Chronic Obstructive Pulmonary Disease, Pulmonary Hypertension
Conditions
Keywords
PH, COPD
Brief summary
This is a phase 2, Multi-center, double-blind, randomized, placebo-controlled study to evaluate the effects of inhaled Iloprost in patients with pulmonary hypertension secondary to COPD. The main objective is to investigate the effect of iloprost on exercise endurance time during constant work rate cardiopulmonary exercise testing. Other efficacy and safety endpoints will additionally be analyzed.
Interventions
DRUGIloprost
5ug dose of inhaled iloprost (20ug/mL solution) administered 6 to 9 times per day for 4 weeks
DRUGPlacebo
matching placebo
Sponsors
Actelion
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent prior to initiation of any study mandated procedure 2. Male or female ≥ 40 and ≤ 75 years of age 3. Women of childbearing potential1 must use a reliable method of contraception 4. Clinical diagnosis of moderate to severe COPD, with an obstructive pattern on pulmonary function tests 5. Current or past smokers of ≥ 10 pack years 6. Ability to perform exercise testing without supplemental oxygen (in the best opinion of the investigator) 7. Confirmed pulmonary hypertension by right heart catheterization (RHC)
Exclusion criteria
1. Other causes of pulmonary hypertension than COPD 2. BMI \> 35 kg/m2 3. Conditions considered as contraindications for cardiopulmonary exercise testing (CPET) and/or inability to pedal on a cycle ergometer 4. Pregnant or nursing 5. Currently (within 30 days prior to RHC) taking specific pulmonary arterial hypertension (PAH) therapy (e.g., bosentan, ambrisentan, tadalafil, sildenafil, epoprostenol, treprostinil, iloprost, beraprost) 6. Participation in any other clinical trial, except observational, or receipt of an investigational product within 30 days prior to RHC visit 7. Known concomitant life-threatening disease with a life expectancy \< 12 months 8. Known hypersensitivity to iloprost or any of the excipients of the drug formulations
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Endurance Time | Baseline to week 4 | Change from baseline to week 4 in endurance time during constant work rate exercise testing |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Treatment-emergent Adverse Events | Baseline up to 24 hours post-EOT, approximately 4 weeks | Treatment-emergent adverse events up to 24 hours post-end of treatment (EOT), approximately 4 weeks |
| Change in Systolic Pulmonary Arterial Pressure | 15 minutes | On Day 1 patients underwent acute hemodynamic testing prior to and immediately after (no more than 15 minutes) the first dose of inhaled iloprost or placebo. All hemodynamic variables were measured using a Swan-Ganz catheter. |
| Change in Mean Pulmonary Arterial Pressure | 15 minutes | On Day 1 patients underwent acute hemodynamic testing prior to and immediately after (no more than 15 minutes) the first dose of inhaled iloprost or placebo. All hemodynamic variables were measured using a Swan-Ganz catheter. |
| Change in Mean Right Atrial Pressure | 15 minutes | On Day 1 patients underwent acute hemodynamic testing prior to and immediately after (no more than 15 minutes) the first dose of inhaled iloprost or placebo. All hemodynamic variables were measured using a Swan-Ganz catheter. |
| Change in Cardiac Output | 15 minutes | On Day 1 patients underwent acute hemodynamic testing prior to and immediately after (no more than 15 minutes) the first dose of inhaled iloprost or placebo. All hemodynamic variables were measured using a Swan-Ganz catheter. |
| Change in Right Ventricular Pressure | 15 minutes | On Day 1 patients underwent acute hemodynamic testing prior to and immediately after (no more than 15 minutes) the first dose of inhaled iloprost or placebo. All hemodynamic variables were measured using a Swan-Ganz catheter. |
| Change in Pulmonary Vascular Resistance | 15 minutes | On Day 1 patients underwent acute hemodynamic testing prior to and immediately after (no more than 15 minutes) the first dose of inhaled iloprost or placebo. All hemodynamic variables were measured using a Swan-Ganz catheter. |
| Change in End Tidal Partial Pressure of Carbon Dioxide | Baseline to week 4 | Change from baseline to week 4. Pulmonary gas exchange was measured during incremental and constant work rate exercise testing. |
