Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

An Open-Label Extension Trial of UT-15C Sustained-release (SR) in Subjects With Pulmonary Arterial Hypertension (FREEDOM-EXT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01027949
Recruitment Status : Completed
First Posted : December 9, 2009
Results First Posted : May 10, 2021
Last Update Posted : May 10, 2021
Sponsor:
Information provided by (Responsible Party):
United Therapeutics

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Pulmonary Arterial Hypertension
Intervention Drug: Oral Treprostinil
Enrollment 894
Recruitment Details Baseline values for demographic parameters were defined and collected in the same manner for subjects who received either placebo or oral treprostinil in the preceding studies. Note that Studies TDE-PH-202 (NCT01104870), TDE-PH-203 (NCT01477333), and TDE-PH-205 (NCT01588405) had an open-label design; therefore, all Baseline demographic parameters were based on values collected at the time of enrollment in the previous study.
Pre-assignment Details Subjects eligible for TDE-PH-304 previously participated in Studies TDE-PH-202 (NCT01104870), TDE-PH-203 (NCT01477333), and TDE-PH-205 (NCT01588405), TDE-PH-301 (NCT00325442), TDE-PH-302 (NCT00325403), or TDE PH-308 (NCT00887978).
Arm/Group Title Oral Treprostinil
Hide Arm/Group Description Subjects eligible for TDE-PH-304 previously participated in Studies TDE-PH-202 (NCT01104870), TDE-PH-203 (NCT01477333), and TDE-PH-205 (NCT01588405), TDE-PH-301 (NCT00325442), TDE-PH-302 (NCT00325403), or TDE PH-308 (NCT00887978)
Period Title: Overall Study
Started 894
Completed 208
Not Completed 686
Reason Not Completed
Death             174
Progressive Disease             163
Adverse Event             172
Withdrawal by Subject             113
Lost to Follow-up             17
Protocol Violation             13
PI Decision             8
Limited Study Drug Effectiveness             7
Non-compliance with Study Procedures             7
Lung Transplant             5
Unable to Tolerate Study Drug             2
Use of Excluded Medication             2
Patient Self-discontinuation             1
Pregnancy             1
Surgery             1
Arm/Group Title Oral Treprostinil
Hide Arm/Group Description Subjects eligible for TDE-PH-304 previously participated in Studies TDE PH-202, TDE-PH-203, TDE-PH-205, TDE-PH-301, TDE-PH-302, or TDE PH-308.
Overall Number of Baseline Participants 894
Hide Baseline Analysis Population Description
All subjects enrolled in the study.
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 894 participants
47.7
(12 to 80)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 894 participants
Female
696
  77.9%
Male
198
  22.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 894 participants
Hispanic or Latino
83
   9.3%
Not Hispanic or Latino
809
  90.5%
Unknown or Not Reported
2
   0.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 894 participants
American Indian or Alaska Native
34
   3.8%
Asian
219
  24.5%
Native Hawaiian or Other Pacific Islander
2
   0.2%
Black or African American
46
   5.1%
White
589
  65.9%
More than one race
0
   0.0%
Unknown or Not Reported
4
   0.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 894 participants
Puerto Rico 1
United States 436
United Kingdom 27
Portugal 1
India 79
Spain 6
Canada 19
Austria 7
Netherlands 15
Sweden 2
Belgium 6
Ireland 2
Poland 16
Italy 13
Mexico 38
Israel 22
Australia 44
France 22
Germany 14
China 124
PAH Etiology  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 894 participants
Idiopathic Pulmonary Arterial Hypertension/ Heritable Pulmonary Arterial Hypertension
608
  68.0%
Collagen Vascular Disease
224
  25.1%
Other
60
   6.7%
Missing
2
   0.2%
World Health Organization (WHO) Functional Class   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 894 participants
I
18
   2.0%
II
298
  33.3%
III
527
  58.9%
IV
11
   1.2%
Missing
40
   4.5%
[1]
Measure Description:

WHO PAH Groups are defined as follows. The groups are categorical classifications for subjects with PAH and are not a severity grading system.

I = Pulmonary Arterial Hypertension II = Pulmonary Hypertension due to left heart disease III = Pulmonary Hypertension due to lung disease IV = Pulmonary Hypertension due to blood clots in the lungs V = Blood and other rare disorders that lead to Pulmonary Hypertension

1.Primary Outcome
Title Change in Exercise Capacity at Month 12
Hide Description Assess the effect of continued therapy with oral treprostinil on exercise capacity as assessed by the change from Baseline in 6-Minute Walk Test (6MWT) after 1 year of treatment. The 6MWT is the clinical standard for assessing subject functional status in the treatment of PAH and has been considered an objective measure of subject functional status by the American Thoracic Society. The distance a subject can walk in 6 minutes is recorded in meters.
