Chronic Thromboembolic Pulmonary Hypertension
Conditions
Keywords
Chronic thromboembolic pulmonary hypertension (CTEPH)
Brief summary
Long-term study to evaluate if macitentan is safe, tolerable and efficient enough to be used for treatment of inoperable chronic thromboembolic pulmonary hypertension (CTEPH)
Interventions
DRUGMacitentan
Macitentan 10mg, oral tablet, once daily
Sponsors
Actelion
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent * Subject with CTEPH having completed the double-blind (DB) AC-055E201/ MERIT-1 study as scheduled (i.e., who remained in the DB study up to Week 24). * Females of childbearing potential must have a negative pre-treatment serum pregnancy test, be advised on appropriate methods of contraception, and agree to use 2 reliable methods of contraception.
Exclusion criteria
* Permanent discontinuation of DB study treatment due to an hepatic adverse event or liver aminotransferase abnormalities. * Any known factor (e.g., drug or substance abuse) or disease (e.g., unstable psychiatric illness) that, in the opinion of the investigator, may interfere with treatment compliance or interpretation of the results, or that may influence the ability to comply with any of the study requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to 30 days after study treatment discontinuation (treatment exposure ranged from 1 to 82 months) | An adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. TEAEs are those events that started after administration of the first dose and up to safety follow-up visit/end of study, that is, 30 days after the last dose of study medication. |
| Number of Participants With AEs Leading to Study Drug Discontinuation | Up to 30 days after study treatment discontinuation (treatment exposure ranged from 1 to 82 months) | Number of participants with AEs leading to study drug discontinuation was reported. |
| Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) | Up to 30 days after study treatment discontinuation (treatment exposure ranged from 1 to 82 months) | A serious adverse event (SAE) is any untoward medical occurrence that at any dose resulting in any of following outcomes: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product. Treatment-emergent SAEs were those events that started after administration of the first dose and up to safety follow-up visit/end of study, that is, 30 days after the last dose of study medication. |
| Number of Participants With Hemoglobin Abnormalities | Up to 30 days after study treatment discontinuation (treatment exposure ranged from 1 to 82 months) | Number of participants with hemoglobin abnormalities were reported. It included hemoglobin less than (\<) 80 grams per liter (g/L), hemoglobin \<100 g/L, hemoglobin greater than or equal to (\>=) 80 g/L and \<100 g/L, hemoglobin \<100g/L and a decrease of \>20 g/L from baseline, decrease of \>20 g/L in hemoglobin from baseline, decrease of \>20 g/L and \<=50 g/L in hemoglobin from baseline, and decrease of \>50 g/L in hemoglobin from baseline. |
| Number of Participants With Liver Tests Abnormalities | Up to 30 days after study treatment discontinuation (treatment exposure ranged from 1 to 82 months) | Number of participants with liver tests abnormalities were reported. It included alanine aminotransferase (ALT) or aspartate aminotransferase (AST): \>=3 x Upper limit of the normal range (ULN), \>=3 and \<5 x ULN, \>=5 ULN, and \>=5 and \<8 x ULN, \>= 8 x ULN, and total bilirubin \>=2 x ULN. |
| Change From Baseline in Blood Pressure at Month 6 | Baseline and Month 6 | Change from baseline in blood pressure at Month 6 (both systolic blood pressure \[SBP\] and diastolic blood pressure \[DBP\]) was reported. |
| Change From Baseline in Pulse Rate at Month 6 | Baseline and Month 6 | Change from baseline in pulse rate at Month 6 was reported. |
| Change From Baseline in Body Weight at Month 6 | Baseline and Month 6 | Change from baseline in body weight at Month 6 was reported. |
Countries
Belgium, China, Czechia, France, Germany, Hungary, Lithuania, Mexico, Poland, Russia, Switzerland, Thailand, Turkey (Türkiye), Ukraine, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Macitentan 10 Milligrams (mg) Eligible participants who were either randomized to macitentan 10 mg or placebo group during 24 weeks double-blind MERIT-1 (NCT02021292) study, were rolled-over to this open-label extension study and received macitentan 10 mg tablet orally once daily starting from Day 1 to the end of treatment (treatment exposure ranged from 1 to 82 months). | 76 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Compliance with local regulation: enrolled in China | 19 |
| Overall Study | Death | 14 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Macitentan 10 Milligrams (mg) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 28 Participants |
| Age, Categorical Between 18 and 65 years | 48 Participants |
| Age, Continuous | 57.8 years STANDARD_DEVIATION 13.99 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 74 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 27 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 49 Participants |
| Sex: Female, Male Female | 48 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 14 / 76 |
| other Total, other adverse events | 67 / 76 |
| serious Total, serious adverse events | 44 / 76 |
Outcome results
Primary
Change From Baseline in Blood Pressure at Month 6
Change from baseline in blood pressure at Month 6 (both systolic blood pressure \[SBP\] and diastolic blood pressure \[DBP\]) was reported.
Time frame: Baseline and Month 6
Population: OLAS included all data from participants who were enrolled into this open-label extension study, from the time they entered this open-label extension study. Here, 'N' (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Macitentan 10 Milligrams (mg) | Change From Baseline in Blood Pressure at Month 6 | SBP | -0.4 Millimeters of mercury (mmHg) | Standard Deviation 13.15 |
| Macitentan 10 Milligrams (mg) | Change From Baseline in Blood Pressure at Month 6 | DBP | -2.8 Millimeters of mercury (mmHg) | Standard Deviation 9.51 |
Primary
Change From Baseline in Body Weight at Month 6
Change from baseline in body weight at Month 6 was reported.
