Trial Outcomes & Findings for A Phase 3 Adaptive Study to Evaluate the Safety and Efficacy of Inhaled Treprostinil in Participants With Pulmonary Hypertension (PH) Due to Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT03496623)

NCT ID: NCT03496623

Last Updated: 2023-11-24

Results Overview

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

188 participants

Primary outcome timeframe

Baseline, Week 12

Results posted on

2023-11-24

Participant Flow

188 participants were enrolled; 80 of the 188 enrolled participants were screen failures prior to the Run-In Period. Per prespecified analysis, data were not collected for the participants who were screen failures.

In the Original Crossover Design, a total of 64 participants were randomized to 1 of 2 treatment sequences (treprostinil-placebo) or (placebo-treprostinil) in a crossover study design for 12 weeks during 2 dosing periods. There was a washout of at least 7 days between the dosing periods. 12 participants were randomized to receive either treprostinil or placebo during the single treatment period in Contingent Parallel Design.

Participant milestones

Participant milestones
Measure	Run-In Participants received low dose treprostinil for inhalation for up to 2 weeks before randomization	Original Crossover Design - Treprostinil, Then Placebo Participants received either treprostinil or placebo in the following order: Period 1: Up to 72 micrograms (μg) of treprostinil for inhalation four times daily (QID), for up to 12 weeks Period 2: Placebo QID for up to 12 weeks	Original Crossover Design - Placebo, Then Treprostinil Participants received either treprostinil or placebo in the following order: Period 1: Placebo QID for up to 12 weeks Period 2: Up to 72 μg of treprostinil for inhalation QID, for up to 12 weeks	Contingent Parallel Design - Treprostinil Participants received up to 72 μg of treprostinil for inhalation QID, for up to 12 weeks	Contingent Parallel Design - Placebo Participants received placebo to match treprostinil QID, for up to 12 weeks
Run-In Period (2 Weeks) STARTED	108	0	0	0	0
Run-In Period (2 Weeks) Received At Least 1 Dose of Study Drug	108	0	0	0	0
Run-In Period (2 Weeks) COMPLETED	76	0	0	0	0
Run-In Period (2 Weeks) NOT COMPLETED	32	0	0	0	0
Period 1 (12 Weeks) STARTED	0	32	32	6	6
Period 1 (12 Weeks) Received At Least 1 Dose of Study Drug	0	32	32	6	6
Period 1 (12 Weeks) COMPLETED	0	26	29	5	4
Period 1 (12 Weeks) NOT COMPLETED	0	6	3	1	2
Period 2 (12 Weeks) STARTED	0	26	29	0	0
Period 2 (12 Weeks) Received At Least 1 Dose of Study Drug	0	20	28	0	0
Period 2 (12 Weeks) COMPLETED	0	19	21	0	0
Period 2 (12 Weeks) NOT COMPLETED	0	7	8	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Run-In Participants received low dose treprostinil for inhalation for up to 2 weeks before randomization	Original Crossover Design - Treprostinil, Then Placebo Participants received either treprostinil or placebo in the following order: Period 1: Up to 72 micrograms (μg) of treprostinil for inhalation four times daily (QID), for up to 12 weeks Period 2: Placebo QID for up to 12 weeks	Original Crossover Design - Placebo, Then Treprostinil Participants received either treprostinil or placebo in the following order: Period 1: Placebo QID for up to 12 weeks Period 2: Up to 72 μg of treprostinil for inhalation QID, for up to 12 weeks	Contingent Parallel Design - Treprostinil Participants received up to 72 μg of treprostinil for inhalation QID, for up to 12 weeks	Contingent Parallel Design - Placebo Participants received placebo to match treprostinil QID, for up to 12 weeks
Run-In Period (2 Weeks) Death	1	0	0	0	0
Run-In Period (2 Weeks) Discontinued Prior to Randomization	31	0	0	0	0
Period 1 (12 Weeks) Death	0	3	0	0	0
Period 1 (12 Weeks) Study Terminated by Sponsor	0	0	0	1	2
Period 1 (12 Weeks) Withdrawal by Subject	0	3	3	0	0
Period 2 (12 Weeks) COVID-19 Pandemic Impact	0	4	5	0	0
Period 2 (12 Weeks) Lost to Follow-up	0	0	1	0	0
Period 2 (12 Weeks) Study Terminated by Sponsor	0	0	1	0	0
Period 2 (12 Weeks) Withdrawal by Subject	0	3	1	0	0