Time Frame From First Visit (Visit 1) to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects enrolled in the study with Baseline and matched follow-up 6MWTs.
Arm/Group Title Oral Treprostinil
Hide Arm/Group Description:
Subjects eligible for TDE-PH-304 previously participated in Studies TDE PH-202, TDE-PH-203, TDE-PH-205, TDE-PH-301, TDE-PH-302, or TDE PH-308.
Overall Number of Participants Analyzed 572
Median (Full Range)
Unit of Measure: meters
22.0
(-345.0 to 282.0)
Time Frame From the time of subject enrollment until exit from the study (up to 13 years).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Oral Treprostinil
Hide Arm/Group Description Subjects eligible for TDE-PH-304 previously participated in Studies TDE PH-202, TDE-PH-203, TDE-PH-205, TDE-PH-301, TDE-PH-302, or TDE PH-308.
All-Cause Mortality
Oral Treprostinil
Affected / at Risk (%)
Total   174/894 (19.46%)    
Hide Serious Adverse Events
Oral Treprostinil
Affected / at Risk (%) # Events
Total   547/894 (61.19%)    
Blood and lymphatic system disorders   
Anaemia  1  28/894 (3.13%)  32
Iron deficiency anaemia  1  6/894 (0.67%)  6
Pancytopenia  1  5/894 (0.56%)  5
Coagulopathy  1  2/894 (0.22%)  2
Thrombocytopenia  1  2/894 (0.22%)  2
Anaemia macrocytic  1  1/894 (0.11%)  1
Antiphospholipid syndrome  1  1/894 (0.11%)  1
Disseminated intravascular coagulation  1  1/894 (0.11%)  1
Febrile neutropenia  1  1/894 (0.11%)  1
Haemolytic anaemia  1  1/894 (0.11%)  1
Hypersplenism  1  1/894 (0.11%)  1
Lymphadenopathy  1  1/894 (0.11%)  1
Normocytic anaemia  1  1/894 (0.11%)  1
Evans syndrome  1  1/894 (0.11%)  1
Cardiac disorders   
Right ventricular failure  1  129/894 (14.43%)  188
Cardiac failure  1  36/894 (4.03%)  43
Cardiac failure congestive  1  19/894 (2.13%)  26
Atrial fibrillation  1  15/894 (1.68%)  18
Atrial flutter  1  14/894 (1.57%)  14
Cardiogenic shock  1  9/894 (1.01%)  10
Supraventricular tachycardia  1  9/894 (1.01%)  13
Cardiac arrest  1  7/894 (0.78%)  7
Pericardial effusion  1  6/894 (0.67%)  7
Palpitations  1  5/894 (0.56%)  5
Cardio-respiratory arrest  1  4/894 (0.45%)  4
Ventricular extrasystoles  1  4/894 (0.45%)  4
Atrial tachycardia  1  3/894 (0.34%)  3
Coronary artery disease  1  3/894 (0.34%)  4
Acute myocardial infarction  1  2/894 (0.22%)  2
Arrhythmia  1  2/894 (0.22%)  2
Bradycardia  1  2/894 (0.22%)  2
Cardiac tamponade  1  2/894 (0.22%)  2
Cor pulmonale  1  2/894 (0.22%)  2
Tachycardia  1  2/894 (0.22%)  2
Ventricular tachycardia  1  2/894 (0.22%)  2
Left ventricular dysfunction  1  2/894 (0.22%)  2
Arrhythmia supraventricular  1  1/894 (0.11%)  1
Cardiac failure acute  1  1/894 (0.11%)  1
Cardiac failure chronic  1  1/894 (0.11%)  1
Cardiac failure high output  1  1/894 (0.11%)  1
Cardiomegaly  1  1/894 (0.11%)  1
Hypertensive heart disease  1  1/894 (0.11%)  1
Left ventricular failure  1  1/894 (0.11%)  1
Myocardial infarction  1  1/894 (0.11%)  1
Pericardial haemorrhage  1  1/894 (0.11%)  1
Pericarditis  1  1/894 (0.11%)  1
Pulseless electrical activity  1  1/894 (0.11%)  1
Right ventricular dysfunction  1  1/894 (0.11%)  1
Cardiac disorder  1  1/894 (0.11%)  1
