Pulmonary Arterial HypertensionPhase 2NCT01588405
Remodulin® to Oral Treprostinil Transition
A Phase 2 study testing UT-15C SR in people with Pulmonary Arterial Hypertension, run by United Therapeutics at 6 sites in United States.
Trial summary
This multi-center, open-label study will assess the tolerability and safety of transitioning subjects with stable Pulmonary Arterial Hypertension (PAH) from continuous intravenous (IV) or subcutaneous (SC) Remodulin infusion to oral treprostinil (UT-15C sustained release (SR) tablets). Read more about this study
- Who is it for?
- Ages 15 to 80 years
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- UT-15C SR
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 6 sitesUnited States
- Study dates
- Apr 2012to Dec 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Between 15 and 80 years of age, inclusive, weigh at least 40 kg and have a diagnosis of PAH
- Have stable disease as confirmed by recent right heart catheterization and a Baseline 6MWD of at least 250 meters
- Have been receiving Remodulin for at least 90 days and at a stable dose for at least 30 days prior to the Baseline visit; the dose of Remodulin must be between 25-75 ng/kg/min, inclusive
- Must be also receiving an endothelin receptor antagonist (ERA) and/or a phosphodiesterase-5 inhibitor (PDE-5i) for at least 90 days and have been at a stable dose for at least 30 days prior to Baseline
Who cannot join
- WHO functional class III and IV subjects will be excluded
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
The Ohio State University
Columbus, Ohio, 43221
Arizona Pulmonary Specialists
Phoenix, Arizona, 85013
University of Pittsburgh Medical Center (UPMC)
Pittsburgh, Pennsylvania, 15213
University of Rochester
Rochester, New York, 14642
Washington University School of Medicine
St Louis, Missouri, 63110
University of Arizona Clinical and Translational Science (CATS) Research Center
Tucson, Arizona, 85724
About this study
Official title: A Multicenter, Open-Label Study of the Safety and Tolerability of Transitioning From Remodulin® to Oral Treprostinil in Subjects With Pulmonary Arterial Hypertension
This multi-center, open-label study will assess the tolerability and safety of transitioning subjects with stable Pulmonary Arterial Hypertension (PAH) from continuous intravenous (IV) or subcutaneous (SC) Remodulin infusion to oral treprostinil (UT-15C sustained release (SR) tablets).
This study will consist of an in-hospital transition phase, dose optimization/evaluation phase, and follow up phase.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- UT-15C SR
- Keywords
- Pulmonary Arterial Hypertension, UT-15C SR, PAH
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UT-15C SRDrug
Subjects will transition in the hospital from Remodulin to UT-15C SR within 5 days of the start of the transition. The dose of Remodulin will be decreased as the dose of UT-15C SR is increased over the 5 days. Once subjects have been transitioned from Remodulin, the dose of UT-15C SR will continue to be modified / titrated to the appropriate optimal dose for that subject throughout the rest of the study.
| Study group | Role | What they receive |
|---|---|---|
| UT-15C SR | Experimental | Not described Receives: Drug: UT-15C SR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants That Were Succesfully Transitioned From Parenteral Remodulin to UT-15C.
Successful transition was based on the number of participants that completely transitioned to oral treprostinil by the week 4 study visit and clinically maintained on oral treprostinil treatment through Week 24.
Measured: Up to 24 weeks
Secondary outcomes (14)
Change From Baseline in Six-minute Walk Distance at Week 24
The purpose of the 6MWT is to evaluate exercise capacity associated with carrying out activities of daily living. Patients were instructed to walk down a corridor at a comfortable speed as far as they could manage for six minutes, resting whenever they needed. Distance <500 meters suggests considerable exercise limitation; Distance 500-800 meters suggests moderate limitation; Distance >800 meters (with no rests) suggests mild or no limitation.
Measured: Baseline and week 24
Change in Borg Dyspnea Score (Following 6MWT) From Baseline to Week 24
The Borg dyspnea score is a 10-point scale rating the maximum level of dyspnea (difficulty in breathing) experienced during the six-minute walk test (6MWT). The Borg dyspnea score was assessed immediately following the 6MWT. Scores ranged from 0 (for no shortness of breath) to 10 (for the greatest shortness of breath ever experienced).
Measured: Baseline and week 24
Change in Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) From Baseline to Week 24
The CAMPHOR is a health related quality of life instrument validated for pulmonary hypertension that assesses impairment (symptoms), disability (activities) and quality of life. The questionnaire is divided into three sections; Symptoms (Scores 0-25; high scores indicate more symptoms), Activity (Score 0-30; low score indicates good functioning) and Quality of Life (0-25; high scores indicate poor QoL). The sum of these scores equates to the Total score (0-80). In the CAMPHOR scores, lower scores indicate improvements.
