Study to Assess the Tolerability and the Safety of the Transition From Inhaled Treprostinil to Oral Selexipag in Patients With Pulmonary Arterial Hypertension (TRANSIT-1)
|ClinicalTrials.gov Identifier: NCT02471183|
Recruitment Status : Completed
First Posted : June 15, 2015
Results First Posted : December 28, 2017
Last Update Posted : January 23, 2018
|Condition or disease||Intervention/treatment||Phase|
|Pulmonary Arterial Hypertension||Drug: Selexipag||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||34 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Multicenter, Open-label, Single-group Study to Assess the Tolerability and the Safety of the Transition From Inhaled Treprostinil to Oral Selexipag in Adult Patients With Pulmonary Arterial Hypertension|
|Actual Study Start Date :||October 12, 2015|
|Actual Primary Completion Date :||December 5, 2016|
|Actual Study Completion Date :||December 5, 2016|
Experimental: Selexipag, Open Label
Subjects on inhaled treprostinil treatment participate in a 16-week main treatment period including down-titration of treprostinil to end of Week 8 and parallel up-titration of selexipag to the maximum tolerated dose (MTD) up to Week 12, for each individual patient but not above 1600 mcg twice daily.
From Week 12 up to Week 16, patients continue selexipag at their individual MTD. Patients could continue the study drug selexipag during the extended treatment period from Week 16 until commercial availability of selexipag.
Tablets for oral administration containing 200 micrograms (mcg) of selexipag to be administered twice a day. The individual dose is to be established during the first 12 weeks of the study. Doses are in the range from 200 micrograms (1 tablet) to 1,600 micrograms (8 tablets).
- Percentage of Subjects With Sustained Treatment Transition [ Time Frame: At Week 16 ]
A sustained treatment transition is considered if the 3 following criteria are met a) being on study treatment (selexipag) at Week 16, and b) not having a study treatment interruption(s) of a total of 8 days or more prior to Week 16, and c) absence of inhaled treprostinil or any prostanoid treatment after Week 8 up to Week 16.
The percentage of subjects with a sustained treatment transition is calculated with 95% confidence interval (CI) using the Clopper-Pearson method.
- Percentage of Subjects With Treatment-emergent Adverse Events (AEs), [ Time Frame: 26 weeks on average (from the first dose of selexipag up to 30 days after the last dose of selexipag) ]Percentage of subjects with treatment-emergent AEs (serious and non serious), regardless of relationship to selexipag
- Number of Subjects With Adverse Events Leading to Premature Discontinuation of Selexipag [ Time Frame: Up to 22 weeks on average ]Number of subjects with adverse events leading to premature discontinuation of selexipag is determined from the first dose of selexipag up to the last dose of selexipag
- Absolute Change From Baseline Over Time in Blood Pressure [ Time Frame: Baseline, Week 4, Week 12, Week 16 ]Both systolic(SBP) and diastolic (DBP) arterial blood pressure were measured in a sitting position after at least 5 minutes of rest at scheduled time points. Median change from baseline to pre-specified post-baseline visits are calculated
- Absolute Change From Baseline Over Time in Heart Rate (HR) [ Time Frame: Baseline, Week 4, Week 12, Week 16 ]Pulse rate is measured after at least 5 minutes of rest in a sitting position. Median change from baseline to pre-specified post-baseline visits are calculated.
- Maximal Tolerated Dose [ Time Frame: At Week 12, in subjects still on selexipag at Week 16 ]
This is the individual maximal tolerated dose (MTD) observed at Week 12 in the subjects still on selexipag at Week 16.
MTD is defined as the dose of selexipag reached with the last dose change up to Week 12
- Time to Discontinuation of Inhaled Treprostinil. [ Time Frame: Baseline to Week 16 ]Median time from baseline (Day1) to the end of down-titration of inhaled treprostinil is calculated
- Percentage of Subjects With WHO Functional Class (FC) Change From Baseline [ Time Frame: Baseline and Week 16 ]
The World Health Organization (WHO) defines 4 classes to classify the functional status of patients with pulmonary hypertension:
Class I (FC I): No limitation of physical activity. Class II (FC II): Slight limitation of physical activity. Class III (FC III): Marked limitation of physical activity. Class IV (FC IV): Inability to carry out any physical activity without symptoms.