Congenital, familial and genetic disorders   
Heart disease congenital  1  1/894 (0.11%)  1
Hamartoma  1  1/894 (0.11%)  1
Ear and labyrinth disorders   
Vertigo  1  1/894 (0.11%)  1
Endocrine disorders   
Hyperthyroidism  1  3/894 (0.34%)  3
Hypopituitarism  1  2/894 (0.22%)  2
Eye disorders   
Visual impairment  1  2/894 (0.22%)  2
Ocular discomfort  1  1/894 (0.11%)  1
Gastrointestinal disorders   
Diarrhoea  1  13/894 (1.45%)  15
Gastrointestinal haemorrhage  1  12/894 (1.34%)  16
Nausea  1  11/894 (1.23%)  11
Gastritis  1  10/894 (1.12%)  11
Gastroenteritis  1  10/894 (1.12%)  10
Vomiting  1  10/894 (1.12%)  10
Ascites  1  8/894 (0.89%)  9
Abdominal pain  1  6/894 (0.67%)  6
Upper gastrointestinal haemorrhage  1  6/894 (0.67%)  6
Dysphagia  1  4/894 (0.45%)  4
Large intestine polyp  1  4/894 (0.45%)  4
Abdominal pain upper  1  3/894 (0.34%)  3
Melaena  1  3/894 (0.34%)  3
Rectal haemorrhage  1  3/894 (0.34%)  3
Haematemesis  1  2/894 (0.22%)  2
Intestinal obstruction  1  2/894 (0.22%)  2
Oesophagitis  1  2/894 (0.22%)  2
Pancreatitis  1  2/894 (0.22%)  2
Rectal ulcer  1  2/894 (0.22%)  2
Abdominal distension  1  1/894 (0.11%)  1
Colitis  1  1/894 (0.11%)  1
Diarrhoea haemorrhagic  1  1/894 (0.11%)  1
Duodenal ulcer haemorrhage  1  1/894 (0.11%)  1
Duodenitis  1  1/894 (0.11%)  1
Enteritis  1  1/894 (0.11%)  1
Enterocolitis  1  1/894 (0.11%)  1
Food poisoning  1  1/894 (0.11%)  1
Gastric ulcer  1  1/894 (0.11%)  1
Gastric ulcer haemorrhage  1  1/894 (0.11%)  1
Gastritis erosive  1  1/894 (0.11%)  1
Gastrointestinal disorder  1  1/894 (0.11%)  1
Haemorrhoids  1  1/894 (0.11%)  1
Hiatus hernia  1  1/894 (0.11%)  1
Ileus  1  1/894 (0.11%)  1
Impaired gastric emptying  1  1/894 (0.11%)  1
Inguinal hernia  1  1/894 (0.11%)  1
Mallory-Weiss syndrome  1  1/894 (0.11%)  1
Mouth haemorrhage  1  1/894 (0.11%)  1
Oesophageal haemorrhage  1  1/894 (0.11%)  1
Pancreatitis acute  1  1/894 (0.11%)  1
Peptic ulcer  1  1/894 (0.11%)  1
Rectal ulcer haemorrhage  1  1/894 (0.11%)  1
Small intestinal obstruction  1  1/894 (0.11%)  2
Lower gastrointestinal haemorrhage  1  1/894 (0.11%)  1
Acquired oesophageal web  1  1/894 (0.11%)  1
Intra-abdominal haematoma  1  1/894 (0.11%)  1
Retroperitoneal haematoma  1  1/894 (0.11%)  1
Intra-abdominal haemorrhage  1  1/894 (0.11%)  1
Eosinophilic oesophagitis  1  1/894 (0.11%)  1
General disorders   
Chest pain  1  28/894 (3.13%)  33
Sudden death  1  15/894 (1.68%)  15
Sudden cardiac death  1  10/894 (1.12%)  10
Death  1  7/894 (0.78%)  7
Pyrexia  1  6/894 (0.67%)  6
Oedema peripheral  1  5/894 (0.56%)  6
Non-cardiac chest pain  1  5/894 (0.56%)  6
Multiple organ dysfunction syndrome  1  4/894 (0.45%)  4
Asthenia  1  3/894 (0.34%)  3
Fatigue  1  3/894 (0.34%)  3
Generalised oedema  1  3/894 (0.34%)  4
Chest discomfort  1  2/894 (0.22%)  2
General physical health deterioration  1  2/894 (0.22%)  2
Impaired healing  1  1/894 (0.11%)  2
Mass  1  1/894 (0.11%)  1
Oedema  1  1/894 (0.11%)  1
Catheter site inflammation  1  1/894 (0.11%)  1
Hepatobiliary disorders   
Cholecystitis  1  5/894 (0.56%)  5
Portal hypertension  1  3/894 (0.34%)  3
