Notes
[27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	11
Units: percent
arithmetic mean (standard deviation)	4.91 ± 3.34

No statistical analyses for this end point

Primary: Part 2 Ae τ,ss

Top of page

End point title

Part 2 Ae τ,ss ^[28]

End point description

Cumulative urinary excretion of unchanged drug from administration during a dosage interval τ at steady-state (on Day 21).

End point type

Primary

End point timeframe

From administration during a dosage interval τ at steady-state (on Day 21).

Notes
[28] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	9
Units: mg
arithmetic mean (standard deviation)	16.74 ± 10.05

No statistical analyses for this end point

Primary: Part 2 Fess

Top of page

End point title

Part 2 Fess ^[29]

End point description

Fraction excreted into urine as an unchanged drug at steady-state (on Day 21).

End point type

Primary

End point timeframe

At steady-state (on Day 21).

Notes
[29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	PK Population
Number of subjects analysed	9
Units: percent
arithmetic mean (standard deviation)	16.74 ± 10.05

No statistical analyses for this end point

Primary: Part 1 AUClast (total GB1211)

Top of page

End point title

Part 1 AUClast (total GB1211)

End point description

Area under the total plasma concentration versus time curve from time 0 to the time of last quantifiable concentration (Tlast).

End point type

Primary

End point timeframe

From time zero to the last quantifiable concentration t.

End point values	Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)	Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	6	6
Units: h.ng/mL
arithmetic mean (standard deviation)	8415.95 ± 5440.60	6444.39 ± 3630.03

ANOVA for AUClast

Comparison groups

Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg) v Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

≤ 0.05

Method

ANOVA

Parameter type

Geometric mean Ratio (%)

Point estimate

128.79

Confidence interval

level

90%

sides

2-sided

lower limit

74.89

upper limit

221.51

Primary: Part 1 AUCinf (total GB1211)

Top of page

End point title

Part 1 AUCinf (total GB1211)

End point description

Area under the total plasma concentration versus time curve from time 0 to infinity.

End point type

Primary

End point timeframe

Extrapolation to infinity.

End point values	Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)	Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	4	6
Units: h.ng/mL
arithmetic mean (standard deviation)	10949.80 ± 6001.70	6679.97 ± 3734.07

ANOVA for AUCinf

Comparison groups

Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg) v Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

≤ 0.05

Method

ANOVA

Parameter type

Geometric mean Ratio (%)

Point estimate

156.82

Confidence interval

level

90%

sides

2-sided

lower limit

72.32

upper limit

340.03

Primary: Part 1 Cmax (total GB1211)

Top of page

End point title

Part 1 Cmax (total GB1211)

End point description

Maximum measured total plasma drug concentration.

End point type

Primary

End point timeframe

From time zero to t.

End point values	Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)	Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	6	6
Units: ng/mL
arithmetic mean (standard deviation)	587.40 ± 432.06	621.89 ± 488.74

ANOVA for Cmax

Comparison groups

Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg) v Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

≤ 0.05

Method

ANOVA

Parameter type

Geometric mean Ratio (%)

Point estimate

96.33

Confidence interval

level

90%

sides

2-sided

lower limit

49.56

upper limit

187.27

Primary: Part 1 AUCextr (total GB1211)

Top of page

End point title

Part 1 AUCextr (total GB1211) ^[30]

End point description

Extrapolated area under the curve from the last quantifiable concentration to infinity as a percentage of AUCinf.

End point type

Primary

End point timeframe

Extrapolation to infinity.

Notes
[30] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)	Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	4	6
Units: percent
arithmetic mean (standard deviation)	7.38 ± 3.91	3.66 ± 3.40

No statistical analyses for this end point

Primary: Part 1 tmax (total GB1211)

Top of page

End point title

Part 1 tmax (total GB1211) ^[31]

End point description

Time to reach maximum total plasma concentration after drug administration.

End point type

Primary

End point timeframe

Time to maximum observed plasma concentration.

Notes
[31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)	Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	6	6
Units: hour
median (full range (min-max))	3.49 (2.00 to 4.00)	3.00 (3.00 to 4.00)

No statistical analyses for this end point

Primary: Part 1 λz (total GB1211)

Top of page

End point title

Part 1 λz (total GB1211) ^[32]

End point description

First order terminal elimination rate.

