Trial Outcomes & Findings for Study of PXL065 in Patients With Nonalcoholic Steatohepatitis (NASH) (NCT NCT04321343)

Results Overview

MRI-PDFF was performed using a standardized imaging protocol, and a central reader analyzed the results. The central reader for this study trained the local imaging centers and provided the imaging manual. Relative change from baseline to Week 36 was calculated as follows: (LFC at Week 36 - LFC at baseline) / LFC at baseline x 100. The primary analysis was performed for the Intent-to-treat Set (ITTS) using an analysis of covariance (ANCOVA) model adjusting for treatment, for stratification factors, and for the baseline LFC as a continuous covariate. LFC missing values at Week 36 were imputed using a multivariate imputation approach by fully conditional specification regression method assuming Missing At Random Mechanism.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

117 participants

Primary outcome timeframe

Baseline and Week 36

Results posted on

2023-08-29

Participant Flow

Patients were screened for the study at 28 sites in the United States between 01Sep2020 and 07Sep2021.

Following a Screening period of maximum 12 weeks, patients who have met all the applicable Inclusion criteria and none of the Exclusion criteria were to be randomized.

Participant milestones

Participant milestones
Measure	PXL065 7.5 mg QD PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo Placebo oral tablets
Overall Study STARTED	25	32	30	30
Overall Study Completed the Double-blind Period	21	23	27	24
Overall Study COMPLETED	21	23	27	23
Overall Study NOT COMPLETED	4	9	3	7

Reasons for withdrawal

Reasons for withdrawal
Measure	PXL065 7.5 mg QD PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo Placebo oral tablets
Overall Study Adverse Event	0	0	1	0
Overall Study Death	0	0	0	1
Overall Study Pregnancy	1	0	0	0
Overall Study Protocol Violation	1	1	1	1
Overall Study Withdrawal by Subject	0	6	0	2
Overall Study Lost to Follow-up	2	2	1	3

Baseline Characteristics

Study of PXL065 in Patients With Nonalcoholic Steatohepatitis (NASH)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PXL065 7.5 mg QD n=25 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=32 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=30 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=30 Participants Placebo oral tablets	Total n=117 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Age, Categorical Between 18 and 65 years	19 Participants n=93 Participants	27 Participants n=4 Participants	23 Participants n=27 Participants	23 Participants n=483 Participants	92 Participants n=36 Participants
Age, Categorical >=65 years	6 Participants n=93 Participants	5 Participants n=4 Participants	7 Participants n=27 Participants	7 Participants n=483 Participants	25 Participants n=36 Participants
Age, Continuous	50.7 years STANDARD_DEVIATION 17.28 • n=93 Participants	54.1 years STANDARD_DEVIATION 10.86 • n=4 Participants	53.4 years STANDARD_DEVIATION 12.36 • n=27 Participants	54.8 years STANDARD_DEVIATION 10.15 • n=483 Participants	53.4 years STANDARD_DEVIATION 12.63 • n=36 Participants
Sex: Female, Male Female	14 Participants n=93 Participants	18 Participants n=4 Participants	14 Participants n=27 Participants	21 Participants n=483 Participants	67 Participants n=36 Participants
Sex: Female, Male Male	11 Participants n=93 Participants	14 Participants n=4 Participants	16 Participants n=27 Participants	9 Participants n=483 Participants	50 Participants n=36 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=93 Participants	8 Participants n=4 Participants	13 Participants n=27 Participants	9 Participants n=483 Participants	41 Participants n=36 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=93 Participants	24 Participants n=4 Participants	17 Participants n=27 Participants	21 Participants n=483 Participants	76 Participants n=36 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	2 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	2 Participants n=36 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants	2 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=483 Participants	5 Participants n=36 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants
Race (NIH/OMB) White	22 Participants n=93 Participants	26 Participants n=4 Participants	29 Participants n=27 Participants	29 Participants n=483 Participants	106 Participants n=36 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	2 Participants n=36 Participants
T2DM status (stratification group) T2DM patients	10 Participants n=93 Participants	13 Participants n=4 Participants	12 Participants n=27 Participants	13 Participants n=483 Participants	48 Participants n=36 Participants
T2DM status (stratification group) Non-T2DM patients	15 Participants n=93 Participants	19 Participants n=4 Participants	18 Participants n=27 Participants	17 Participants n=483 Participants	69 Participants n=36 Participants
NASH CRN fibrosis score (stratification group) F1	9 Participants n=93 Participants	11 Participants n=4 Participants	11 Participants n=27 Participants	10 Participants n=483 Participants	41 Participants n=36 Participants
NASH CRN fibrosis score (stratification group) F2 or F3	16 Participants n=93 Participants	21 Participants n=4 Participants	19 Participants n=27 Participants	20 Participants n=483 Participants	76 Participants n=36 Participants

PRIMARY outcome

Timeframe: Baseline and Week 36

Population: Intent-to-treat set (ITTS), defined as all as-randomized patients who received at least one dose of study treatment.