Drug-induced liver injury  1  3/894 (0.34%)  3
Cholelithiasis  1  2/894 (0.22%)  2
Bile duct stone  1  1/894 (0.11%)  1
Cholecystitis acute  1  1/894 (0.11%)  1
Hepatic function abnormal  1  1/894 (0.11%)  1
Hepatitis  1  1/894 (0.11%)  1
Hydrocholecystis  1  1/894 (0.11%)  1
Cryptogenic cirrhosis  1  1/894 (0.11%)  1
Immune system disorders   
Hypersensitivity  1  2/894 (0.22%)  2
Infections and infestations   
Pneumonia  1  63/894 (7.05%)  76
Bronchitis  1  11/894 (1.23%)  13
Lower respiratory tract infection  1  11/894 (1.23%)  12
Sepsis  1  10/894 (1.12%)  11
Cellulitis  1  8/894 (0.89%)  9
Upper respiratory tract infection  1  8/894 (0.89%)  8
Urinary tract infection  1  7/894 (0.78%)  7
Respiratory tract infection  1  4/894 (0.45%)  4
Viral infection  1  3/894 (0.34%)  3
Urosepsis  1  3/894 (0.34%)  3
Clostridium difficile infection  1  3/894 (0.34%)  3
Appendicitis  1  2/894 (0.22%)  2
Clostridium difficile colitis  1  2/894 (0.22%)  2
Diverticulitis  1  2/894 (0.22%)  2
Herpes zoster  1  2/894 (0.22%)  2
Osteomyelitis  1  2/894 (0.22%)  2
Pyelonephritis  1  2/894 (0.22%)  3
Septic shock  1  2/894 (0.22%)  2
Typhoid fever  1  2/894 (0.22%)  2
Staphylococcal sepsis  1  2/894 (0.22%)  2
Pneumonia bacterial  1  2/894 (0.22%)  2
Bacteraemia  1  1/894 (0.11%)  1
Bronchiolitis  1  1/894 (0.11%)  1
Campylobacter gastroenteritis  1  1/894 (0.11%)  1
Chronic sinusitis  1  1/894 (0.11%)  1
Cytomegalovirus infection  1  1/894 (0.11%)  1
Dengue fever  1  1/894 (0.11%)  1
Escherichia sepsis  1  1/894 (0.11%)  1
Gastroenteritis viral  1  1/894 (0.11%)  1
Gastrointestinal infection  1  1/894 (0.11%)  1
Infected skin ulcer  1  1/894 (0.11%)  1
Influenza  1  1/894 (0.11%)  1
Meningitis bacterial  1  1/894 (0.11%)  1
Pneumonia cytomegaloviral  1  1/894 (0.11%)  1
Pneumonia klebsiella  1  1/894 (0.11%)  1
Pneumonia legionella  1  1/894 (0.11%)  1
Pneumonia pseudomonal  1  1/894 (0.11%)  1
Pneumonia streptococcal  1  1/894 (0.11%)  1
Pulmonary tuberculosis  1  1/894 (0.11%)  1
Sialoadenitis  1  1/894 (0.11%)  1
Sinusitis  1  1/894 (0.11%)  1
Tracheobronchitis  1  1/894 (0.11%)  1
Viral upper respiratory tract infection  1  1/894 (0.11%)  1
Urinary tract infection fungal  1  1/894 (0.11%)  1
Streptococcal bacteraemia  1  1/894 (0.11%)  1
Sepsis syndrome  1  1/894 (0.11%)  1
Central line infection  1  1/894 (0.11%)  1
Staphylococcal infection  1  1/894 (0.11%)  1
Bacterial infection  1  1/894 (0.11%)  1
Parainfluenzae virus infection  1  1/894 (0.11%)  1
Cholecystitis infective  1  1/894 (0.11%)  1
Lower respiratory tract infection viral  1  1/894 (0.11%)  1
Metapneumovirus infection  1  1/894 (0.11%)  1
Pseudomonas bronchitis  1  1/894 (0.11%)  1
Post procedural infection  1  1/894 (0.11%)  1
Infective exacerbation of bronchiectasis  1  1/894 (0.11%)  1
Injury, poisoning and procedural complications   
Subdural haematoma  1  6/894 (0.67%)  6
Fall  1  4/894 (0.45%)  4
Post procedural haemorrhage  1  3/894 (0.34%)  3
Accidental overdose  1  2/894 (0.22%)  2
Tibia fracture  1  2/894 (0.22%)  2
Upper limb fracture  1  2/894 (0.22%)  2