End point type

Primary

End point timeframe

At terminal phase.

Notes
[32] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)	Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	5	6
Units: h-1
arithmetic mean (standard deviation)	0.03 ± 0.01	0.04 ± 0.02

No statistical analyses for this end point

Primary: Part 1 t1/2 (total GB1211)

Top of page

End point title

Part 1 t1/2 (total GB1211) ^[33]

End point description

Terminal elimination half-life.

End point type

Primary

End point timeframe

Time until quantity reduce to half of its initial value.

Notes
[33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)	Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	5	6
Units: hour
arithmetic mean (standard deviation)	35.03 ± 30.89	17.21 ± 6.05

No statistical analyses for this end point

Primary: Part 1 CL/F (total GB1211)

Top of page

End point title

Part 1 CL/F (total GB1211) ^[34]

End point description

Apparent oral clearance.

End point type

Primary

End point timeframe

From time 0 to infinity.

Notes
[34] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)	Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	4	6
Units: L/h
arithmetic mean (standard deviation)	10.76 ± 4.05	18.52 ± 8.15

No statistical analyses for this end point

Primary: Part 1 Vz/F (total GB1211)

Top of page

End point title

Part 1 Vz/F (total GB1211) ^[35]

End point description

Apparent volume of distribution.

End point type

Primary

End point timeframe

From time 0 to infinity.

Notes
[35] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)	Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	4	6
Units: litre(s)
arithmetic mean (standard deviation)	343.24 ± 158.24	449.90 ± 243.18

No statistical analyses for this end point

Primary: Part 1 AUClast (unbound GB1211)

Top of page

End point title

Part 1 AUClast (unbound GB1211)

End point description

Area under the total plasma concentration versus time curve from time 0 to the time of last quantifiable concentration (Tlast).

End point type

Primary

End point timeframe

From time zero to the last quantifiable concentration t.

End point values	Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)	Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	6	6
Units: h.ng/mL
arithmetic mean (standard deviation)	495.04 ± 303.87	328.72 ± 157.15

ANOVA for AUClast

Comparison groups

Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg) v Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

≤ 0.05

Method

ANOVA

Parameter type

Geometric mean Ratio (%)

Point estimate

144.85

Confidence interval

level

90%

sides

2-sided

lower limit

87.99

upper limit

238.47

Primary: Part 1 AUCinf (unbound GB1211)

Top of page

End point title

Part 1 AUCinf (unbound GB1211)

End point description

Area under the total plasma concentration versus time curve from time 0 to infinity.

End point type

Primary

End point timeframe

Extrapolation to infinity.

End point values	Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)	Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	4	6
Units: h.ng/mL
arithmetic mean (standard deviation)	646.02 ± 319.48	354.99 ± 159.35

ANOVA for AUCinf

Comparison groups

Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg) v Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

≤ 0.05

Method

ANOVA

Parameter type

Geometric mean Ratio (%)

Point estimate

167.77

Confidence interval

level

90%

sides

2-sided

lower limit

upper limit

319.85

Primary: Part 1 Cmax (unbound GB1211)

Top of page

End point title

Part 1 Cmax (unbound GB1211)

End point description

Maximum measured total plasma drug concentration.

End point type

Primary

End point timeframe

From time zero to t.

End point values	Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)	Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	6	6
Units: ng/mL
arithmetic mean (standard deviation)	29.26 ± 18.01	28.60 ± 19.56

ANOVA for Cmax

Comparison groups

Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg) v Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

≤ 0.05

Method

ANOVA

Parameter type

Geometric mean Ratio (%)

Point estimate

102.62

Confidence interval

level

90%

sides

2-sided

lower limit

57.31

upper limit

183.74

Primary: Part 1 AUCextr (unbound GB1211)

Top of page

End point title

Part 1 AUCextr (unbound GB1211) ^[36]

End point description

Extrapolated area under the curve from the last quantifiable concentration to infinity as a percentage of AUCinf.

End point type

Primary

End point timeframe

Extrapolation to infinity.

Notes
[36] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)	Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	4	6
Units: percent
arithmetic mean (standard deviation)	8.04 ± 5.41	8.28 ± 3.20

No statistical analyses for this end point

Primary: Part 1 tmax (unbound GB1211)

Top of page

End point title

Part 1 tmax (unbound GB1211) ^[37]

End point description

Time to reach maximum total plasma concentration after drug administration.

