| Primary | Relative Change in the Percentage of Liver Fat Mass (Assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction [MRI-PDFF]) From Baseline to Week 12/End of Treatment (EOT) | MRI acquisitions were performed at pre-qualified local MRI facilities using qualified and standardized instruments at high field strength (3 T or 1.5T) without oral or intravenous contrast. All acquisitions images were transferred to a central reader vendor for central calculation and measurement of MRI-PDFF using the method of Zhong et al. to estimate water and fat components. A 3 cm2 region of interest (ROI) was placed in each Couinaud segment. Central reading was masked to treatment group, clinical data, study site of origin and timepoint. | Intent-to-treat set (ITTS), defined as all as-randomized patients who received at least one dose of study treatment. | Posted | | Least Squares Mean | Standard Error | percentage | | Baseline to Week 12 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks | | OG001 | PXL770 250 mg QD | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks. | | OG002 | PXL770 250 mg BID | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks. | | OG003 | PXL770 500 mg QD | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks. |
| | Units | Counts |
|---|
| Participants | - OG00031
- OG00130
- OG00230
- OG003
|
| | Title | Denominators | Categories |
|---|
| | | Title | Measurements |
|---|
| - OG000-1.14± 6.344
- OG001-1.03± 6.764
- OG002-14.28± 6.697
- OG003
|
|
| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
|---|
| | ANCOVA | ANCOVA model using a multiple imputation procedure based on the fully conditional specification method. | 0.9883 | | Mean Difference (Final Values) | 0.12 | Standard Error of the Mean | 7.926 | 2-Sided | 95 | -15.42 | 15.66 | | | Mean difference (final values) is the difference in Least Squares (LS) Means estimated in the ANCOVA model. | | Superiority | | | |
|
| Primary | Relative Change in the Percentage of Liver Fat Mass (Assessed by MRI-PDFF) From Baseline to Week 12/End of Treatment (Per Protocol Sensitivity Analysis) | MRI acquisitions were performed at pre-qualified local MRI facilities using qualified and standardized instruments at high field strength (3 T or 1.5T) without oral or intravenous contrast. All acquisitions images were transferred to a central reader vendor for central calculation and measurement of MRI-PDFF using the method of Zhong et al. to estimate water and fat components. A 3 cm2 ROI was placed in each Couinaud segment. Central reading was masked to treatment group, clinical data, study site of origin and timepoint. | Per Protocol Set (PPS), defined as all patients in the ITTS who complete the double-blind treatment period and have an overall treatment duration ≥8 weeks (≥56 days) without any CSR reportable protocol deviations (PD) that is deemed to affect the primary efficacy endpoint of MRI-PDFF. | Posted | | Least Squares Mean | Standard Error | percentage | | Baseline to Week 12 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks | | OG001 | PXL770 250 mg QD | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks. | |
|
| Primary | Relative Change in the Percentage of Liver Fat Mass (Assessed by MRI-PDFF) From Baseline to Week 12/End of Treatment (Unstratified Wilcoxon Sensitivity Analysis) | MRI acquisitions were performed at pre-qualified local MRI facilities using qualified and standardized instruments at high field strength (3 T or 1.5T) without oral or intravenous contrast. All acquisitions images were transferred to a central reader vendor for central calculation and measurement of MRI-PDFF using the method of Zhong et al. to estimate water and fat components. A 3 cm2 ROI was placed in each Couinaud segment. Central reading was masked to treatment group, clinical data, study site of origin and timepoint. | ITTS, defined as all as-randomized patients who received at least one dose of study treatment. | Posted | | Median | Inter-Quartile Range | percentage | | Baseline to Week 12 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks | | OG001 | PXL770 250 mg QD | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks. | | OG002 | PXL770 250 mg BID | |
|
| Primary | Relative Change in the Percentage of Liver Fat Mass (Assessed by MRI-PDFF) From Baseline to Week 12/End of Treatment (Subgroup Analysis - Type 2 Diabetes Mellitus [T2DM]) | MRI acquisitions were performed at pre-qualified local MRI facilities using qualified and standardized instruments at high field strength (3 T or 1.5T) without oral or intravenous contrast. All acquisitions images were transferred to a central reader vendor for central calculation and measurement of MRI-PDFF using the method of Zhong et al. to estimate water and fat components. A 3 cm2 ROI was placed in each Couinaud segment. Central reading was masked to treatment group, clinical data, study site of origin and timepoint. | ITTS T2DM subgroup, defined as all as-randomized T2DM patients who received at least one dose of study treatment. | Posted | | Least Squares Mean | Standard Deviation | percentage | | Baseline to Week 12 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks | | OG001 | PXL770 250 mg QD | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks. | | OG002 | PXL770 250 mg BID | |
|