Toxicity to various agents  1  2/894 (0.22%)  2
Ankle fracture  1  1/894 (0.11%)  1
Corneal abrasion  1  1/894 (0.11%)  1
Facial bones fracture  1  1/894 (0.11%)  1
Femur fracture  1  1/894 (0.11%)  1
Fibula fracture  1  1/894 (0.11%)  1
Gun shot wound  1  1/894 (0.11%)  1
Hip fracture  1  1/894 (0.11%)  1
Incisional hernia  1  1/894 (0.11%)  1
Intentional overdose  1  1/894 (0.11%)  1
Jaw fracture  1  1/894 (0.11%)  1
Overdose  1  1/894 (0.11%)  1
Rib fracture  1  1/894 (0.11%)  1
Road traffic accident  1  1/894 (0.11%)  1
Spinal fracture  1  1/894 (0.11%)  1
Vascular pseudoaneurysm  1  1/894 (0.11%)  1
Incision site haemorrhage  1  1/894 (0.11%)  1
Post procedural bile leak  1  1/894 (0.11%)  1
Skin laceration  1  1/894 (0.11%)  1
Pelvic fracture  1  1/894 (0.11%)  1
Chemical peritonitis  1  1/894 (0.11%)  1
Post procedural fever  1  1/894 (0.11%)  1
Investigations   
International normalised ratio increased  1  3/894 (0.34%)  3
Hepatic enzyme increased  1  3/894 (0.34%)  4
Blood glucose decreased  1  2/894 (0.22%)  2
Blood sodium decreased  1  1/894 (0.11%)  1
Chest X-ray abnormal  1  1/894 (0.11%)  1
International normalised ratio abnormal  1  1/894 (0.11%)  1
Weight decreased  1  1/894 (0.11%)  1
Paracentesis  1  1/894 (0.11%)  1
Metabolism and nutrition disorders   
Fluid overload  1  21/894 (2.35%)  27
Hypokalaemia  1  12/894 (1.34%)  13
Dehydration  1  9/894 (1.01%)  13
Hypoglycaemia  1  5/894 (0.56%)  5
Fluid retention  1  4/894 (0.45%)  6
Hyponatraemia  1  3/894 (0.34%)  3
Gout  1  2/894 (0.22%)  2
Hypercalcaemia  1  2/894 (0.22%)  2
Hyperglycaemia  1  2/894 (0.22%)  2
Metabolic acidosis  1  2/894 (0.22%)  2
Cachexia  1  1/894 (0.11%)  1
Diabetes mellitus  1  1/894 (0.11%)  1
Electrolyte imbalance  1  1/894 (0.11%)  1
Hyperkalaemia  1  1/894 (0.11%)  1
Hypocalcaemia  1  1/894 (0.11%)  1
Hypovolaemia  1  1/894 (0.11%)  1
Decreased appetite  1  1/894 (0.11%)  1
Musculoskeletal and connective tissue disorders   
Back pain  1  6/894 (0.67%)  8
Pain in extremity  1  4/894 (0.45%)  4
Systemic lupus erythematosus  1  4/894 (0.45%)  5
Musculoskeletal pain  1  3/894 (0.34%)  3
Costochondritis  1  2/894 (0.22%)  2
Haemarthrosis  1  2/894 (0.22%)  2
Osteoarthritis  1  2/894 (0.22%)  3
Bone pain  1  1/894 (0.11%)  1
Flank pain  1  1/894 (0.11%)  1
Fracture malunion  1  1/894 (0.11%)  1
Myalgia  1  1/894 (0.11%)  1
Myositis  1  1/894 (0.11%)  1
Neck pain  1  1/894 (0.11%)  1
Osteoporosis  1  1/894 (0.11%)  2
Rheumatoid arthritis  1  1/894 (0.11%)  1
Rotator cuff syndrome  1  1/894 (0.11%)  1
Scleroderma  1  1/894 (0.11%)  1
Synovial cyst  1  1/894 (0.11%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Lung adenocarcinoma  1  3/894 (0.34%)  3
Colon cancer  1  2/894 (0.22%)  2
Lung neoplasm malignant  1  2/894 (0.22%)  2
Hepatic cancer  1  2/894 (0.22%)  2
Adenocarcinoma of colon  1  1/894 (0.11%)  1
Angiosarcoma  1  1/894 (0.11%)  1
Bladder transitional cell carcinoma  1  1/894 (0.11%)  1
Borderline ovarian tumour  1  1/894 (0.11%)  1
Breast cancer  1  1/894 (0.11%)  1
Breast mass  1  1/894 (0.11%)  1
Breast neoplasm  1  1/894 (0.11%)  1
Bronchial carcinoma  1  1/894 (0.11%)  1
