Trial Outcomes & Findings for Investigation of the Safety and Pharmacology of Dry Powder Inhalation of Treprostinil (NCT NCT03399604)
NCT ID: NCT03399604
Last Updated: 2024-07-30
Results Overview
There were two treatment arms analyzed for events in the study. All subjects that participated in the PK study were part of the transition group and not analyzed separately for adverse events. Treatment-Emergent Adverse Events and Serious Adverse Events will be grouped by MedDRA System Organ Class, dose level, time on drug, and relationship to dose titration
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
121 participants
Primary outcome timeframe
Baseline, Week 2, Month 1, Month 2 Visits, with bimonthly follow up for up to 16 months.
Results posted on
2024-07-30
Participant Flow
Of the 146 subjects screened for the study, 121 (55 Transition Group, 66 Add On Group) were enrolled.
Participant milestones
| Measure |
LIQ861 Inhaled Treprostinil
LIQ861 inhaled treprostinil at capsule strengths of 25 μg, 50 μg, 75 μg and 100 μg.
LIQ861 will be administered using the RS00 Model 8 dry powder inhalation (DPI) device (Plastiape S.p.A.; Osnago, Italy) at dose levels of 25 μg to 150 μg treprostinil QID in individual patients.
LIQ861 Inhaled Treprostinil: LIQ861 bulk powder is generated from a treprostinil/excipient matrix from which particles of precise size and shape are created and filled into a hydroxypropyl methylcellulose (HPMC) capsule (size 3). LIQ861 capsules are provided in capsule strengths of 25 μg, 50 μg, 75 μg and 100 μg treprostinil.
|
|---|---|
|
Overall Study
STARTED
|
121
|
|
Overall Study
COMPLETED
|
92
|
|
Overall Study
NOT COMPLETED
|
29
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Investigation of the Safety and Pharmacology of Dry Powder Inhalation of Treprostinil
Baseline characteristics by cohort
| Measure |
LIQ861 Inhaled Treprostinil
n=121 Participants
LIQ861 inhaled treprostinil at capsule strengths of 25 μg, 50 μg, 75 μg and 100 μg.
LIQ861 will be administered using the RS00 Model 8 dry powder inhalation (DPI) device (Plastiape S.p.A.; Osnago, Italy) at dose levels of 25 μg to 150 μg treprostinil QID in individual patients.
LIQ861 Inhaled Treprostinil: LIQ861 bulk powder is generated from a treprostinil/excipient matrix from which particles of precise size and shape are created and filled into a hydroxypropyl methylcellulose (HPMC) capsule (size 3). LIQ861 capsules are provided in capsule strengths of 25 μg, 50 μg, 75 μg and 100 μg treprostinil.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
95 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
26 Participants
n=5 Participants
|
|
Age, Continuous
|
54.2 years
STANDARD_DEVIATION 14.33 • n=5 Participants
|
|
Sex: Female, Male
Female
|
99 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
20 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
101 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
15 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
96 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
121 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 2, Month 1, Month 2 Visits, with bimonthly follow up for up to 16 months.Population: The Safety Population included all subjects who received at least 1 inhalation of LIQ861.
There were two treatment arms analyzed for events in the study. All subjects that participated in the PK study were part of the transition group and not analyzed separately for adverse events. Treatment-Emergent Adverse Events and Serious Adverse Events will be grouped by MedDRA System Organ Class, dose level, time on drug, and relationship to dose titration
Outcome measures
| Measure |
LIQ861 Inhaled Treprostinil
n=121 Participants
LIQ861 inhaled treprostinil at capsule strengths of 25 μg, 50 μg, 75 μg and 100 μg.
LIQ861 will be administered using the RS00 Model 8 dry powder inhalation (DPI) device (Plastiape S.p.A.; Osnago, Italy) at dose levels of 25 μg to 150 μg treprostinil QID in individual patients.
LIQ861 Inhaled Treprostinil: LIQ861 bulk powder is generated from a treprostinil/excipient matrix from which particles of precise size and shape are created and filled into a hydroxypropyl methylcellulose (HPMC) capsule (size 3). LIQ861 capsules are provided in capsule strengths of 25 μg, 50 μg, 75 μg and 100 μg treprostinil.
|
|---|---|
|
Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events
|
121 Participants
|
Adverse Events
LIQ861 Add-On
Serious events: 15 serious events
Other events: 66 other events
Deaths: 0 deaths
Tyvaso Transition
Serious events: 6 serious events
Other events: 55 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
LIQ861 Add-On
n=121 participants at risk
LIQ861 inhaled treprostinil at capsule strengths of 25 μg, 50 μg, 75 μg and 100 μg.
