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Clinical Trial Results:
A Multicentre, Randomized, Double Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of GFT505 once daily on Steatohepatitis in Patients with Non-Alcoholic Steatohepatitis (NASH).

Summary
EudraCT number	2012-000295-42
Trial protocol	BE DE ES GB NL IT
Global end of trial date	27 Feb 2015

Results information
Results version number	v2(current)
This version publication date	29 Jan 2023
First version publication date	12 May 2022
Other versions	v1
Version creation reason	Correction of full data set Corrected following updates to clinicaltrials.gov

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

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Trial information

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Sponsor protocol code

GFT505-212-7

ISRCTN number

US NCT number

NCT01694849

WHO universal trial number (UTN)

Sponsor organisation name

GENFIT

Sponsor organisation address

Parc Eurasanté, 885, avenue Eugène Avinée, Loos, France, 59120

Public contact

Genfit, Genfit, +33 3 20 16 40 00, clinicaltrial@genfit.com

Scientific contact

Carol Addy, MD MMSc, Genfit, +33 6179536469,

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

28 Dec 2015

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

27 Feb 2015

Was the trial ended prematurely?

Main objective of the trial

To evaluate the efficacy of GFT505 80mg and GFT505 120mg once daily for 52 weeks versus placebo in reversing histological steatohepatitis without worsening of fibrosis. Worsening of fibrosis is evaluated using NASH CRN fibrosis staging system and defined as: - Progression to stage 3 or 4 for patients at stage 0, 1 or 2 on diagnostic liver biopsy, - Progression to stage 4 for patients at stage 3 on diagnostic liver biopsy.

Protection of trial subjects

Continuing safety of trial participants in this Phase IIB study was ensured through regular safety reviews and DSMB analyses.

Background therapy

Evidence for comparator

Actual start date of recruitment

27 Sep 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Netherlands: 11

Country: Number of subjects enrolled

Spain: 18

Country: Number of subjects enrolled

United Kingdom: 9

Country: Number of subjects enrolled

Belgium: 37

Country: Number of subjects enrolled

France: 69

Country: Number of subjects enrolled

Germany: 3

Country: Number of subjects enrolled

Italy: 9

Country: Number of subjects enrolled

Romania: 10

Country: Number of subjects enrolled

United States: 108

Worldwide total number of subjects

274

EEA total number of subjects

166

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)

240

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Recruitment for the GFT505-212-7 study began in September 2012. This was a phase IIb, double-blind, randomized, placebo-controlled study conducted in three parallel groups: placebo, GFT505 80mg and GFT505 120mg (after DSMB review of 6 month safety data of the 80mg dose on at least 50% of participants) once daily for 52 weeks.

Screening details

Random allocation was done in two phases. First phase, participants were randomly allocated to GFT505 80 mg or placebo (ratio 2:1). Second phase (after DSMB review of 6-month safety data of 80-mg dose on ≥ 50% of participants), participants were assigned to GFT505 120 mg or placebo(ratio 2:1) in order to balance the 3 treatments in 1:1:1 ratio.

Period 1 title

Treatment Period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

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

Blinding implementation details

The Investigator, patient, and study personnel were blinded to the treatment. Identification’s number were assigned to a patient at the selection visit. Upon completion of the baseline visit(s), eligible patients were randomly assigned to active treatment (GFT505 80mg or GFT505 120mg or placebo).

Are arms mutually exclusive

Yes

Placebo

Arm description

Arm type

Placebo

Investigational medicinal product name

GFT505 placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

3 capsules of placebo / day

GFT505 120mg

Arm description

90 subjects were randomised to GFT505 120mg arm but one subject was not treated, and is not counted in this arm. This subject is excluded from the baseline characteristics reporting and the safety data analysis population

Arm type

Experimental

Investigational medicinal product name

GFT505 40mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

GFT505 120mg arm: 3 capsules of GFT505 40 mg / day

GFT505 80mg

Arm description

Arm type

Experimental

Investigational medicinal product name

GFT505 placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

GFT505 80mg arm: 3 capsules / day : 2 capsules of GFT505 40 mg and 1 capsule of placebo

Investigational medicinal product name

GFT505 40mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

GFT505 80mg arm: 3 capsules / day : 2 capsules of GFT505 40 mg and 1 capsule of placebo

Number of subjects in period 1	Placebo	GFT505 120mg	GFT505 80mg
Started	92	89	93
Completed	78	79	84
Not completed	14	10	9
Consent withdrawn by subject	7	3	1
Adverse event, non-fatal	4	7	6
Non-compliance	1	-	1
Protocol specific withdrawal criterion	1	-	1
Lost to follow-up	1	-	-

Period 2 title

Follow-up period

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

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

Are arms mutually exclusive

Yes

Placebo

Arm description

Arm type

Placebo

Investigational medicinal product name

GFT505 placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

3 capsules of placebo / day

GFT505 120mg

Arm description

Arm type

Experimental

Investigational medicinal product name

GFT505 40mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

GFT505 120mg arm: 3 capsules of GFT505 40 mg / day

GFT505 80mg

Arm description

Arm type

Experimental

Investigational medicinal product name

GFT505 placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

GFT505 80mg arm: 3 capsules / day : 2 capsules of GFT505 40 mg and 1 capsule of placebo

Investigational medicinal product name

GFT505 40mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

GFT505 80mg arm: 3 capsules / day : 2 capsules of GFT505 40 mg and 1 capsule of placebo

Number of subjects in period 2	Placebo	GFT505 120mg	GFT505 80mg
Started	78	79	84
Completed	77	76	83
Not completed	1	3	1
Consent withdrawn by subject	-	1	-
Lost to follow-up	1	2	1

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Reporting group title

GFT505 120mg

Reporting group description

Reporting group title

GFT505 80mg

Reporting group description

Reporting group values	Placebo	GFT505 120mg	GFT505 80mg	Total
Number of subjects	92	89	93	274
Age categorical
Units: Subjects
In utero				0
Preterm newborn infants (gestational age < 37 wks)				0
Newborns (0-27 days)				0
Infants and toddlers (28 days-23 months)				0
Children (2-11 years)				0
Adolescents (12-17 years)				0
Adults (18-64 years)				0
From 65-84 years				0
85 years and over				0
Age continuous
Units: years
arithmetic mean (standard deviation)	52.88 ± 11.99	52.88 ± 11.63	53.26 ± 11.02	-
Gender categorical
Units: Subjects
Female	37	42	44	123
Male	55	47	49	151
Race
Units: Subjects
Caucasian	85	71	88	244
Black	3	5	2	10
Asian	1	6	0	7
Other	3	7	3	13
Prevalence of type 2 diabetes mellitus
Units: Subjects
Type 2 diabetes- Yes	33	37	37	107
Type 2 diabetes- No	59	52	56	167
Body Mass Index
Units: kilogram(s)/square meter
arithmetic mean (standard deviation)	30.91 ± 4.15	31.04 ± 4.39	31.80 ± 5.20	-
Waist circumference
Units: centimeter
arithmetic mean (standard deviation)	104.68 ± 10.52	106.26 ± 10.28	106.41 ± 13.09	-
Height
Units: cm
arithmetic mean (standard deviation)	169.21 ± 10.23	170.21 ± 10.69	167.77 ± 9.30	-
Weight
Units: kg
arithmetic mean (standard deviation)	88.72 ± 15.79	90.15 ± 15.57	88.72 ± 15.79	-

End points

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Reporting group title

Placebo

Reporting group description

Reporting group title

GFT505 120mg

Reporting group description

Reporting group title

GFT505 80mg

Reporting group description

Reporting group title

Placebo

Reporting group description

Reporting group title

GFT505 120mg

Reporting group description

Reporting group title

GFT505 80mg

Reporting group description

Subject analysis set title

EES (ITT)- Placebo

Subject analysis set type

Intention-to-treat

Subject analysis set description

The ITT population or Efficacy Evaluable Set (EES) included all randomised and treated patients with a liver biopsy at endpoint.

Subject analysis set title

EES (ITT)- GFT505 80mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

The ITT population or Efficacy Evaluable Set (EES) included all randomised and treated patients with a liver biopsy at endpoint.

Subject analysis set title

EES (ITT)- GFT505 120mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

The ITT population or Efficacy Evaluable Set (EES) included all randomised and treated patients with a liver biopsy at endpoint.

Primary: EES- Percentage of Responders With Disappearance of Steatohepatitis Without Worsening of Fibrosis (ie, Participants no Longer Meeting the Criteria for Steatohepatitis)

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End point title

EES- Percentage of Responders With Disappearance of Steatohepatitis Without Worsening of Fibrosis (ie, Participants no Longer Meeting the Criteria for Steatohepatitis)

End point description

The primary endpoint was the percentage of responders at W52, defined by the disappearance of steatohepatitis (i.e. patients no longer meeting the criteria for steatohepatitis) without worsening of fibrosis (worsening of fibrosis was evaluated using NASH CRN fibrosis staging system and was defined as progression to stage 3 or 4 for patients at stage 0, 1 or 2 on diagnostic liver biopsy or progression to stage 4 for patients at stage 3 on diagnostic liver biopsy.

End point type

Primary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: percent
number (not applicable)	20.8	25.6	24.4

EES (ITT) GFT505 120mg vs Placebo

Statistical analysis description

H_01: OR_80 less than or equal to 1 versus H_11 : OR_80 greater than 1 H_02: OR_120 less than or equal to 1 versus H_12 : OR_120 greater than 1

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

P-value

= 0.816 ^[2]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.897

Confidence interval

level

95%

sides

2-sided

lower limit

0.361

upper limit

2.232

Variability estimate

Standard error of the mean

Notes
[1] - Baseline NAS, Log transformed baseline aspartate aminotransferase and baseline plasminogen activator inhibitor 1 values
[2] - To deal with multiplicity of comparisons, a step-down approach was adopted to control the type I error to 0.05. The contrast GFT120 mg versus placebo was examined first. If not significant the GFT 80mg versus placebo contrast was not examined.

EES (ITT) GFT505 80mg vs Placebo

Statistical analysis description

H_01: OR_80 less than or equal to 1 versus H_11 : OR_80 greater than 1 H_02: OR_120 less than or equal to 1 versus H_12 : OR_120 greater than 1

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

= 0.8539 ^[4]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.092

Confidence interval

level

95%

sides

2-sided

lower limit

0.427

upper limit

2.795

Variability estimate

Standard error of the mean

Notes
[3] - Baseline NAS, Log transformed baseline aspartate aminotransferase and baseline plasminogen activator inhibitor 1 values
[4] - To deal with multiplicity of comparisons, a step-down approach was adopted to control the type I error to 0.05. The contrast GFT120 mg versus placebo was examined first. If not significant the GFT 80mg versus placebo contrast was not examined.