MRI-PDFF was performed using a standardized imaging protocol, and a central reader analyzed the results. The central reader for this study trained the local imaging centers and provided the imaging manual. Relative change from baseline to Week 36 was calculated as follows: (LFC at Week 36 - LFC at baseline) / LFC at baseline x 100. The primary analysis was performed for the Intent-to-treat Set (ITTS) using an analysis of covariance (ANCOVA) model adjusting for treatment, for stratification factors, and for the baseline LFC as a continuous covariate. LFC missing values at Week 36 were imputed using a multivariate imputation approach by fully conditional specification regression method assuming Missing At Random Mechanism.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=25 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=32 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=30 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=30 Participants Placebo oral tablets
Relative Change From Baseline to Week 36 in the Percentage of Liver Fat Content (LFC) (Assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction [MRI-PDFF])	-22.900 percentage of change in LFC Standard Error 7.104	-18.590 percentage of change in LFC Standard Error 6.904	-21.335 percentage of change in LFC Standard Error 6.446	2.413 percentage of change in LFC Standard Error 6.619

PRIMARY outcome

Timeframe: Baseline and Week 36

Population: Intent-to-treat set (ITTS), defined as all as-randomized patients who received at least one dose of study treatment.

MRI-PDFF was performed using a standardized imaging protocol, and a central reader analyzed the results. The central reader for this study trained the local imaging centers and provided the imaging manual. The sensitivity analysis was performed for the Intent-to-treat Set (ITTS) using a non parametric pairwise Wilcoxon test stratified according to T2DM status and NASH CRN fibrosis scoring system. LFC missing values at Week 36 were imputed using a multivariate imputation approach by fully conditional specification regression method assuming Missing At Random Mechanism.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=25 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=32 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=30 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=30 Participants Placebo oral tablets
Relative Change From Baseline to Week 36 in the Percentage of LFC (Assessed by MRI-PDFF) (Wilcoxon Test Sensitivity Analysis)	-26.555 percentage of change in LFC Interval -42.7 to -5.664	-25.353 percentage of change in LFC Interval -36.586 to -9.826	-24.782 percentage of change in LFC Interval -48.391 to -9.096	0.937 percentage of change in LFC Interval -21.632 to 26.116

SECONDARY outcome

Timeframe: Baseline and Week 36

Population: Intent-to-treat set (ITTS), defined as all as-randomized patients who received at least one dose of study treatment.

MRI-PDFF was performed using a standardized imaging protocol, and a central reader analyzed the results. The central reader for this study trained the local imaging centers and provided the imaging manual. Absolute change from baseline to Week 36 was calculated as follows: LFC at Week 36 - LFC at baseline. The analysis of the absolute change in LFC was performed for the Intent-to-treat Set (ITTS) using an ANCOVA model adjusting for treatment, for stratification factors, and for the baseline LFC as a continuous covariate. LFC missing values at Week 36 were imputed using a multivariate imputation approach by fully conditional specification regression method assuming Missing At Random Mechanism.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=25 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=32 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=30 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=30 Participants Placebo oral tablets
Absolute Change From Baseline to Week 36 in the Percentage of LFC (Assessed by MRI-PDFF)	-4.934 percentage of LFC Standard Error 1.381	-4.360 percentage of LFC Standard Error 1.305	-4.584 percentage of LFC Standard Error 1.207	-0.263 percentage of LFC Standard Error 1.228

SECONDARY outcome

Timeframe: Baseline and Week 36

Population: ITTS, defined as all as-randomized patients who received at least one dose of study treatment. For patients with missing Week 36/Early termination, multiple imputation by fully conditional specification methods was used for analysis, although the n counts and percentages reflect only the observed data.