| Secondary | Absolute Change in the Percentage of Liver Fat Mass (Assessed by MRI-PDFF) From Baseline to Week 12/End of Treatment | MRI acquisitions were performed at pre-qualified local MRI facilities using qualified and standardized instruments at high field strength (3 T or 1.5T) without oral or intravenous contrast. All acquisitions images were transferred to a central reader vendor for central calculation and measurement of MRI-PDFF using the method of Zhong et al. to estimate water and fat components. A 3 cm2 ROI was placed in each Couinaud segment. Central reading was masked to treatment group, clinical data, study site of origin and timepoint. | ITTS, defined as all as-randomized patients who received at least one dose of study treatment. | Posted | | Least Squares Mean | Standard Error | percentage | | Baseline to Week 12 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG001 | PXL770 250 mg QD | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG002 | PXL770 250 mg BID | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | |
|
| Secondary | Percentage of Responders (Relative Reduction of at Least 30% in Liver Fat Mass) at Week 12/End of Treatment | Responders were defined as patients who achieved a clinically meaningful relative reduction of at least 30% in liver fat mass From baseline to Week 12/EOT as assessed by MRI-PDFF | ITTS, defined as all as-randomized patients who received at least one dose of study treatment. For patients with missing Week 12/End of Treatment, multiple imputation by fully conditional specification methods was used for analysis, although the n counts and percentages reflect only the observed data. | Posted | | Count of Participants | | Participants | | Baseline to Week 12 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG001 | PXL770 250 mg QD | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG002 | PXL770 250 mg BID | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG003 | PXL770 500 mg QD |
|
| Secondary | Change in Alanine Amino Transferase (ALT) From Baseline to Week 12/End of 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. | ITTS, defined as all as-randomized patients who received at least one dose of study treatment. | Posted | | Least Squares Mean | Standard Error | U/L | | Baseline to Week 12 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG001 | PXL770 250 mg QD | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG002 | PXL770 250 mg BID | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG003 | PXL770 500 mg QD | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks |
| |
| Secondary | Change in Aspartate Amino Transferase (AST) From Baseline to Week 12/End of 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. | ITTS, defined as all as-randomized patients who received at least one dose of study treatment. | Posted | | Least Squares Mean | Standard Error | U/L | | Baseline to Week 12 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG001 | PXL770 250 mg QD | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG002 | PXL770 250 mg BID | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG003 | PXL770 500 mg QD | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks |
| |
| Secondary | Change in Fasting Plasma Glucose (FPG) From Baseline to Week12/End of 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. | ITTS, defined as all as-randomized patients who received at least one dose of study treatment. | Posted | | Least Squares Mean | Standard Error | mmol/L | | Baseline to Week 12 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG001 | PXL770 250 mg QD | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG002 | PXL770 250 mg BID | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG003 | PXL770 500 mg QD | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks |
| |
| Secondary | Change in Glycated Hemoglobin (HbA1c) From Baseline to Week12/End of 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. | ITTS, defined as all as-randomized patients who received at least one dose of study treatment. | Posted | | Least Squares Mean | Standard Error | percent | | Baseline to Week 12 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG001 | PXL770 250 mg QD | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG002 | PXL770 250 mg BID | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG003 | PXL770 500 mg QD | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks |
| |
| Secondary | Change in Total Cholesterol From Baseline to Week12/End of 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. | ITTS, defined as all as-randomized patients who received at least one dose of study treatment. | Posted | | Least Squares Mean | Standard Error | mmol/L | | Baseline to Week 12 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG001 | PXL770 250 mg QD | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG002 | PXL770 250 mg BID | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG003 | PXL770 500 mg QD | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks |
| |
| Secondary | Change in High Density Lipoprotein-Cholesterol (HDL-C) From Baseline to Week12/End of 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. | ITTS, defined as all as-randomized patients who received at least one dose of study treatment. | Posted | | Least Squares Mean | Standard Error | mmol/L | | Baseline to Week 12 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG001 | PXL770 250 mg QD | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG002 | PXL770 250 mg BID | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG003 | PXL770 500 mg QD | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks |
| |