Carotid body tumour  1  1/894 (0.11%)  1
Diffuse large B-cell lymphoma  1  1/894 (0.11%)  1
Lung adenocarcinoma stage IV  1  1/894 (0.11%)  1
Lung carcinoma cell type unspecified stage IV  1  1/894 (0.11%)  1
Malignant neoplasm of renal pelvis  1  1/894 (0.11%)  2
Malignant neoplasm of spinal cord  1  1/894 (0.11%)  1
Metastases to bone  1  1/894 (0.11%)  1
Metastases to lung  1  1/894 (0.11%)  1
Myelodysplastic syndrome  1  1/894 (0.11%)  1
Neoplasm malignant  1  1/894 (0.11%)  1
Papillary thyroid cancer  1  1/894 (0.11%)  1
Rectal cancer  1  1/894 (0.11%)  1
Renal cancer  1  1/894 (0.11%)  1
Small cell lung cancer limited stage  1  1/894 (0.11%)  1
Colon cancer metastatic  1  1/894 (0.11%)  1
Brain neoplasm  1  1/894 (0.11%)  1
Metastatic neoplasm  1  1/894 (0.11%)  1
Polyp  1  1/894 (0.11%)  1
Non-small cell lung cancer  1  1/894 (0.11%)  1
Metastasis  1  1/894 (0.11%)  1
Renal cell carcinoma  1  1/894 (0.11%)  1
Brenner tumour  1  1/894 (0.11%)  1
Nervous system disorders   
Syncope  1  30/894 (3.36%)  33
Headache  1  7/894 (0.78%)  7
Dizziness  1  5/894 (0.56%)  5
Presyncope  1  5/894 (0.56%)  5
Cerebrovascular accident  1  2/894 (0.22%)  2
Seizure  1  2/894 (0.22%)  2
Altered state of consciousness  1  1/894 (0.11%)  1
Cerebral haemorrhage  1  1/894 (0.11%)  1
Coma hepatic  1  1/894 (0.11%)  1
Depressed level of consciousness  1  1/894 (0.11%)  1
Dysarthria  1  1/894 (0.11%)  1
Encephalopathy  1  1/894 (0.11%)  2
Epilepsy  1  1/894 (0.11%)  1
Facial paralysis  1  1/894 (0.11%)  1
Hepatic encephalopathy  1  1/894 (0.11%)  6
Transient ischaemic attack  1  1/894 (0.11%)  1
Ischaemic stroke  1  1/894 (0.11%)  1
Intensive care unit acquired weakness  1  1/894 (0.11%)  1
Pregnancy, puerperium and perinatal conditions   
Ectopic pregnancy  1  1/894 (0.11%)  1
Psychiatric disorders   
Mental status changes  1  5/894 (0.56%)  5
Suicidal ideation  1  2/894 (0.22%)  4
Anxiety  1  1/894 (0.11%)  1
Completed suicide  1  1/894 (0.11%)  1
Confusional state  1  1/894 (0.11%)  1
Depression  1  1/894 (0.11%)  1
Post-traumatic stress disorder  1  1/894 (0.11%)  1
Renal and urinary disorders   
Acute kidney injury  1  37/894 (4.14%)  48
Renal failure  1  6/894 (0.67%)  7
Haematuria  1  3/894 (0.34%)  5
Lupus nephritis  1  2/894 (0.22%)  2
Chronic kidney disease  1  2/894 (0.22%)  2
Hydronephrosis  1  1/894 (0.11%)  1
Oliguria  1  1/894 (0.11%)  1
Renal failure acute  1  1/894 (0.11%)  2
Renal mass  1  1/894 (0.11%)  1
Renal impairment  1  1/894 (0.11%)  1
Reproductive system and breast disorders   
Ovarian cyst  1  1/894 (0.11%)  1
Ovarian cyst ruptured  1  1/894 (0.11%)  1
Ovarian rupture  1  1/894 (0.11%)  1
Vaginal haemorrhage  1  1/894 (0.11%)  1
Adnexa uteri mass  1  1/894 (0.11%)  1
Haemorrhagic ovarian cyst  1  1/894 (0.11%)  1
Respiratory, thoracic and mediastinal disorders   
Pulmonary Hypertension  1  129/894 (14.43%)  147
Dyspnoea  1  41/894 (4.59%)  51
Respiratory failure  1  15/894 (1.68%)  17
Hypoxia  1  13/894 (1.45%)  14
Chronic obstructive pulmonary disease  1  11/894 (1.23%)  17
Haemoptysis  1  10/894 (1.12%)  10
Asthma  1  6/894 (0.67%)  12