Baseline Characteristics

A Phase 3 Adaptive Study to Evaluate the Safety and Efficacy of Inhaled Treprostinil in Participants With Pulmonary Hypertension (PH) Due to Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Original Crossover Design n=64 Participants Participants were randomized to one of two treatment sequences: treprostinil-placebo, or placebo-treprostinil during two dosing periods, each up to 12 weeks	Contingent Parallel Design - Treprostinil n=6 Participants Participants received up to 72 μg of treprostinil for inhalation QID, for up to 12 weeks	Contingent Parallel Design - Placebo n=6 Participants Participants received placebo to match treprostinil QID, for up to 12 weeks	Total n=76 Participants Total of all reporting groups
Age, Continuous	67.6 years STANDARD_DEVIATION 7.83 • n=5 Participants	70.3 years STANDARD_DEVIATION 6.71 • n=7 Participants	73.3 years STANDARD_DEVIATION 2.16 • n=5 Participants	69.7 years STANDARD_DEVIATION 8.01 • n=4 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	33 Participants n=4 Participants
Sex: Female, Male Male	33 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	43 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	62 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	72 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	15 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	18 Participants n=4 Participants
Race (NIH/OMB) White	47 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	56 Participants n=4 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: Full Analysis Set included all participants who were randomized and received at least one dose of study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants evaluable at the specified timeframe.

Outcome measures

Outcome measures
Measure	Original Crossover Design - Treprostinil n=46 Participants Participants received up to 72 μg of treprostinil for inhalation QID, for up to 12 weeks	Original Crossover Design - Placebo n=47 Participants Participants received placebo to match treprostinil for inhalation QID, for up to 12 weeks	Contingent Parallel Design - Treprostinil n=6 Participants Participants received up to 72 μg of treprostinil for inhalation QID, for up to 12 weeks	Contingent Parallel Design - Placebo n=5 Participants Participants received placebo to match treprostinil QID, for up to 12 weeks
Change From Baseline to Week 12 in 6-Minute Walk Distance (6MWD) Baseline	225.07 meters Standard Deviation 77.41	220.47 meters Standard Deviation 77.64	231.50 meters Standard Deviation 60.77	283.00 meters Standard Deviation 67.78
Change From Baseline to Week 12 in 6-Minute Walk Distance (6MWD) Change at Week 12	-4.47 meters Standard Deviation 39.01	-5.14 meters Standard Deviation 50.71	20.33 meters Standard Deviation 116.99	18.5 meters Standard Deviation 42.49

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Full Analysis Set included all participants who were randomized and received at least one dose of study drug. Data were not collected for this outcome measure due to study termination and lack of appropriate sample size.

MVPA was defined as the number of minutes spent in moderate to vigorous physical activity as measured via a wrist-worn medical grade physical activity monitor. The screening data were used to establish a baseline level of physical activity.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 12

Overall activity was defined as the number of minutes spent in overall activity (non-sedentary activity) as measured via a wrist-worn medical grade physical activity monitor. The screening data will be used to establish a baseline level of physical activity.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 12

The Borg Dyspnea Score was a 11-point scale rating the maximum level of dyspnea experienced during the 6-minute walking test (6MWT). Scores range from 0 (no dyspnea at all) to 10 (very, very severe dyspnea), with lower scores indicating a less exertion (a better outcome). The Borg Dyspnea Score was to be evaluated immediately after the 6MWT.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 12

6MWD was calculated at peak exposure (10 to 60 minutes after dosing). 6MWT was performed by standardized procedures for all participants. Participants were asked to walk a set course for 6 minutes (timed) and the distance walked (in meters) was recorded. The Borg Dyspnea Score was an 11-point scale rating the maximum level of dyspnea experienced during the 6MWT. Scores range from 0 (no dyspnea at all) to 10 (very, very severe dyspnea), with lower scores indicating less exertion (a better outcome). The Borg Dyspnea Score was to be evaluated immediately after the 6MWT. The average 6WMWD data and the average Borg Dyspnea Composite Score data were summed and reported as the composite score.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 12

