Trial Outcomes & Findings for Safety Evaluation of Inhaled Treprostinil Administration Following Transition From Inhaled Ventavis in Pulmonary Arterial Hypertension (PAH) Subjects (NCT NCT00741819)

NCT ID: NCT00741819

Last Updated: 2013-02-20

Results Overview

Overall safety of transitioning from inhaled iloprost to inhaled treprostinil was assessed by type and frequency of adverse events.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 73 participants
• Primary outcome timeframe: up to 24 months
• Results posted on: 2013-02-20

Participant Flow

Recruitment began 09-Dec-2008 and ended 09-Mar-2010. All recruitment took place in medical clinic settings.

Not applicable given this was an open-label study.

Participant milestones

Measure	Inhaled Treprostinil Inhaled treprostinil was given four times daily at doses titrated up to 12 breaths.
Overall Study STARTED	73
Overall Study COMPLETED	65
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Measure	Inhaled Treprostinil Inhaled treprostinil was given four times daily at doses titrated up to 12 breaths.
Overall Study Adverse Event	3
Overall Study Withdrawal by Subject	3
Overall Study Death	1
Overall Study Disease progression	1

Baseline Characteristics

Safety Evaluation of Inhaled Treprostinil Administration Following Transition From Inhaled Ventavis in Pulmonary Arterial Hypertension (PAH) Subjects

Baseline characteristics by cohort

Measure	Inhaled Treprostinil n=73 Participants Inhaled treprostinil was titrated up to 12 breaths four times daily.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	63 Participants n=93 Participants
Age, Categorical >=65 years	10 Participants n=93 Participants
Age Continuous	49.4 years STANDARD_DEVIATION 12.6 • n=93 Participants
Sex: Female, Male Female	57 Participants n=93 Participants
Sex: Female, Male Male	16 Participants n=93 Participants
Region of Enrollment United States	73 participants n=93 Participants
Pulmonary Arterial Hypertension (PAH) etiology Idiopathic PAH or familial PAH	35 participants n=93 Participants
Pulmonary Arterial Hypertension (PAH) etiology Connective Tissue Diseases (CTD)	16 participants n=93 Participants
Pulmonary Arterial Hypertension (PAH) etiology Congenital heart disease (CHD)-repaired shunt	4 participants n=93 Participants
Pulmonary Arterial Hypertension (PAH) etiology CHD-unrepaired shunt	15 participants n=93 Participants
Pulmonary Arterial Hypertension (PAH) etiology HIV	3 participants n=93 Participants
Background PAH therapy None	3 participants n=93 Participants
Background PAH therapy Endothelin receptor antagonist (ERA)	19 participants n=93 Participants
Background PAH therapy Phosphodiesterase-5 inhibitor (PDE-5i)	8 participants n=93 Participants
Background PAH therapy ERA and PDE-5i	43 participants n=93 Participants
Six-minute walk distance (6MWD)	378 meters FULL_RANGE 78 • n=93 Participants
N-terminal prohormone brain natriuretic peptide (NT-proBNP)	626 pg/mL n=93 Participants

PRIMARY outcome

Timeframe: up to 24 months

Population: All subjects who received at least one dose of inhaled treprostinil were included in the safety analysis population.

Overall safety of transitioning from inhaled iloprost to inhaled treprostinil was assessed by type and frequency of adverse events.

Outcome measures

Measure	Inhaled Treprostinil n=73 Participants up to 12 breaths four times daily
Number of Adverse Events Overall events	440 number of events
Number of Adverse Events Possibly or Probably related events	266 number of events
Number of Adverse Events Severe events	41 number of events
Number of Adverse Events Serious events	15 number of events

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: Subjects enrolled at Week 12 visit.

Change in 6MWD from Baseline to Week 12. The 6-minute walk test (6MWT) was conducted at Baseline (10-30 minutes following the last dose of inhaled iloprost) and at Week 12 (10-60 minutes following the dose of inhaled treprostinil). The change in distance (meters) between Baseline and Week 12 is reported below.