| Change in Diastolic Pulmonary Arterial Pressure | 15 minutes | On Day 1 patients underwent acute hemodynamic testing prior to and immediately after (no more than 15 minutes) the first dose of inhaled iloprost or placebo. All hemodynamic variables were measured using a Swan-Ganz catheter. |
| Change in Oxygen Uptake | Baseline to week 4 | Change from baseline to week 4. Pulmonary gas exchange was measured during incremental and constant work rate exercise testing. |
| Change in Carbon Dioxide Output | Baseline to week 4 | Change from baseline to week 4. Pulmonary gas exchange was measured during incremental and constant work rate exercise testing. |
| Change in Oxygen Uptake Per Heartbeat | Baseline to week 4 | Change from baseline to week 4. Pulmonary gas exchange was measured during incremental and constant work rate exercise testing. |
| Change in Heart Rate | Baseline to week 4 | Change from baseline to week 4. Heart rate was measured during incremental and constant work rate exercise testing. |
| Change in Arterial Oxygen Saturation as Indicated by Pulse Oximetry | Baseline to week 4 | Change from baseline to week 4. Arterial oxygen was determined by pulse oximetry during incremental and constant work rate exercise testing. |
| Change in Tidal Volume | Baseline to week 4 | Change from baseline to week 4. Tidal volume was measured during incremental and constant work rate exercise testing. |
| Change in Minute Ventilation | Baseline to week 4 | Change from baseline to week 4. Minute ventilation was measured during incremental and constant work rate exercise testing. |
| Change in End Tidal Partial Pressure of Oxygen | Baseline to week 4 | Change from baseline to week 4. Pulmonary gas exchange was measured during incremental and constant work rate exercise testing. |
Countries
France, Spain, United States
Participant flow
Recruitment details
Patients were screened at 4 centres in the US, one centre in France, and one site in Spain. First patient, first visit was 1 March 2012 and last patient, last visit was 30 November 2012.
Pre-assignment details
A total of 22 patients were screened for the study, of these 20 were not randomized because they did not meet the selection criteria.
Participants by arm
| Arm | Count |
|---|---|
| Iloprost single dose inhalation using the power disc-6 with I-neb AAD system
Iloprost: 5ug dose of inhaled iloprost (20ug/mL solution) administered 6 to 9 times per day for 4 weeks | 1 |
| Placebo matching placebo using the power disc-6 with I-neb AAD system
Placebo: matching placebo | 1 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Iloprost | Placebo | Total |
|---|---|---|---|
| Age, Customized Age 64 years | 1 participants | 0 participants | 1 participants |
| Age, Customized Age 74 years | 0 participants | 1 participants | 1 participants |
| Region of Enrollment France | 1 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 0 participants | 1 participants | 1 participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 1 | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 |
Outcome results
Primary
Change in Endurance Time
Change from baseline to week 4 in endurance time during constant work rate exercise testing
Time frame: Baseline to week 4
Population: The study was prematurely terminated as after 1 year it was not possible to identify a suitable number of patients who satisfied the selection criteria. Only 2 patients were randomized prior to the termination of the study, and 1 patient received a single dose of active treatment. Therefore, there are inadequate data to evaluate efficacy.
Secondary
Change in Arterial Oxygen Saturation as Indicated by Pulse Oximetry
Change from baseline to week 4. Arterial oxygen was determined by pulse oximetry during incremental and constant work rate exercise testing.
Time frame: Baseline to week 4
Population: The study was prematurely terminated as after 1 year it was not possible to identify a suitable number of patients who satisfied the selection criteria. Only 2 patients were randomized prior to the termination of the study, and 1 patient received a single dose of active treatment. Therefore, there are inadequate data to evaluate efficacy.
Secondary
Change in Carbon Dioxide Output
Change from baseline to week 4. Pulmonary gas exchange was measured during incremental and constant work rate exercise testing.
