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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-000499-83 | EudraCT Number |
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The primary objective of this study is the proof of mechanism and support of dose finding, together with the safety evaluation in patients with clinical evidence of NASH.
To gain further insight into clinical effects of AOC3 inhibition on NASH further exploratory analyses of biomarkers related to NASH and liver fibrosis will be performed. This will include the effect of BI 1467335 on reduction of secondary biomarker endpoints (ALT, AST, AP, γ-GT and CK18 fragments). Safety will be assessed throughout the study to provide key information regarding the use of BI 1467335 in patients with NASH.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BI 1467335 dose 1 | Experimental |
| |
| BI 1467335 dose 2 | Experimental |
| |
| BI 1467335 dose 3 | Experimental |
| |
| BI 1467335 dose 4 | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BI 1467335 | Drug | once daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Amine Oxidase Copper-containing 3 (AOC3) Activity After 12 Weeks of Treatment, Relative to Baseline in Percent | The patient-specific plasma AOC3 activity at time t (24 hours after the last dose in week 12) relative to baseline in percentage was calculated as follows: %AOC3at = [(AOC3at - AOC3at,back) ⁄ (AOC3abase - AOC3abase,back)]*100 With AOC3at the AOC3 activity measured at time t, AOC3at,back the background noise at time t, AOC3abase the AOC3 activity measured at baseline and AOC3abase,back the background noise at baseline. A dose-response relationship was analysed using a non-linear regression model to estimate the daily dosage needed to reach 10% of AOC3 activity (i.e. 90% inhibition) 12 weeks after treatment. | Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Drug-related Adverse Events (AEs) | Percentage of participants with drug-related adverse events (AEs). Percentages are calculated using total number of patients per treatment as the denominator. | Start of treatment till end of treatment + 28 days, up to 113 days. |
| Alanine Aminotransaminase (ALT) After 12 Weeks of Treatment, Relative to Baseline in Percent |
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Inclusion criteria:
Exclusion criteria:
Current or history of significant alcohol consumption (defined as intake of >210g/week in males and >140g/week in females on average over a consecutive period of more than 3 months) or inability to reliably quantify alcohol consumption based on investigator judgement.
Prior participation in an interventional NASH trial 6 months before baseline or 5 times halflife of the investigational drug, whichever is longer.
Prior or planned bariatric surgery during study conduct, except gastric-band surgery more than 2 years prior to screening (including adjustments) with a stable body weight within the last 12 months.
Use of drugs historically associated with liver injury, hepatic steatosis or steatohepatitis in the 4 weeks prior to screening.
History of liver cirrhosis (fibrosis stage 4), or hepatic decompensation (e.g. ascites, hepatic encephalopathy, variceal bleeding, etc.) or history of other forms of chronic liver disease (for example Hepatitis B, Hepatitis C, autoimmune liver disease, primary biliary sclerosis, primary sclerosing cholangitis, Wilsons disease, hemochromatosis, A1At deficiency, history of liver transplantation).
Active known chronic or relevant acute infections, such as HIV (Human Immunodeficiency Virus), \viral hepatitis, or tuberculosis. QuantiFERON® TB test and HBs Ag test will be performed during screening. Patients with a positive test result may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the patient has no evidence of active infection.
Solid liver lesions other than haemangiomas.
-- Suspicion or diagnosis or history of hepatocellular carcinoma (HCC)
eGFR <60ml/min/1.73m2 at screening (CKD-EPI formula).
ALT >5.0 ULN at screening.
Platelet count < 150.000/μL
Bilirubin level > ULN (except for known Gilbert´s disease with a conjugated bilirubin of < 0.3 mg/dL))
Uncontrolled diabetes defined as an HbA1c ≥9.5% in the 3 months prior to or at screening.
Diagnosis of a serious or unstable disease including hepatic (other than NASH), renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic , psychiatric, immunologic, or hematologic disease and other conditions that, in the clinical judgment of the investigator, are likely to interfere with the analyses of safety and efficacy in this study. Patients with an expected life expectancy of less than 2 years are also excluded.
Major surgery (major according to the investigator's assessment) performed within 12 weeks prior to randomisation or planned during study conduct, e.g. hip replacement.
Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix.
Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.
Previous randomisation in this trial.
Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational treatment(s).
Chronic drug abuse or any condition that, in the investigator's opinion, makes them an unreliable study subject or unlikely to complete the trial.
Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
Patients with Wolff-Parkinson-White Syndrome, baseline QTc > 450 ms, family history of long QT, or on medication prolonging QT time at screening or planned initiation during the trial.
Any other clinical condition that, in the opinion of the investigator, would jeopardize patient safety while participating in this clinical trial.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Southern California Research Center | Coronado | California | 92118 | United States | ||
| University of California San Diego |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37932258 | Derived | Newsome PN, Sanyal AJ, Neff G, Schattenberg JM, Ratziu V, Ertle J, Link J, Mackie A, Schoelch C, Lawitz E; BI 1467335 NASH Phase IIa trial team. A randomised Phase IIa trial of amine oxidase copper-containing 3 (AOC3) inhibitor BI 1467335 in adults with non-alcoholic steatohepatitis. Nat Commun. 2023 Nov 6;14(1):7151. doi: 10.1038/s41467-023-42398-w. |
| Label | URL |
|---|---|
| Related Info | View source |
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All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
This study is a multi-centre, double-blind, parallel-group, randomised, placebo-controlled phase IIa study to investigate safety, tolerability, pharmacodynamics, and pharmacokinetics of different doses of orally administered BI 1467335 (for 12-weeks) compared to placebo in patients with clinical evidence of Non-alcoholic steato-hepatitis (NASH).
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Matching placebo taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated placebo tablets were supplied. For blinding reasons, all patients took 5 tablets placebo daily. |
| FG001 | BI 1467335 1 Milligram (mg) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 12, 2018 | May 27, 2020 |
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| Placebo | Drug | once daily |
|
Alanine aminotransaminase (ALT) after 12 weeks of treatment, relative to baseline in percent. Number analyzed lower than N in PPS if there is missing data for specific timepoints. The unit of measure is: percentage relative to baseline = [post baseline (time t)/baseline]*100% Statistical analyses description: A Mixed effects Model for Repeated Measurements (MMRM) over time including fixed effects for 'base', 'treatment', 'time', 'base*time' interaction, and 'treatment*time' interaction was performed. The MMRM estimates for the treatment effects at Week 12 and the corresponding covariance matrix were used to analyse the dose-response relationship using the Multiple contrast test (MCPMod). A test for non-flat dose-response relationship was first performed. If this relationship could be shown, the best fitting model out of a set of candidate models (Sigmoidal Emax, Logistic, Quadratic, Linear, Exponential, Linear logistic, Emax and Betamod) was to be selected and fitted. |
| Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335. |
| Aspartate Aminotransferase (AST) After 12 Weeks of Treatment, Relative to Baseline in Percent | Aspartate aminotransferase (AST) after 12 weeks of treatment, relative to baseline in percent. Number analyzed lower than N in PPS if there is missing data for specific timepoints. The unit of measure is: percentage relative to baseline = [post baseline (time t)/baseline]*100% Statistical analyses description: A Mixed effects Model for Repeated Measurements (MMRM) over time including fixed effects for 'base', 'treatment', 'time', 'base*time' interaction, and 'treatment*time' interaction was performed. The MMRM estimates for the treatment effects at Week 12 and the corresponding covariance matrix were used to analyse the dose-response relationship using the Multiple contrast test (MCPMod). A test for non-flat dose-response relationship was first performed. If this relationship could be shown, the best fitting model out of a set of candidate models (Sigmoidal Emax, Logistic, Quadratic, Linear, Exponential, Linear logistic, Emax and Betamod) was to be selected and fitted. | Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335. |
| Alkaline Phosphatase (AP) After 12 Weeks of Treatment, Relative to Baseline in Percent | Alkaline phosphatase (AP) after 12 weeks of treatment, relative to baseline in percent. Number analyzed lower than N in PPS if there is missing data for specific timepoints. The unit of measure is: percentage relative to baseline = [post baseline (time t)/baseline]*100% Statistical analyses description: A Mixed effects Model for Repeated Measurements (MMRM) over time including fixed effects for 'base', 'treatment', 'time', 'base*time' interaction, and 'treatment*time' interaction was performed. The MMRM estimates for the treatment effects at Week 12 and the corresponding covariance matrix were used to analyse the dose-response relationship using the Multiple contrast test (MCPMod). A test for non-flat dose-response relationship was first performed. If this relationship could be shown, the best fitting model out of a set of candidate models (Sigmoidal Emax, Logistic, Quadratic, Linear, Exponential, Linear logistic, Emax and Betamod) was to be selected and fitted. | Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335. |