LIQ861 will be administered using the RS00 Model 8 dry powder inhalation (DPI) device (Plastiape S.p.A.; Osnago, Italy) at dose levels of 25 μg to 150 μg treprostinil QID in individual patients.
LIQ861 Inhaled Treprostinil: LIQ861 bulk powder is generated from a treprostinil/excipient matrix from which particles of precise size and shape are created and filled into a hydroxypropyl methylcellulose (HPMC) capsule (size 3). LIQ861 capsules are provided in capsule strengths of 25 μg, 50 μg, 75 μg and 100 μg treprostinil.
|
Tyvaso Transition
n=121 participants at risk
LIQ861 inhaled treprostinil at capsule strengths of 25 μg, 50 μg, 75 μg and 100 μg.
LIQ861 will be administered using the RS00 Model 8 dry powder inhalation (DPI) device (Plastiape S.p.A.; Osnago, Italy) at dose levels of 25 μg to 150 μg treprostinil QID in individual patients.
LIQ861 Inhaled Treprostinil: LIQ861 bulk powder is generated from a treprostinil/excipient matrix from which particles of precise size and shape are created and filled into a hydroxypropyl methylcellulose (HPMC) capsule (size 3). LIQ861 capsules are provided in capsule strengths of 25 μg, 50 μg, 75 μg and 100 μg
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
|
Cardiac disorders
Cardiac Failure
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Arterial Hypertension
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian Neoplasm
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
0.00%
0/121 • 1 year, 8 months
|
|
Respiratory, thoracic and mediastinal disorders
Alveolitis Allergic
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
0.00%
0/121 • 1 year, 8 months
|
|
Cardiac disorders
Atrial Fibrillation
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
0.00%
0/121 • 1 year, 8 months
|
|
General disorders
Pyrexia
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
0.00%
0/121 • 1 year, 8 months
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
0.00%
0/121 • 1 year, 8 months
|
|
Respiratory, thoracic and mediastinal disorders
Diaphragmatic Paralysis
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
0.00%
0/121 • 1 year, 8 months
|
|
Infections and infestations
Pneumonia
|
1.7%
2/121 • Number of events 2 • 1 year, 8 months
|
0.00%
0/121 • 1 year, 8 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.7%
2/121 • Number of events 2 • 1 year, 8 months
|
0.00%
0/121 • 1 year, 8 months
|
|
Nervous system disorders
Syncope
|
1.7%
2/121 • Number of events 2 • 1 year, 8 months
|
0.00%
0/121 • 1 year, 8 months
|
|
Vascular disorders
Hypertensive Crisis
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
0.00%
0/121 • 1 year, 8 months
|
|
Infections and infestations
Viral Infection
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
0.00%
0/121 • 1 year, 8 months
|
|
Infections and infestations
Sepsis
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
0.00%
0/121 • 1 year, 8 months
|
|
Renal and urinary disorders
Acute Kidney Injury
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
0.00%
0/121 • 1 year, 8 months
|
|
Nervous system disorders
Seizure
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
0.00%
0/121 • 1 year, 8 months
|
|
Infections and infestations
Parainfluenzae Virus Infection
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
0.00%
0/121 • 1 year, 8 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
0.00%
0/121 • 1 year, 8 months
|
|
Cardiac disorders
Acute Myocardial Infarction
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
0.00%
0/121 • 1 year, 8 months
|
|
Injury, poisoning and procedural complications
Open Fracture
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
0.00%
0/121 • 1 year, 8 months
|
|
General disorders
Oedema Peripheral
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
0.00%
0/121 • 1 year, 8 months
|
|
Nervous system disorders
Carotid Artery Stenosis
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
0.00%
0/121 • 1 year, 8 months
|
|
Metabolism and nutrition disorders
Fluid Overload
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
0.00%
0/121 • 1 year, 8 months
|
|
Infections and infestations
Overgrowth Bacterial
|
0.00%
0/121 • 1 year, 8 months
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
0.00%
0/121 • 1 year, 8 months
|
1.7%
2/121 • Number of events 2 • 1 year, 8 months
|
|
Gastrointestinal disorders
Gastrointestinal Hemorrhage
|
0.00%
0/121 • 1 year, 8 months
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
Other adverse events
| Measure |
LIQ861 Add-On
n=121 participants at risk
LIQ861 inhaled treprostinil at capsule strengths of 25 μg, 50 μg, 75 μg and 100 μg.