| Secondary | Change in Low Density Lipoprotein-Cholesterol (LDL-C) From Baseline to Week12/End of 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. | ITTS, defined as all as-randomized patients who received at least one dose of study treatment. | Posted | | Least Squares Mean | Standard Error | mmol/L | | Baseline to Week 12 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG001 | PXL770 250 mg QD | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG002 | PXL770 250 mg BID | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG003 | PXL770 500 mg QD | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks |
| |
| Secondary | Change in Triglycerides From Baseline to Week12/End of 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. | ITTS, defined as all as-randomized patients who received at least one dose of study treatment. | Posted | | Least Squares Mean | Standard Error | mmol/L | | Baseline to Week 12 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG001 | PXL770 250 mg QD | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG002 | PXL770 250 mg BID | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG003 | PXL770 500 mg QD | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks |
| |
| Secondary | Change in Fibrosis-4 (Fib-4) Score From Baseline to Week 12/End of 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. | ITTS, defined as all as-randomized patients who received at least one dose of study treatment. | Posted | | Least Squares Mean | Standard Error | Fib-4 score | | Baseline to Week 12 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG001 | PXL770 250 mg QD | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG002 | PXL770 250 mg BID | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks |
|
| Secondary | Change in Body Weight From Baseline to Week 12/End of 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. | ITTS, defined as all as-randomized patients who received at least one dose of study treatment. | Posted | | Least Squares Mean | Standard Error | kg | | Baseline to Week 12 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG001 | PXL770 250 mg QD | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG002 | PXL770 250 mg BID | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks | | OG003 | PXL770 500 mg QD | Two capsules were taken BID at least 15 minutes before a meal for 12 weeks |
| |
| Post-Hoc | Percentage of Responders (Relative Reduction of at Least 30% in Liver Fat Mass) at Week 12/End of Treatment (T2DM Subgroup) | Responders were defined as patients who achieved a clinically meaningful relative reduction of at least 30% in liver fat mass From baseline to Week 12/EOT as assessed by MRI-PDFF | ITTS T2DM subgroup, defined as all as-randomized T2DM patients who received at least one dose of study treatment. For patients with missing Week 12/End of Treatment, multiple imputation by fully conditional specification methods was used for analysis, although the n counts and percentages reflect only the observed data. | Posted | | Count of Participants | | Participants | | Baseline to Week 12 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks | | OG001 | PXL770 250 mg QD | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks. | | OG002 | PXL770 250 mg BID | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks. |
|
| Post-Hoc | Change in ALT From Baseline to Week 12/End of Treatment (T2DM Subgroup) | 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. | ITTS T2DM subgroup, defined as all as-randomized T2DM patients who received at least one dose of study treatment. | Posted | | Least Squares Mean | Standard Error | U/L | | Baseline to Week 12 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks | | OG001 | PXL770 250 mg QD | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks. | | OG002 | PXL770 250 mg BID | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks. | | OG003 | PXL770 500 mg QD | |
|
| Post-Hoc | Change in AST From Baseline to Week 12/End of Treatment (T2DM Subgroup) | 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. | ITTS T2DM subgroup, defined as all as-randomized T2DM patients who received at least one dose of study treatment. | Posted | | Least Squares Mean | Standard Deviation | U/L | | Baseline to Week 12 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks | | OG001 | PXL770 250 mg QD | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks. | | OG002 | PXL770 250 mg BID | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks. | | OG003 | PXL770 500 mg QD | |
|
| Post-Hoc | Change in FPG From Baseline to Week12/End of Treatment (T2DM Subgroup) | 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. | ITTS T2DM subgroup, defined as all as-randomized T2DM patients who received at least one dose of study treatment. | Posted | | Least Squares Mean | Standard Error | mmol/L | | Baseline to Week 12 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks | | OG001 | PXL770 250 mg QD | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks. | | OG002 | PXL770 250 mg BID | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks. | | OG003 | PXL770 500 mg QD | |
|
| Post-Hoc | Change in HbA1c From Baseline to Week12/End of Treatment (T2DM Subgroup) | 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. | ITTS T2DM subgroup, defined as all as-randomized T2DM patients who received at least one dose of study treatment. | Posted | | Least Squares Mean | Standard Error | percent | | Baseline to Week 12 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks | | OG001 | PXL770 250 mg QD | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks. | | OG002 | PXL770 250 mg BID | Two capsules were taken BID with a glass of water at least 15 minutes before a meal in the morning and in the evening time for 12 weeks. | | OG003 | PXL770 500 mg QD | |
|