The SGRQ is a designed to measure how breathing impacts overall health, daily life, and perceived well-being in participants with obstructive airways disease. Scores range from 0 to 100, with lower scores indicating a better QoL.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 12

The UCSD SOBQ is a self-administered rating of dyspnea associated with activities of daily living. The questionnaire uses a 6-point scale where 0 = "not at all" and 5 = "maximal or unable to do because of breathlessness". Lower scores indicate a better QoL.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 12

The NT-proBNP concentration is a biomarker associated with changes in right heart morphology and function. Improvement is defined as a decrease in the NT-proBNP plasma concentration.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 12

The PGA is used to rate participant fatigue and shortness of breath. Participants will use the Sponsor-provided smart device for at-home capture of PGA data. The PGA used a 5-point response scale of: "never," "rarely," "sometimes," "often," or "always" with higher scores indicating a worse symptom rating.

Outcome measures

Outcome data not reported

Adverse Events

Run-In

Serious events: 9 serious events

Other events: 50 other events

Deaths: 1 deaths

Treprostinil

Serious events: 17 serious events

Other events: 36 other events

Deaths: 5 deaths

Placebo

Serious events: 6 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Run-In n=108 participants at risk Participants received low dose treprostinil for inhalation for up to 2 weeks before randomization	Treprostinil n=66 participants at risk Participants who received up to 72 μg of treprostinil for inhalation QID, for up to 12 weeks during both the original cross-over design and the contingent parallel design combined	Placebo n=58 participants at risk Participants who received placebo to match treprostinil QID, for up to 12 weeks during both the original cross-over design and the contingent parallel design combined
General disorders Fatigue	1.9% 2/108 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	10.6% 7/66 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	3.4% 2/58 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.
General disorders Chest discomfort	2.8% 3/108 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	7.6% 5/66 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	0.00% 0/58 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.
Infections and infestations Upper respiratory tract infection	0.93% 1/108 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	3.0% 2/66 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	6.9% 4/58 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/108 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	3.0% 2/66 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	5.2% 3/58 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.
Musculoskeletal and connective tissue disorders Pain in jaw	0.00% 0/108 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	1.5% 1/66 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	5.2% 3/58 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.
Nervous system disorders Headache	8.3% 9/108 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	10.6% 7/66 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	6.9% 4/58 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.
Nervous system disorders Dizziness	1.9% 2/108 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	6.1% 4/66 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	3.4% 2/58 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.
Respiratory, thoracic and mediastinal disorders Dyspnoea	17.6% 19/108 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	28.8% 19/66 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	15.5% 9/58 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.
Respiratory, thoracic and mediastinal disorders Cough	14.8% 16/108 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	16.7% 11/66 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	5.2% 3/58 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.3% 9/108 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	4.5% 3/66 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	3.4% 2/58 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.
Respiratory, thoracic and mediastinal disorders Productive cough	4.6% 5/108 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	6.1% 4/66 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	3.4% 2/58 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.
Respiratory, thoracic and mediastinal disorders Hypoxia	3.7% 4/108 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	4.5% 3/66 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	5.2% 3/58 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	2.8% 3/108 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	4.5% 3/66 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.	5.2% 3/58 • Up to 6 months Safety Analysis Set included all participants who received at least one dose of study drug. Data were prespecified to be collected by the treatment received for both treprostinil or placebo regardless of whether the treatment was received during the Original Crossover Design or the Contingent Parallel Design. Number of deaths that led to study discontinuation are reported in Participant Flow and number of deaths due to All-Cause Mortality are reported below.

Additional Information

United Therapeutics Global Medical Information

United Therapeutics

Phone: 240-821-1881

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Institution clinical trial centers and PIs agreed not to publish or publicly present any results of clinical trial without prior written consent of sponsor, not to be withheld or delayed except as necessary to require removal of any sponsor confidential information (other than as necessary to fully disclose the trial design and results in accordance with applicable publication standards) or as necessary to provide reasonable time for sponsor to perfect any arising intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER