INTRODUCTION
METHODS
Ethics
Subjects
Trial Drug
Study Design
Outcome Measures
Safety/Tolerability
Efficacy Endpoints
Treatment Satisfaction
Statistical Analysis
RESULTS
Patients
Background factors |
N = 8 |
---|---|
Sex, n (%) | |
Male | 1 (12.5) |
Female | 7 (87.5) |
Age, years | |
Mean ± SD | 47.6 ± 12.5 |
Median | 46.0 |
[Min, Max] | [25, 69] |
Age in class | |
20–64 years | 7 (87.5) |
≥65 years | 1 (12.5) |
Race, n (%) | |
Asian | 8 (100.0) |
Body mass index, kg/m2
| |
Mean ± SD | 19.94 ± 2.21 |
Median | 20.40 |
[Min, Max] | [15.4, 23.0] |
Etiology of PAH, n (%) | |
IPAH | 7 (87.5) |
HPAH | 1 (12.5) |
APAH-DT | 0 (0.0) |
APAH-CTD | 0 (0.0) |
Time since PAH diagnosis, years | |
Mean ± SD | 6.21 ± 5.24 |
Median | 5.26 |
[Min, Max] | [0.6, 13.9] |
WHO functional class, n (%) | |
I | 1 (12.5) |
II | 5 (62.5) |
III | 2 (25.0) |
IV | 0 (0.0) |
Safety
Asymptomatic | Mild | Moderate | Severe | Total (n = 8) | |
---|---|---|---|---|---|
All system organ classes | |||||
Total pts with at least one AE | 0 (0.0%) | 7 (87.5) | 3 (37.5%) | 0 (0.0%) | 7 (87.5%) |
Total number of AEs | 0 | 11 | 7 | 0 | 18 |
Gastrointestinal disorders | |||||
Total pts with at least one AE | 0 (0.0%) | 3 (37.5%) | 3 (37.5%) | 0 (0.0%) | 5 (62.5%) |
Total number of AEs | 0 | 3 | 3 | 0 | 6 |
Nausea | 0 (0.0%) | 0 (0.0%) | 2 (25.0%) | 0 (0.0%) | 2 (25.0%) |
Diarrhea | 0 (0.0%) | 0 (0.0%) | 1 (12.5%) | 0 (0.0%) | 1 (12.5%) |
Gastritis | 0 (0.0%) | 1 (12.5%) | 0 (0.0%) | 0 (0.0%) | 1 (12.5%) |
Vomiting | 0 (0.0%) | 1 (12.5%) | 0 (0.0%) | 0 (0.0%) | 1 (12.5%) |
Mikulicz’s disease | 0 (0.0%) | 1 (12.5%) | 0 (0.0%) | 0 (0.0%) | 1 (12.5%) |
Infections and infestations | |||||
Total pts with at least one AE | 0 (0.0%) | 1 (12.5%) | 2 (25.0%) | 0 (0.0%) | 3 (37.5%) |
Total number of AEs | 0 | 1 | 2 | 0 | 3 |
Pharyngitis | 0 (0.0%) | 0 (0.0%) | 1 (12.5%) | 0 (0.0%) | 1 (12.5%) |
Pneumonia | 0 (0.0%) | 0 (0.0%) | 1 (12.5%) | 0 (0.0%) | 1 (12.5%) |
Cellulitis | 0 (0.0%) | 1 (12.5%) | 0 (0.0%) | 0 (0.0%) | 1 (12.5%) |
General disorders and administrations site conditions | |||||
Total pts with at least one AE | 0 (0.0%) | 2 (25.0%) | 0 (0.0%) | 0 (0.0%) | 2 (25.0%) |
Total number of AEs | 0 | 2 | 0 | 0 | 2 |
Device dislocation | 0 (0.0%) | 1 (12.5%) | 0 (0.0%) | 0 (0.0%) | 1 (12.5%) |
Injury associated with device | 0 (0.0%) | 1 (12.5%) | 0 (0.0%) | 0 (0.0%) | 1 (12.5%) |
Skin and subcutaneous tissue disorders | |||||
Total pts with at least one AE | 0 (0.0%) | 2 (25.0%) | 0 (0.0%) | 0 (0.0%) | 2 (25.0%) |
Total number of AEs | 0 | 3 | 0 | 0 | 3 |
Dermatitis allergic | 0 (0.0%) | 1 (12.5%) | 0 (0.0%) | 0 (0.0%) | 1 (12.5%) |
Drug eruption | 0 (0.0%) | 1 (12.5%) | 0 (0.0%) | 0 (0.0%) | 1 (12.5%) |
Rash | 0 (0.0%) | 1 (12.5%) | 0 (0.0%) | 0 (0.0%) | 1 (12.5%) |
Ear and labyrinth disorders | |||||
Total pts with at least one AE | 0 (0.0%) | 1 (12.5%) | 0 (0.0%) | 0 (0.0%) | 1 (12.5%) |
Total number of AEs | 0 | 1 | 0 | 0 | 1 |
Vertigo | 0 (0.0%) | 1 (12.5%) | 0 (0.0%) | 0 (0.0%) | 1 (12.5%) |
Musculoskeletal and connective tissue disorders | |||||
Total pts with at least one AE | 0 (0.0%) | 1 (12.5%) | 0 (0.0%) | 0 (0.0%) | 1 (12.5%) |
Total number of AEs | 0 | 1 | 0 | 0 | 1 |
Arthralgia | 0 (0.0%) | 1 (12.5%) | 0 (0.0%) | 0 (0.0%) | 1 (12.5%) |
Nervous system disorders | |||||
Total pts with at least one AE | 0 (0.0%) | 0 (0.0%) | 1 (12.5%) | 0 (0.0%) | 1 (12.5%) |
Total number of AEs | 0 | 0 | 1 | 0 | 1 |
Hypoasthesia | 0 (0.0%) | 0 (0.0%) | 1 (12.5%) | 0 (0.0%) | 1 (12.5%) |
Respiratory, thoracic and mediastinal disorders | |||||
Total pts with at least one AE | 0 (0.0%) | 0 (0.0%) | 1 (12.5%) | 0 (0.0%) | 1 (12.5%) |
Total number of AEs | 0 | 0 | 1 | 0 | 1 |
Pleurisy | 0 (0.0%) | 0 (0.0%) | 1 (12.5%) | 0 (0.0%) | 1 (12.5%) |
Efficacy
Hemodynamic parameter | Baseline (n = 8) | After 60 min (n = 8) | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Actual value | Actual value | Changes from baseline |
P valuea
| |||||||
Mean ± SD | Median | [Min, Max] | Mean ± SD | Median | [Min, Max] | Mean ± SD | Median | [Min, Max] | ||
Systolic pulmonary artery pressure, mmHg | 50.6 ± 12.4 | 46.0 | [34, 69] | 50.5 ± 12.5 | 48.0 | [33, 72] | −0.1 ± 4.2 | −0.5 | [−7, 6] | 0.8438 |
Diastolic pulmonary artery pressure, mmHg | 17.1 ± 2.2 | 17.0 | [14, 22] | 16.5 ± 2.2 | 16.0 | [13, 20] | −0.6 ± 1.8 | −0.5 | [−4, 2] | 0.5313 |
Mean pulmonary artery pressure, mmHg | 31.1 ± 5.1 | 31.5 | [22, 40] | 30.4 ± 4.6 | 30.0 | [22, 37] | −0.8 ± 2.2 | −0.5 | [−4, 2] | 0.4375 |
Pulmonary capillary wedge pressure, mmHg | 8.4 ± 1.8 | 8.0 | [5, 11] | 7.1 ± 1.7 | 6.5 | [5, 10] | −1.3 ± 1.3 | −1.5 | [−3, 1] | 0.0625 |
Cardiac output, L/min | 4.829 ± 1.057 | 4.440 | [2.72, 5.99] | 4.834 ± 1.349 | 4.535 | [3.45, 6.76] | 0.545 ± 0.782 | 0.420 | [−0.31, 1.84] | 0.1094 |
Mean right arterial pressure, mmHg | 4.8 ± 1.8 | 4.5 | [3, 8] | 3.6 ± 1.5 | 3.5 | [1, 6] | −1.1 ± 2.0 | −1.5 | [−3, 3] | 0.2031 |
Mixed venous oxygen saturation, % | 73.43 ± 5.50 | 73.20 | [63.4, 83.2] | 73.86 ± 5.82 | 72.15 | [66.0, 84.5] | 0.44 ± 2.73 | 0.30 | [−3.9, 3.7] | 0.8438 |
Cardiac input, L/min/m2
| 2.98 ± 0.86 | 2.80 | [2.0, 4.3] | 3.39 ± 1.20 | 2.95 | [2.2, 5.4] | 0.41 ± 0.60 | 0.20 | [−0.2, 1.5] | 0.1250 |
Pulmonary vascular resistance, dyn·s/cm5
| 448.3 ± 158.1 | 429.5 | [201, 676] | 406.0 ± 143.6 | 380.0 | [232, 680] | −42.3 ± 84.1 | −14.0 | [−166, 41] | 0.4609 |
Pulmonary vascular resistance index, dyn·s/cm5/m2
| 646.5 ± 223.1 | 598.0 | [338, 1,000] | 594.8 ± 237.3 | 534.5 | [384, 1,091] | −51.8 ± 124.3 | −22.5 | [−239, 91] | 0.4609 |