End point type

Primary

End point timeframe

Time to maximum observed plasma concentration.

Notes
[37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)	Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	6	6
Units: hour
median (full range (min-max))	3.50 (2.00 to 6.00)	3.00 (2.00 to 4.00)

No statistical analyses for this end point

Primary: Part 1 Rmax

Top of page

End point title

Part 1 Rmax ^[38]

End point description

Maximal rate of urinary excretion.

End point type

Primary

End point timeframe

From time zero to t.

Notes
[38] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)	Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	6	6
Units: mg/h
arithmetic mean (standard deviation)	0.55 ± 0.43	0.56 ± 0.15

No statistical analyses for this end point

Primary: Part 1 Ae(0-t)

Top of page

End point title

Part 1 Ae(0-t) ^[39]

End point description

Cumulative urinary excretion of unchanged drug from administration until time t.

End point type

Primary

End point timeframe

From administration until time t.

Notes
[39] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)	Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	6	6
Units: mg
arithmetic mean (standard deviation)	9.59 ± 7.76	7.84 ± 1.87

No statistical analyses for this end point

Primary: Part 1 Fe

Top of page

End point title

Part 1 Fe ^[40]

End point description

Fraction excreted into urine as unchanged drug after single dosing.

End point type

Primary

End point timeframe

From administration after single dosing.

Notes
[40] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)	Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	6	6
Units: percent
arithmetic mean (standard deviation)	9.59 ± 7.76	7.84 ± 1.87

No statistical analyses for this end point

Primary: Part 1 ResAe

Top of page

End point title

Part 1 ResAe ^[41]

End point description

Cumulative urinary excretion of unchanged drug from the time of the last quantifiable concentration (Tlast) to infinity, expressed as a percentage of total cumulative urinary excretion.

End point type

Primary

End point timeframe

From the time of the last quantifiable concentration (Tlast) to infinity.

Notes
[41] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)	Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	2	3
Units: percent
arithmetic mean (standard deviation)	9.04 ± 1.97	1.19 ± 0.63

No statistical analyses for this end point

Primary: Part 3 AUClast (total GB1211)

Top of page

End point title

Part 3 AUClast (total GB1211)

End point description

Area under the total plasma concentration versus time curve from time 0 to the time of last quantifiable concentration (Tlast).

End point type

Primary

End point timeframe

From time zero to the last quantifiable concentration t.

End point values	Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)	Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	6	6
Units: h.ng/mL
arithmetic mean (standard deviation)	12477.52 ± 5659.07	7566.33 ± 3096.46

ANOVA for AUClast

Comparison groups

Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg) v Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

≤ 0.05

Method

ANOVA

Parameter type

Geometric mean Ratio (%)

Point estimate

159.62

Confidence interval

level

90%

sides

2-sided

lower limit

100.14

upper limit

254.43

Primary: Part 3 AUCinf (total GB1211)

Top of page

End point title

Part 3 AUCinf (total GB1211)

End point description

Area under the total plasma concentration versus time curve from time 0 to infinity.

End point type

Primary

End point timeframe

Extrapolation to infinity.

End point values	Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)	Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	4	6
Units: h.ng/mL
arithmetic mean (standard deviation)	12424.07 ± 7303.42	7892.42 ± 3157.95

ANOVA for AUCinf

Comparison groups

Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg) v Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

≤ 0.05

Method

ANOVA

Parameter type

Geometric mean Ratio (%)

Point estimate

161.59

Confidence interval

level

90%

sides

2-sided

lower limit

78.08

upper limit

334.43

Primary: Part 3 Cmax (total GB1211)

Top of page

End point title

Part 3 Cmax (total GB1211)

End point description

Maximum measured total plasma drug concentration.

End point type

Primary

End point timeframe

From time zero to t.

End point values	Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)	Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	6	6
Units: ng/mL
arithmetic mean (standard deviation)	727.31 ± 355.34	549.95 ± 330.67

ANOVA for Cmax

Comparison groups

Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg) v Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

≤ 0.05

Method

ANOVA

Parameter type

Geometric mean Ratio (%)

Point estimate

134.49

Confidence interval

level

90%

sides

2-sided

lower limit

79.26

upper limit

228.22

Primary: Part 3 AUCextr (total GB1211)

Top of page

End point title

Part 3 AUCextr (total GB1211) ^[42]

End point description

Extrapolated area under the curve from the last quantifiable concentration to infinity as a percentage of AUCinf.