Pulmonary embolism  1  5/894 (0.56%)  5
Acute respiratory failure  1  4/894 (0.45%)  4
Pulmonary haemorrhage  1  4/894 (0.45%)  4
Disease progression  1  4/894 (0.45%)  4
Epistaxis  1  3/894 (0.34%)  3
Pleural effusion  1  3/894 (0.34%)  3
Respiratory distress  1  3/894 (0.34%)  3
Pulmonary arterial hypertension  1  3/894 (0.34%)  3
Lung infiltration  1  2/894 (0.22%)  2
Pneumonia aspiration  1  2/894 (0.22%)  2
Pulmonary fibrosis  1  2/894 (0.22%)  2
Pulmonary oedema  1  2/894 (0.22%)  2
Respiratory arrest  1  2/894 (0.22%)  2
Acute pulmonary oedema  1  1/894 (0.11%)  1
Acute respiratory distress syndrome  1  1/894 (0.11%)  1
Aspiration  1  1/894 (0.11%)  2
Chronic respiratory failure  1  1/894 (0.11%)  1
Cough  1  1/894 (0.11%)  1
Cyanosis central  1  1/894 (0.11%)  1
Eosinophilic pneumonia  1  1/894 (0.11%)  1
Haemothorax  1  1/894 (0.11%)  1
Interstitial lung disease  1  1/894 (0.11%)  2
Lung consolidation  1  1/894 (0.11%)  1
Nasal congestion  1  1/894 (0.11%)  1
Nasal turbinate hypertrophy  1  1/894 (0.11%)  1
Orthopnoea  1  1/894 (0.11%)  1
Pleurisy  1  1/894 (0.11%)  1
Pleuritic pain  1  1/894 (0.11%)  1
Pneumonitis  1  1/894 (0.11%)  1
Pneumothorax  1  1/894 (0.11%)  1
Pulmonary artery aneurysm  1  1/894 (0.11%)  1
Sleep apnoea syndrome  1  1/894 (0.11%)  1
Pulmonary mass  1  1/894 (0.11%)  1
Mediastinal disorder  1  1/894 (0.11%)  1
Skin and subcutaneous tissue disorders   
Skin ulcer  1  2/894 (0.22%)  3
Angioedema  1  1/894 (0.11%)  1
Psoriasis  1  1/894 (0.11%)  1
Stasis dermatitis  1  1/894 (0.11%)  1
Surgical and medical procedures   
Abortion induced  1  6/894 (0.67%)  7
Palliative care  1  1/894 (0.11%)  1
Cardiac ablation  1  1/894 (0.11%)  1
Balloon atrial septostomy  1  1/894 (0.11%)  1
Vascular disorders   
Hypotension  1  23/894 (2.57%)  26
Deep vein thrombosis  1  6/894 (0.67%)  6
Flushing  1  2/894 (0.22%)  2
Shock  1  2/894 (0.22%)  2
Thrombosis  1  2/894 (0.22%)  2
Aortic dissection  1  1/894 (0.11%)  1
Blood pressure fluctuation  1  1/894 (0.11%)  1
Circulatory collapse  1  1/894 (0.11%)  1
Haematoma  1  1/894 (0.11%)  1
Hypertensive crisis  1  1/894 (0.11%)  1
Orthostatic hypotension  1  1/894 (0.11%)  1
Peripheral ischaemia  1  1/894 (0.11%)  1
Raynaud's phenomenon  1  1/894 (0.11%)  1
Angiodysplasia  1  1/894 (0.11%)  1
Aortic arteriosclerosis  1  1/894 (0.11%)  1
Vascular compression  1  1/894 (0.11%)  1
1
Term from vocabulary, MedDRA (22.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Oral Treprostinil
Affected / at Risk (%) # Events
Total   890/894 (99.55%)    
Blood and lymphatic system disorders   
Anaemia  1  84/894 (9.40%)  112
Cardiac disorders   
Dizziness  1  248/894 (27.74%)  320
Palpitations  1  145/894 (16.22%)  175
Right ventricular failure  1  136/894 (15.21%)  202
Cardiac failure  1  42/894 (4.70%)  54
Gastrointestinal disorders   
Diarrhoea  1  592/894 (66.22%)  808
Nausea  1  505/894 (56.49%)  673
Vomiting  1  349/894 (39.04%)  485
Abdominal pain  1  121/894 (13.53%)  144
Abdominal pain upper  1  97/894 (10.85%)  111
Abdominal distension  1  92/894 (10.29%)  102
Dyspepsia  1  92/894 (10.29%)  95
