| Primary | Change From Baseline in Peak Oxygen Uptake/Consumption (VO2) Up to Week 16 | Change from baseline in peak VO2 up to Week 16 was reported. | Full analysis set (FAS) included all participants randomized to the study treatment. | Posted | | Mean | Standard Deviation | Milliliter/kilogram/minute (mL/kg/min) | | Baseline up to Week 16 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| | | Title | Denominators | Categories |
|---|
| | | Title | Measurements |
|---|
| - OG000-0.67± 2.657(2.657 to )
- OG001-0.16± 2.855(2.855 to )
|
|
| | 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 |
|---|
| Due to adaptive nature of the design, the main analysis was conducted on FAS using the inverse normal combination method with pre-specified weights to combine first and second stage p-values. | ANCOVA | | = 0.1930 | Final adjusted p-value (from weighted inverse normal combination test) | Median unbiased estimate and repeated CI | 0.62 | | | 2-Sided | 99 | -0.62 | 1.85 | | | | | Superiority | For each stage, the p-value from the ANCOVA model including randomized treatment, geographical region, and baseline peak VO2 was used to construct the final adjusted p-value. |
|
| Secondary | Change From Baseline in Peak VO2 Up to Week 52 | Change from baseline in peak VO2 up to Week 52 was reported. | FAS included all participants randomized to the study treatment. | Posted | | Least Squares Mean | Standard Error | mL/kg/min | | Baseline up to Week 52 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Change From Baseline in Mean Count Per Minute of Daily Physical Activity Measured by Accelerometer (PA-Ac) Up to Week 16 | Change from baseline in mean count per minute of daily PA-Ac up to Week 16 was reported. The daily physical activity (counts per min) of the participant was assessed via accelerometer during daytime. The accelerometer was given to the participant at Visit 1, and data was collected for 9 consecutive daily daytime periods after Visit 1 (baseline) to Visit 4 (Week 16). | FAS included all participants randomized to the study treatment. Here, N (number of participants analyzed) is defined as the number of participants evaluable for this outcome measure. | Posted | | Mean | Standard Deviation | counts per minute | | Baseline up to Week 16 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) | SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. | The Safety analysis set included all participants who received at least one dose of study treatment. | Posted | | Count of Participants | | Participants | | Up to 56 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Number of Participants With Treatment-emergent Adverse Events (AEs) | An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. | The Safety analysis set included all participants who received at least one dose of study treatment. | Posted | | Count of Participants | | Participants | | Up to 56 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Number of Participants With AEs Leading to Premature Discontinuation of Study Treatment | Number of participants with AEs leading to premature discontinuation of study treatment was reported. AEs leading to premature discontinuation of study treatment were those with action taken with study drug reported as 'permanently discontinued' by the investigator. | Safety set included all participants who received at least one dose of study treatment. | Posted | | Count of Participants | | Participants | | Up to 56 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) | Change from baseline in systolic and diastolic arterial BP at Week 8, Week 16, Week 32 and Week 52 was reported. | Safety analysis set included all participants who received at least one dose of study treatment. Here, N (number of participants analyzed) signifies participants evaluable for this outcome measure. Here "n" signifies number of participants evaluable at different timepoints. | Posted | | Mean | Standard Deviation | millimeters of mercury (mmHg) | | Baseline, Week 8, Week 16, Week 32 and Week 52 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Change From Baseline in Pulse Rate | Change from baseline in pulse rate at Week 8, Week 16, Week 32 and Week 52 was reported. | Safety analysis set included all participants who received at least one dose of study treatment. Here "n" signifies number of participants evaluable at different timepoints. | Posted | | Mean | Standard Deviation | beats per minute (bpm) | | Baseline, Week 8, Week 16, Week 32 and Week 52 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Change From Baseline in Oxygen Saturation (SpO2) | Change from baseline in SpO2 was reported. | Safety set included all participants who received at least one dose of study treatment. Here "n" signifies number of participants