End point type

Primary

End point timeframe

Extrapolation to infinity.

Notes
[42] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)	Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	4	6
Units: percent
arithmetic mean (standard deviation)	6.27 ± 5.13	4.21 ± 2.39

No statistical analyses for this end point

Primary: Part 3 tmax (total GB1211)

Top of page

End point title

Part 3 tmax (total GB1211) ^[43]

End point description

Time to reach maximum total plasma concentration after drug administration.

End point type

Primary

End point timeframe

Time to maximum observed plasma concentration.

Notes
[43] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)	Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	6	6
Units: hour
median (full range (min-max))	4.00 (2.00 to 6.00)	4.50 (2.00 to 6.02)

No statistical analyses for this end point

Primary: Part 3 λz (total GB1211)

Top of page

End point title

Part 3 λz (total GB1211) ^[44]

End point description

First order terminal elimination rate.

End point type

Primary

End point timeframe

At terminal phase.

Notes
[44] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)	Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	6	6
Units: h-1
arithmetic mean (standard deviation)	0.04 ± 0.02	0.04 ± 0.01

No statistical analyses for this end point

Primary: Part 3 t1/2 (total GB1211)

Top of page

End point title

Part 3 t1/2 (total GB1211) ^[45]

End point description

Terminal elimination half-life.

End point type

Primary

End point timeframe

Time until quantity reduce to half of its initial value.

Notes
[45] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)	Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	6	6
Units: hour
arithmetic mean (standard deviation)	23.45 ± 11.82	16.29 ± 2.49

No statistical analyses for this end point

Primary: Part 3 CL/F (total GB1211)

Top of page

End point title

Part 3 CL/F (total GB1211) ^[46]

End point description

Apparent oral clearance.

End point type

Primary

End point timeframe

From time 0 to infinity.

Notes
[46] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)	Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	4	6
Units: L/h
arithmetic mean (standard deviation)	10.50 ± 6.28	14.28 ± 4.97

No statistical analyses for this end point

Primary: Part 3 Vz/F (total GB1211)

Top of page

End point title

Part 3 Vz/F (total GB1211) ^[47]

End point description

Apparent volume of distribution.

End point type

Primary

End point timeframe

From time 0 to infinity.

Notes
[47] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)	Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	4	6
Units: litre(s)
arithmetic mean (standard deviation)	251.31 ± 161.95	332.21 ± 105.92

No statistical analyses for this end point

Primary: Part 3 AUClast (unbound GB1211)

Top of page

End point title

Part 3 AUClast (unbound GB1211)

End point description

Area under the total plasma concentration versus time curve from time 0 to the time of last quantifiable concentration (Tlast).

End point type

Primary

End point timeframe

From time zero to the last quantifiable concentration t.

End point values	Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)	Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	6	6
Units: h.ng/mL
arithmetic mean (standard deviation)	746.15 ± 381.23	439.19 ± 174.23

ANOVA for AUClast

Comparison groups

Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg) v Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

≤ 0.05

Method

ANOVA

Parameter type

Geometric mean Ratio (%)

Point estimate

162.67

Confidence interval

level

90%

sides

2-sided

lower limit

99.55

upper limit

265.81

Primary: Part 3 AUCinf (unbound GB1211)

Top of page

End point title

Part 3 AUCinf (unbound GB1211)

End point description

Area under the total plasma concentration versus time curve from time 0 to infinity.

End point type

Primary

End point timeframe

Extrapolation to infinity.

End point values	Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)	Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	4	6
Units: h.ng/mL
arithmetic mean (standard deviation)	735.75 ± 505.43	466.13 ± 173.82

ANOVA for AUCinf

Comparison groups

Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg) v Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

≤ 0.05

Method

ANOVA

Parameter type

Geometric mean Ratio (%)

Point estimate

165.64

Confidence interval

level

90%

sides

2-sided

lower limit

80.8

upper limit

339.59

Primary: Part 3 Cmax (unbound GB1211)

Top of page

End point title

Part 3 Cmax (unbound GB1211)

End point description

Maximum measured total plasma drug concentration.