Constipation  1  65/894 (7.27%)  74
Gastrooesophageal reflux disease  1  46/894 (5.15%)  48
Abdominal discomfort  1  45/894 (5.03%)  48
General disorders   
Fatigue  1  201/894 (22.48%)  228
Oedema peripheral  1  192/894 (21.48%)  240
Chest pain  1  135/894 (15.10%)  180
Pain  1  97/894 (10.85%)  102
Pyrexia  1  83/894 (9.28%)  100
Chest discomfort  1  57/894 (6.38%)  70
Asthenia  1  51/894 (5.70%)  64
Oedema  1  43/894 (4.81%)  44
Infections and infestations   
Upper respiratory tract infection  1  222/894 (24.83%)  334
Nasopharyngitis  1  185/894 (20.69%)  316
Bronchitis  1  103/894 (11.52%)  153
Pneumonia  1  94/894 (10.51%)  118
Urinary tract infection  1  89/894 (9.96%)  115
Sinusitis  1  80/894 (8.95%)  108
Influenza  1  54/894 (6.04%)  64
Investigations   
Weight decreased  1  47/894 (5.26%)  49
Metabolism and nutrition disorders   
Decreased appetite  1  129/894 (14.43%)  142
Hypokalaemia  1  94/894 (10.51%)  119
Fluid overload  1  44/894 (4.92%)  58
Fluid retention  1  43/894 (4.81%)  54
Musculoskeletal and connective tissue disorders   
Pain in jaw  1  313/894 (35.01%)  360
Pain in extremity  1  255/894 (28.52%)  337
Arthralgia  1  140/894 (15.66%)  163
Myalgia  1  123/894 (13.76%)  143
Back pain  1  105/894 (11.74%)  127
Muscle spasms  1  64/894 (7.16%)  71
Musculoskeletal pain  1  42/894 (4.70%)  44
Nervous system disorders   
Headache  1  698/894 (78.08%)  994
Syncope  1  101/894 (11.30%)  141
Presyncope  1  51/894 (5.70%)  55
Psychiatric disorders   
Insomnia  1  95/894 (10.63%)  98
Anxiety  1  57/894 (6.38%)  60
Depression  1  56/894 (6.26%)  59
Renal and urinary disorders   
Acute kidney injury  1  52/894 (5.82%)  69
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  207/894 (23.15%)  294
Pulmonary hypertension  1  190/894 (21.25%)  215
Cough  1  159/894 (17.79%)  202
Nasal congestion  1  98/894 (10.96%)  103
Epistais  1  77/894 (8.61%)  88
Haemoptysis  1  45/894 (5.03%)  57
Skin and subcutaneous tissue disorders   
Rash  1  79/894 (8.84%)  87
Pruritus  1  43/894 (4.81%)  50
Vascular disorders   
Flushing  1  416/894 (46.53%)  499
Hypotension  1  79/894 (8.84%)  91
1
Term from vocabulary, MedDRA (22.1)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Institution and/or Principal Investigator agree not to publish or publicly present any results of the Study without the prior written consent of Sponsor, not to be unreasonably withheld or delayed. Institution and/or Principal Investigator further agree to provide Sponsor with drafts of any such publication or presentation for review and approval no less than 30 days prior to submission for publication or the date of public presentation.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Louis Holdstock, PhD
Organization: United Therapeutics
Phone: 919-425-8866
EMail: lholdstock@unither.com
Layout table for additonal information
Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT01027949    
Other Study ID Numbers: TDE-PH-304
First Submitted: December 4, 2009
First Posted: December 9, 2009
Results First Submitted: February 8, 2021
Results First Posted: May 10, 2021
Last Update Posted: May 10, 2021