evaluable at different timepoints. | Posted | | Mean | Standard Deviation | percent of oxygen saturation | | Baseline, Week 8, Week 16, Week 32 and Week 52 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Change From Baseline in Body Weight | Change from baseline in body weight was reported. | Safety analysis set included all participants who received at least one dose of study treatment. Here "n" signifies number of participants evaluable at different timepoints. | Posted | | Mean | Standard Deviation | kilograms (kg) | | Baseline, Week 8, Week 16, Week 32 and Week 52 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values | Number of participants with treatment-emergent markedly laboratory abnormal laboratory values were reported. Abnormal values for platelets (LL < 75); Lymphocytes (HH > 4.0); Neutrophils (LL < 1.5); Prothrombin International Normalized Ratio: HH (greater than and equal to [>=] 1.5 upper limit of normal [ULN]), Ratio: HH >= 2.5 ULN); Bilirubin (HH >= 2 ULN); Alkaline Phosphatase (HH > 2.5 ULN); Glomerular Filtration Rate (LL < 60); Glucose (HH > 8.9); Triglycerides (HH > 3.42). Here "HH" refers to values above the normal range, where H stands for "high" and "LL" refers to values below the normal range where L stands for "low". | Safety analysis set included all participants who received at least one dose of study treatment. Here, N (number of participants analyzed) signifies participants evaluable for this outcome measure. | Posted | | Count of Participants | | Participants | | Up to 56 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Change From Baseline in Hemoglobin | Change from baseline in hemoglobin was reported. | Safety analysis set included all participants who received at least one dose of study treatment. Here, N (number of participants analyzed) signifies number of participants evaluable for this outcome measure. Here "n" signifies number of participants evaluable at different timepoints. | Posted | | Mean | Standard Deviation | grams per liter (g/L) | | Baseline, Week 8, Week 16, Week 32 and Week 52 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Change From Baseline in Hematocrit | Change from baseline in hematocrit was reported. | Safety analysis set included all participants who received at least one dose of study treatment. Here, N (number of participants analyzed) signifies participants evaluable for this outcome measure. Here "n" signifies number of participants evaluable at different timepoints. | Posted | | Mean | Standard Deviation | Liter/Liter (L/L) | | Baseline, Week 8, Week 16, Week 32 and Week 52 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Change From Baseline in Erythrocytes and Reticulocytes | Change from baseline in erythrocytes and reticulocytes at Week 8, Week 16, Week 32 and Week 52 was reported. | Safety analysis set included all participants who received at least one dose of study treatment. Here, N (number of participants analyzed) signifies participants evaluable for this outcome measure. Here "n" signifies number of participants evaluable at different timepoints. | Posted | | Mean | Standard Deviation | 10^12 cells per liter | | Baseline, Week 8, Week 16, Week 32 and Week 52 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets | Change from baseline in leucocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils and platelets at Week 8, Week 16, Week 32 and Week 52 was reported. | Safety analysis set included all participants who received at least one dose of study treatment. Here, N (number of participants analyzed) signifies participants evaluable for this outcome measure. Here "n" signifies number of participants evaluable at different timepoints. | Posted | | Mean | Standard Deviation | 10^9 cells per liter | | Baseline, Week 8, Week 16, Week 32 and Week 52 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Change From Baseline in Prothrombin Time | Change from baseline in prothrombin time was reported. | Safety analysis set included all participants who received at least one dose of study treatment. Here, N (number of participants analyzed) signifies participants evaluable for this outcome measure. Here "n" signifies number of participants evaluable at different timepoints. | Posted | | Mean | Standard Deviation | Seconds (sec) | | Baseline, Week 8, Week 16, Week 32 and Week 52 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Change From Baseline in Prothrombin International Normalized Ratio | Change from baseline in prothrombin international normalized ratio was reported. | Safety analysis set included all participants who received at least one dose of study treatment. Here, N (number of participants analyzed) signifies participants evaluable for this outcome measure. Here "n" signifies number of participants evaluable at different timepoints. | Posted | | Mean | Standard Deviation | Ratio | | Baseline, Week 8, Week 16, Week 32 and Week 52 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (AP) | Change from baseline in ALT, AST and AP were reported. | Safety analysis set included all participants who received at least one dose of study treatment. Here "n" signifies number of participants evaluable at different timepoints. | Posted | | Mean | Standard Deviation | Units per liter (U/L) | | Baseline, Week 8, Week 16, Week 32 and Week 52 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Change From Baseline in Bilirubin and Direct Bilirubin | Change from baseline in bilirubin and direct bilirubin was reported. | Safety analysis set included all participants who received at least one dose of study treatment. Here "n" signifies number of participants evaluable at different timepoints. | Posted | | Mean | Standard Deviation | micromole per liter (umol/L) | | Baseline, Week 8, Week 16, Week 32 and Week 52 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Change From Baseline in Gamma Glutamyl Transferase | Change from baseline in gamma glutamyl transferase was reported. | Safety analysis set included all participants who received at least one dose of study treatment. Here "n" signifies number of participants evaluable at different timepoints. | Posted | | Mean | Standard Deviation | Units per liter (U/L) | | Baseline, Week 8, Week 16, Week 32 and Week 52 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Change From Baseline in Creatinine | Change from baseline in creatinine was reported. | Safety analysis set included all participants who received at least one dose of study treatment. Here, N (number of participants analyzed) signifies participants evaluable for this outcome measure. Here "n" signifies number of participants evaluable at different timepoints. | Posted | | Mean | Standard Deviation | micromole/liter (umol/L) | | Baseline, Week 8, Week 16, Week 32 and Week 52 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Change From Baseline in Urea Nitrogen | Change from baseline in urea nitrogen was reported. | Safety analysis set included all participants who received at least one dose of study treatment. Here "n" signifies number of participants evaluable at different timepoints. | Posted | | Mean | Standard Deviation | millimoles per liter (mmol/L) | | Baseline, Week 8, Week 16, Week 32 and Week 52 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Change From Baseline in Urate | Change from baseline in urate was reported. | Safety analysis set included all participants who received at least one dose of study treatment. Here "n" signifies number of participants evaluable at different timepoints. | Posted | | Mean | Standard Deviation | umol/L | | Baseline, Week 8, Week 16, Week 32 and Week 52 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium | Change from baseline in glucose, cholesterol, triglycerides, sodium, potassium, chloride and calcium was reported. | Safety analysis set included all participants who received at least one dose of study treatment. Here "n" signifies number of participants evaluable at different timepoints. | Posted | | Mean | Standard Deviation | mmol/L | | Baseline, Week 8, Week 16, Week 32 and Week 52 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Change From Baseline in Albumin and Protein | Change from baseline in albumin and protein was reported. | Safety analysis set included all participants who received at least one dose of study treatment. Here "n" signifies number of participants evaluable at different timepoints. | Posted | | Mean | Standard Deviation | grams per liter (g/L) | | Baseline, Week 8, Week 16, Week 32 and Week 52 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Change From Baseline in Alpha Fetoprotein | Change from baseline in alpha fetoprotein was reported. | Safety analysis set included all participants who received at least one dose of study treatment. Here "n" signifies number of participants evaluable at different timepoints. | Posted | | Mean | Standard Deviation | micrograms per milliliter (ug/L) | | Baseline, Week 8, Week 16, Week 32 and Week 52 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |
| Secondary | Change From Baseline in Cystatin C | Change from baseline in cystatin C was reported. | Safety analysis set included all participants who received at least one dose of study treatment. Here "n" signifies number of participants evaluable at different timepoints. | Posted | | Mean | Standard Deviation | milligrams per liter (mg/L) | | Baseline, Week 8, Week 16, Week 32 and Week 52 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52. | | OG001 | Macitentan | Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52. |
| |