| Gamma-glutamyltransferase (GGT) After 12 Weeks of Treatment, Relative to Baseline in Percent | Gamma-glutamyltransferase (GGT) after 12 weeks of treatment, relative to baseline in percent. Number analyzed lower than N in PPS if there is missing data for specific timepoints. The unit of measure is: percentage relative to baseline = [post baseline (time t)/baseline]*100% Statistical analyses description: A Mixed effects Model for Repeated Measurements (MMRM) over time including fixed effects for 'base', 'treatment', 'time', 'base*time' interaction, and 'treatment*time' interaction was performed. The MMRM estimates for the treatment effects at Week 12 and the corresponding covariance matrix were used to analyse the dose-response relationship using the Multiple contrast test (MCPMod). A test for non-flat dose-response relationship was first performed. If this relationship could be shown, the best fitting model out of a set of candidate models (Sigmoidal Emax, Logistic, Quadratic, Linear, Exponential, Linear logistic, Emax and Betamod) was to be selected and fitted. | Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335. |
| Caspase-cleaved Cytokeratin 18 (CK-18 Caspase) After 12 Weeks of Treatment, Relative to Baseline in Percent | Caspase-cleaved cytokeratin 18 (CK-18 caspase) after 12 weeks of treatment, relative to baseline in percent. Number analyzed lower than N in PPS if there is missing data for specific timepoints. The unit of measure is: percentage relative to baseline = [post baseline (time t)/baseline]*100% Statistical analyses description: A MMRM over time including fixed effects for 'base', 'treatment', 'time', 'base*time' interaction, and 'treatment*time' interaction was performed. The MMRM estimates for the treatment effects at Week 12 and the corresponding covariance matrix were used to analyse the dose-response relationship using the Multiple contrast test (MCPMod). A test for non-flat dose-response relationship was first performed. If this relationship could be shown, the best fitting model out of a set of candidate models (Sigmoidal Emax, Logistic, Quadratic, Linear, Exponential, Linear logistic, Emax and Betamod) was to be selected and fitted. | Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335. |
| Total Cytokeratin 18 (CK-18 Total) After 12 Weeks of Treatment, Relative to Baseline in Percent | Total cytokeratin 18 (CK-18 total) after 12 weeks of treatment, relative to baseline in percent. Number analyzed lower than N in PPS if there is missing data for specific timepoints. The unit of measure is: percentage relative to baseline = [post baseline (time t)/baseline]*100%. Statistical analyses description: A Mixed effects Model for Repeated Measurements (MMRM) over time including fixed effects for 'base', 'treatment', 'time', 'base*time' interaction, and 'treatment*time' interaction was performed. The MMRM estimates for the treatment effects at Week 12 and the corresponding covariance matrix were used to analyse the dose-response relationship using the Multiple contrast test (MCPMod). A test for non-flat dose-response relationship was first performed. If this relationship could be shown, the best fitting model out of a set of candidate models (Sigmoidal Emax, Logistic, Quadratic, Linear, Exponential, Linear logistic, Emax and Betamod) was to be selected and fitted. | Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335. |
| La Jolla |
| California |
| 92037 |
| United States |
| eStudySite | La Mesa | California | 91942 | United States |
| National Research Institute | Los Angeles | California | 90057 | United States |
| National Research Institute | Los Angeles | California | 90255 | United States |
| Quest Clinical Research | San Francisco | California | 94115 | United States |
| Florida Research Institute | Lakewood Rch | Florida | 34211 | United States |
| Genoma Research Group, Inc | Miami | Florida | 33165 | United States |
| Rutgers Robert Wood Johnson Medical School | New Brunswick | New Jersey | 08901 | United States |
| Northwell Health | Manhasset | New York | 11030 | United States |
| The University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | 27599 | United States |
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| Diabetes and Endocrinology Consultants, PC | Morehead City | North Carolina | 28557 | United States |
| Dallas Diabetes and Endocrine Center | Dallas | Texas | 75230 | United States |
| Pinnacle Clinical Research | Live Oak | Texas | 78233 | United States |
| American Research Corporation at the Texas Liver Institute | San Antonio | Texas | 78215 | United States |
| Virginia Commonwealth University | Richmond | Virginia | 23298 | United States |