Outcome measures

Measure	Inhaled Treprostinil n=68 Participants up to 12 breaths four times daily
Six-minute Walk Distance (6MWD) Week 12	392.5 meters Interval 220.0 to 708.0
Six-minute Walk Distance (6MWD) Change from Baseline	16 meters Full Range 78 • Interval -51.0 to 108.0

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: Subjects who were still enrolled and completed the questionnaire at Baseline and Week 12. Total analysis population was less for the activity score and total score (N = 67).

Change in CAMPHOR Scores from Baseline to Week 12. The CAMPHOR is a health related quality of life instrument validated for pulmonary hypertension that assesses impairment (symptoms), disability (activities) and quality of life. The questionnaire is divided into three sections; Symptoms (Scores 0-25; high scores indicate more symptoms), Activity (Score 0-30; low score indicates good functioning)and Quality of Life (0-25; high scores indicate poor QoL). The sum of these scores equates to the Total score (0-80). In the CAMPHOR scores, lower scores indicate improvements.

Outcome measures

Measure	Inhaled Treprostinil n=69 Participants up to 12 breaths four times daily
Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Symptom Score at Week 12	5.3 units on a scale Interval 0.0 to 21.0
Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Change in Symptom Score	-2.9 units on a scale Full Range 3.9 • Interval -13.0 to 8.0
Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Activity Score at Week 12	6.6 units on a scale Interval 0.0 to 16.0
Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Change in Activity Score	-1.2 units on a scale Full Range 2.5 • Interval -9.0 to 5.0
Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life Score at Week 12	4.9 units on a scale Interval 0.0 to 20.0
Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Change in Quality of Life Score	-2.4 units on a scale Full Range 3.9 • Interval -14.0 to 5.0
Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Total Score at Week 12	16.8 units on a scale Interval 0.0 to 53.0
Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Change in Total Score	-6.4 units on a scale Full Range 7.7 • Interval -29.0 to 7.0

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: Subjects who completed the TSQM at Baseline and Week 12. Total analysis population was less for the Convenience Score (N=67) and Global Satisfaction Score (N=66).

Change in TSQM score from Baseline to Week 12. The TSQM is a validated instrument (Health and Quality of Life Outcomes 2004, 2:12) that measures major dimensions of patient satisfaction with medications. The questionnaire is comprised of 15 questions which fall into one of four categories; Effectiveness, Side-Effects, Convenience, and Global Satisfaction. Responses are scaled on a seven point bipolar scale from 'Extremely Satisfied' to 'Extremely Dissatisfied' where higher scores indicate improvements (total scores from 0-100). The questionnaire was completed at Baseline and Week 12. The Baseline questionnaire focused on the subject's satisfaction with inhaled iloprost treatment, while the questionnaire completed at Week 12 focused on the subject's satisfaction with inhaled treprostinil.

Outcome measures

Measure	Inhaled Treprostinil n=68 Participants up to 12 breaths four times daily
Treatment Satisfaction Questionnaire of Medication (TSQM) Effectiveness Score at Week 12	81.9 units on a scale Interval 44.0 to 100.0
Treatment Satisfaction Questionnaire of Medication (TSQM) Change in Effectiveness Score	19.9 units on a scale Full Range 21.5 • Interval -28.0 to 94.0
Treatment Satisfaction Questionnaire of Medication (TSQM) Side-effects Score at Week 12	84.4 units on a scale Interval 25.0 to 100.0
Treatment Satisfaction Questionnaire of Medication (TSQM) Change in Side-Effects Score	-0.5 units on a scale Full Range 21.3 • Interval -75.0 to 56.0
Treatment Satisfaction Questionnaire of Medication (TSQM) Convenience Score at Week 12	83.3 units on a scale Interval 33.0 to 100.0
Treatment Satisfaction Questionnaire of Medication (TSQM) Change in Convenience Score	38.3 units on a scale Full Range 25.9 • Interval 0.0 to 100.0
Treatment Satisfaction Questionnaire of Medication (TSQM) Global Satisfaction Score at Week 12	81.9 units on a scale Interval 36.0 to 100.0
Treatment Satisfaction Questionnaire of Medication (TSQM) Change in Global Satisfaction	20.0 units on a scale Full Range 23.7 • Interval -36.0 to 100.0