Hemodynamic parameter | Baseline (n = 8) | After 60 min (n = 8) | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Actual value | Actual value | Changes from baseline |
P valuea
| |||||||
Mean ± SD | Median | [Min, Max] | Mean ± SD | Median | [Min, Max] | Mean ± SD | Median | [Min, Max] | ||
Systolic pulmonary artery pressure, mmHg | 50.6 ± 12.4 | 46.0 | [34, 69] | 49.8 ± 14.1 | 44.5 | [29, 70] | −0.9 ± 3.5 | −1.0 | [−5, 4] | 0.4375 |
Diastolic pulmonary artery pressure, mmHg | 17.1 ± 2.2 | 17.0 | [14, 22] | 18.8 ± 4.6 | 19.0 | [11, 24] | 1.6 ± 3.7 | 2.0 | [−3, 7] | 0.4844 |
Mean pulmonary artery pressure, mmHg | 31.1 ± 5.1 | 31.5 | [22, 40] | 31.4 ± 7.2 | 32.0 | [18, 41] | 0.3 ± 2.8 | 0.5 | [−4, 4] | 0.8906 |
Pulmonary capillary wedge pressure, mmHg | 8.4 ± 1.8 | 8.0 | [5, 11] | 7.3 ± 1.2 | 7.5 | [6, 9] | −1.1 ± 2.3 | −2.0 | [−4, 3] | 0.2344 |
Cardiac output, L/min | 4.829 ± 1.057 | 4.440 | [2.72, 5.99] | 4.499 ± 1.005 | 4.095 | [3.25, 5.98] | 0.210 ± 0.790 | 0.310 | [−0.91, 1.35] | 0.4609 |
Mean right arterial pressure, mmHg | 4.8 ± 1.8 | 4.5 | [3, 8] | 4.8 ± 1.8 | 4.5 | [3, 7] | 0.0 ± 1.7 | 0.0 | [−3, 3] | 1.0000 |
Mixed venous oxygen saturation, % | 73.43 ± 5.50 | 73.20 | [63.4, 83.2] | 72.10 ± 3.28 | 72.75 | [67.1, 76.3] | −1.33 ± 4.64 | −0.50 | [−8.4, 4.7] | 0.5469 |
Cardiac input, L/min/m2
| 2.98 ± 0.86 | 2.80 | [2.0, 4.3] | 3.11 ± 0.72 | 3.00 | [2.4, 4.3] | 0.14 ± 0.52 | −0.25 | [−0.6, 0.9] | 0.6563 |
Pulmonary vascular resistance, dyn·s/cm5
| 448.3 ± 158.1 | 429.5 | [201, 676] | 453.6 ± 175.3 | 424.5 | [154, 686] | 5.4 ± 78.3 | −25.0 | [−61, 182] | 0.5469 |
Pulmonary vascular resistance index, dyn·s/cm5/m2
| 646.5 ± 223.1 | 598.0 | [338, 1,000] | 648.5 ± 239.6 | 640.5 | [251, 992] | 2.4 ± 98.4 | −15.5 | [−87, 212] | 0.7109 |
WHO FC | ||||||
---|---|---|---|---|---|---|
Baseline | Week 12 | |||||
I | II | III | IV | |||
N
|
N
| [N] | [N] | [N] | [N] | |
8 | I | 1 | 1 | – | – | – |
II | 5 | – | 5 | – | – | |
III | 2 | – | – | 2 | – | |
IV | 0 | – | – | – | 0 |
Treatment Satisfaction
TSQM-9 domain | Baseline (n = 8) | 12 weeks of administration (n = 8) | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Actual scale | Actual scale | Changes from baseline | ||||||||
Mean ± SD | Median | [Min, Max] | Mean ± SD | Median | [Min, Max] | Mean ± SD | Median | [Min, Max] |
P valuea
| |
Effectiveness | 56.25 ± 7.55 | 58.4 | [44.4, 66.7] | 58.31 ± 14.55 | 61.1 | [33.3, 72.2] | 2.06 ± 10.68 | 0.0 | [−11.1, 22.2] | 0.9063 |
Convenience | 51.40 ± 10.19 | 55.6 | [33.3, 61.1] | 58.33 ± 12.96 | 61.1 | [33.3, 72.2] | 6.93 ± 5.73 | 5.6 | [0.0, 16.6] | 0.0313 |
Global satisfaction | 54.01 ± 31.30 | 60.5 | [−8.3, 91.7] | 54.19 ± 25.94 | 52.8 | [22.2, 93.1] | 0.18 ± 23.09 | 1.4 | [−40.2, 30.5] | 0.7188 |