Responders were defined as patients who achieved a clinically meaningful relative reduction of at least 30% in LFC from baseline to Week 36 as assessed by MRI-PDFF

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=20 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=24 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=27 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=25 Participants Placebo oral tablets
Percentage of Responders (Relative Reduction of at Least 30% in LFC) at Week 36 Responder	8 Participants	11 Participants	12 Participants	5 Participants
Percentage of Responders (Relative Reduction of at Least 30% in LFC) at Week 36 Non-responder	12 Participants	13 Participants	15 Participants	20 Participants

SECONDARY outcome

Timeframe: Baseline to Week 36

Population: ITTS, defined as all as-randomized patients who received at least one dose of study treatment.

Blood samples were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=25 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=32 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=30 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=30 Participants Placebo oral tablets
Change From Baseline to Week 36 in Alanine Amino Transferase (ALT)	-18.4 U/L Standard Error 6.0	-13.6 U/L Standard Error 5.9	-6.7 U/L Standard Error 5.4	-11.9 U/L Standard Error 5.6

SECONDARY outcome

Timeframe: Baseline to Week 36

Population: Subset of patients with increased baseline value from the ITTS, defined as all as-randomized patients who received at least one dose of study treatment.

Normalization of ALT was analyzed in the subset of patients with baseline greater than the upper reference range. Patients were classed as responders if ALT normalized, i.e. decreased to \< upper reference range at a post baseline visit.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=17 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=24 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=24 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=18 Participants Placebo oral tablets
Percentage of Responders (Normalization of ALT) Responder	3 Participants	12 Participants	10 Participants	4 Participants
Percentage of Responders (Normalization of ALT) Non-responder	14 Participants	12 Participants	14 Participants	14 Participants

SECONDARY outcome

Timeframe: Baseline to Week 36

Population: ITTS, defined as all as-randomized patients who received at least one dose of study treatment.

Blood samples were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=25 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=32 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=30 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=30 Participants Placebo oral tablets
Change From Baseline to Week 36 in Aspartate Amino Transferase (AST)	-10.1 U/L Standard Error 6.5	-10.2 U/L Standard Error 6.3	-4.9 U/L Standard Error 5.8	-7.2 U/L Standard Error 6.0

SECONDARY outcome

Timeframe: Baseline to Week 36

Population: Subset of patients with increased baseline value from the ITTS, defined as all as-randomized patients who received at least one dose of study treatment.

Normalization of AST was analyzed in the subset of patients with baseline greater than the upper reference range. Patients were classed as responders if AST normalized, i.e. decreased to \< upper reference range at a post baseline visit.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=17 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=17 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=19 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=16 Participants Placebo oral tablets
Percentage of Responders (Normalization of AST) Responder	9 Participants	4 Participants	11 Participants	4 Participants
Percentage of Responders (Normalization of AST) Non-responder	8 Participants	13 Participants	8 Participants	12 Participants

SECONDARY outcome

Timeframe: Baseline to Week 36

Population: ITTS, defined as all as-randomized patients who received at least one dose of study treatment.

Blood samples were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=25 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=32 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=30 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=30 Participants Placebo oral tablets
Change From Baseline to Week 36 in Gamma Glutamyltransferase (GGT)	-12.2 U/L Standard Error 7.6	-21.8 U/L Standard Error 7.5	-6.9 U/L Standard Error 6.9	-4.2 U/L Standard Error 7.1

SECONDARY outcome

Timeframe: Baseline to Week 36

Population: ITTS, defined as all as-randomized patients who received at least one dose of study treatment.

Blood samples were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=25 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=32 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=30 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=30 Participants Placebo oral tablets
Change From Baseline to Week 36 in Alkaline Phosphatase (ALP)	-2.8 U/L Standard Error 2.7	-8.0 U/L Standard Error 2.7	-5.8 U/L Standard Error 2.5	3.1 U/L Standard Error 2.6

SECONDARY outcome

Timeframe: Baseline and Week 36

Population: ITTS, defined as all as-randomized patients who received at least one dose of study treatment.

Pro-C3 is the released N-terminal pro-peptide of type III collagen. It is a fibrosis marker. Blood samples were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=25 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=32 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=30 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=30 Participants Placebo oral tablets
Change From Baseline to Week 36 in Pro-C3	-2.054 ng/mL Standard Error 1.182	-1.753 ng/mL Standard Error 1.089	-2.481 ng/mL Standard Error 1.050	-1.041 ng/mL Standard Error 0.893

SECONDARY outcome

Timeframe: Baseline and Week 36

Population: ITTS, defined as all as-randomized patients who received at least one dose of study treatment.