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: Subjects who completed questionnaire at Baseline and Week 12

The patient impression of change (PIC) was three single therapy-related questions related to the subjects overall impression of the transition from inhaled iloprost to inhaled treprostinil. Subjects were surveyed related to their overall impression of the transition from inhaled iloprost to inhaled treprostinil at Week 12.

Outcome measures

Measure	Inhaled Treprostinil n=67 Participants up to 12 breaths four times daily
Patient Impression of Change Improvement of Symptoms	73 percentage of patients 80.5
Patient Impression of Change Improvment in Time Spent	91 percentage of patients
Patient Impression of Change Overall Satisfaction	94 percentage of patients

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Subjects with a NTproBNP sample drawn at Baseline and Week 12

Change in NTpro-BNP from Baseline to Week 12. Blood samples were collected for plasma NTpro-BNP analysis during the study.

Outcome measures

Measure	Inhaled Treprostinil n=68 Participants up to 12 breaths four times daily
N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP)	-74 pg/mL Interval -4728.0 to 3837.0

SECONDARY outcome

Timeframe: Baseline and 12 Weeks

Population: Subjects still enrolled at Week 12 with a WHO Functional Class at Baseline and Week 12.

Change in WHO Functional Class (FC) from Baseline to Week 12. Data presented as percent of subjects who either improved FC, worsened FC, or had no change in FC from Baseline to Week 12.

Outcome measures

Measure	Inhaled Treprostinil n=69 Participants up to 12 breaths four times daily
World Health Organization (WHO) Functional Class Improvement	6 percentage of subjects
World Health Organization (WHO) Functional Class No Change	87 percentage of subjects
World Health Organization (WHO) Functional Class Worsened	7 percentage of subjects

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: Subjects who completed the questionnaire at Baseline and Week 12.

Change in tasks from Baseline to Week 12. At Baseline and Week 12, subjects provided information related to the daily administration and time requirements of inhaled iloprost (Baseline) and inhaled treprostinil (Week 12).

Outcome measures

Measure	Inhaled Treprostinil n=61 Participants up to 12 breaths four times daily
Drug Administration Activities Questionnaire Week 12 Total Daily Dosing Time	39.1 minutes Standard Deviation 25.1
Drug Administration Activities Questionnaire Change in Time Total Daily Dosing Time	-79.3 minutes Standard Deviation 80.5

Adverse Events

Inhaled Treprostinil

Serious events: 10 serious events

Other events: 71 other events

Deaths: 0 deaths

Serious adverse events

Measure	Inhaled Treprostinil n=73 participants at risk Inhaled treprostinil was titrated up to 12 breaths four times daily.
Infections and infestations Pneumonia	2.7% 2/73 • Number of events 2 • up to 56 weeks
Cardiac disorders Pulmonary hypertension	2.7% 2/73 • Number of events 2 • up to 56 weeks
Cardiac disorders Cor pulmonale	1.4% 1/73 • Number of events 2 • up to 56 weeks
Respiratory, thoracic and mediastinal disorders Asthma	1.4% 1/73 • Number of events 1 • up to 56 weeks
Cardiac disorders Atrial fibrillation	1.4% 1/73 • Number of events 1 • up to 56 weeks
Metabolism and nutrition disorders Dehydration	1.4% 1/73 • Number of events 1 • up to 56 weeks
Gastrointestinal disorders gastrointestinal hemorrhage	1.4% 1/73 • Number of events 1 • up to 56 weeks
Infections and infestations Influenza	1.4% 1/73 • Number of events 1 • up to 56 weeks
Cardiac disorders Myocardial infarction	1.4% 1/73 • Number of events 1 • up to 56 weeks
Cardiac disorders Sick sinus syndrome	1.4% 1/73 • Number of events 1 • up to 56 weeks
Nervous system disorders Syncope	1.4% 1/73 • Number of events 1 • up to 56 weeks
Psychiatric disorders psychotic disorder	1.4% 1/73 • Number of events 1 • up to 56 weeks