| Edegem - UNIV UZ Antwerpen | Edegem | 2650 | Belgium |
| AZ Maria Middelares | Ghent | 9000 | Belgium |
| UZ Leuven | Leuven | 3000 | Belgium |
| Centre Hospitalier Universitaire de Liège | Liège | 4000 | Belgium |
| University of Calgary | Calgary | Alberta | T2N 4Z6 | Canada |
| Toronto Liver Centre | Toronto | Ontario | M6H 3M1 | Canada |
| HOP Claude Huriez | Lille | 59037 | France |
| HOP La Pitié Salpêtrière | Paris | 75651 | France |
| Universitätsklinikum Aachen, AöR | Aachen | 52074 | Germany |
| Universitätsklinikum Köln (AöR) | Cologne | 50937 | Germany |
| Universitätsklinikum Frankfurt | Frankfurt am Main | 60590 | Germany |
| Universitätsklinikum Leipzig | Leipzig | 04103 | Germany |
| Universitätsmedizin der Johannes Gutenberg-Universität Mainz | Mainz | 55131 | Germany |
| Universitätsklinikum Würzburg | Würzburg | 97080 | Germany |
| St James's Hospital | Dublin | 8 | Ireland |
| Amsterdam UMC, Locatie AMC | Amsterdam | 1105 AZ | Netherlands |
| Maastricht Universitair Medisch Centrum | Maastricht | 6229 HX | Netherlands |
| Radboud Universitair Medisch Centrum | Nijmegen | 6525 GA | Netherlands |
| Hospital Vall d'Hebron | Barcelona | 08035 | Spain |
| Hospital Virgen de la Victoria | Málaga | 29010 | Spain |
| Hospital Universitario Marqués de Valdecilla | Santander | 39008 | Spain |
| Hospital Virgen del Rocío | Seville | 41013 | Spain |
| Hospital General Universitario de Valencia | Valencia | 46014 | Spain |
| Queen Elizabeth Hospital | Birmingham | B15 2TH | United Kingdom |
| Aintree University Hospital | Liverpool | L9 7AL | United Kingdom |
| Manchester Royal Infirmary | Manchester | M13 9WL | United Kingdom |
| Royal Stoke University Hospital | Stoke-on-Trent | ST4 6QG | United Kingdom |
1 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| FG002 | BI 1467335 3 Milligram (mg) | 3 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| FG003 | BI 1467335 6 Milligram (mg) | 6 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| FG004 | BI 1467335 10 Milligram (mg) | 10 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| Treated |
|
| COMPLETED |
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| NOT COMPLETED |
|
|
Treated Set (TS): all patients who signed the informed consent and were treated with at least one dose of the trial medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Matching placebo taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated placebo tablets were supplied. For blinding reasons, all patients took 5 tablets placebo daily. |
| BG001 | BI 1467335 1 Milligram (mg) | 1 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| BG002 | BI 1467335 3 Milligram (mg) | 3 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| BG003 | BI 1467335 6 Milligram (mg) | 6 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| BG004 | BI 1467335 10 Milligram (mg) | 10 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Plasma amine oxidase copper-containing 3 (AOC3) baseline concentration | Plasma amine oxidase copper-containing 3 (AOC3) baseline concentration | Treated Set (TS): all patients who signed the informed consent and were treated with at least one dose of the trial medication. For 3 patients no AOC3 baseline data was collected. | Mean | Standard Deviation | microgram per liter (µg/l) |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Plasma Amine Oxidase Copper-containing 3 (AOC3) Activity After 12 Weeks of Treatment, Relative to Baseline in Percent | The patient-specific plasma AOC3 activity at time t (24 hours after the last dose in week 12) relative to baseline in percentage was calculated as follows: %AOC3at = [(AOC3at - AOC3at,back) ⁄ (AOC3abase - AOC3abase,back)]*100 With AOC3at the AOC3 activity measured at time t, AOC3at,back the background noise at time t, AOC3abase the AOC3 activity measured at baseline and AOC3abase,back the background noise at baseline. A dose-response relationship was analysed using a non-linear regression model to estimate the daily dosage needed to reach 10% of AOC3 activity (i.e. 90% inhibition) 12 weeks after treatment. | Per Protocol Set (PPS): Patients who signed informed consent, were treated with at least one dose of the trial medication, without any important protocol deviations leading to exclusion and who had non-missing baseline and at least one non-missing post-baseline and on-treatment measurement on any primary, secondary or further biomarker endpoint. | Posted | Mean | Standard Deviation | Percentage relative to baseline | Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335. |
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| Secondary | Percentage of Participants With Drug-related Adverse Events (AEs) | Percentage of participants with drug-related adverse events (AEs). Percentages are calculated using total number of patients per treatment as the denominator. | Treated Set (TS): All patients who signed the informed consent and were treated with at least one dose of the trial medication. | Posted | Number | Percentage of participants | Start of treatment till end of treatment + 28 days, up to 113 days. |