ELF score is an extracellular matrix marker set consisting of tissue inhibitor of metalloproteinases 1 (TIMP-1), amino-terminal propeptide of type III procollagen (PIIINP) and hyaluronic acid (HA) showing good correlations with fibrosis stages in chronic liver disease.The set cutoffs for this scoring are: ELF \< 7.7: no to mild fibrosis; ELF between 7.7 - 9.8: moderate fibrosis; ELF between 9.8 - 11.3: severe fibrosis; and ELF \> or = 11.3: cirrhosis. Blood samples used for TIMP-1, PIIINP and HA were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=25 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=32 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=30 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=30 Participants Placebo oral tablets
Change From Baseline to Week 36 in Enhanced Liver Fibrosis (ELF) Score	-0.142 Score Standard Error 0.168	-0.206 Score Standard Error 0.153	-0.358 Score Standard Error 0.130	-0.079 Score Standard Error 0.130

SECONDARY outcome

Timeframe: Baseline and Week 36

Population: ITTS, defined as all as-randomized patients who received at least one dose of study treatment.

Fib-4 score is a non invasive method based on clinical determinations that indicates the level of fibrosis/ scarring of the liver. The set cutoffs for this scoring are: Fib-4 \< 1.45: absence of cirrhosis; Fib-4 between 1.45 - 3.25: inconclusive and Fib-4 \> 3.25: cirrhosis. Fib-4 score was calculated as (Age \[years\] × AST \[U/L\]) / (platelet \[10\^9/L\] × √\[ALT \[U/L\]\]). Blood samples used for AST, ALT and platelet counts were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=25 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=32 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=30 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=30 Participants Placebo oral tablets
Change From Baseline to Week 36 in Fibrosis-4 (Fib-4) Score	-0.040 Score Standard Error 0.127	-0.107 Score Standard Error 0.124	-0.198 Score Standard Error 0.109	-0.012 Score Standard Error 0.110

SECONDARY outcome

Timeframe: Baseline and Week 36

Population: ITTS, defined as all as-randomized patients who received at least one dose of study treatment.

The NFS is based on a combination of clinical and laboratory measurements (i.e. age, glycemia, BMI, platelet, albumin and AST/ALT ratio). The set cutoffs for this scoring are: \< -1.455 for exclusion of advance fibrosis, \> -1.455 to \< or = 0.675 for indetermined, and \> 0.675 for presence of advance fibrosis. NFS was calculated as: 1.675 + 0.037 x age (years) + 0.094 x BMI (kg/m²) + 1.13 x Impaired Fasting Glucose or Diabetes (yes =1; no=0) + 0.99 x AST/ALT ratio - 0.013 x platelet (10\^9/L) - 0.66 x albumin (g/dL)

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=25 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=32 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=30 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=30 Participants Placebo oral tablets
Change From Baseline to Week 36 in NAFLD Fibrosis Score	0.170 Score Standard Error 0.192	-0.006 Score Standard Error 0.188	-0.264 Score Standard Error 0.167	0.215 Score Standard Error 0.167

SECONDARY outcome

Timeframe: Baseline and Week 36

Population: Patients With Week 36 Assessment from the Intent-to-treat set (ITTS), defined as all as-randomized patients who received at least one dose of study treatment.

Improvement in fibrosis is defined as a decrease of at least one stage in NASH CRN fibrosis score.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=21 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=22 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=26 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=23 Participants Placebo oral tablets
Improvement of at Least 1 Point in NASH CRN Fibrosis Score From Baseline to Week 36 Responder	9 Participants	11 Participants	9 Participants	4 Participants
Improvement of at Least 1 Point in NASH CRN Fibrosis Score From Baseline to Week 36 Non-responder	12 Participants	11 Participants	17 Participants	19 Participants

SECONDARY outcome

Timeframe: Baseline and Week 36

Population: Patients With Week 36 Assessment from the Intent-to-treat set (ITTS), defined as all as-randomized patients who received at least one dose of study treatment.