Other adverse events

Measure	Inhaled Treprostinil n=73 participants at risk Inhaled treprostinil was titrated up to 12 breaths four times daily.
Respiratory, thoracic and mediastinal disorders Cough	74.0% 54/73 • Number of events 55 • up to 56 weeks
Nervous system disorders Headache	43.8% 32/73 • Number of events 32 • up to 56 weeks
Gastrointestinal disorders Nausea	30.1% 22/73 • Number of events 23 • up to 56 weeks
General disorders Chest discomfort	16.4% 12/73 • Number of events 12 • up to 56 weeks
Infections and infestations upper respiratory tract infection	15.1% 11/73 • Number of events 13 • up to 56 weeks
Respiratory, thoracic and mediastinal disorders nasopharyngitis	15.1% 11/73 • Number of events 12 • up to 56 weeks
Vascular disorders flushing	15.1% 11/73 • Number of events 11 • up to 56 weeks
Nervous system disorders dizziness	13.7% 10/73 • Number of events 13 • up to 56 weeks
Cardiac disorders palpitations	12.3% 9/73 • Number of events 9 • up to 56 weeks
Respiratory, thoracic and mediastinal disorders throat irritation	12.3% 9/73 • Number of events 9 • up to 56 weeks
General disorders fatigue	11.0% 8/73 • Number of events 8 • up to 56 weeks
Respiratory, thoracic and mediastinal disorders productive cough	9.6% 7/73 • Number of events 7 • up to 56 weeks
Respiratory, thoracic and mediastinal disorders oropharyngeal pain	9.6% 7/73 • Number of events 7 • up to 56 weeks
Gastrointestinal disorders diarrhea	8.2% 6/73 • Number of events 6 • up to 56 weeks
Infections and infestations bronchitis	6.8% 5/73 • Number of events 5 • up to 56 weeks
General disorders chest pain	6.8% 5/73 • Number of events 5 • up to 56 weeks
Respiratory, thoracic and mediastinal disorders dyspnea	6.8% 5/73 • Number of events 5 • up to 56 weeks
Musculoskeletal and connective tissue disorders pain in jaw	6.8% 5/73 • Number of events 5 • up to 56 weeks
Skin and subcutaneous tissue disorders rash	6.8% 5/73 • Number of events 5 • up to 56 weeks
Nervous system disorders somnolence	6.8% 5/73 • Number of events 5 • up to 56 weeks
Respiratory, thoracic and mediastinal disorders epistaxis	5.5% 4/73 • Number of events 4 • up to 56 weeks
Musculoskeletal and connective tissue disorders back pain	5.5% 4/73 • Number of events 4 • up to 56 weeks
Metabolism and nutrition disorders fluid retention	5.5% 4/73 • Number of events 4 • up to 56 weeks
Musculoskeletal and connective tissue disorders pain in extremity	5.5% 4/73 • Number of events 4 • up to 56 weeks
Infections and infestations sinusitis	5.5% 4/73 • Number of events 4 • up to 56 weeks

Additional Information

Inhaled Treprostinil Program Head

United Therpaeutics Corporation

Phone: 919-485-8350

Email: clinicalrecordsmanagment@unither.com

Results disclosure agreements

• Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the United Therapeutics publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
• Publication restrictions are in place

Restriction type: OTHER