End point type

Primary

End point timeframe

From time zero to t.

End point values	Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)	Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	5	6
Units: ng/mL
arithmetic mean (standard deviation)	34.41 ± 13.18	28.08 ± 12.95

ANOVA for Cmax

Comparison groups

Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg) v Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

≤ 0.05

Method

ANOVA

Parameter type

Geometric mean Ratio (%)

Point estimate

111.99

Confidence interval

level

90%

sides

2-sided

lower limit

69.9

upper limit

179.44

Primary: Part 3 AUCextr (unbound GB1211)

Top of page

End point title

Part 3 AUCextr (unbound GB1211) ^[48]

End point description

Extrapolated area under the curve from the last quantifiable concentration to infinity as a percentage of AUCinf.

End point type

Primary

End point timeframe

Extrapolation to infinity.

Notes
[48] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)	Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	4	6
Units: percent
arithmetic mean (standard deviation)	6.57 ± 5.27	6.55 ± 3.96

No statistical analyses for this end point

Primary: Part 3 tmax (unbound GB1211)

Top of page

End point title

Part 3 tmax (unbound GB1211) ^[49]

End point description

Time to reach maximum total plasma concentration after drug administration.

End point type

Primary

End point timeframe

Time to maximum observed plasma concentration.

Notes
[49] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)	Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	5	6
Units: hour
median (full range (min-max))	3.00 (3.00 to 6.00)	3.00 (1.50 to 8.03)

No statistical analyses for this end point

Primary: Part 3 Rmax

Top of page

End point title

Part 3 Rmax ^[50]

End point description

Maximal rate of urinary excretion.

End point type

Primary

End point timeframe

From time zero to t.

Notes
[50] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)	Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	6	6
Units: mg/h
arithmetic mean (standard deviation)	0.16 ± 0.06	0.22 ± 0.11

No statistical analyses for this end point

Primary: Part 3 Ae(0-t)

Top of page

End point title

Part 3 Ae(0-t) ^[51]

End point description

Cumulative urinary excretion of unchanged drug from administration until time t.

End point type

Primary

End point timeframe

From administration until time t.

Notes
[51] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)	Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	6	6
Units: mg
arithmetic mean (standard deviation)	3.13 ± 1.57	4.72 ± 2.03

No statistical analyses for this end point

Primary: Part 3 Fe

Top of page

End point title

Part 3 Fe ^[52]

End point description

Fraction excreted into urine as unchanged drug after single dosing.

End point type

Primary

End point timeframe

From administration after single dosing.

Notes
[52] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)	Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	6	6
Units: percent
arithmetic mean (standard deviation)	3.13 ± 1.57	4.72 ± 2.03

No statistical analyses for this end point

Primary: Part 3 ResAe

Top of page

End point title

Part 3 ResAe ^[53]

End point description

Cumulative urinary excretion of unchanged drug from the time of the last quantifiable concentration (Tlast) to infinity, expressed as a percentage of total cumulative urinary excretion.

End point type

Primary

End point timeframe

From the time of the last quantifiable concentration (Tlast) to infinity.

Notes
[53] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics.

End point values	Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)	Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)
Number of subjects analysed	2	2
Units: percent
arithmetic mean (standard deviation)	5.19 ± 6.89	4.00 ± 2.52

No statistical analyses for this end point

Secondary: Part 2 LiMAx test (mITT Population)

Top of page

End point title

Part 2 LiMAx test (mITT Population)

End point description

Maximum liver function capacity assessment (the LiMAx® test is a dynamic liver function test based on the metabolism of 13C-methacetin by the liver-specific cytochrome P450 1A2 system).

End point type

Secondary

End point timeframe

Percent change from Baseline at Day 84.

End point values	Part 2 GB1211 100 mg (2 x 50 mg)	Part 2 Placebo (2 x 0 mg)
Number of subjects analysed	13	15
Units: percent
arithmetic mean (standard deviation)	6.32 ± 39.30	15.15 ± 36.90

No statistical analyses for this end point

Secondary: Part 2 LiMAx test (PP Population)

Top of page

End point title

Part 2 LiMAx test (PP Population)

End point description

Maximum liver function capacity assessment (the LiMAx® test is a dynamic liver function test based on the metabolism of 13C-methacetin by the liver-specific cytochrome P450 1A2 system).