NAS is the NAFLD activity score, calculated as the sum of steatosis, lobular inflammation and ballooning scores. Improvement in NAS is defined as a decrease of at least 2 points. No worsening in NASH CRN fibrosis score means that the score remained stable or decreased.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=21 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=22 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=26 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=23 Participants Placebo oral tablets
Improvement in NAS of at Least 2 Points With no Worsening in NASH CRN Fibrosis Score From Baseline to Week 36 Responder	8 Participants	11 Participants	13 Participants	7 Participants
Improvement in NAS of at Least 2 Points With no Worsening in NASH CRN Fibrosis Score From Baseline to Week 36 Non-responder	13 Participants	11 Participants	13 Participants	16 Participants

SECONDARY outcome

Timeframe: Baseline and Week 36

Population: Patients With Week 36 Assessment from the Intent-to-treat set (ITTS), defined as all as-randomized patients who received at least one dose of study treatment.

NASH resolution is defined as a NAS score of 0-1 for inflammation, 0 for ballooning, and any value for steatosis. No worsening in NASH CRN fibrosis score means that the score remained stable or decreased.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=21 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=22 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=26 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=23 Participants Placebo oral tablets
NASH Resolution With no Worsening in NASH CRN Fibrosis Score at Week 36 Responder	8 Participants	8 Participants	8 Participants	7 Participants
NASH Resolution With no Worsening in NASH CRN Fibrosis Score at Week 36 Non-responder	13 Participants	14 Participants	18 Participants	16 Participants

SECONDARY outcome

Timeframe: Baseline and Week 36

Population: Patients With Week 36 Assessment from the Intent-to-treat set (ITTS), defined as all as-randomized patients who received at least one dose of study treatment.

NASH resolution is defined as a NAS score of 0-1 for inflammation, 0 for ballooning, and any value for steatosis. Improvement in fibrosis is defined as a decrease of at least one stage in NASH CRN fibrosis score.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=21 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=22 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=26 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=23 Participants Placebo oral tablets
NASH Resolution With Improvement of at Least 1 Point in NASH CRN Fibrosis Score at Week 36 Responder	7 Participants	7 Participants	4 Participants	3 Participants
NASH Resolution With Improvement of at Least 1 Point in NASH CRN Fibrosis Score at Week 36 Non-responder	14 Participants	15 Participants	22 Participants	20 Participants

SECONDARY outcome

Timeframe: Baseline to Week 36

Population: ITTS, defined as all as-randomized patients who received at least one dose of study treatment.

Blood samples were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=25 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=32 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=30 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=30 Participants Placebo oral tablets
Change From Baseline to Week 36 in Glycated Hemoglobin (HbA1c)	0.14 percentage of glycated hemoglobin Standard Error 0.11	-0.06 percentage of glycated hemoglobin Standard Error 0.10	-0.20 percentage of glycated hemoglobin Standard Error 0.10	0.21 percentage of glycated hemoglobin Standard Error 0.10

SECONDARY outcome

Timeframe: Baseline to Week 36

Population: ITTS, defined as all as-randomized patients who received at least one dose of study treatment.

Blood samples were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=25 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=32 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=30 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=30 Participants Placebo oral tablets
Change From Baseline to Week 36 in Fasting Plasma Glucose (FPG)	0.147 mmol/L Standard Error 0.286	0.361 mmol/L Standard Error 0.278	0.205 mmol/L Standard Error 0.251	0.198 mmol/L Standard Error 0.269

SECONDARY outcome

Timeframe: Baseline to Week 36

Population: ITTS, defined as all as-randomized patients who received at least one dose of study treatment.

Blood samples were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=25 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=32 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=30 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=30 Participants Placebo oral tablets
Change From Baseline to Week 36 in Serum Insulin	-78.08 pmol/L Standard Error 28.01	-39.76 pmol/L Standard Error 26.71	-56.55 pmol/L Standard Error 23.40	6.85 pmol/L Standard Error 24.06

SECONDARY outcome

Timeframe: Baseline to Week 36

Population: ITTS, defined as all as-randomized patients who received at least one dose of study treatment.

Blood samples were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=25 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=32 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=30 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=30 Participants Placebo oral tablets
Change From Baseline to Week 36 in Serum C-peptide	-0.205 nmol/L Standard Error 0.116	-0.222 nmol/L Standard Error 0.110	-0.250 nmol/L Standard Error 0.095	0.051 nmol/L Standard Error 0.102

SECONDARY outcome

Timeframe: Baseline to Week 36

Population: ITTS, defined as all as-randomized patients who received at least one dose of study treatment.