Time frame: Baseline to week 4
Population: The study was prematurely terminated as after 1 year it was not possible to identify a suitable number of patients who satisfied the selection criteria. Only 2 patients were randomized prior to the termination of the study, and 1 patient received a single dose of active treatment. Therefore, there are inadequate data to evaluate efficacy.
Secondary
Change in Cardiac Output
On Day 1 patients underwent acute hemodynamic testing prior to and immediately after (no more than 15 minutes) the first dose of inhaled iloprost or placebo. All hemodynamic variables were measured using a Swan-Ganz catheter.
Time frame: 15 minutes
Population: The study was prematurely terminated as after 1 year it was not possible to identify a suitable number of patients who satisfied the selection criteria. Only 2 patients were randomized prior to the termination of the study, and 1 patient received a single dose of active treatment. Therefore, there are inadequate data to evaluate efficacy.
Secondary
Change in Diastolic Pulmonary Arterial Pressure
On Day 1 patients underwent acute hemodynamic testing prior to and immediately after (no more than 15 minutes) the first dose of inhaled iloprost or placebo. All hemodynamic variables were measured using a Swan-Ganz catheter.
Time frame: 15 minutes
Population: The study was prematurely terminated as after 1 year it was not possible to identify a suitable number of patients who satisfied the selection criteria. Only 2 patients were randomized prior to the termination of the study, and 1 patient received a single dose of active treatment. Therefore, there are inadequate data to evaluate efficacy.
Secondary
Change in End Tidal Partial Pressure of Carbon Dioxide
Change from baseline to week 4. Pulmonary gas exchange was measured during incremental and constant work rate exercise testing.
Time frame: Baseline to week 4
Population: The study was prematurely terminated as after 1 year it was not possible to identify a suitable number of patients who satisfied the selection criteria. Only 2 patients were randomized prior to the termination of the study, and 1 patient received a single dose of active treatment. Therefore, there are inadequate data to evaluate efficacy.
Secondary
Change in End Tidal Partial Pressure of Oxygen
Change from baseline to week 4. Pulmonary gas exchange was measured during incremental and constant work rate exercise testing.
Time frame: Baseline to week 4
Population: The study was prematurely terminated as after 1 year it was not possible to identify a suitable number of patients who satisfied the selection criteria. Only 2 patients were randomized prior to the termination of the study, and 1 patient received a single dose of active treatment. Therefore, there are inadequate data to evaluate efficacy.
Secondary
Change in Heart Rate
Change from baseline to week 4. Heart rate was measured during incremental and constant work rate exercise testing.
Time frame: Baseline to week 4
Population: The study was prematurely terminated as after 1 year it was not possible to identify a suitable number of patients who satisfied the selection criteria. Only 2 patients were randomized prior to the termination of the study, and 1 patient received a single dose of active treatment. Therefore, there are inadequate data to evaluate efficacy.
Secondary
Change in Mean Pulmonary Arterial Pressure
On Day 1 patients underwent acute hemodynamic testing prior to and immediately after (no more than 15 minutes) the first dose of inhaled iloprost or placebo. All hemodynamic variables were measured using a Swan-Ganz catheter.
Time frame: 15 minutes
Population: The study was prematurely terminated as after 1 year it was not possible to identify a suitable number of patients who satisfied the selection criteria. Only 2 patients were randomized prior to the termination of the study, and 1 patient received a single dose of active treatment. Therefore, there are inadequate data to evaluate efficacy.
Secondary
Change in Mean Right Atrial Pressure
On Day 1 patients underwent acute hemodynamic testing prior to and immediately after (no more than 15 minutes) the first dose of inhaled iloprost or placebo. All hemodynamic variables were measured using a Swan-Ganz catheter.
Time frame: 15 minutes
Population: The study was prematurely terminated as after 1 year it was not possible to identify a suitable number of patients who satisfied the selection criteria. Only 2 patients were randomized prior to the termination of the study, and 1 patient received a single dose of active treatment. Therefore, there are inadequate data to evaluate efficacy.
