Idiopathic Pulmonary Fibrosis
Conditions
Keywords
Actelion, Idiopathic Pulmonary Fibrosis, bosentan, Tracleer, Interstitial Lung Disease, BUILD 3 (NCT00391443)
Brief summary
This Open-label extension study in patients with Idiopathic Pulmonary Fibrosis who completed protocol AC-052-321 / BUILD 3 (NCT00391443) will asses the long term safety and tolerability of bosentan in patients with idiopathic pulmonary fibrosis (IPF).
Interventions
DRUGBosentan
For patients who were administered Bosentan during BUILD 3 (NCT00391443): continue on same dose For patients who were administered placebo during BUILD 3 (NCT00391443): Oral Bosentan 62.5 mg for 4 weeks; maintenance dose: 125 mg ( 62.5 if patient weighs \< 90 lbs.)
Sponsors
Actelion
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients should have completed all the assessments from the BUILD 3 (NCT00391443) end of study (EOS) visit. * Signed informed consent prior to initiation of any study-related procedures. * Women of childbearing potential must have a negative serum pregnancy test and use reliable methods of contraception during study treatment and for 3 months after study treatment termination.
Exclusion criteria
* Any major violation of protocol AC-052-321 / BUILD 3 (NCT00391443). * Pregnancy or breast-feeding. * AST and/or ALT \> 3 times the upper limit of the normal range. * Any known factor or disease that might interfere with treatment compliance, study conduct or interpretation of the results, such as drug or alcohol dependence or psychiatric disease. * Known hypersensitivity to bosentan or any of the excipients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Extent of Exposure to Bosentan in Patients With Idiopathic Pulmonary Fibrosis (IPF) | Start of study to end of study, up to 21 months | Mean extent of exposure to bosentan treatment in months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Exposed to Bosentan Over Time | Start to end of study, up to 21 months | Numbers of participants exposed to bosentan treatment over time |
| Adverse Events (AE) Leading to Discontinuation of Study Drug. | Start to end of study, up to 21 months | Number of participants with at least one AE that led to permanent discontinuation of study treatment. |
| Treatment-emergent Serious Adverse Events (SAE) | up to 21 months plus 28 days after the end of study drug | Number of participants with at least one SAE during the study. |
| Occurrence of Liver Function Test (LFT: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)) Abnormality. | up to 21 months, plus 24 hours after the end of study treatment | Number of participants with an increase in ALT and/or AST to \> 3 times upper limit of normal during the study. |
Participant flow
Recruitment details
Patients were enrolled at 61 centers in 15 countries (Australia, Belgium, Canada, Czech Republic, France, Germany, Ireland, Israel, Italy, Japan, South Korea, , Spain, Switzerland, UK, and USA. The first patient started on 5 March 2008 and the last patient, last visit was on 01 April 2010.
Pre-assignment details
In total, 128 of the 615 patients who received randomized treatment in BUILD 3 (NCT00391443) rolled over into the BUILD 3 OL extension.
Participants by arm
| Arm | Count |
|---|---|
| Bosentan Treatment Oral bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks, and oral bosentan 125 mg b.i.d. (62.5 mg b.i.d. if \</= 40 kg) thereafter | 128 |
| Total | 128 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 14 |
| Overall Study | Death | 18 |
| Overall Study | Preparation for lung transplant | 8 |
| Overall Study | Withdrew consent | 5 |
Baseline characteristics
| Characteristic | Bosentan Treatment |
|---|---|
| Age, Continuous | 65.4 years STANDARD_DEVIATION 8.2 |
| Age, Customized 18-40 years | 1 participants |
| Age, Customized 41-60 years | 33 participants |
| Age, Customized 61-70 years | 62 participants |
| Age, Customized >70 years | 32 participants |
| Region of Enrollment Australia | 12 participants |
| Region of Enrollment Belgium | 1 participants |
| Region of Enrollment Canada | 14 participants |
| Region of Enrollment Czech Republic | 1 participants |
| Region of Enrollment France | 3 participants |
| Region of Enrollment Germany | 11 participants |
| Region of Enrollment Ireland | 1 participants |
| Region of Enrollment Israel | 4 participants |
| Region of Enrollment Italy | 2 participants |
| Region of Enrollment Japan | 8 participants |
| Region of Enrollment Korea, Republic of | 5 participants |
| Region of Enrollment Spain | 8 participants |
| Region of Enrollment Switzerland | 4 participants |
| Region of Enrollment United Kingdom | 3 participants |
| Region of Enrollment United States | 51 participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 97 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 128 |
| serious Total, serious adverse events | 51 / 128 |
Outcome results
Primary
Extent of Exposure to Bosentan in Patients With Idiopathic Pulmonary Fibrosis (IPF)
Mean extent of exposure to bosentan treatment in months
Time frame: Start of study to end of study, up to 21 months
Population: For two patients, the exact treatment stop date was missing and the duration could not be calculated, but these patients received at least 345 and 127 days of open label (OL) treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bosentan Treatment | Extent of Exposure to Bosentan in Patients With Idiopathic Pulmonary Fibrosis (IPF) | 6.4 months | Standard Deviation 4.6 |
Secondary
Adverse Events (AE) Leading to Discontinuation of Study Drug.
Number of participants with at least one AE that led to permanent discontinuation of study treatment.
Time frame: Start to end of study, up to 21 months
Population: Study population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bosentan Treatment | Adverse Events (AE) Leading to Discontinuation of Study Drug. | 32 participants |
Secondary
Number of Patients Exposed to Bosentan Over Time
Numbers of participants exposed to bosentan treatment over time
Time frame: Start to end of study, up to 21 months
Population: For two patients, the exact treatment stop date was missing and the duration could not be calculated, but these patients received at least 345 and 127 days of OL treatment, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bosentan Treatment | Number of Patients Exposed to Bosentan Over Time | For at least 4 months | 74 Participants |
| Bosentan Treatment | Number of Patients Exposed to Bosentan Over Time | For at least 8 months | 44 Participants |
| Bosentan Treatment | Number of Patients Exposed to Bosentan Over Time | For at least 12 months | 17 Participants |
| Bosentan Treatment | Number of Patients Exposed to Bosentan Over Time | For at least 16 months | 7 Participants |
| Bosentan Treatment | Number of Patients Exposed to Bosentan Over Time | For at least 20 months | 2 Participants |
Secondary
Occurrence of Liver Function Test (LFT: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)) Abnormality.
Number of participants with an increase in ALT and/or AST to \> 3 times upper limit of normal during the study.
Time frame: up to 21 months, plus 24 hours after the end of study treatment
Population: Study population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bosentan Treatment | Occurrence of Liver Function Test (LFT: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)) Abnormality. | 3 participants |
Secondary
Treatment-emergent Serious Adverse Events (SAE)
Number of participants with at least one SAE during the study.
Time frame: up to 21 months plus 28 days after the end of study drug
Population: Study population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bosentan Treatment | Treatment-emergent Serious Adverse Events (SAE) | 51 participants |