HOMA-IR was calculated as: Serum C-peptide (ng/mL) × FPG (mg/dL) / 405 Blood samples were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory. HOMA-IR is an indicator of insulin resistance. The higher the value, the greater the insulin resistance. There is no minimum or maximum index score.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=25 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=32 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=30 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=30 Participants Placebo oral tablets
Change From Baseline to Week 36 in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)	-0.086 Index Standard Error 0.134	-0.123 Index Standard Error 0.127	-0.210 Index Standard Error 0.106	0.111 Index Standard Error 0.116

SECONDARY outcome

Timeframe: Baseline to Week 36

Population: ITTS, defined as all as-randomized patients who received at least one dose of study treatment.

The QUICKI was calculated as: 1 / (log (FPG \[mg/dL\]) + log (C-peptide \[ng/mL\])). Blood samples were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory. QUICKI is an indicator of insulin resistance. Lower numbers reflect greater insulin resistance. There is no minimum or maximum index score.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=25 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=32 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=30 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=30 Participants Placebo oral tablets
Change From Baseline to Week 36 in Quantitative Insulin Sensitivity Check Index (QUICKI)	0.006 Index Standard Error 0.009	0.007 Index Standard Error 0.009	0.012 Index Standard Error 0.008	-0.005 Index Standard Error 0.008

SECONDARY outcome

Timeframe: Baseline to Week 36

Population: ITTS, defined as all as-randomized patients who received at least one dose of study treatment.

The Adipo-IR was calculated as: Fasting serum Free Fatty Acids (mmol/L) x Fasting serum insulin (μIU/mL) Blood samples were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory. The Adipo-IR is a marker of adipose tissue insulin resistance. Higher the value, the greater the insulin resistance. There is no minimum or maximum index score.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=25 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=32 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=30 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=30 Participants Placebo oral tablets
Change From Baseline to Week 36 in Adipo-IR	-36.18 Index Standard Error 16.53	-17.01 Index Standard Error 13.78	-41.87 Index Standard Error 12.37	12.77 Index Standard Error 13.03

SECONDARY outcome

Timeframe: Baseline to Week 36

Population: ITTS, defined as all as-randomized patients who received at least one dose of study treatment.

Blood samples were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=25 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=32 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=30 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=30 Participants Placebo oral tablets
Change From Baseline to Week 36 in Adiponectin	1.532 µg/mL Standard Error 0.679	2.688 µg/mL Standard Error 0.646	4.734 µg/mL Standard Error 0.624	-0.143 µg/mL Standard Error 0.595

SECONDARY outcome

Timeframe: Baseline to Week 36

Population: Safety Set, defined as all as-treated patients who received at least one dose of study treatment.

Body weight was measured using a scale with appropriate resolution, placed on a stable, flat surface. Shoes, bulky layers of clothing, and jackets had to be removed so that only light clothing remained.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=25 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=32 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=30 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=30 Participants Placebo oral tablets
Change From Baseline to Week 36 in Weight	1.080 kg Standard Error 0.673	2.356 kg Standard Error 0.636	0.577 kg Standard Error 0.603	-0.103 kg Standard Error 0.623

POST_HOC outcome

Timeframe: Baseline and Week 36

Population: ITTS, defined as all as-randomized patients who received at least one dose of study treatment.

PIIINP is the amino-terminal propeptide of type III procollagen. It is a fibrosis marker. Blood samples were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=25 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=32 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=30 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=30 Participants Placebo oral tablets
Change From Baseline to Week 36 in PIIINP	-2.385 µg/mL Standard Error 0.875	-2.732 µg/mL Standard Error 0.796	-3.354 µg/mL Standard Error 0.674	-1.134 µg/mL Standard Error 0.672

POST_HOC outcome

Timeframe: Baseline and Week 36

Population: Patients With Week 36 Assessment from the Intent-to-treat set (ITTS), defined as all as-randomized patients who received at least one dose of study treatment.

NAS is the NAFLD activity score, calculated as the sum of steatosis, lobular inflammation and ballooning scores. Improvement in NAS is defined as a decrease of at least 2 points.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=21 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=22 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=26 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=23 Participants Placebo oral tablets
Improvement of at Least 2 Points in NAS Responder	9 Participants	11 Participants	15 Participants	7 Participants
Improvement of at Least 2 Points in NAS Non-responder	12 Participants	11 Participants	11 Participants	16 Participants

POST_HOC outcome

Timeframe: Baseline and Week 36

Population: Patients With Week 36 Assessment from the Intent-to-treat set (ITTS), defined as all as-randomized patients who received at least one dose of study treatment.