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| Secondary | Alanine Aminotransaminase (ALT) After 12 Weeks of Treatment, Relative to Baseline in Percent | Alanine aminotransaminase (ALT) after 12 weeks of treatment, relative to baseline in percent. Number analyzed lower than N in PPS if there is missing data for specific timepoints. The unit of measure is: percentage relative to baseline = [post baseline (time t)/baseline]*100% Statistical analyses description: A Mixed effects Model for Repeated Measurements (MMRM) over time including fixed effects for 'base', 'treatment', 'time', 'base*time' interaction, and 'treatment*time' interaction was performed. The MMRM estimates for the treatment effects at Week 12 and the corresponding covariance matrix were used to analyse the dose-response relationship using the Multiple contrast test (MCPMod). A test for non-flat dose-response relationship was first performed. If this relationship could be shown, the best fitting model out of a set of candidate models (Sigmoidal Emax, Logistic, Quadratic, Linear, Exponential, Linear logistic, Emax and Betamod) was to be selected and fitted. | Per Protocol Set (PPS): Patients who signed informed consent, were treated with at least one dose of the trial medication, without any important protocol deviations leading to exclusion and who had non-missing baseline and at least one non-missing post-baseline and on-treatment measurement on any primary, secondary or further biomarker endpoint. | Posted | Mean | Standard Error | Percentage relative to baseline | Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335. |
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| Secondary | Aspartate Aminotransferase (AST) After 12 Weeks of Treatment, Relative to Baseline in Percent | Aspartate aminotransferase (AST) after 12 weeks of treatment, relative to baseline in percent. Number analyzed lower than N in PPS if there is missing data for specific timepoints. The unit of measure is: percentage relative to baseline = [post baseline (time t)/baseline]*100% Statistical analyses description: A Mixed effects Model for Repeated Measurements (MMRM) over time including fixed effects for 'base', 'treatment', 'time', 'base*time' interaction, and 'treatment*time' interaction was performed. The MMRM estimates for the treatment effects at Week 12 and the corresponding covariance matrix were used to analyse the dose-response relationship using the Multiple contrast test (MCPMod). A test for non-flat dose-response relationship was first performed. If this relationship could be shown, the best fitting model out of a set of candidate models (Sigmoidal Emax, Logistic, Quadratic, Linear, Exponential, Linear logistic, Emax and Betamod) was to be selected and fitted. | Per Protocol Set (PPS): Patients who signed informed consent, were treated with at least one dose of the trial medication, without any important protocol deviations leading to exclusion and who had non-missing baseline and at least one non-missing post-baseline and on-treatment measurement on any primary, secondary or further biomarker endpoint. | Posted | Mean | Standard Error | Percentage relative to baseline | Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335. |
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| Secondary | Alkaline Phosphatase (AP) After 12 Weeks of Treatment, Relative to Baseline in Percent | Alkaline phosphatase (AP) after 12 weeks of treatment, relative to baseline in percent. Number analyzed lower than N in PPS if there is missing data for specific timepoints. The unit of measure is: percentage relative to baseline = [post baseline (time t)/baseline]*100% Statistical analyses description: A Mixed effects Model for Repeated Measurements (MMRM) over time including fixed effects for 'base', 'treatment', 'time', 'base*time' interaction, and 'treatment*time' interaction was performed. The MMRM estimates for the treatment effects at Week 12 and the corresponding covariance matrix were used to analyse the dose-response relationship using the Multiple contrast test (MCPMod). A test for non-flat dose-response relationship was first performed. If this relationship could be shown, the best fitting model out of a set of candidate models (Sigmoidal Emax, Logistic, Quadratic, Linear, Exponential, Linear logistic, Emax and Betamod) was to be selected and fitted. | Per Protocol Set (PPS): Patients who signed informed consent, were treated with at least one dose of the trial medication, without any important protocol deviations leading to exclusion and who had non-missing baseline and at least one non-missing post-baseline and on-treatment measurement on any primary, secondary or further biomarker endpoint. | Posted | Mean | Standard Error | Percentage relative to baseline | Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335. |
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| Secondary | Gamma-glutamyltransferase (GGT) After 12 Weeks of Treatment, Relative to Baseline in Percent | Gamma-glutamyltransferase (GGT) after 12 weeks of treatment, relative to baseline in percent. Number analyzed lower than N in PPS if there is missing data for specific timepoints. The unit of measure is: percentage relative to baseline = [post baseline (time t)/baseline]*100% Statistical analyses description: A Mixed effects Model for Repeated Measurements (MMRM) over time including fixed effects for 'base', 'treatment', 'time', 'base*time' interaction, and 'treatment*time' interaction was performed. The MMRM estimates for the treatment effects at Week 12 and the corresponding covariance matrix were used to analyse the dose-response relationship using the Multiple contrast test (MCPMod). A test for non-flat dose-response relationship was first performed. If this relationship could be shown, the best fitting model out of a set of candidate models (Sigmoidal Emax, Logistic, Quadratic, Linear, Exponential, Linear logistic, Emax and Betamod) was to be selected and fitted. | Per Protocol Set (PPS): Patients who signed informed consent, were treated with at least one dose of the trial medication, without any important protocol deviations leading to exclusion and who had non-missing baseline and at least one non-missing post-baseline and on-treatment measurement on any primary, secondary or further biomarker endpoint. | Posted | Mean | Standard Error | Percentage relative to baseline | Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335. |
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| Secondary | Caspase-cleaved Cytokeratin 18 (CK-18 Caspase) After 12 Weeks of Treatment, Relative to Baseline in Percent | Caspase-cleaved cytokeratin 18 (CK-18 caspase) after 12 weeks of treatment, relative to baseline in percent. Number analyzed lower than N in PPS if there is missing data for specific timepoints. The unit of measure is: percentage relative to baseline = [post baseline (time t)/baseline]*100% Statistical analyses description: A MMRM over time including fixed effects for 'base', 'treatment', 'time', 'base*time' interaction, and 'treatment*time' interaction was performed. The MMRM estimates for the treatment effects at Week 12 and the corresponding covariance matrix were used to analyse the dose-response relationship using the Multiple contrast test (MCPMod). A test for non-flat dose-response relationship was first performed. If this relationship could be shown, the best fitting model out of a set of candidate models (Sigmoidal Emax, Logistic, Quadratic, Linear, Exponential, Linear logistic, Emax and Betamod) was to be selected and fitted. | Per Protocol Set (PPS): Patients who signed informed consent, were treated with at least one dose of the trial medication, without any important protocol deviations leading to exclusion and who had non-missing baseline and at least one non-missing post-baseline and on-treatment measurement on any primary, secondary or further biomarker endpoint. | Posted | Mean | Standard Error | Percentage relative to baseline | Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335. |
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| Secondary | Total Cytokeratin 18 (CK-18 Total) After 12 Weeks of Treatment, Relative to Baseline in Percent | Total cytokeratin 18 (CK-18 total) after 12 weeks of treatment, relative to baseline in percent. Number analyzed lower than N in PPS if there is missing data for specific timepoints. The unit of measure is: percentage relative to baseline = [post baseline (time t)/baseline]*100%. Statistical analyses description: A Mixed effects Model for Repeated Measurements (MMRM) over time including fixed effects for 'base', 'treatment', 'time', 'base*time' interaction, and 'treatment*time' interaction was performed. The MMRM estimates for the treatment effects at Week 12 and the corresponding covariance matrix were used to analyse the dose-response relationship using the Multiple contrast test (MCPMod). A test for non-flat dose-response relationship was first performed. If this relationship could be shown, the best fitting model out of a set of candidate models (Sigmoidal Emax, Logistic, Quadratic, Linear, Exponential, Linear logistic, Emax and Betamod) was to be selected and fitted. | Per Protocol Set (PPS): patients who signed informed consent, were treated with at least one dose of the trial medication, without any important protocol deviations leading to exclusion and who had non-missing baseline and at least one non-missing post-baseline and on-treatment measurement on any primary, secondary or further biomarker endpoint. | Posted | Mean | Standard Error | Percentage relative to baseline | Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335. |
|
start of treatment till end of treatment + 28 days, up to 113 days.
Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Matching placebo taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated placebo tablets were supplied. For blinding reasons, all patients took 5 tablets placebo daily. | 0 | 32 | 1 | 32 | 18 | 32 |
| EG001 | BI 1467335 1 Milligram (mg) | 1 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. | 0 | 16 | 1 | 16 | 12 | 16 |
| EG002 | BI 1467335 3 Milligram (mg) | 3 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. | 0 | 16 | 1 | 16 | 12 | 16 |
| EG003 | BI 1467335 6 Milligram (mg) | 6 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. | 0 | 17 | 0 | 17 | 13 | 17 |
| EG004 | BI 1467335 10 Milligram (mg) | 10 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. | 0 | 32 | 0 | 32 | 17 | 32 |
| EG005 | Total BI 1467335 | All participant who took a dose of BI 1467335. | 0 | 81 | 2 | 81 | 54 | 81 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pancreatitis | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| H1N1 influenza | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Nasal septum deviation | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vertigo | Ear and labyrinth disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Abdominal pain lower | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Pouchitis | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Early satiety | General disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hepatic pain | Hepatobiliary disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Gastroenteritis bacterial | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Otitis media | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Tooth abscess | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Tooth infection | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Concussion | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment |
| |
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment |
| |
| Post-traumatic neck syndrome | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment |
| |
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment |
| |
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment |
| |
| Vascular procedure complication | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Blood glucose increased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Weight increased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Diabetes mellitus inadequate control | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hyperlipidaemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Anogenital warts | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.0 | Systematic Assessment |
| |
| Disturbance in attention | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Sciatica | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Tension headache | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Dry throat | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Paranasal sinus discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Sinus pain | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Orthostatic hypotension | Vascular disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Subclavian steal syndrome | Vascular disorders | MedDRA 22.0 | Systematic Assessment |
|
Global Amendment 5 (dated 12 Sep 2018): Sample size reduction from 147 to 108 randomised patients due to a lower expected variability for ALT based on new external and blinded internal data.
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 10, 2017 | May 27, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
Not provided
Not provided
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|
| OG003 | BI 1467335 6 Milligram (mg) | 6 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| OG004 | BI 1467335 10 Milligram (mg) | 10 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
|
|
| OG001 | BI 1467335 1 Milligram (mg) | 1 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| OG002 | BI 1467335 3 Milligram (mg) | 3 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| OG003 | BI 1467335 6 Milligram (mg) | 6 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| OG004 | BI 1467335 10 Milligram (mg) | 10 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
|
|
|
| OG001 | BI 1467335 1 Milligram (mg) | 1 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| OG002 | BI 1467335 3 Milligram (mg) | 3 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| OG003 | BI 1467335 6 Milligram (mg) | 6 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| OG004 | BI 1467335 10 Milligram (mg) | 10 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
|
|
|
| OG001 | BI 1467335 1 Milligram (mg) | 1 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| OG002 | BI 1467335 3 Milligram (mg) | 3 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| OG003 | BI 1467335 6 Milligram (mg) | 6 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| OG004 | BI 1467335 10 Milligram (mg) | 10 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
|
|
|
| OG001 | BI 1467335 1 Milligram (mg) | 1 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| OG002 | BI 1467335 3 Milligram (mg) | 3 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| OG003 | BI 1467335 6 Milligram (mg) | 6 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| OG004 | BI 1467335 10 Milligram (mg) | 10 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
|
|
|
| OG001 | BI 1467335 1 Milligram (mg) | 1 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| OG002 | BI 1467335 3 Milligram (mg) | 3 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| OG003 | BI 1467335 6 Milligram (mg) | 6 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| OG004 | BI 1467335 10 Milligram (mg) | 10 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
|
|
|
| OG001 | BI 1467335 1 Milligram (mg) | 1 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| OG002 | BI 1467335 3 Milligram (mg) | 3 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| OG003 | BI 1467335 6 Milligram (mg) | 6 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
| OG004 | BI 1467335 10 Milligram (mg) | 10 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily. |
|
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|