Secondary
Change in Minute Ventilation
Change from baseline to week 4. Minute ventilation was measured during incremental and constant work rate exercise testing.
Time frame: Baseline to week 4
Population: The study was prematurely terminated as after 1 year it was not possible to identify a suitable number of patients who satisfied the selection criteria. Only 2 patients were randomized prior to the termination of the study, and 1 patient received a single dose of active treatment. Therefore, there are inadequate data to evaluate efficacy.
Secondary
Change in Oxygen Uptake
Change from baseline to week 4. Pulmonary gas exchange was measured during incremental and constant work rate exercise testing.
Time frame: Baseline to week 4
Population: The study was prematurely terminated as after 1 year it was not possible to identify a suitable number of patients who satisfied the selection criteria. Only 2 patients were randomized prior to the termination of the study, and 1 patient received a single dose of active treatment. Therefore, there are inadequate data to evaluate efficacy.
Secondary
Change in Oxygen Uptake Per Heartbeat
Change from baseline to week 4. Pulmonary gas exchange was measured during incremental and constant work rate exercise testing.
Time frame: Baseline to week 4
Population: The study was prematurely terminated as after 1 year it was not possible to identify a suitable number of patients who satisfied the selection criteria. Only 2 patients were randomized prior to the termination of the study, and 1 patient received a single dose of active treatment. Therefore, there are inadequate data to evaluate efficacy.
Secondary
Change in Pulmonary Vascular Resistance
On Day 1 patients underwent acute hemodynamic testing prior to and immediately after (no more than 15 minutes) the first dose of inhaled iloprost or placebo. All hemodynamic variables were measured using a Swan-Ganz catheter.
Time frame: 15 minutes
Population: The study was prematurely terminated as after 1 year it was not possible to identify a suitable number of patients who satisfied the selection criteria. Only 2 patients were randomized prior to the termination of the study, and 1 patient received a single dose of active treatment. Therefore, there are inadequate data to evaluate efficacy.
Secondary
Change in Right Ventricular Pressure
On Day 1 patients underwent acute hemodynamic testing prior to and immediately after (no more than 15 minutes) the first dose of inhaled iloprost or placebo. All hemodynamic variables were measured using a Swan-Ganz catheter.
Time frame: 15 minutes
Population: The study was prematurely terminated as after 1 year it was not possible to identify a suitable number of patients who satisfied the selection criteria. Only 2 patients were randomized prior to the termination of the study, and 1 patient received a single dose of active treatment. Therefore, there are inadequate data to evaluate efficacy.
Secondary
Change in Systolic Pulmonary Arterial Pressure
On Day 1 patients underwent acute hemodynamic testing prior to and immediately after (no more than 15 minutes) the first dose of inhaled iloprost or placebo. All hemodynamic variables were measured using a Swan-Ganz catheter.
Time frame: 15 minutes
Population: The study was prematurely terminated as after 1 year it was not possible to identify a suitable number of patients who satisfied the selection criteria. Only 2 patients were randomized prior to the termination of the study, and 1 patient received a single dose of active treatment. Therefore, there are inadequate data to evaluate efficacy.
Secondary
Change in Tidal Volume
Change from baseline to week 4. Tidal volume was measured during incremental and constant work rate exercise testing.
Time frame: Baseline to week 4
Population: The study was prematurely terminated as after 1 year it was not possible to identify a suitable number of patients who satisfied the selection criteria. Only 2 patients were randomized prior to the termination of the study, and 1 patient received a single dose of active treatment. Therefore, there are inadequate data to evaluate efficacy.
Secondary
Participants With Treatment-emergent Adverse Events
Treatment-emergent adverse events up to 24 hours post-end of treatment (EOT), approximately 4 weeks
Time frame: Baseline up to 24 hours post-EOT, approximately 4 weeks
Population: Total population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Iloprost | Participants With Treatment-emergent Adverse Events | 0 participants |
| Placebo | Participants With Treatment-emergent Adverse Events | 0 participants |