End point type

Secondary

End point timeframe

Percent change from Baseline at Day 84.

End point values	Part 2 GB1211 100 mg (2 x 50 mg)	Part 2 Placebo (2 x 0 mg)
Number of subjects analysed	12	15
Units: percent
arithmetic mean (standard deviation)	4.43 ± 40.43	15.15 ± 36.90

No statistical analyses for this end point

Secondary: Part 2 FibroScan Liver stiffness (mITT Population)

Top of page

End point title

Part 2 FibroScan Liver stiffness (mITT Population)

End point description

FibroScan®: Liver and spleen stiffness and liver steatosis measured by centrally-read transient elastography.

End point type

Secondary

End point timeframe

Percent change from Baseline at Day 84.

End point values	Part 2 GB1211 100 mg (2 x 50 mg)	Part 2 Placebo (2 x 0 mg)
Number of subjects analysed	13	15
Units: percent
arithmetic mean (standard deviation)	-10.84 ± 66.26	-21.42 ± 31.88

No statistical analyses for this end point

Secondary: Part 2 FibroScan CAP (Liver steatosis) (mITT Population)

Top of page

End point title

Part 2 FibroScan CAP (Liver steatosis) (mITT Population)

End point description

FibroScan®: Liver and spleen stiffness and liver steatosis measured by centrally-read transient elastography.

End point type

Secondary

End point timeframe

Percent change from Baseline at Day 84.

End point values	Part 2 GB1211 100 mg (2 x 50 mg)	Part 2 Placebo (2 x 0 mg)
Number of subjects analysed	13	15
Units: percent
arithmetic mean (standard deviation)	-6.83 ± 14.24	8.75 ± 31.49

No statistical analyses for this end point

Secondary: Part 2 FibroScan Spleen Stiffness (mITT Population)

Top of page

End point title

Part 2 FibroScan Spleen Stiffness (mITT Population)

End point description

FibroScan®: Liver and spleen stiffness and liver steatosis measured by centrally-read transient elastography.

End point type

Secondary

End point timeframe

Percent change from Baseline at Day 84.

End point values	Part 2 GB1211 100 mg (2 x 50 mg)	Part 2 Placebo (2 x 0 mg)
Number of subjects analysed	13	15
Units: percent
arithmetic mean (standard deviation)	1.90 ± 30.25	2.29 ± 35.27

No statistical analyses for this end point

Secondary: Part 2 FibroScan Liver stiffness (PP Population)

Top of page

End point title

Part 2 FibroScan Liver stiffness (PP Population)

End point description

FibroScan®: Liver and spleen stiffness and liver steatosis measured by centrally-read transient elastography.

End point type

Secondary

End point timeframe

Percent change from Baseline at Day 84.

End point values	Part 2 GB1211 100 mg (2 x 50 mg)	Part 2 Placebo (2 x 0 mg)
Number of subjects analysed	12	15
Units: percent
arithmetic mean (standard deviation)	-10.00 ± 69.13	-21.42 ± 31.88

No statistical analyses for this end point

Secondary: Part 2 FibroScan CAP (Liver steatosis) (PP Population)

Top of page

End point title

Part 2 FibroScan CAP (Liver steatosis) (PP Population)

End point description

FibroScan®: Liver and spleen stiffness and liver steatosis measured by centrally-read transient elastography.

End point type

Secondary

End point timeframe

Percent change from Baseline at Day 84.

End point values	Part 2 GB1211 100 mg (2 x 50 mg)	Part 2 Placebo (2 x 0 mg)
Number of subjects analysed	12	15
Units: percent
arithmetic mean (standard deviation)	-6.48 ± 14.82	8.75 ± 31.49

No statistical analyses for this end point

Secondary: Part 2 FibroScan Liver stiffness (PP Population)

Top of page

End point title

Part 2 FibroScan Liver stiffness (PP Population)

End point description

FibroScan®: Liver and spleen stiffness and liver steatosis measured by centrally-read transient elastography.

End point type

Secondary

End point timeframe

Percent change from Baseline at Day 84.