Secondary: EES- Change From Baseline to Week 52 in Non-alcoholic Fatty Liver Disease Activity Score

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End point title

EES- Change From Baseline to Week 52 in Non-alcoholic Fatty Liver Disease Activity Score

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg the change from baseline to Week 52, in Non-alcoholic Fatty Liver Disease Activity Score (NAS score).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: NAS score delta
arithmetic mean (standard deviation)	-0.45 ± 1.34	-0.65 ± 1.33	-0.64 ± 1.68

Difference in LS mean 80mg vs placebo

Statistical analysis description

H0: difference in least squares (LS) mean change from baseline equal to 0 H1: difference in LS mean change from baseline not equal to 0 Population with baseline Non-Alcoholic Fatty Liver Disease Activity Score greater than or equal to 4

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.225 ^[5]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.27

Confidence interval

level

95%

sides

2-sided

lower limit

-0.75

upper limit

0.2

Variability estimate

Standard error of the mean

Notes
[5] - Baseline Non-Alcoholic Fatty Liver Disease Activity Score

Difference in LS mean 120mg vs placebo

Statistical analysis description

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.254 ^[6]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.28

Confidence interval

level

95%

sides

2-sided

lower limit

-0.76

upper limit

0.2

Variability estimate

Standard error of the mean

Notes
[6] - Baseline Non-Alcoholic Fatty Liver Disease Activity Score

Secondary: EES- Number of Participants With Decrease in Steatosis Score of at Least 1 Point Between Baseline and Week 52

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End point title

EES- Number of Participants With Decrease in Steatosis Score of at Least 1 Point Between Baseline and Week 52

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, number of participants with a decrease in steatosis score of at least 1 point between baseline and Week 52

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77 ^[7]	82 ^[8]	78 ^[9]
Units: number of subjects
number (not applicable)
Mild (NFLDA score 3)	0	1	1
Moderate (NFLDA score 4-5)	12	13	10
Severe (NFLDA score 6-8)	3	3	10
Total	15	17	21

Notes
[7] - Mild 14 subjects analysed, Moderate 41 subjects analysed, Severe 22 subjects analysed.
[8] - Mild 10 subjects analysed, Moderate 49 subjects analysed, Severe 23 subjects analysed.
[9] - Mild 11 subjects analysed, Moderate 40 subjects analysed, Severe 27 subjects analysed.

GFT505 80mg, Placebo

Statistical analysis description

Population with baseline Non-Alcoholic Fatty Liver Disease Activity Score greater than or equal to 4

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5231 ^[10]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.723

Confidence interval

level

95%

sides

2-sided

lower limit

0.267

upper limit

1.958

Variability estimate

Standard error of the mean

Notes
[10] - Baseline value of the analyzed parameter

GFT505 120mg, Placebo

Statistical analysis description

Population with baseline Non-Alcoholic Fatty Liver Disease Activity Score greater than or equal to 4

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8459 ^[11]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.102

Confidence interval

level

95%

sides

2-sided

lower limit

0.415

upper limit

2.924

Variability estimate

Standard error of the mean

Notes
[11] - Baseline value of the analyzed parameter

Secondary: EES- Number of Participants With Decrease in Lobular Inflammation Score of at Least 1 Point Between Baseline and Week 52

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End point title

EES- Number of Participants With Decrease in Lobular Inflammation Score of at Least 1 Point Between Baseline and Week 52

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, number of participants with a decrease in lobular inflammation score of at least 1 point between baseline and Week 52

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77 ^[12]	82 ^[13]	78 ^[14]
Units: number of subjects
number (not applicable)
Mild (NFLDA score 3)	7	1	2
Moderate (NFLDA score 4-5)	8	10	11
Severe (NFLDA score 6-8)	12	14	16
Total	27	25	29

Notes
[12] - Mild 14 subjects analysed, Moderate 41 subjects analysed, Severe 22 subjects analysed.
[13] - Mild 10 subjects analysed, Moderate 49 subjects analysed, Severe 23 subjects analysed.
[14] - Mild 11 subjects analysed, Moderate 40 subjects analysed, Severe 27 subjects analysed.

GFT505 80mg, Placebo

Statistical analysis description

Population with baseline Non-Alcoholic Fatty Liver Disease Activity Score greater than or equal to 4

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5229 ^[15]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.638

Confidence interval

level

95%

sides

2-sided

lower limit

0.161

upper limit

2.529

Variability estimate

Standard error of the mean

Notes
[15] - Baseline value of the analyzed parameter

GFT505 120mg, Placebo

Statistical analysis description

Population with baseline Non-Alcoholic Fatty Liver Disease Activity Score greater than or equal to 4

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5646 ^[16]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.433

Confidence interval

level

95%

sides

2-sided

lower limit

0.421

upper limit

4.875

Variability estimate

Standard error of the mean

Notes
[16] - Baseline value of the analyzed parameter

Secondary: EES - Decrease in Ballooning Score of at Least 1 Point Between Baseline and Week 52

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End point title

EES - Decrease in Ballooning Score of at Least 1 Point Between Baseline and Week 52

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, number of participants with a decrease in ballooning score of at least 1 point between baseline and Week 52

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: percent
number (not applicable)	31.17	37.80	38.46

GFT505 80mg, Placebo

Statistical analysis description

Population with baseline Non-Alcoholic Fatty Liver Disease Activity Score greater than or equal to 4

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1983 ^[17]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.382

Confidence interval

level

95%

sides

2-sided

lower limit

0.088

upper limit

1.656

Variability estimate

Standard error of the mean

Notes
[17] - Baseline value of the analyzed parameter

GFT505 120mg, Placebo

Statistical analysis description

Population with baseline Non-Alcoholic Fatty Liver Disease Activity Score greater than or equal to 4

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 1 ^[18]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.268

upper limit

3.466

Variability estimate

Standard error of the mean

Notes
[18] - Baseline value of the analyzed parameter

Secondary: EES - Changes From Baseline to Week 52 in the Stages of Fibrosis

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End point title

EES - Changes From Baseline to Week 52 in the Stages of Fibrosis

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to Week 52, in stages of fibrosis (based on Non-Alcoholic Steatohepatitis Clinical Research Network [NASH CRN] scoring).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: change in fibrosis score
arithmetic mean (standard deviation)	-0.23 ± 0.90	-0.23 ± 0.84	-0.06 ± 0.96

GFT505 80mg, vsPlacebo

Statistical analysis description

Population with baseline Non-Alcoholic Fatty Liver Disease Activity Score greater than or equal to 4

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3543

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.653

Confidence interval

level

95%

sides

2-sided

lower limit

0.265

upper limit

1.609

Variability estimate

Standard error of the mean

GFT505 120mg vs Placebo

Statistical analysis description

Population with baseline Non-Alcoholic Fatty Liver Disease Activity Score greater than or equal to 4

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.578

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.27

Confidence interval

level

95%

sides

2-sided

lower limit

0.547

upper limit

2.953

Variability estimate

Standard error of the mean

Secondary: EES - Changes From Baseline to Visit 8 (Week 52) in Gamma-glutamyl transferase (GGT)

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End point title

EES - Changes From Baseline to Visit 8 (Week 52) in Gamma-glutamyl transferase (GGT)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in liver enzymes.

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: U/L
arithmetic mean (standard deviation)	6.22 ± 50.64	-24.32 ± 36.39	-20.59 ± 40.45

GFT505 80mg, Placebo

Statistical analysis description

Change in Gamma-glutamyl transferase (U/L)

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-31.41

Confidence interval

level

95%

sides

2-sided

lower limit

-43.78

upper limit

-19.15

Variability estimate

Standard error of the mean

GFT505 120mg, Placebo

Statistical analysis description

Change in Gamma-glutamyl transferase (U/L)

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-29.31

Confidence interval

level

95%

sides

2-sided

lower limit

-41.84

upper limit

-16.77

Variability estimate

Standard error of the mean

Secondary: EES- Changes From Baseline to Visit 8 (Week 52) in Aspartate Transaminase/Alanine Aminotransferase Ratio

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End point title

EES- Changes From Baseline to Visit 8 (Week 52) in Aspartate Transaminase/Alanine Aminotransferase Ratio

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in aspartate transaminase/alanine aminotransferase ratio.

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: AST/ALT delta
arithmetic mean (standard deviation)	0.01 ± 0.25	0.15 ± 0.21	0.20 ± 0.25

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[19]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

0.14

Confidence interval

level

95%

sides

2-sided

lower limit

0.06

upper limit

0.21

Variability estimate

Standard error of the mean

Notes
[19] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[20]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

0.19

Confidence interval

level

95%

sides

2-sided

lower limit

0.11

upper limit

0.26

Variability estimate

Standard error of the mean

Notes
[20] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES- Change From Baseline to Week 52 in Non-alcoholic Fatty Liver Disease Activity Score of at least 2 points.

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End point title

EES- Change From Baseline to Week 52 in Non-alcoholic Fatty Liver Disease Activity Score of at least 2 points.

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg the change from baseline to Week 52, in Non-alcoholic Fatty Liver Disease Activity Score (NAS score) of at least 2 points.

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: percent
number (not applicable)	27.27	25.61	33.33

GFT505 80mg, Placebo

Statistical analysis description

Population with baseline Non-Alcoholic Fatty Liver Disease Activity Score greater than or equal to 4

Comparison groups

EES (ITT)- GFT505 80mg v EES (ITT)- Placebo

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority ^[21]

P-value

= 0.8586 ^[22]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.073

Confidence interval

level

95%

sides

2-sided

lower limit

0.493

upper limit

2.339

Variability estimate

Standard error of the mean

Notes
[21] - To take into account the inflation of type I error due to multiple comparisons without changing the nominal type I error risk, a step-down approach was adopted. .The first contrast to be examined was the contrast GFT120 mg versus placebo. If not significant the GFT 80mg versus placebo contrast was not examined. Therefore the type I error risk was set at 0.05
[22] - Baseline Non-Alcoholic Fatty Liver Disease Activity Score

GFT505 120mg, Placebo

Statistical analysis description

Population with baseline Non-Alcoholic Fatty Liver Disease Activity Score greater than or equal to 4

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority ^[23]

P-value

= 0.2255 ^[24]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.601

Confidence interval

level

95%

sides

2-sided

lower limit

0.747

upper limit

2.432

Variability estimate

Standard error of the mean

Notes
[23] - To take into account the inflation of type I error due to multiple comparisons without changing the nominal type I error risk, a step-down approach was adopted. .The first contrast to be examined was the contrast GFT120 mg versus placebo. If not significant the GFT 80mg versus placebo contrast was not examined. Therefore the type I error risk was set at 0.05
[24] - Baseline Non-Alcoholic Fatty Liver Disease Activity Score

Secondary: EES - Changes From Baseline to Visit 8 (Week 52) in alkaline phosphatases

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End point title

EES - Changes From Baseline to Visit 8 (Week 52) in alkaline phosphatases

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in liver enzymes.

