Phase 3 N=137 Randomized Quadruple-blind Treatment

Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects

Congenital Heart Disease

Bottom Line

View on ClinicalTrials.gov: NCT03153137 ↗

Enrolled (actual)

137

Serious AEs

16.1%

Results posted

Sep 2022

Primary outcome: Primary: Change From Baseline in Peak Oxygen Uptake/Consumption (VO2) Up to Week 16 — -0.67; -0.16 Milliliter/kilogram/minute (mL/kg/min) — p== 0.1930

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Macitentan 10 mg (Drug); Placebo (Drug)
Age: Pediatric, Adult, Older Adult · 12+ yrs
Sex: All
Sponsor: Actelion
Primary completion: Jun 2021

Outcome Measures

Outcome	Result	p-value
PRIMARY Change From Baseline in Peak Oxygen Uptake/Consumption (VO2) Up to Week 16	-0.67; -0.16	= 0.1930
SECONDARY Change From Baseline in Peak VO2 Up to Week 52	-0.92; -0.31	—
SECONDARY Change From Baseline in Mean Count Per Minute of Daily Physical Activity Measured by Accelerometer (PA-Ac) Up to Week 16	-14.34; -3.02	—
SECONDARY Number of Participants With Treatment-emergent Serious Adverse Events (SAEs)	9; 13	—
SECONDARY Number of Participants With Treatment-emergent Adverse Events (AEs)	44; 48	—
SECONDARY Number of Participants With AEs Leading to Premature Discontinuation of Study Treatment	1; 3	—
SECONDARY Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP)	116.0; 117.0; 2.5; -0.4; 0.5; -4.6	—
SECONDARY Change From Baseline in Pulse Rate	81.3; 78.2; -3.9; -5.9; 0.1; -0.1	—
SECONDARY Change From Baseline in Oxygen Saturation (SpO2)	92.6; 92.8; 0.0; 1.2; 0.5; 0.8	—
SECONDARY Change From Baseline in Body Weight	68.89; 67.38; -0.38; 0.43; 0.21; 0.58	—
SECONDARY Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values	2; 1; 0; 1; 0; 2	—
SECONDARY Change From Baseline in Hemoglobin	160.4; 159.5; 0.0; -8.7; 0.0; -8.7	—
SECONDARY Change From Baseline in Hematocrit	0.472; 0.471; 0.002; -0.030; 0.003; -0.023	—
SECONDARY Change From Baseline in Erythrocytes and Reticulocytes	5.251; 5.205; 0.048; -0.297; 0.012; -0.264	—
SECONDARY Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets	6.270; 5.693; -0.242; -1.001; -0.199; -0.378	—
SECONDARY Change From Baseline in Prothrombin Time	14.72; 15.37; -0.23; -0.53; 0.04; 0.36	—
SECONDARY Change From Baseline in Prothrombin International Normalized Ratio	1.434; 1.516; -0.009; -0.054; 0.015; 0.049	—
SECONDARY Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (AP)	26.7; 28.5; -0.8; -1.8; -0.2; -1.6	—
SECONDARY Change From Baseline in Bilirubin and Direct Bilirubin	14.65; 17.28; 0.62; -1.08; 1.98; -1.76	—
SECONDARY Change From Baseline in Gamma Glutamyl Transferase	67.6; 79.4; -4.8; -5.5; -4.4; 0.7	—
SECONDARY Change From Baseline in Creatinine	78.1; 78.9; -2.0; -6.2; -1.1; -0.3	—
SECONDARY Change From Baseline in Urea Nitrogen	5.26; 5.08; -0.30; -0.09; -0.04; 0.06	—
SECONDARY Change From Baseline in Urate	360.0; 372.7; -0.8; -53.6; 2.8; -37.8	—
SECONDARY Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium	4.97; 5.15; 0.00; -0.46; 0.17; -0.04	—
SECONDARY Change From Baseline in Albumin and Protein	48.64; 49.56; -0.74; -1.73; 0.61; -0.82	—
SECONDARY Change From Baseline in Alpha Fetoprotein	3.145; 3.326; 0.006; -0.061; 0.055; 0.160	—
SECONDARY Change From Baseline in Cystatin C	0.742; 0.718; -0.026; -0.019; -0.017; -0.019	—

Summary

The primary objective is to assess the effect of macitentan 10 mg as compared to placebo on exercise capacity through cardiopulmonary exercise testing.

Eligibility Criteria

Inclusion Criteria

Written informed consent/assent from the subject and/or a legal representative prior to initiation of any study-mandated procedures
Fontan-palliated subjects with either intra-atrial lateral tunnel total cavopulmonary connection (LT-TCPC), or extra cardiac tunnel TCPC (EC-TCPC) surgery > 1 year before Screening. Either LT- or EC-TCPC can be primary or secondary to atrio-pulmonary connection
New York Heart Association (NYHA) functional class (FC) II or III (assessed by the investigator using the Specific Activity Scale
Women of childbearing potential must have a negative serum pregnancy test use reliable contraception

Exclusion Criteria

Pattern of Fontan circulation severity
Deterioration of the Fontan-palliated condition.
Limitations to Cardiopulmonary exercise testing (CPET)
Peak VO2 < 15 mL/kg/min.
Any known factor or disease that may interfere with treatment compliance or full participation in the study

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03153137). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.