Number of patients with improvement (shift from a higher to a lower class), worsening (shift from a lower to a higher class) or no change in WHO functional class at end of study compared to baseline are determined.
- Absolute Change in 6-minute Walk Distance (6MWD) at Trough [ Time Frame: Baseline and Week 16 ]
The 6MWT is a non-encouraged test, which measures the distance (in meters) covered by the subject during a 6-minute walk. It is performed in a 30-meters long flat corridor, where the patient is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed.
Absolute change from baseline to Week 16 in 6MWD is measured at trough levels of inhaled treprostinil and/or selexipag. The trough level of inhaled treprostinil is defined as the last dose having been taken not less than 4 hours and not more than 48 hours prior to the 6MWT at Visit 1 (screening). The trough level of selexipag was defined as the last dose having been taken not less than 8 hours and not more than 7 days prior to the 6MWT at Visit 5 (Week 16).
- Percentage of Patients With Change in 6-minute Walk Distance (6MWD) [ Time Frame: Baseline and Week 16 ]
Percentage of patients with an increase (> 8% of baseline), maintenance (+/- 8% of baseline), or decrease (< -8% of baseline) in their 6MWD (at trough) from baseline to Week 16. The ± 8% boundaries for change in 6MWD reflect the approximately 8% coefficient of variation in the reproducibility of the 6MWD.
The trough level of inhaled treprostinil is defined as the last dose having been taken not less than 4 hours and not more than 48 hours prior to the 6MWD test at Visit 1 (screening). The trough level of selexipag was defined as the last dose having been taken not less than 8 hours and not more than 7 days prior to the 6MWD test at Visit 5 (Week 16).
- Geometric Mean of the Ratio in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) of Week 16 to Baseline [ Time Frame: Baseline and Week 16 ]Changes in NT-proBNP levels in plasma are expressed by the geometric mean of the ratio of Week 16 to baseline
- Change From Baseline to Week 16 in the Treatment Satisfaction Questionnaire for Medication Questionnaire (TSQM II) [ Time Frame: Baseline and Week 16 ]
The Treatment Satisfaction Questionnaire for Medication, Version II (TSQM II) is a validated tool that evaluate the subject's satisfaction with the study treatment. It includes a total of 11 questions related to satisfaction with treatment effectiveness, side effects,convenience, and global satisfaction.
TSQM scores range from 0 to 100 for each domain; a higher score indicates higher satisfaction with treatment.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02471183
|United States, California|
|UCSD Medical Center -La Jolla|
|La Jolla, California, United States|
|UCSF Medical Center|
|San Francisco, California, United States|
|Harbor UCLA Medical Center|
|Torrance, California, United States|
|United States, Georgia|
|Atlanta, Georgia, United States|
|Piedmont Healthcare Research Institute|
|Austell, Georgia, United States|
|United States, Kentucky|
|Kentuckiana Pulmonary Associates|
|Louisville, Kentucky, United States|
|United States, Michigan|
|University of Michigan Health System|
|Ann Arbor, Michigan, United States|
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States|
|United States, North Carolina|
|Durham, North Carolina, United States|
|United States, Pennsylvania|
|University of Pennsylvania|
|Philadelphia, Pennsylvania, United States|
|Allegheny General Hospital|
|Pittsburgh, Pennsylvania, United States|
|University of Pittsburgh Medical Center Health System|
|Pittsburgh, Pennsylvania, United States|
|United States, Texas|
|Dallas, Texas, United States|
|Houston Methodist Hospital|
|Houston, Texas, United States|
|United States, Virginia|
|Sentara Cardiovascular Research Instistute|
|Norfolk, Virginia, United States|