Improvement in fibrosis is defined as a decrease of at least one stage in NASH CRN fibrosis score. No worsening of NASH is defined as no increase in steatosis, inflammation or ballooning

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=21 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=22 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=26 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=23 Participants Placebo oral tablets
Improvement of at Least 1 Point in NASH CRN Fibrosis Score With no Worsening of NASH From Baseline to Week 36 Responder	8 Participants	11 Participants	8 Participants	4 Participants
Improvement of at Least 1 Point in NASH CRN Fibrosis Score With no Worsening of NASH From Baseline to Week 36 Non-responder	13 Participants	11 Participants	18 Participants	19 Participants

POST_HOC outcome

Timeframe: Baseline to Week 36

Population: Safety Set, defined as all as-treated patients who received at least one dose of study treatment, Excluding Week 36 for one patient (erroneous data), and Excluding Patients With Weight Loss \> 10kg from Baseline to Week 36.

Body weight was measured using a scale with appropriate resolution, placed on a stable, flat surface. Shoes, bulky layers of clothing, and jackets had to be removed so that only light clothing remained.

Outcome measures

Outcome measures
Measure	PXL065 7.5 mg QD n=25 Participants PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=32 Participants PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=30 Participants PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=30 Participants Placebo oral tablets
Change in Weight Excluding Week 36 for One Patient (Erroneous Data), and Excluding Patients With Weight Loss > 10kg From Baseline to Week 36	0.599 kg Standard Error 0.656	2.304 kg Standard Error 0.614	0.543 kg Standard Error 0.583	0.319 kg Standard Error 0.612

Adverse Events

PXL065 7.5 mg QD

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

PXL065 15 mg QD

Serious events: 3 serious events

Other events: 19 other events

Deaths: 0 deaths

PXL065 22.5 mg QD

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 14 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	PXL065 7.5 mg QD n=25 participants at risk PXL065 7.5 mg oral tablet + Placebo oral tablet	PXL065 15 mg QD n=32 participants at risk PXL065 15 mg oral tablet + Placebo oral tablet	PXL065 22.5 mg QD n=30 participants at risk PXL065 7.5 mg oral tablet + PXL065 15 mg oral tablet	Placebo n=30 participants at risk Placebo oral tablets
Infections and infestations COVID-19	0.00% 0/25 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	0.00% 0/32 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	3.3% 1/30 • Number of events 1 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	3.3% 1/30 • Number of events 1 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.
Infections and infestations Cellulitis	0.00% 0/25 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	3.1% 1/32 • Number of events 1 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	0.00% 0/30 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	0.00% 0/30 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.
Infections and infestations Gastroenteritis	0.00% 0/25 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	3.1% 1/32 • Number of events 1 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	0.00% 0/30 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	0.00% 0/30 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.
General disorders Death	0.00% 0/25 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	0.00% 0/32 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	0.00% 0/30 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	3.3% 1/30 • Number of events 1 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.
Hepatobiliary disorders Biliary dyskinesia	4.0% 1/25 • Number of events 1 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	0.00% 0/32 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	0.00% 0/30 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	0.00% 0/30 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.
Injury, poisoning and procedural complications Procedural pain	4.0% 1/25 • Number of events 1 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	0.00% 0/32 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	0.00% 0/30 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	0.00% 0/30 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/25 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	3.1% 1/32 • Number of events 1 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	0.00% 0/30 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	0.00% 0/30 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.
Metabolism and nutrition disorders Metabolic acidosis	0.00% 0/25 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	3.1% 1/32 • Number of events 1 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	0.00% 0/30 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	0.00% 0/30 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/25 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	3.1% 1/32 • Number of events 1 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	0.00% 0/30 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.	0.00% 0/30 • All AEs were collected from the time of ICF signature to the End-of-study Visit, ie 38 weeks on average. Only events that occur after the first dose intake of IMP of the Double-blind (DB) treatment period or if they were present prior to the first intake of IMP of the DB treatment period and increased in severity or relationship to IMP after the first intake of IMP of the DB treatment period were considered as Treatment Emergent Adverse Events (TEAEs). Only TEAEs (regardless of the relationship) are presented in this section.

Other adverse events

Additional Information

Director, Medical Operations

POXEL

Phone: +33 (0)4 37 37 20 10

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place