End point values	Part 2 GB1211 100 mg (2 x 50 mg)	Part 2 Placebo (2 x 0 mg)
Number of subjects analysed	12	15
Units: percent
arithmetic mean (standard deviation)	-0.47 ± 30.31	2.29 ± 35.27

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

From Screening until End of Study Visit

Adverse event reporting additional description

The safety of the test product was assessed on the basis of clinical and laboratory examinations, local and general tolerability (vital signs, electrocardiogram (ECG), physical examination) and recording of all AEs and/or TEAEs.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.0

Reporting group title

Part 2 GB1211 100 mg (2 x 50 mg)

Reporting group description

Reporting group title

Part 2 Placebo (2 x 0 mg)

Reporting group description

Reporting group title

Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)

Reporting group description

Reporting group title

Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)

Reporting group description

Reporting group title

Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)

Reporting group description

Reporting group title

Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)

Reporting group description

Serious adverse events	Part 2 GB1211 100 mg (2 x 50 mg)	Part 2 Placebo (2 x 0 mg)	Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)	Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)	Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)	Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 15 (6.67%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
number of deaths (all causes)	1	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0
Nervous system disorders
ENCEPHALOPATHY
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 15 (6.67%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COMA HEPATIC
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 15 (6.67%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
OESOPHAGEAL VARICES HAEMORRHAGE
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 15 (6.67%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Part 2 GB1211 100 mg (2 x 50 mg)	Part 2 Placebo (2 x 0 mg)	Part 1 Child-Pugh B Participants 100 mg GB1211 (2 x 50 mg)	Part 1 Healthy Control 100 mg GB1211 (2 x 50 mg)	Part 3 Child-Pugh C Participants 100 mg GB1211 (2 x 50 mg)	Part 3 Healthy Control 100 mg GB1211 (2 x 50 mg)
Total subjects affected by non serious adverse events
subjects affected / exposed	4 / 15 (26.67%)	4 / 15 (26.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
Investigations
Blood creatinine increased
subjects affected / exposed	1 / 15 (6.67%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0
Blood sodium decreased
subjects affected / exposed	1 / 15 (6.67%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0
Blood urea increased
subjects affected / exposed	1 / 15 (6.67%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0
SARS-CoV-2 test positive
subjects affected / exposed	0 / 15 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0
Nervous system disorders
Headache
subjects affected / exposed	0 / 15 (0.00%)	2 / 15 (13.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	3	0	0	0	0
Blood and lymphatic system disorders
Blood loss anemia
subjects affected / exposed	1 / 15 (6.67%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 15 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Epistaxis
subjects affected / exposed	0 / 15 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0
Hemoptysis
subjects affected / exposed	0 / 15 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0
Skin and subcutaneous tissue disorders
Pruritus
subjects affected / exposed	1 / 15 (6.67%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0
Renal and urinary disorders
Azotemia
subjects affected / exposed	1 / 15 (6.67%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 15 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0
Infections and infestations
COVID-19
subjects affected / exposed	1 / 15 (6.67%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0
Nasopharyngitis
subjects affected / exposed	1 / 15 (6.67%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

23 Nov 2021

Main Exclusion Criteria: Have previously completed or withdrawn from a study investigating GB1211 and have previously received the investigational product was applicable for Parts 1 and 3 only, not for Part 2. On Day 1 the time of twelve-lead ECG measurement was changed from 4h (± 15 min) pre-dose to 4h (± 15 min) post-dose. The pregnancy test at the Screening Visit for all parts was amended. Urine pregnancy test was not performed, a serum pregnancy was completed. On day 21 and Day 63 (± 2 days): Clinical Laboratory testing Blood chemistry and hematology at pre-dose were not performed and the time of twelve-lead ECG measurement was changed from 4h (± 15 min) pre-dose to 4h (± 15 min) post-dose. In Section 13.1 Appendix 1, the Assigning a Child-Pugh score table was updated.

20 May 2022

The change was to indicate the samples for investigating the potential metabolites of GB1211. They were investigated using surplus plasma from GB1211 PK blood samples for all parts of the study.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

The objective was to assess GB1211 in subjects with hepatic impairment. Three months of exposure was sufficient to examine the safety, tolerability and PK parameters, but may not be sufficient for the clinical endpoints in the secondary objectives.

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: Single (open-label) and repeat dose (randomized, placebo-controlled) trial to assess the safety, tolerability and pharmacokinetics of GB1211 (Gal-3 inhibitor) in participants with hepatic impairment (Child-Pugh B and Child-Pugh C).

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Part 2 AUC(0-τ),ss (total GB1211)

Primary: Part 2 AUC(0-τ),ss (total GB1211)

Primary: Part 2 AUC(0-τ) (total GB1211)

Primary: Part 2 AUC(0-τ) (total GB1211)

Primary: Part 2 Cmax,ss (total GB1211)

Primary: Part 2 Cmax,ss (total GB1211)

Primary: Part 2 Cmax (total GB1211)

Primary: Part 2 Cmax (total GB1211)

Primary: Part 2 Cmin,ss (total GB1211)

Primary: Part 2 Cmin,ss (total GB1211)

Primary: Part 2 Cav,ss (total GB1211)

Primary: Part 2 Cav,ss (total GB1211)

Primary: Part 2 CLss/F (total GB1211)

Primary: Part 2 CLss/F (total GB1211)

Primary: Part 2 CL/F (total GB1211)

Primary: Part 2 CL/F (total GB1211)

Primary: Part 2 Vzss/F (total GB1211)

Primary: Part 2 Vzss/F (total GB1211)

Primary: Part 2 Vz/F (total GB1211)

Primary: Part 2 Vz/F (total GB1211)

Primary: Part 2 tmax,ss (total GB1211)

Primary: Part 2 tmax,ss (total GB1211)

Primary: Part 2 tmax (total GB1211)

Primary: Part 2 tmax (total GB1211)

Primary: Part 2 t1/2,ss (total GB1211)

Primary: Part 2 t1/2,ss (total GB1211)

Primary: Part 2 t1/2 (total GB1211)

Primary: Part 2 t1/2 (total GB1211)

Primary: Part 2 PTF (total GB1211)

Primary: Part 2 PTF (total GB1211)

Primary: Part 2 RAC(Cmax) (total GB1211)

Primary: Part 2 RAC(Cmax) (total GB1211)

Primary: Part 2 RAC(AUC) (total GB1211)

Primary: Part 2 RAC(AUC) (total GB1211)

Primary: Part 2 AUC(0-τ),ss (unbound GB1211)

Primary: Part 2 AUC(0-τ),ss (unbound GB1211)

Primary: Part 2 AUC(0-τ) (unbound GB1211)

Primary: Part 2 AUC(0-τ) (unbound GB1211)

Primary: Part 2 Cmax,ss (unbound GB1211)

Primary: Part 2 Cmax,ss (unbound GB1211)

Primary: Part 2 Cmax (unbound GB1211)

Primary: Part 2 Cmax (unbound GB1211)

Primary: Part 2 Cmin,ss (unbound GB1211)

Primary: Part 2 Cmin,ss (unbound GB1211)

Primary: Part 2 Cav,ss (unbound GB1211)

Primary: Part 2 Cav,ss (unbound GB1211)

Primary: Part 2 tmax,ss (unbound GB1211)

Primary: Part 2 tmax,ss (unbound GB1211)

Primary: Part 2 tmax (unbound GB1211)

Primary: Part 2 tmax (unbound GB1211)

Primary: Part 2 Aeτ

Primary: Part 2 Aeτ

Primary: Part 2 Fe

Primary: Part 2 Fe

Primary: Part 2 Ae τ,ss

Primary: Part 2 Ae τ,ss

Primary: Part 2 Fess

Primary: Part 2 Fess

Primary: Part 1 AUClast (total GB1211)

Primary: Part 1 AUClast (total GB1211)

Primary: Part 1 AUCinf (total GB1211)

Primary: Part 1 AUCinf (total GB1211)

Primary: Part 1 Cmax (total GB1211)

Primary: Part 1 Cmax (total GB1211)

Primary: Part 1 AUCextr (total GB1211)

Primary: Part 1 AUCextr (total GB1211)

Primary: Part 1 tmax (total GB1211)

Primary: Part 1 tmax (total GB1211)

Primary: Part 1 λz (total GB1211)

Primary: Part 1 λz (total GB1211)

Clinical Trial Results:
Single (open-label) and repeat dose (randomized, placebo-controlled) trial to assess the safety, tolerability and pharmacokinetics of GB1211 (Gal-3 inhibitor) in participants with hepatic impairment (Child-Pugh B and Child-Pugh C).