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: U/L
arithmetic mean (standard deviation)	3.44 ± 13.16	-18.82 ± 13.23	-20.44 ± 16.47

GFT505 80mg, Placebo

Statistical analysis description

Change in Alkaline phosphatases (U/L)

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[25]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-23.02

Confidence interval

level

95%

sides

2-sided

lower limit

-27.16

upper limit

-18.88

Variability estimate

Standard error of the mean

Notes
[25] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Statistical analysis description

Change in Alkaline phosphatases (U/L)

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[26]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-23.85

Confidence interval

level

95%

sides

2-sided

lower limit

-28.04

upper limit

2.12

Variability estimate

Standard error of the mean

Notes
[26] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in triglycerides

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End point title

EES - Changes From Baseline to Week 52 in triglycerides

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in lipid parameters (used to assess cardiovascular risk)

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: millimole(s)/litre
arithmetic mean (standard deviation)	0.16 ± 1.12	-0.33 ± 0.76	-0.48 ± 0.90

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[27]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.47

Confidence interval

level

95%

sides

2-sided

lower limit

-0.73

upper limit

-0.21

Variability estimate

Standard error of the mean

Notes
[27] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[28]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.55

Confidence interval

level

95%

sides

2-sided

lower limit

-0.81

upper limit

-0.29

Variability estimate

Standard error of the mean

Notes
[28] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in cholesterol

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End point title

EES - Changes From Baseline to Week 52 in cholesterol

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in lipid parameters (used to assess cardiovascular risk)

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: millimole(s)/litre
arithmetic mean (standard deviation)	0.02 ± 0.66	-0.42 ± 0.78	-0.42 ± 0.72

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- GFT505 80mg v EES (ITT)- Placebo

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[29]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.35

Confidence interval

level

95%

sides

2-sided

lower limit

-0.56

upper limit

-0.14

Variability estimate

Standard error of the mean

Notes
[29] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[30]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.43

Confidence interval

level

95%

sides

2-sided

lower limit

-0.64

upper limit

-0.23

Variability estimate

Standard error of the mean

Notes
[30] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Change in Non-high Density Lipoproteins Cholesterol (nHDL-c)

Top of page

End point title

EES - Change in Non-high Density Lipoproteins Cholesterol (nHDL-c)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in lipid parameters (used to assess cardiovascular risk)

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: millimole(s)/litre
arithmetic mean (standard deviation)	0.07 ± 0.67	-0.45 ± 0.79	-0.47 ± 0.71

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[31]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.46

Confidence interval

level

95%

sides

2-sided

lower limit

-0.67

upper limit

-0.24

Variability estimate

Standard error of the mean

Notes
[31] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[32]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.54

Confidence interval

level

95%

sides

2-sided

lower limit

-0.75

upper limit

-0.32

Variability estimate

Standard error of the mean

Notes
[32] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Change in High Density Lipoproteins Cholesterol (HDL-c)

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End point title

EES - Change in High Density Lipoproteins Cholesterol (HDL-c)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in lipid parameters (used to assess cardiovascular risk)

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: millimole(s)/litre
arithmetic mean (standard deviation)	-0.06 ± 0.21	0.02 ± 0.17	0.06 ± 0.23

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- GFT505 80mg v EES (ITT)- Placebo

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.005 ^[33]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

0.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.03

upper limit

0.15

Variability estimate

Standard error of the mean

Notes
[33] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[34]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

0.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.05

upper limit

0.17

Variability estimate

Standard error of the mean

Notes
[34] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Change in Very Low Density Lipoproteins Cholesterol (VLDL-c)

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End point title

EES - Change in Very Low Density Lipoproteins Cholesterol (VLDL-c)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in lipid parameters (used to assess cardiovascular risk)

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	74	82	75
Units: millimole(s)/litre
arithmetic mean (standard deviation)	0.05 ± 0.23	-0.17 ± 0.28	-0.17 ± 0.32

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

156

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[35]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.18

Confidence interval

level

95%

sides

2-sided

lower limit

-0.26

upper limit

-0.11

Variability estimate

Standard error of the mean

Notes
[35] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

149

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[36]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.25

upper limit

-0.09

Variability estimate

Standard error of the mean

Notes
[36] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES- Change in Low Density Lipoproteins Cholesterol (LDL-c)

Top of page

End point title

EES- Change in Low Density Lipoproteins Cholesterol (LDL-c)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in lipid parameters (used to assess cardiovascular risk)

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	74	82	75
Units: millimole(s)/litre
arithmetic mean (standard deviation)	-0.01 ± 0.51	-0.27 ± 0.70	-0.25 ± 0.61

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

156

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.031 ^[37]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.38

upper limit

-0.02

Variability estimate

Standard error of the mean

Notes
[37] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

149

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.009 ^[38]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.24

Confidence interval

level

95%

sides

2-sided

lower limit

-0.42

upper limit

-0.06

Variability estimate

Standard error of the mean

Notes
[38] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Visit 8 (Week 52) in Aspartate Transaminase (AST)

Top of page

End point title

EES - Changes From Baseline to Visit 8 (Week 52) in Aspartate Transaminase (AST)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in liver enzymes.

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: U/L
arithmetic mean (standard deviation)	-1.32 ± 16.63	1.88 ± 27.76	-1.37 ± 24.74

GFT505 80mg, Placebo

Statistical analysis description

Change in aspartate transaminase (U/L)

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.711 ^[39]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

1.24

Confidence interval

level

95%

sides

2-sided

lower limit

-5.33

upper limit

7.81

Variability estimate

Standard error of the mean

Notes
[39] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Statistical analysis description

Change in aspartate transaminase (U/L)

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.78 ^[40]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.94

Confidence interval

level

95%

sides

2-sided

lower limit

-7.58

upper limit

5.7

Variability estimate

Standard error of the mean

Notes
[40] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES -Changes From Baseline to Visit 8 (Week 52) in Alanine aminotransferase (ALT)

Top of page

End point title

EES -Changes From Baseline to Visit 8 (Week 52) in Alanine aminotransferase (ALT)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in liver enzymes.

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: U/L
arithmetic mean (standard deviation)	-3.26 ± 24.67	-7.02 ± 36.21	-12.54 ± 44.72

GFT505 80mg, Placebo

Statistical analysis description

Change in alanine aminotransferase (U/L)

Comparison groups

EES (ITT)- GFT505 80mg v EES (ITT)- Placebo

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.221 ^[41]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-6.13

Confidence interval

level

95%

sides

2-sided

lower limit

-15.97

upper limit

3.71

Variability estimate

Standard error of the mean

Notes
[41] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Statistical analysis description

Change in alanine aminotransferase (U/L)

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.062 ^[42]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-9.45

Confidence interval

level

95%

sides

2-sided

lower limit

-19.4

upper limit

0.49

Variability estimate

Standard error of the mean

Notes
[42] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: CK 18-M65

Top of page

End point title

EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: CK 18-M65

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in CK 18-M65 (non-invasive markers of fibrosis and steatosis).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: U/L
arithmetic mean (standard deviation)	-45.53 ± 437.21	104.04 ± 804.96	-185.01 ± 658.14

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.095 ^[43]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

141.78

Confidence interval

level

95%

sides

2-sided

lower limit

-24.99

upper limit

308.55

Variability estimate

Standard error of the mean

Notes
[43] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.412 ^[44]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-70.57

Confidence interval

level

95%

sides

2-sided

lower limit

-239.85

upper limit

98.71

Variability estimate

Standard error of the mean

Notes
[44] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: CK18 M30

Top of page

End point title

EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: CK18 M30

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in CK18 M30 (non-invasive markers of fibrosis and steatosis).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	76	82	78
Units: pmol/L
arithmetic mean (standard deviation)	-51.39 ± 349.64	-28.08 ± 574.50	-66.40 ± 432.02

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.592 ^[45]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

32.39

Confidence interval

level

95%

sides

2-sided

lower limit

-86.63

upper limit

151.42

Variability estimate

Standard error of the mean

Notes
[45] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.61 ^[46]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

31.35

Confidence interval

level

95%

sides

2-sided

lower limit

-89.42

upper limit

152.12

Variability estimate

Standard error of the mean

Notes
[46] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Adiponectin

Top of page

End point title

EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Adiponectin

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in adiponectin (non-invasive markers of fibrosis and steatosis).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: μg/mL
arithmetic mean (standard deviation)	2.54 ± 9.48	4.98 ± 20.25	1.90 ± 8.34

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.459 ^[47]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

1.67

Confidence interval

level

95%

sides

2-sided

lower limit

-2.77

upper limit

6.11

Variability estimate

Standard error of the mean

Notes
[47] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.764 ^[48]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.67

Confidence interval

level

95%

sides

2-sided

lower limit

-5.06

upper limit

3.72

Variability estimate

Standard error of the mean

Notes
[48] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Ferritin

Top of page

End point title

EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Ferritin

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in ferritin (non-invasive markers of fibrosis and steatosis).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	76	81	77
Units: μg/L
arithmetic mean (standard deviation)	-19.26 ± 122.57	-23.52 ± 145.61	-19.68 ± 81.91

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.466 ^[49]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-12.92

Confidence interval

level

95%

sides

2-sided

lower limit

-47.79

upper limit

21.95

Variability estimate

Standard error of the mean

Notes
[49] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.745 ^[50]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-5.82

Confidence interval

level

95%

sides

2-sided

lower limit

-41.07

upper limit

29.42

Variability estimate

Standard error of the mean

Notes
[50] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: FG19

Top of page

End point title

EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: FG19

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in FG19 (non-invasive marker of fibrosis and steatosis).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: pg/mL
arithmetic mean (standard deviation)	11.64 ± 87.10	-27.25 ± 94.19	-26.03 ± 91.59

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.018 ^[51]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-26.57

Confidence interval

level

95%

sides

2-sided

lower limit

-48.59

upper limit

-4.54

Variability estimate

Standard error of the mean

Notes
[51] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[52]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-40.39

Confidence interval

level

95%

sides

2-sided

lower limit

-62.61

upper limit

-18.17

Variability estimate

Standard error of the mean

Notes
[52] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: FG21

Top of page

End point title

EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: FG21

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in FG21 (non-invasive marker of fibrosis and steatosis).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: pg/mL
arithmetic mean (standard deviation)	73.05 ± 360.41	258.74 ± 1138.36	319.68 ± 433.63

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.101 ^[53]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

190.07

Confidence interval

level

95%

sides

2-sided

lower limit

-37.38

upper limit

417.52

Variability estimate

Standard error of the mean

Notes
[53] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.052 ^[54]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

228.33

Confidence interval

level

95%

sides

2-sided

lower limit

-2.16

upper limit

458.82

Variability estimate

Standard error of the mean

Notes
[54] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Alpha2 Macroglobulin

Top of page

End point title

EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Alpha2 Macroglobulin

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in alpha2 macroglobulin (a non-invasive marker of fibrosis and steatosis).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	76	82	76
Units: g/L
arithmetic mean (standard deviation)	0.01 ± 0.28	-0.14 ± 0.29	-0.26 ± 0.36

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[55]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.14

Confidence interval

level

95%

sides

2-sided

lower limit

-0.29

upper limit

-0.01

Variability estimate

Standard error of the mean

Notes
[55] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

> 0.001 ^[56]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.24

Confidence interval

level

95%

sides

2-sided

lower limit

-0.34

upper limit

-0.15

Variability estimate

Standard error of the mean

Notes
[56] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Hyaluronic Acid

Top of page

End point title

EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Hyaluronic Acid

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in hyaluronic acid

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	76	82	78
Units: ng/mL
arithmetic mean (standard deviation)	12.49 ± 48.68	26.12 ± 230.97	12.14 ± 48.04

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.203 ^[57]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-16.54

Confidence interval

level

95%

sides

2-sided

lower limit

-42.07

upper limit

8.98

Variability estimate

Standard error of the mean

Notes
[57] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.603 ^[58]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-6.79

Confidence interval

level

95%

sides

2-sided

lower limit

-32.49

upper limit

18.9

Variability estimate

Standard error of the mean

Notes
[58] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: N-terminal Pro-peptide of Collagen Type III (PIIINP)

Top of page

End point title

EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: N-terminal Pro-peptide of Collagen Type III (PIIINP)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in N-terminal pro-peptide of collagen type III (PIIINP),

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	81	78
Units: ng/mL
arithmetic mean (standard deviation)	0.29 ± 4.87	-0.50 ± 3.43	-0.57 ± 3.75

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.235 ^[59]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.73

Confidence interval

level

95%

sides

2-sided

lower limit

-1.95

upper limit

0.48

Variability estimate

Standard error of the mean

Notes
[59] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.193 ^[60]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.81

Confidence interval

level

95%

sides

2-sided

lower limit

-2.04

upper limit

0.41

Variability estimate

Standard error of the mean

Notes
[60] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Tissue Inhibitor of Matrix Metalloprotease-1 (TIMP-1)

Top of page

End point title

EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Tissue Inhibitor of Matrix Metalloprotease-1 (TIMP-1)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in tissue inhibitor of matrix metalloprotease-1 (TIMP-1)

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	81	78
Units: ng/mL
arithmetic mean (standard deviation)	9.08 ± 49.54	15.21 ± 35.38	-6.32 ± 39.75

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.348 ^[61]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

6.21

Confidence interval

level

95%

sides

2-sided

lower limit

-6.81

upper limit

19.22

Variability estimate

Standard error of the mean

Notes
[61] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.029 ^[62]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-14.56

Confidence interval

level

95%

sides

2-sided

lower limit

-27.81

upper limit

1.51

Variability estimate

Standard error of the mean

Notes
[62] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Fibrotest

Top of page

End point title

EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Fibrotest

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in fibrotest

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	76	81	77
Units: score
arithmetic mean (standard deviation)	-0.01 ± 0.1	-0.06 ± 0.08	-0.07 ± 0.09

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- GFT505 80mg v EES (ITT)- Placebo

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[63]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.07

upper limit

-0.02

Variability estimate

Standard error of the mean

Notes
[63] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[64]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.08

upper limit

-0.02

Variability estimate

Standard error of the mean

Notes
[64] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES- Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Steatotest

Top of page

End point title

EES- Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Steatotest

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in Steatotest

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	74	81	77
Units: Score
arithmetic mean (standard deviation)	0.03 ± 0.11	-0.09 ± 0.11	-0.08 ± 0.15

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[65]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.11

Confidence interval

level

95%

sides

2-sided

lower limit

-0.15

upper limit

-0.07

Variability estimate

Standard error of the mean

Notes
[65] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

151

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[66]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.11

Confidence interval

level

95%

sides

2-sided

lower limit

-0.15

upper limit

-0.07

Variability estimate

Standard error of the mean

Notes
[66] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Angulo test

Top of page

End point title

EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Angulo test

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in angulo index

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	76	82	75
Units: score
arithmetic mean (standard deviation)	-0.01 ± 0.51	0.06 ± 0.53	-0.26 ± 0.57

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.471 ^[67]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.11

upper limit

0.23

Variability estimate

Standard error of the mean

Notes
[67] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

151

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.005 ^[68]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.25

Confidence interval

level

95%

sides

2-sided

lower limit

-0.42

upper limit

-0.08

Variability estimate

Standard error of the mean

Notes
[68] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis:Enhanced Liver Fibrosis (ELF)

Top of page

End point title

EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis:Enhanced Liver Fibrosis (ELF)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in enhanced liver fibrosis (ELF)

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	76	81	78
Units: score
arithmetic mean (standard deviation)	0.08 ± 0.70	-0.01 ± 0.54	-0.01 ± 0.64

GFT505 80mg, Placebo

Statistical analysis description

Enhanced Liver Fibrosis

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.457 ^[69]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-0.27

upper limit

0.12

Variability estimate

Standard error of the mean

Notes
[69] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Statistical analysis description

Enhanced Liver Fibrosis

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.428 ^[70]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.08

Confidence interval

level

95%

sides

2-sided

lower limit

-0.28

upper limit

0.12

Variability estimate

Standard error of the mean

Notes
[70] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Fatty Liver Index (FLI)

Top of page

End point title

EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Fatty Liver Index (FLI)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in fatty liver index (FLI)

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	76	82	77
Units: score
arithmetic mean (standard deviation)	1.34 ± 11.65	-7.94 ± 11.74	-7.81 ± 14.29

GFT505 80mg, Placebo

Statistical analysis description

Fatty Liver Index

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[71]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-9.22

Confidence interval

level

95%

sides

2-sided

lower limit

-13.19

upper limit

-5.24

Variability estimate

Standard error of the mean

Notes
[71] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Statistical analysis description

Fatty Liver Index

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[72]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-9.08

Confidence interval

level

95%

sides

2-sided

lower limit

-13.12

upper limit

-5.04

Variability estimate

Standard error of the mean

Notes
[72] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Fibrometer

Top of page

End point title

EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Fibrometer

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in Fibrometer

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	71	81	74
Units: score
arithmetic mean (standard deviation)	0.02 ± 0.22	0.04 ± 0.23	0 ± 0.20

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.531 ^[73]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.05

upper limit

0.09

Variability estimate

Standard error of the mean

Notes
[73] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

145

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.638 ^[74]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.08

upper limit

0.05

Variability estimate

Standard error of the mean

Notes
[74] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Insulin Resistance: Plasma Glucose

Top of page

End point title

EES - Changes From Baseline to Week 52 in Insulin Resistance: Plasma Glucose

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to Week 52, in plasma glucose (to assess insulin resistance).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	75	82	78
Units: mmol/L
arithmetic mean (standard deviation)	0.67 ± 1.95	0.17 ± 1.23	0.22 ± 1.70

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.077 ^[75]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.46

Confidence interval

level

95%

sides

2-sided

lower limit

-0.96

upper limit

0.05

Variability estimate

Standard error of the mean

Notes
[75] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.172 ^[76]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.36

Confidence interval

level

95%

sides

2-sided

lower limit

-0.87

upper limit

0.16

Variability estimate

Standard error of the mean

Notes
[76] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Insulin Resistance: Glycosylated Haemoglobin A1c (HbA1c)

Top of page

End point title

EES - Changes From Baseline to Week 52 in Insulin Resistance: Glycosylated Haemoglobin A1c (HbA1c)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to Week 52, in glycosylated haemoglobin A1c (HbA1c; to assess insulin resistance).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	81	77
Units: percent
arithmetic mean (standard deviation)	0.25 ± 0.69	0.22 ± 0.56	0.03 ± 0.70

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.732 ^[77]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.24

upper limit

0.17

Variability estimate

Standard error of the mean

Notes
[77] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.062 ^[78]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

0.01

Variability estimate

Standard error of the mean

Notes
[78] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Insulin Resistance: Fructosamine

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End point title

EES - Changes From Baseline to Week 52 in Insulin Resistance: Fructosamine

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to Week 52, in fructosamine (to assess insulin resistance).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: μmol/L
arithmetic mean (standard deviation)	11.29 ± 28.62	16.27 ± 27.53	-8.24 ± 28.21

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4 ^[79]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

3.66

Confidence interval

level

95%

sides

2-sided

lower limit

-4.89

upper limit

12.2

Variability estimate

Standard error of the mean

Notes
[79] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[80]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-16.22

Confidence interval

level

95%

sides

2-sided

lower limit

-24.99

upper limit

-7.44

Variability estimate

Standard error of the mean

Notes
[80] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Insulin Resistance: Leptin

Top of page

End point title

EES - Changes From Baseline to Week 52 in Insulin Resistance: Leptin

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to Week 52, in leptin (to assess insulin resistance).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: ng/mL
arithmetic mean (standard deviation)	3.01 ± 8.08	-0.21 ± 9.55	3.51 ± 10.67

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.066 ^[81]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-2.8

Confidence interval

level

95%

sides

2-sided

lower limit

-5.79

upper limit

0.18

Variability estimate

Standard error of the mean

Notes
[81] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.615 ^[82]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

0.77

Confidence interval

level

95%

sides

2-sided

lower limit

-2.24

upper limit

3.77

Variability estimate

Standard error of the mean

Notes
[82] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Insulin Resistance: Insulin

Top of page

End point title

EES - Changes From Baseline to Week 52 in Insulin Resistance: Insulin

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to Week 52, in insulin (to assess insulin resistance).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	76	82	78
Units: pmol/L
arithmetic mean (standard deviation)	8.92 ± 112.26	-33.88 ± 189.64	-26.12 ± 111.76

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.307 ^[83]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-17.4

Confidence interval

level

95%

sides

2-sided

lower limit

-50.88

upper limit

16.08

Variability estimate

Standard error of the mean

Notes
[83] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.213 ^[84]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-21.41

Confidence interval

level

95%

sides

2-sided

lower limit

-55.17

upper limit

12.34

Variability estimate

Standard error of the mean

Notes
[84] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Insulin Resistance: C Peptide

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End point title

EES - Changes From Baseline to Week 52 in Insulin Resistance: C Peptide

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to Week 52, in C peptide (to assess insulin resistance).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	76	81	77
Units: nmol/L
arithmetic mean (standard deviation)	0.12 ± 0.58	-0.17 ± 0.55	-0.03 ± 0.48

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- GFT505 80mg v EES (ITT)- Placebo

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[85]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.23

Confidence interval

level

95%

sides

2-sided

lower limit

-0.37

upper limit

-0.08

Variability estimate

Standard error of the mean

Notes
[85] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.068 ^[86]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.14

Confidence interval

level

95%

sides

2-sided

lower limit

-0.29

upper limit

0.01

Variability estimate

Standard error of the mean

Notes
[86] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Insulin Resistance: Homeostatic Model Assessment-insulin Resistance (HOMA-IR)

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End point title

EES - Changes From Baseline to Week 52 in Insulin Resistance: Homeostatic Model Assessment-insulin Resistance (HOMA-IR)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to Week 52, in homeostatic model assessment-insulin resistance (HOMA-IR; to assess insulin resistance).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	76	81	78
Units: total HOMA IR
arithmetic mean (standard deviation)	1.01 ± 4.96	-1.10 ± 10.76	-1 ± 6.86

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.448 ^[87]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.86

upper limit

1.27

Variability estimate

Standard error of the mean

Notes
[87] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.267 ^[88]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-1.17

Confidence interval

level

95%

sides

2-sided

lower limit

-3.25

upper limit

0.9

Variability estimate

Standard error of the mean

Notes
[88] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Insulin Resistance: Free Fatty Acids (FFA)

Top of page

End point title

EES - Changes From Baseline to Week 52 in Insulin Resistance: Free Fatty Acids (FFA)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to Week 52, in free fatty acids (FFA; to assess insulin resistance).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	76	78	78
Units: mmol/L
arithmetic mean (standard deviation)	0.05 ± 0.26	-0.04 ± 0.25	-0.04 ± 0.24

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.095 ^[89]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.11

upper limit

0.01

Variability estimate

Standard error of the mean

Notes
[89] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.022 ^[90]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-0.13

upper limit

-0.01

Variability estimate

Standard error of the mean

Notes
[90] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Inflammatory Markers: Fibrinogen

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End point title

EES - Changes From Baseline to Week 52 in Inflammatory Markers: Fibrinogen

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to Week 52, in fibrinogen (inflammatory markers).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	75	82	76
Units: g/L
arithmetic mean (standard deviation)	-0.05 ± 0.66	-0.37 ± 0.70	-0.37 ± 0.79

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- GFT505 80mg v EES (ITT)- Placebo

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[91]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.36

Confidence interval

level

95%

sides

2-sided

lower limit

-0.54

upper limit

-0.17

Variability estimate

Standard error of the mean

Notes
[91] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

151

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.005 ^[92]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.27

Confidence interval

level

95%

sides

2-sided

lower limit

-0.46

upper limit

-0.08

Variability estimate

Standard error of the mean

Notes
[92] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES -Changes From Baseline to Week 52 in Inflammatory Markers: Haptoglobin

Top of page

End point title

EES -Changes From Baseline to Week 52 in Inflammatory Markers: Haptoglobin

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to Week 52, in haptoglobin (inflammatory markers).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	76	81	77
Units: g/L
arithmetic mean (standard deviation)	0.09 ± 0.35	-0.19 ± 0.32	-0.20 ± 0.40

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[93]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.25

Confidence interval

level

95%

sides

2-sided

lower limit

-0.35

upper limit

-0.15

Variability estimate

Standard error of the mean

Notes
[93] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[94]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.27

Confidence interval

level

95%

sides

2-sided

lower limit

-0.37

upper limit

-0.17

Variability estimate

Standard error of the mean

Notes
[94] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Inflammatory Markers: Tumour Necrosis Factor Alpha

Top of page

End point title

EES - Changes From Baseline to Week 52 in Inflammatory Markers: Tumour Necrosis Factor Alpha

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to Week 52, in tumour necrosis factor alpha (inflammatory markers).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	81	78
Units: pg/mL
arithmetic mean (standard deviation)	0.19 ± 10.46	1.37 ± 6.14	-2.45 ± 38.58

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.742 ^[95]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

0.57

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

4.06

Variability estimate

Standard error of the mean

Notes
[95] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.107 ^[96]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

2.9

Confidence interval

level

95%

sides

2-sided

lower limit

-0.63

upper limit

6.43

Variability estimate

Standard error of the mean

Notes
[96] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Inflammatory Markers: interleukine 6

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End point title

EES - Changes From Baseline to Week 52 in Inflammatory Markers: interleukine 6

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to Week 52, in interleukine 6 (inflammatory markers).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	76	82	78
Units: pg/mL
arithmetic mean (standard deviation)	-0.06 ± 1.37	0.37 ± 4.20	-1.14 ± 10.33

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.362 ^[97]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.58

upper limit

1.59

Variability estimate

Standard error of the mean

Notes
[97] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.894 ^[98]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-1.03

upper limit

1.18

Variability estimate

Standard error of the mean

Notes
[98] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Inflammatory Markers: Plasminogen Activator Inhibitor 1 (PAI-1)

Top of page

End point title

EES - Changes From Baseline to Week 52 in Inflammatory Markers: Plasminogen Activator Inhibitor 1 (PAI-1)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to Week 52, in plasminogen activator inhibitor 1 (PAI-1; inflammatory marker).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	66	68	77
Units: ng/mL
arithmetic mean (standard deviation)	-0.14 ± 4.74	-0.51 ± 3.51	0.21 ± 4.28

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

134

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.229 ^[99]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.76

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

0.48

Variability estimate

Standard error of the mean

Notes
[99] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

143

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.463 ^[100]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.45

Confidence interval

level

95%

sides

2-sided

lower limit

-1.67

upper limit

0.76

Variability estimate

Standard error of the mean

Notes
[100] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Inflammatory Markers: C-Reactive Protein (CRP)

Top of page

End point title

EES - Changes From Baseline to Week 52 in Inflammatory Markers: C-Reactive Protein (CRP)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to Week 52, in C-Reactive Protein (CRP; inflammatory marker).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: log (mg/L)
arithmetic mean (standard deviation)	0.20 ± 0.74	-0.04 ± 0.72	-0.05 ± 0.81

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- GFT505 80mg v EES (ITT)- Placebo

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.065 ^[101]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.21

Confidence interval

level

95%

sides

2-sided

lower limit

-0.42

upper limit

0.01

Variability estimate

Standard error of the mean

Notes
[101] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.098 ^[102]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-0.41

upper limit

0.03

Variability estimate

Standard error of the mean

Notes
[102] - Baseline parameter value and presence of diabetes as random factors

Secondary: Safety population - Changes From Baseline to Week 52 in Safety Markers: N-terminal Prohormone of Brain Natriuretic Peptide (NTproBNP; Cardiac Function Parameter)

Top of page

End point title

Safety population - Changes From Baseline to Week 52 in Safety Markers: N-terminal Prohormone of Brain Natriuretic Peptide (NTproBNP; Cardiac Function Parameter)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to week 52, in N-terminal prohormone of brain natriuretic peptide (NT-proBNP; safety marker; cardiac function parameter).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	Placebo	GFT505 120mg	GFT505 80mg
Number of subjects analysed	89	87	93
Units: pmol/L
arithmetic mean (standard deviation)	-1.24 ± 5.35	0.38 ± 4.81	1.54 ± 4.16

GFT505 80mg, Placebo

Comparison groups

Placebo v GFT505 80mg

Number of subjects included in analysis

182

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[103]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

2.41

Confidence interval

level

95%

sides

2-sided

lower limit

1.1

upper limit

3.72

Variability estimate

Standard error of the mean

Notes
[103] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

Placebo v GFT505 120mg

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.019 ^[104]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

1.59

Confidence interval

level

95%

sides

2-sided

lower limit

0.26

upper limit

2.91

Variability estimate

Standard error of the mean

Notes
[104] - Baseline parameter value and presence of diabetes as random factors

Secondary: Safety population - Changes From Baseline to Week 52 in Safety Markers: Troponin T (Cardiac Function Parameter)

Top of page

End point title

Safety population - Changes From Baseline to Week 52 in Safety Markers: Troponin T (Cardiac Function Parameter)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to week 52, in troponin T (safety marker; cardiac function parameter).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	Placebo	GFT505 120mg	GFT505 80mg
Number of subjects analysed	89	87	92
Units: μg/L
arithmetic mean (standard deviation)	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00

GFT505 80mg, Placebo

Comparison groups

Placebo v GFT505 80mg

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.447 ^[105]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Variability estimate

Standard error of the mean

Notes
[105] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

Placebo v GFT505 120mg

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.758 ^[106]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Variability estimate

Standard error of the mean

Notes
[106] - Baseline parameter value and presence of diabetes as random factors

Secondary: Safety population -Changes From Baseline to Week 52 in Safety Markers: Creatinine (Renal Function Parameter)

Top of page

End point title

Safety population -Changes From Baseline to Week 52 in Safety Markers: Creatinine (Renal Function Parameter)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to week 52, in creatinine (safety markers; renal function parameter).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	Placebo	GFT505 120mg	GFT505 80mg
Number of subjects analysed	92	89	93
Units: μmol/L
arithmetic mean (standard deviation)	1.27 ± 7.85	5.61 ± 8.18	2.03 ± 7.89

GFT505 80mg, Placebo

Comparison groups

Placebo v GFT505 80mg

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.553 ^[107]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.61

upper limit

3.01

Variability estimate

Standard error of the mean

Notes
[107] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

Placebo v GFT505 120mg

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[108]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

4.31

Confidence interval

level

95%

sides

2-sided

lower limit

1.97

upper limit

6.64

Variability estimate

Standard error of the mean

Notes
[108] - Baseline parameter value and presence of diabetes as random factors

Secondary: Safety population - Changes From Baseline to Week 52 in Safety Markers: Creatinine Clearance (Renal Function Parameter)

Top of page

End point title

Safety population - Changes From Baseline to Week 52 in Safety Markers: Creatinine Clearance (Renal Function Parameter)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to week 52, in creatinine clearance (safety marker; renal function parameter).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	Placebo	GFT505 120mg	GFT505 80mg
Number of subjects analysed	92	89	93
Units: mL/min
arithmetic mean (standard deviation)	-0.09 ± 0.62	-0.56 ± 2.22	-0.06 ± 0.94

GFT505 80mg, Placebo

Comparison groups

Placebo v GFT505 80mg

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.861 ^[109]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.37

upper limit

0.44

Variability estimate

Standard error of the mean

Notes
[109] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

Placebo v GFT505 120mg

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.052 ^[110]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.81

upper limit

Variability estimate

Standard error of the mean

Notes
[110] - Baseline parameter value and presence of diabetes as random factors

Secondary: Safety population - Changes From Baseline to Week 52 in Safety Markers: Uric Acid (Renal Function Parameter)

Top of page

End point title

Safety population - Changes From Baseline to Week 52 in Safety Markers: Uric Acid (Renal Function Parameter)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to week 52, in uric acid (safety marker; renal function parameter).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	Placebo	GFT505 120mg	GFT505 80mg
Number of subjects analysed	92	89	93
Units: mmol/L
arithmetic mean (standard deviation)	-0.01 ± 0.06	0.01 ± 0.05	0 ± 0.06

GFT505 80mg, Placebo

Comparison groups

Placebo v GFT505 80mg

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.473 ^[111]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.01

upper limit

0.02

Variability estimate

Standard error of the mean

Notes
[111] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

Placebo v GFT505 120mg

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.124 ^[112]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

0.01

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

0.03

Variability estimate

Standard error of the mean

Notes
[112] - Baseline parameter value and presence of diabetes as random factors

Secondary: Safety population - Changes From Baseline to Week 52 in Safety Markers: Blood Urea Nitrogen (BUN; Renal Function Parameter)

Top of page

End point title

Safety population - Changes From Baseline to Week 52 in Safety Markers: Blood Urea Nitrogen (BUN; Renal Function Parameter)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to week 52, in blood urea nitrogen (BUN; safety marker; renal function parameter).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	Placebo	GFT505 120mg	GFT505 80mg
Number of subjects analysed	92	89	93
Units: mmol urea/L
arithmetic mean (standard deviation)	-0.17 ± 1.14	0.67 ± 1.22	0.61 ± 1.28

GFT505 80mg, Placebo

Comparison groups

Placebo v GFT505 80mg

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[113]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.47

upper limit

1.15

Variability estimate

Standard error of the mean

Notes
[113] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

Placebo v GFT505 120mg

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[114]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

1.19

Variability estimate

Standard error of the mean

Notes
[114] - Baseline parameter value and presence of diabetes as random factors

Secondary: Safety population -Changes From Baseline to Week 52 in Safety Markers: Cystatin C (Renal Function Parameter)

Top of page

End point title

Safety population -Changes From Baseline to Week 52 in Safety Markers: Cystatin C (Renal Function Parameter)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to week 52, in cystatin C (safety marker; renal function parameter).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	Placebo	GFT505 120mg	GFT505 80mg
Number of subjects analysed	89	87	93
Units: mg/L
arithmetic mean (standard deviation)	0.04 ± 0.13	0.04 ± 0.22	0.05 ± 0.10

GFT505 80mg, Placebo

Comparison groups

GFT505 80mg v Placebo

Number of subjects included in analysis

182

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.842 ^[115]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.04

upper limit

0.04

Variability estimate

Standard error of the mean

Notes
[115] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

Placebo v GFT505 120mg

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.589 ^[116]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.03

upper limit

0.05

Variability estimate

Standard error of the mean

Notes
[116] - Baseline parameter value and presence of diabetes as random factors

Secondary: Safety population -Changes From Baseline to Week 52 in Safety Markers: Beta2-microglobulin (Renal Function Parameter)

Top of page

End point title

Safety population -Changes From Baseline to Week 52 in Safety Markers: Beta2-microglobulin (Renal Function Parameter)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to week 52, in beta2-microglobulin (safety marker; renal function parameter).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	Placebo	GFT505 120mg	GFT505 80mg
Number of subjects analysed	89	87	93
Units: μg/L
arithmetic mean (standard deviation)	-83.48 ± 279.31	0.11 ± 466.43	-22.26 ± 326.42

GFT505 80mg, Placebo

Comparison groups

Placebo v GFT505 80mg

Number of subjects included in analysis

182

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.325 ^[117]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

48.93

Confidence interval

level

95%

sides

2-sided

lower limit

-8.73

upper limit

146.6

Variability estimate

Standard error of the mean

Notes
[117] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

Placebo v GFT505 120mg

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.066 ^[118]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

93.21

Confidence interval

level

95%

sides

2-sided

lower limit

-6.06

upper limit

192.49

Variability estimate

Standard error of the mean

Notes
[118] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES -Changes From Baseline to Week 52 in Body Weight

Top of page

End point title

EES -Changes From Baseline to Week 52 in Body Weight

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to Week 52, in body weight.

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: kilogram(s)
arithmetic mean (standard deviation)	-0.04 ± 3.4	0.11 ± 3.61	-0.69 ± 4.09

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.942 ^[119]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-1.12

upper limit

1.04

Variability estimate

Standard error of the mean

Notes
[119] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.304 ^[120]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

0.57

Confidence interval

level

95%

sides

2-sided

lower limit

-0.52

upper limit

1.66

Variability estimate

Standard error of the mean

Notes
[120] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Outcomes Related to Biochemistry: Apo A1

Top of page

End point title

EES - Changes From Baseline to Week 52 in Outcomes Related to Biochemistry: Apo A1

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in secondary outcomes related to biochemistry

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: mg/dL
arithmetic mean (standard deviation)	-3.90 ± 16.53	1.63 ± 15.59	2.85 ± 20.42

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.038 ^[121]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

5.73

Confidence interval

level

95%

sides

2-sided

lower limit

0.31

upper limit

11.14

Variability estimate

Standard error of the mean

Notes
[121] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.012 ^[122]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

7.07

Confidence interval

level

95%

sides

2-sided

lower limit

1.59

upper limit

12.55

Variability estimate

Standard error of the mean

Notes
[122] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Outcomes Related to Biochemistry: Apo B

Top of page

End point title

EES - Changes From Baseline to Week 52 in Outcomes Related to Biochemistry: Apo B

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in secondary outcomes related to biochemistry

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: mg/dL
arithmetic mean (standard deviation)	0.94 ± 14.29	-12.80 ± 20.87	-8.42 ± 16.03

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[123]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-12.41

Confidence interval

level

95%

sides

2-sided

lower limit

-17.56

upper limit

-7.25

Variability estimate

Standard error of the mean

Notes
[123] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[124]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-9.61

Confidence interval

level

95%

sides

2-sided

lower limit

-14.81

upper limit

-4.41

Variability estimate

Standard error of the mean

Notes
[124] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Outcomes Related to Biochemistry: Apo AII

Top of page

End point title

EES - Changes From Baseline to Week 52 in Outcomes Related to Biochemistry: Apo AII

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in secondary outcomes related to biochemistry

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	60	66	65
Units: mg/dL
arithmetic mean (standard deviation)	-3.36 ± 4.82	-0.15 ± 6.63	4.25 ± 4.36

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[125]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

3.55

Confidence interval

level

95%

sides

2-sided

lower limit

2.14

upper limit

4.96

Variability estimate

Standard error of the mean

Notes
[125] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

125

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[126]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

6.1

Confidence interval

level

95%

sides

2-sided

lower limit

4.67

upper limit

7.53

Variability estimate

Standard error of the mean

Notes
[126] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Outcomes Related to Biochemistry: Apo CIII

Top of page

End point title

EES - Changes From Baseline to Week 52 in Outcomes Related to Biochemistry: Apo CIII

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in secondary outcomes related to biochemistry

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	60	66	65
Units: mg/dL
arithmetic mean (standard deviation)	0.77 ± 4.30	-1.79 ± 3.91	-0.69 ± 3.42

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[127]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-2.27

Confidence interval

level

95%

sides

2-sided

lower limit

-3.29

upper limit

-1.25

Variability estimate

Standard error of the mean

Notes
[127] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

125

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004 ^[128]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-1.5

Confidence interval

level

95%

sides

2-sided

lower limit

-2.52

upper limit

-0.49

Variability estimate

Standard error of the mean

Notes
[128] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES -Changes From Baseline to Week 52 in Outcomes Related to Biochemistry: Apo CIII/B

Top of page

End point title

EES -Changes From Baseline to Week 52 in Outcomes Related to Biochemistry: Apo CIII/B

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in secondary outcomes related to biochemistry

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	60	66	65
Units: mg/dL
arithmetic mean (standard deviation)	0.53 ± 3.05	-1.44 ± 2.98	-0.65 ± 2.98

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[129]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-1.78

Confidence interval

level

95%

sides

2-sided

lower limit

-2.63

upper limit

-0.92

Variability estimate

Standard error of the mean

Notes
[129] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

125

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.009 ^[130]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-1.15

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-0.29

Variability estimate

Standard error of the mean

Notes
[130] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Outcomes Related to Biochemistry: Apo CIII/nonB

Top of page

End point title

EES - Changes From Baseline to Week 52 in Outcomes Related to Biochemistry: Apo CIII/nonB

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in secondary outcomes related to biochemistry

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	60	66	65
Units: mg/dL
arithmetic mean (standard deviation)	0.24 ± 2.53	-0.35 ± 1.79	-0.04 ± 0.76

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[131]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.46

Confidence interval

level

95%

sides

2-sided

lower limit

-0.75

upper limit

0.17

Variability estimate

Standard error of the mean

Notes
[131] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

125

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.008 ^[132]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.39

Confidence interval

level

95%

sides

2-sided

lower limit

-0.68

upper limit

-0.1

Variability estimate

Standard error of the mean

Notes
[132] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Outcomes Related to Biochemistry Small dense Low Density Lipoproteins

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End point title

EES - Changes From Baseline to Week 52 in Outcomes Related to Biochemistry Small dense Low Density Lipoproteins

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in secondary outcomes related to biochemistry

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	69	71	69
Units: mg/dL
arithmetic mean (standard deviation)	0.60 ± 7.52	-2.09 ± 11.02	-2.62 ± 6.08

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.069 ^[133]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-2.35

Confidence interval

level

95%

sides

2-sided

lower limit

-4.89

upper limit

0.19

Variability estimate

Standard error of the mean

Notes
[133] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

138

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.01 ^[134]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-3.39

Confidence interval

level

95%

sides

2-sided

lower limit

-5.95

upper limit

-0.84

Variability estimate

Standard error of the mean

Notes
[134] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Outcomes Related to Biochemistry: Lp(a)

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End point title

EES - Changes From Baseline to Week 52 in Outcomes Related to Biochemistry: Lp(a)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in secondary outcomes related to biochemistry

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	60	66	65
Units: mg/dL
arithmetic mean (standard deviation)	0.80 ± 4.46	-0.57 ± 12.24	-0.91 ± 13.75

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.549 ^[135]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

-1.93

upper limit

3.61

Variability estimate

Standard error of the mean

Notes
[135] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

125

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.728 ^[136]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

0.49

Confidence interval

level

95%

sides

2-sided

lower limit

-2.28

upper limit

3.26

Variability estimate

Standard error of the mean

Notes
[136] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Outcomes Related to Biochemistry Apo E

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End point title

EES - Changes From Baseline to Week 52 in Outcomes Related to Biochemistry Apo E

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in secondary outcomes related to biochemistry

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	60	66	65
Units: mg/dL
arithmetic mean (standard deviation)	-0.29 ± 3.67	-1.72 ± 2.75	-1.38 ± 2.99

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- GFT505 80mg v EES (ITT)- Placebo

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[137]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-1.38

Confidence interval

level

95%

sides

2-sided

lower limit

-2.14

upper limit

-0.61

Variability estimate

Standard error of the mean

Notes
[137] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

125

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004 ^[138]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-1.12

Confidence interval

level

95%

sides

2-sided

lower limit

-1.89

upper limit

-0.36

Variability estimate

Standard error of the mean

Notes
[138] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Outcomes Related to Biochemistry: Apo E/B

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End point title

EES - Changes From Baseline to Week 52 in Outcomes Related to Biochemistry: Apo E/B

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in secondary outcomes related to biochemistry

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	60	66	65
Units: mg/dL
arithmetic mean (standard deviation)	-0.21 ± 2.59	-1.43 ± 2.43	-1.48 ± 2.64

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[139]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-1.18

Confidence interval

level

95%

sides

2-sided

lower limit

-1.82

upper limit

-0.53

Variability estimate

Standard error of the mean

Notes
[139] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

125

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[140]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-1.08

Confidence interval

level

95%

sides

2-sided

lower limit

-1.72

upper limit

-0.43

Variability estimate

Standard error of the mean

Notes
[140] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Prothrombin Ratio

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End point title

EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Prothrombin Ratio

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in prothrombin ratio (non-invasive marker of fibrosis and steatosis).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	75	82	76
Units: Ratio
arithmetic mean (standard deviation)	0.51 ± 14.28	-3.85 ± 11.57	1.29 ± 10.03

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.075 ^[141]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-2.83

Confidence interval

level

95%

sides

2-sided

lower limit

-5.95

upper limit

0.29

Variability estimate

Standard error of the mean

Notes
[141] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

151

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.491 ^[142]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-1.11

Confidence interval

level

95%

sides

2-sided

lower limit

-4.29

upper limit

2.07

Variability estimate

Standard error of the mean

Notes
[142] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: total bilirubin

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End point title

EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: total bilirubin

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in total bilirubin (non-invasive markers of fibrosis and steatosis).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: μmol/L
arithmetic mean (standard deviation)	-1.46 ± 3.77	-1.53 ± 3.66	-1.38 ± 4.85

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.831 ^[143]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.14

Confidence interval

level

95%

sides

2-sided

lower limit

-1.39

upper limit

1.12

Variability estimate

Standard error of the mean

Notes
[143] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.754 ^[144]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.07

upper limit

1.47

Variability estimate

Standard error of the mean

Notes
[144] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES -Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: conjugated bilirubin

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End point title

EES -Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: conjugated bilirubin

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in conjugated bilirubin (non-invasive markers of fibrosis and steatosis).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	77	82	78
Units: μmol/L
arithmetic mean (standard deviation)	-0.26 ± 1.05	-0.35 ± 1.26	-0.15 ± 1.24

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.848 ^[145]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.36

upper limit

0.3

Variability estimate

Standard error of the mean

Notes
[145] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.511 ^[146]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

0.11

Confidence interval

level

95%

sides

2-sided

lower limit

-0.22

upper limit

0.45

Variability estimate

Standard error of the mean

Notes
[146] - Baseline parameter value and presence of diabetes as random factors

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: International Normalized Ratio (INR)

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End point title

EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: International Normalized Ratio (INR)

End point description

To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in international normalized ratio (INR; non-invasive marker of fibrosis and steatosis).

End point type

Secondary

End point timeframe

Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

End point values	EES (ITT)- Placebo	EES (ITT)- GFT505 80mg	EES (ITT)- GFT505 120mg
Number of subjects analysed	75	82	76
Units: INR
arithmetic mean (standard deviation)	0.03 ± 0.39	0.03 ± 0.09	-0.01 ± 0.08

GFT505 80mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 80mg

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.393 ^[147]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

0.04

Variability estimate

Standard error of the mean

Notes
[147] - Baseline parameter value and presence of diabetes as random factors

GFT505 120mg, Placebo

Comparison groups

EES (ITT)- Placebo v EES (ITT)- GFT505 120mg

Number of subjects included in analysis

151

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.289 ^[148]

Method

Mixed models analysis

Parameter type

difference in least square mean change

Point estimate

-0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.11

upper limit

0.03

Variability estimate

Standard error of the mean

Notes
[148] - Baseline parameter value and presence of diabetes as random factors

Adverse events

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Timeframe for reporting adverse events

Adverse event information was collected at every study visit from screening up to the termination of the study corresponding to 64 weeks.

Adverse event reporting additional description

The investigator established whether or not any AE had occurred at each visit (from the date of consent to the last visit). The participant was questioned in a general manner to determine specific symptoms without offering the patient any suggestion. Serious AE reporting began from signature of the participant ICF and ended at the last study visit.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.1

Reporting group title

GFT505 80mg Safety Population

Reporting group description

Reporting group title

GFT505 120mg Safety Population

Reporting group description

Reporting group title

Placebo Safety Population

Reporting group description

Serious adverse events	GFT505 80mg Safety Population	GFT505 120mg Safety Population	Placebo Safety Population
Total subjects affected by serious adverse events
subjects affected / exposed	12 / 93 (12.90%)	14 / 89 (15.73%)	9 / 92 (9.78%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer
subjects affected / exposed	1 / 93 (1.08%)	0 / 89 (0.00%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Oesophageal adenocarcinoma
subjects affected / exposed	0 / 93 (0.00%)	0 / 89 (0.00%)	1 / 92 (1.09%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Parathyroid tumour benign
subjects affected / exposed	0 / 93 (0.00%)	1 / 89 (1.12%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal cancer
subjects affected / exposed	0 / 93 (0.00%)	0 / 89 (0.00%)	1 / 92 (1.09%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Breast cancer
subjects affected / exposed	0 / 93 (0.00%)	0 / 89 (0.00%)	1 / 92 (1.09%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bladder transitional cell carcinoma
subjects affected / exposed	0 / 93 (0.00%)	0 / 89 (0.00%)	1 / 92 (1.09%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Sinus operation
subjects affected / exposed	0 / 93 (0.00%)	0 / 89 (0.00%)	1 / 92 (1.09%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thyroidectomy
subjects affected / exposed	0 / 93 (0.00%)	0 / 89 (0.00%)	1 / 92 (1.09%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
subjects affected / exposed	1 / 93 (1.08%)	0 / 89 (0.00%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	1 / 93 (1.08%)	0 / 89 (0.00%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Device breakage
subjects affected / exposed	1 / 93 (1.08%)	0 / 89 (0.00%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Non-cardiac chest pain
subjects affected / exposed	0 / 93 (0.00%)	1 / 89 (1.12%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Benign prostatic hyperplasia
subjects affected / exposed	1 / 93 (1.08%)	0 / 89 (0.00%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
subjects affected / exposed	1 / 93 (1.08%)	0 / 89 (0.00%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Anxiety
subjects affected / exposed	1 / 93 (1.08%)	0 / 89 (0.00%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Depression suicidal
subjects affected / exposed	0 / 93 (0.00%)	1 / 89 (1.12%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychotic disorder
subjects affected / exposed	1 / 93 (1.08%)	0 / 89 (0.00%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
Blood creatinine increased
subjects affected / exposed	1 / 93 (1.08%)	0 / 89 (0.00%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Ankle fracture
subjects affected / exposed	0 / 93 (0.00%)	1 / 89 (1.12%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Overdose
subjects affected / exposed	0 / 93 (0.00%)	1 / 89 (1.12%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Radius fracture
subjects affected / exposed	0 / 93 (0.00%)	0 / 89 (0.00%)	1 / 92 (1.09%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatic haematoma
subjects affected / exposed	1 / 93 (1.08%)	0 / 89 (0.00%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Pericarditis
subjects affected / exposed	0 / 93 (0.00%)	0 / 89 (0.00%)	1 / 92 (1.09%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Ataxia
subjects affected / exposed	1 / 93 (1.08%)	0 / 89 (0.00%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Muscle contractions involuntary
subjects affected / exposed	1 / 93 (1.08%)	0 / 89 (0.00%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Parkinson's disease
subjects affected / exposed	0 / 93 (0.00%)	1 / 89 (1.12%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tremor
subjects affected / exposed	1 / 93 (1.08%)	0 / 89 (0.00%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	0 / 93 (0.00%)	1 / 89 (1.12%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 93 (1.08%)	0 / 89 (0.00%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	0 / 93 (0.00%)	2 / 89 (2.25%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Bladder diverticulum
subjects affected / exposed	1 / 93 (1.08%)	0 / 89 (0.00%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nephrolithiasis
subjects affected / exposed	0 / 93 (0.00%)	1 / 89 (1.12%)	1 / 92 (1.09%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
subjects affected / exposed	1 / 93 (1.08%)	0 / 89 (0.00%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lumbar spinal stenosis
subjects affected / exposed	0 / 93 (0.00%)	1 / 89 (1.12%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	1 / 93 (1.08%)	0 / 89 (0.00%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Clostridium difficile infection
subjects affected / exposed	0 / 93 (0.00%)	0 / 89 (0.00%)	1 / 92 (1.09%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Device related infection
subjects affected / exposed	1 / 93 (1.08%)	0 / 89 (0.00%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 93 (0.00%)	1 / 89 (1.12%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 93 (0.00%)	1 / 89 (1.12%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Diabetes mellitus
subjects affected / exposed	0 / 93 (0.00%)	1 / 89 (1.12%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diabetic ketoacidosis
subjects affected / exposed	0 / 93 (0.00%)	1 / 89 (1.12%)	0 / 92 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 4%

Non-serious adverse events	GFT505 80mg Safety Population	GFT505 120mg Safety Population	Placebo Safety Population
Total subjects affected by non serious adverse events
subjects affected / exposed	85 / 93 (91.40%)	86 / 89 (96.63%)	85 / 92 (92.39%)
Vascular disorders
Hypertension
subjects affected / exposed	5 / 93 (5.38%)	7 / 89 (7.87%)	4 / 92 (4.35%)
occurrences all number	5	7	4
General disorders and administration site conditions
Asthenia
subjects affected / exposed	7 / 93 (7.53%)	0 / 89 (0.00%)	5 / 92 (5.43%)
occurrences all number	10	0	6
Chest pain
subjects affected / exposed	4 / 93 (4.30%)	7 / 89 (7.87%)	3 / 92 (3.26%)
occurrences all number	5	7	3
Fatigue
subjects affected / exposed	13 / 93 (13.98%)	12 / 89 (13.48%)	14 / 92 (15.22%)
occurrences all number	15	14	16
Influenza like illness
subjects affected / exposed	1 / 93 (1.08%)	4 / 89 (4.49%)	1 / 92 (1.09%)
occurrences all number	1	4	1
Reproductive system and breast disorders
Benign prostatic hyperplasia
subjects affected / exposed	4 / 93 (4.30%)	0 / 89 (0.00%)	1 / 92 (1.09%)
occurrences all number	4	0	1
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	2 / 93 (2.15%)	6 / 89 (6.74%)	5 / 92 (5.43%)
occurrences all number	2	6	5
Psychiatric disorders
Anxiety
subjects affected / exposed	6 / 93 (6.45%)	4 / 89 (4.49%)	1 / 92 (1.09%)
occurrences all number	7	4	1
Insomnia
subjects affected / exposed	5 / 93 (5.38%)	5 / 89 (5.62%)	1 / 92 (1.09%)
occurrences all number	5	5	1
Sleep disorder
subjects affected / exposed	5 / 93 (5.38%)	2 / 89 (2.25%)	4 / 92 (4.35%)
occurrences all number	5	2	4
Investigations
Blood creatine phosphokinase increased
subjects affected / exposed	4 / 93 (4.30%)	7 / 89 (7.87%)	2 / 92 (2.17%)
occurrences all number	6	7	2
Blood creatinine increased
subjects affected / exposed	1 / 93 (1.08%)	4 / 89 (4.49%)	0 / 92 (0.00%)
occurrences all number	1	4	0
Glycosylated haemoglobin increased
subjects affected / exposed	1 / 93 (1.08%)	4 / 89 (4.49%)	2 / 92 (2.17%)
occurrences all number	1	4	2
Hepatic enzyme increased
subjects affected / exposed	4 / 93 (4.30%)	3 / 89 (3.37%)	3 / 92 (3.26%)
occurrences all number	4	3	3
Injury, poisoning and procedural complications
Procedural pain
subjects affected / exposed	6 / 93 (6.45%)	11 / 89 (12.36%)	10 / 92 (10.87%)
occurrences all number	6	11	11
Nervous system disorders
Dizziness
subjects affected / exposed	10 / 93 (10.75%)	6 / 89 (6.74%)	9 / 92 (9.78%)
occurrences all number	12	6	9
Headache
subjects affected / exposed	16 / 93 (17.20%)	12 / 89 (13.48%)	15 / 92 (16.30%)
occurrences all number	23	14	17
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	9 / 93 (9.68%)	11 / 89 (12.36%)	11 / 92 (11.96%)
occurrences all number	11	12	12
Abdominal pain upper
subjects affected / exposed	12 / 93 (12.90%)	9 / 89 (10.11%)	13 / 92 (14.13%)
occurrences all number	14	11	15
Constipation
subjects affected / exposed	7 / 93 (7.53%)	5 / 89 (5.62%)	5 / 92 (5.43%)
occurrences all number	8	5	5
Diarrhoea
subjects affected / exposed	14 / 93 (15.05%)	9 / 89 (10.11%)	6 / 92 (6.52%)
occurrences all number	17	9	6
Dyspepsia
subjects affected / exposed	0 / 93 (0.00%)	4 / 89 (4.49%)	4 / 92 (4.35%)
occurrences all number	0	4	4
Flatulence
subjects affected / exposed	2 / 93 (2.15%)	1 / 89 (1.12%)	4 / 92 (4.35%)
occurrences all number	2	1	4
Gastrooesophageal reflux disease
subjects affected / exposed	2 / 93 (2.15%)	2 / 89 (2.25%)	7 / 92 (7.61%)
occurrences all number	3	2	7
Nausea
subjects affected / exposed	18 / 93 (19.35%)	17 / 89 (19.10%)	14 / 92 (15.22%)
occurrences all number	23	20	16
Vomiting
subjects affected / exposed	7 / 93 (7.53%)	8 / 89 (8.99%)	9 / 92 (9.78%)
occurrences all number	8	9	12
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	1 / 93 (1.08%)	2 / 89 (2.25%)	4 / 92 (4.35%)
occurrences all number	1	2	4
Hyperhidrosis
subjects affected / exposed	3 / 93 (3.23%)	4 / 89 (4.49%)	2 / 92 (2.17%)
occurrences all number	3	4	2
Pruritus
subjects affected / exposed	3 / 93 (3.23%)	2 / 89 (2.25%)	4 / 92 (4.35%)
occurrences all number	4	2	4
Rash
subjects affected / exposed	6 / 93 (6.45%)	6 / 89 (6.74%)	4 / 92 (4.35%)
occurrences all number	8	6	4
Renal and urinary disorders
Glycosuria
subjects affected / exposed	1 / 93 (1.08%)	6 / 89 (6.74%)	3 / 92 (3.26%)
occurrences all number	1	6	3
Leukocyturia
subjects affected / exposed	10 / 93 (10.75%)	8 / 89 (8.99%)	12 / 92 (13.04%)
occurrences all number	12	9	17
Proteinuria
subjects affected / exposed	1 / 93 (1.08%)	2 / 89 (2.25%)	6 / 92 (6.52%)
occurrences all number	1	2	6
Renal failure
subjects affected / exposed	1 / 93 (1.08%)	4 / 89 (4.49%)	0 / 92 (0.00%)
occurrences all number	1	5	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	7 / 93 (7.53%)	9 / 89 (10.11%)	6 / 92 (6.52%)
occurrences all number	7	10	9
Back pain
subjects affected / exposed	7 / 93 (7.53%)	9 / 89 (10.11%)	8 / 92 (8.70%)
occurrences all number	9	9	9
Intervertebral disc protrusion
subjects affected / exposed	4 / 93 (4.30%)	0 / 89 (0.00%)	0 / 92 (0.00%)
occurrences all number	4	0	0
Muscle spasms
subjects affected / exposed	2 / 93 (2.15%)	3 / 89 (3.37%)	6 / 92 (6.52%)
occurrences all number	2	3	7
Myalgia
subjects affected / exposed	9 / 93 (9.68%)	3 / 89 (3.37%)	3 / 92 (3.26%)
occurrences all number	9	5	3
Infections and infestations
Bronchitis
subjects affected / exposed	10 / 93 (10.75%)	6 / 89 (6.74%)	8 / 92 (8.70%)
occurrences all number	11	6	8
Influenza
subjects affected / exposed	10 / 93 (10.75%)	3 / 89 (3.37%)	5 / 92 (5.43%)
occurrences all number	12	3	6
Gastroenteritis
subjects affected / exposed	4 / 93 (4.30%)	2 / 89 (2.25%)	0 / 92 (0.00%)
occurrences all number	4	3	0
Nasopharyngitis
subjects affected / exposed	9 / 93 (9.68%)	5 / 89 (5.62%)	5 / 92 (5.43%)
occurrences all number	13	6	5
Sinusitis
subjects affected / exposed	5 / 93 (5.38%)	9 / 89 (10.11%)	2 / 92 (2.17%)
occurrences all number	5	11	2
Upper respiratory tract infection
subjects affected / exposed	1 / 93 (1.08%)	4 / 89 (4.49%)	5 / 92 (5.43%)
occurrences all number	1	5	5
Urinary tract infection
subjects affected / exposed	6 / 93 (6.45%)	6 / 89 (6.74%)	3 / 92 (3.26%)
occurrences all number	10	6	5
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	4 / 93 (4.30%)	5 / 89 (5.62%)	1 / 92 (1.09%)
occurrences all number	4	5	1
Diabetes mellitus inadequate control
subjects affected / exposed	5 / 93 (5.38%)	4 / 89 (4.49%)	5 / 92 (5.43%)
occurrences all number	7	5	5
Hyperglycaemia
subjects affected / exposed	1 / 93 (1.08%)	2 / 89 (2.25%)	4 / 92 (4.35%)
occurrences all number	1	2	4
Hyperlipidaemia
subjects affected / exposed	0 / 93 (0.00%)	0 / 89 (0.00%)	7 / 92 (7.61%)
occurrences all number	0	0	7
Hypertriglyceridaemia
subjects affected / exposed	5 / 93 (5.38%)	3 / 89 (3.37%)	3 / 92 (3.26%)
occurrences all number	5	3	3

More information

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Were there any global substantial amendments to the protocol? Yes

07 Dec 2012

In amendment n°1, main substantial modifications concerned the protocol title, possibility of realization of biology B1 30 days before the liver biopsy, the inclusion criterion n°3 (addition of specific contraceptive measures for male participants and female partner), the list of non-permitted medications (removal of CYP2C9), and modification of discontinuation criteria (stopping rules are no more applicable).

28 Jun 2013

In amendment n°2, main substantial modifications concerned extension of the delay for historical liver biopsies to 9 months, change related to B1 scheduling for patients having a historical liver biopsy and modification of the list of non-permitted medications (removal of CYP2C19).

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.

None reported

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Clinical trials

Clinical Trial Results: A Multicentre, Randomized, Double Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of GFT505 once daily on Steatohepatitis in Patients with Non-Alcoholic Steatohepatitis (NASH).

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: EES- Percentage of Responders With Disappearance of Steatohepatitis Without Worsening of Fibrosis (ie, Participants no Longer Meeting the Criteria for Steatohepatitis)

Primary: EES- Percentage of Responders With Disappearance of Steatohepatitis Without Worsening of Fibrosis (ie, Participants no Longer Meeting the Criteria for Steatohepatitis)

Secondary: EES- Change From Baseline to Week 52 in Non-alcoholic Fatty Liver Disease Activity Score

Secondary: EES- Change From Baseline to Week 52 in Non-alcoholic Fatty Liver Disease Activity Score

Secondary: EES- Number of Participants With Decrease in Steatosis Score of at Least 1 Point Between Baseline and Week 52

Secondary: EES- Number of Participants With Decrease in Steatosis Score of at Least 1 Point Between Baseline and Week 52

Secondary: EES- Number of Participants With Decrease in Lobular Inflammation Score of at Least 1 Point Between Baseline and Week 52

Secondary: EES- Number of Participants With Decrease in Lobular Inflammation Score of at Least 1 Point Between Baseline and Week 52

Secondary: EES - Decrease in Ballooning Score of at Least 1 Point Between Baseline and Week 52

Secondary: EES - Decrease in Ballooning Score of at Least 1 Point Between Baseline and Week 52

Secondary: EES - Changes From Baseline to Week 52 in the Stages of Fibrosis

Secondary: EES - Changes From Baseline to Week 52 in the Stages of Fibrosis

Secondary: EES - Changes From Baseline to Visit 8 (Week 52) in Gamma-glutamyl transferase (GGT)

Secondary: EES - Changes From Baseline to Visit 8 (Week 52) in Gamma-glutamyl transferase (GGT)

Secondary: EES- Changes From Baseline to Visit 8 (Week 52) in Aspartate Transaminase/Alanine Aminotransferase Ratio

Secondary: EES- Changes From Baseline to Visit 8 (Week 52) in Aspartate Transaminase/Alanine Aminotransferase Ratio

Secondary: EES- Change From Baseline to Week 52 in Non-alcoholic Fatty Liver Disease Activity Score of at least 2 points.

Secondary: EES- Change From Baseline to Week 52 in Non-alcoholic Fatty Liver Disease Activity Score of at least 2 points.

Secondary: EES - Changes From Baseline to Visit 8 (Week 52) in alkaline phosphatases

Secondary: EES - Changes From Baseline to Visit 8 (Week 52) in alkaline phosphatases

Secondary: EES - Changes From Baseline to Week 52 in triglycerides

Secondary: EES - Changes From Baseline to Week 52 in triglycerides

Secondary: EES - Changes From Baseline to Week 52 in cholesterol

Secondary: EES - Changes From Baseline to Week 52 in cholesterol

Secondary: EES - Change in Non-high Density Lipoproteins Cholesterol (nHDL-c)

Secondary: EES - Change in Non-high Density Lipoproteins Cholesterol (nHDL-c)

Secondary: EES - Change in High Density Lipoproteins Cholesterol (HDL-c)

Secondary: EES - Change in High Density Lipoproteins Cholesterol (HDL-c)

Secondary: EES - Change in Very Low Density Lipoproteins Cholesterol (VLDL-c)

Secondary: EES - Change in Very Low Density Lipoproteins Cholesterol (VLDL-c)

Secondary: EES- Change in Low Density Lipoproteins Cholesterol (LDL-c)

Secondary: EES- Change in Low Density Lipoproteins Cholesterol (LDL-c)

Secondary: EES - Changes From Baseline to Visit 8 (Week 52) in Aspartate Transaminase (AST)

Secondary: EES - Changes From Baseline to Visit 8 (Week 52) in Aspartate Transaminase (AST)

Secondary: EES -Changes From Baseline to Visit 8 (Week 52) in Alanine aminotransferase (ALT)

Secondary: EES -Changes From Baseline to Visit 8 (Week 52) in Alanine aminotransferase (ALT)

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: CK 18-M65

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: CK 18-M65

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: CK18 M30

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: CK18 M30

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Adiponectin

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Adiponectin

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Ferritin

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Ferritin

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: FG19

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: FG19

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: FG21

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: FG21

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Alpha2 Macroglobulin

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Alpha2 Macroglobulin

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Hyaluronic Acid

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Hyaluronic Acid

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: N-terminal Pro-peptide of Collagen Type III (PIIINP)

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: N-terminal Pro-peptide of Collagen Type III (PIIINP)

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Tissue Inhibitor of Matrix Metalloprotease-1 (TIMP-1)

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Tissue Inhibitor of Matrix Metalloprotease-1 (TIMP-1)

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Fibrotest

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Fibrotest

Secondary: EES- Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Steatotest

Secondary: EES- Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Steatotest

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Angulo test

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Angulo test

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis:Enhanced Liver Fibrosis (ELF)

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis:Enhanced Liver Fibrosis (ELF)

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Fatty Liver Index (FLI)

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Fatty Liver Index (FLI)

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Fibrometer

Secondary: EES - Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Fibrometer

Secondary: EES - Changes From Baseline to Week 52 in Insulin Resistance: Plasma Glucose

Secondary: EES - Changes From Baseline to Week 52 in Insulin Resistance: Plasma Glucose

Clinical Trial Results:
A Multicentre, Randomized, Double Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of GFT505 once daily on Steatohepatitis in Patients with Non-Alcoholic Steatohepatitis (NASH).