LIQ861 will be administered using the RS00 Model 8 dry powder inhalation (DPI) device (Plastiape S.p.A.; Osnago, Italy) at dose levels of 25 μg to 150 μg treprostinil QID in individual patients.
LIQ861 Inhaled Treprostinil: LIQ861 bulk powder is generated from a treprostinil/excipient matrix from which particles of precise size and shape are created and filled into a hydroxypropyl methylcellulose (HPMC) capsule (size 3). LIQ861 capsules are provided in capsule strengths of 25 μg, 50 μg, 75 μg and 100 μg treprostinil.
|
Tyvaso Transition
n=121 participants at risk
LIQ861 inhaled treprostinil at capsule strengths of 25 μg, 50 μg, 75 μg and 100 μg.
LIQ861 will be administered using the RS00 Model 8 dry powder inhalation (DPI) device (Plastiape S.p.A.; Osnago, Italy) at dose levels of 25 μg to 150 μg treprostinil QID in individual patients.
LIQ861 Inhaled Treprostinil: LIQ861 bulk powder is generated from a treprostinil/excipient matrix from which particles of precise size and shape are created and filled into a hydroxypropyl methylcellulose (HPMC) capsule (size 3). LIQ861 capsules are provided in capsule strengths of 25 μg, 50 μg, 75 μg and 100 μg
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
33.9%
41/121 • Number of events 41 • 1 year, 8 months
|
19.0%
23/121 • Number of events 23 • 1 year, 8 months
|
|
Respiratory, thoracic and mediastinal disorders
Dysponea
|
8.3%
10/121 • Number of events 10 • 1 year, 8 months
|
10.7%
13/121 • Number of events 13 • 1 year, 8 months
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
11.6%
14/121 • Number of events 14 • 1 year, 8 months
|
6.6%
8/121 • Number of events 8 • 1 year, 8 months
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.0%
6/121 • Number of events 6 • 1 year, 8 months
|
1.7%
2/121 • Number of events 2 • 1 year, 8 months
|
|
Nervous system disorders
Headache
|
19.0%
23/121 • Number of events 23 • 1 year, 8 months
|
14.9%
18/121 • Number of events 18 • 1 year, 8 months
|
|
Nervous system disorders
Dizziness
|
10.7%
13/121 • Number of events 13 • 1 year, 8 months
|
8.3%
10/121 • Number of events 10 • 1 year, 8 months
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
14.9%
18/121 • Number of events 18 • 1 year, 8 months
|
8.3%
10/121 • Number of events 10 • 1 year, 8 months
|
|
Infections and infestations
Nasopharyngitis
|
5.0%
6/121 • Number of events 6 • 1 year, 8 months
|
5.0%
6/121 • Number of events 6 • 1 year, 8 months
|
|
Infections and infestations
Urinary Tract Infection
|
5.0%
6/121 • Number of events 6 • 1 year, 8 months
|
1.7%
2/121 • Number of events 2 • 1 year, 8 months
|
|
General disorders
Chest Discomfort
|
5.8%
7/121 • Number of events 7 • 1 year, 8 months
|
9.1%
11/121 • Number of events 11 • 1 year, 8 months
|
|
General disorders
Fatigue
|
8.3%
10/121 • Number of events 10 • 1 year, 8 months
|
3.3%
4/121 • Number of events 4 • 1 year, 8 months
|
|
General disorders
Pyrexia
|
5.8%
7/121 • Number of events 7 • 1 year, 8 months
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.0%
6/121 • Number of events 6 • 1 year, 8 months
|
0.83%
1/121 • Number of events 1 • 1 year, 8 months
|
|
Vascular disorders
Flushing
|
5.8%
7/121 • Number of events 7 • 1 year, 8 months
|
2.5%
3/121 • Number of events 3 • 1 year, 8 months
|
|
Gastrointestinal disorders
Diahrrea
|
12.4%
15/121 • Number of events 15 • 1 year, 8 months
|
5.8%
7/121 • Number of events 7 • 1 year, 8 months
|
|
Gastrointestinal disorders
Nausea
|
5.0%
6/121 • Number of events 6 • 1 year, 8 months
|
5.0%
6/121 • Number of events 6 • 1 year, 8 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place