Time frame: Baseline and Month 6
Population: OLAS included all data from participants who were enrolled into this open-label extension study, from the time they entered this open-label extension study. Here, 'N' (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Macitentan 10 Milligrams (mg) | Change From Baseline in Body Weight at Month 6 | -0.35 kilograms (kg) | Standard Deviation 2.871 |
Primary
Change From Baseline in Pulse Rate at Month 6
Change from baseline in pulse rate at Month 6 was reported.
Time frame: Baseline and Month 6
Population: OLAS included all data from participants who were enrolled into this open-label extension study, from the time they entered this open-label extension study. Here, 'N' (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Macitentan 10 Milligrams (mg) | Change From Baseline in Pulse Rate at Month 6 | -1.1 Beats per minute | Standard Deviation 8.76 |
Primary
Number of Participants With AEs Leading to Study Drug Discontinuation
Number of participants with AEs leading to study drug discontinuation was reported.
Time frame: Up to 30 days after study treatment discontinuation (treatment exposure ranged from 1 to 82 months)
Population: OLAS included all data from participants who were enrolled into this open-label extension study, from the time they entered this open-label extension study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Macitentan 10 Milligrams (mg) | Number of Participants With AEs Leading to Study Drug Discontinuation | 9 Participants |
Primary
Number of Participants With Hemoglobin Abnormalities
Number of participants with hemoglobin abnormalities were reported. It included hemoglobin less than (\<) 80 grams per liter (g/L), hemoglobin \<100 g/L, hemoglobin greater than or equal to (\>=) 80 g/L and \<100 g/L, hemoglobin \<100g/L and a decrease of \>20 g/L from baseline, decrease of \>20 g/L in hemoglobin from baseline, decrease of \>20 g/L and \<=50 g/L in hemoglobin from baseline, and decrease of \>50 g/L in hemoglobin from baseline.
Time frame: Up to 30 days after study treatment discontinuation (treatment exposure ranged from 1 to 82 months)
Population: OLAS included all data from participants who were enrolled into this open-label extension study, from the time they entered this open-label extension study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Macitentan 10 Milligrams (mg) | Number of Participants With Hemoglobin Abnormalities | Hemoglobin < 80 g/L | 0 Participants |
| Macitentan 10 Milligrams (mg) | Number of Participants With Hemoglobin Abnormalities | Hemoglobin <100 g/L | 7 Participants |
| Macitentan 10 Milligrams (mg) | Number of Participants With Hemoglobin Abnormalities | Hemoglobin >= 80 g/L and <100 g/L | 7 Participants |
| Macitentan 10 Milligrams (mg) | Number of Participants With Hemoglobin Abnormalities | Hemoglobin <100g/L and a decrease of >20 g/L from baseline | 6 Participants |
| Macitentan 10 Milligrams (mg) | Number of Participants With Hemoglobin Abnormalities | Decrease of >20 g/L in hemoglobin from baseline | 32 Participants |
| Macitentan 10 Milligrams (mg) | Number of Participants With Hemoglobin Abnormalities | Decrease of >20 g/L and <=50 g/L in hemoglobin from baseline | 31 Participants |
| Macitentan 10 Milligrams (mg) | Number of Participants With Hemoglobin Abnormalities | Decrease of >50 g/L in hemoglobin from baseline | 5 Participants |
Primary
Number of Participants With Liver Tests Abnormalities
Number of participants with liver tests abnormalities were reported. It included alanine aminotransferase (ALT) or aspartate aminotransferase (AST): \>=3 x Upper limit of the normal range (ULN), \>=3 and \<5 x ULN, \>=5 ULN, and \>=5 and \<8 x ULN, \>= 8 x ULN, and total bilirubin \>=2 x ULN.
Time frame: Up to 30 days after study treatment discontinuation (treatment exposure ranged from 1 to 82 months)
Population: OLAS included all data from participants who were enrolled into this open-label extension study, from the time they entered this open-label extension study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Macitentan 10 Milligrams (mg) | Number of Participants With Liver Tests Abnormalities | ALT or AST >=3 x ULN | 2 Participants |
| Macitentan 10 Milligrams (mg) | Number of Participants With Liver Tests Abnormalities | ALT or AST >=3 and <5 x ULN | 1 Participants |
| Macitentan 10 Milligrams (mg) | Number of Participants With Liver Tests Abnormalities | ALT or AST >=5 x ULN | 1 Participants |
| Macitentan 10 Milligrams (mg) | Number of Participants With Liver Tests Abnormalities | ALT or AST >=5 and <8 x ULN | 0 Participants |
| Macitentan 10 Milligrams (mg) | Number of Participants With Liver Tests Abnormalities | ALT or AST >=8 x ULN | 1 Participants |
| Macitentan 10 Milligrams (mg) | Number of Participants With Liver Tests Abnormalities | Total Bilirubin >=2 x ULN | 8 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. TEAEs are those events that started after administration of the first dose and up to safety follow-up visit/end of study, that is, 30 days after the last dose of study medication.
Time frame: Up to 30 days after study treatment discontinuation (treatment exposure ranged from 1 to 82 months)
Population: Open-label analysis set (OLAS) included all data from participants who were enrolled into this open-label extension study, from the time they entered this open-label extension study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Macitentan 10 Milligrams (mg) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 72 Participants |
Primary
Number of Participants With Treatment-emergent Serious Adverse Events (SAEs)
A serious adverse event (SAE) is any untoward medical occurrence that at any dose resulting in any of following outcomes: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product. Treatment-emergent SAEs were those events that started after administration of the first dose and up to safety follow-up visit/end of study, that is, 30 days after the last dose of study medication.
Time frame: Up to 30 days after study treatment discontinuation (treatment exposure ranged from 1 to 82 months)
Population: OLAS included all data from participants who were enrolled into this open-label extension study, from the time they entered this open-label extension study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Macitentan 10 Milligrams (mg) | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) | 44 Participants |