Measured: Baseline and week 24
Change in World Health Organization (WHO) Functional Classification From Baseline to Week 24
Class I: No limitation of physical activity. Class II: Slight limitation of physical activity. Class III: Marked limitation of physical activity. Class IV: Inability to carry out any physical activity without symptoms.
Measured: Baseline and Week 24
Change in Dyspnea-fatigue Index From Baseline to Week 24
The dyspnea-fatigue index has three components, each rated on a scale of 0 to 4, for the magnitude of the task that evokes dyspnea or fatigue, the magnitude of the pace (or effort) with which the task is performed and the associated functional impairment in general activities. The ratings for each component were added to form an aggregate score, which could range from 0, for the worst condition, to 12, for the best.
Measured: Baseline and Week 24
Change From Baseline to Week 24 in Pharmacokinetic Parameters: Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), and Trough Plasma Concentration (Cmin)
Treprostinil pharmacokinetics (PK) were evaluated on two occasions during this study, once while the subject was still receiving Remodulin and again at Week 24 when the subject was receiving a stable dose of oral treprostinil. Blood samples were scheduled to be drawn from each subject initially at time 0 and the following subsequent times: 2, 4, 5, 6, 8, 10 and 12 hours after time of study drug administration (time 0) for a total of eight samples.
Measured: Baseline and Week 24
Change From Baseline to Week 24 in Pharmacokinetics Parameter: Peak Time to Reach Peak Plasma Concentration [Tmax (h)]
Treprostinil pharmacokinetics (PK) were evaluated on two occasions during this study, once while the subject was still receiving Remodulin and again at Week 24 when the subject was receiving a stable dose of oral treprostinil. Blood samples were scheduled to be drawn from each subject initially at time 0 and the following subsequent times: 2, 4, 5, 6, 8, 10 and 12 hours after time of study drug administration (time 0) for a total of eight samples.
Measured: Baseline and Week 24
Change From Baseline to Week 24 in Pharmacokinetics Parameters: Area Under the Plasma Concentration Curve (AUC) [h(ng/mL)]
Treprostinil pharmacokinetics (PK) were evaluated on two occasions during this study, once while the subject was still receiving Remodulin and again at Week 24 when the subject was receiving a stable dose of oral treprostinil. Blood samples were scheduled to be drawn from each subject initially at time 0 and the following subsequent times: 2, 4, 5, 6, 8, 10 and 12 hours after time of study drug administration (time 0) for a total of eight samples.
Measured: Baseline and Week 24
Change From Baseline to Week 24 in Hemodynamics Parameters: Mean Pulmonary Artery Pressure (PAPm), Mean Right Atrial Pressure (RAPm) and Mean Pulmonary Capillary Wedge Pressure (PCWPm)
Pulmonary hypertension (PH) is an increase in pressure in the pulmonary vasculature defined as a mean pulmonary artery pressure (PAPm) greater than 25 mmHg at rest or greater than 30 mmHg with exercise, as measured by right heart catheterization. Right Atrial Pressure (RAP) is the pressure of blood in the right atrium of the heart. Pulmonary Capillary Wedge Pressure (PCWP) is used to calculated pulmonary vascular resistance and can help guide therapeutic efficacy. The PAPm, RAPm and PCWPm values and their respective changes from Baseline to Week 24 at peak exercise were measured by Swan-Ganz right heart catheterization.
Measured: Baseline and week 24
Change From Baseline to Week 24 in Hemodynamics Parameters: Arterial Oxygen Saturation (SaO2) (%) and Mixed Venous Oxygen Saturation (SvO2) (%)
SaO2 measured by Arterial Blood Draw and Blood Gas Analyzer and SvO2 measured via Pulmonary Artery Catheter, are both Hemodynamics Parameters collected during right heart catheterization. Mixed venous oxygen saturation (SvO2) can help to determine whether the cardiac output and oxygen delivery is high enough to meet a patient's needs
Measured: Baseline and Week 24
Change From Baseline to Week 24 in Hemodynamics Parameters: Cardiac Output (CO) (L/Min)
Cardiac Output (CO) is the volume of blood ejected by the heart per minute, as measured by right heart catheterization. The value and change from Baseline to Week 24 at peak exercise was measured by Swan-Ganz right heart catheterization.
Measured: Baseline and week 24
Change From Baseline to Week 24 in Hemodynamics Parameters: Cardiac Index (CI) (L/Min/m^2)
Cardiac Index (CI) relates the cardiac output (CO) from left ventricle to body surface area (BSA), thus relating heart performance to the size of the individual. The CI values and their respective changes from Baseline to Week 24 at peak exercise was measured by Swan-Ganz right heart catheterization.
Measured: Baseline and week 24
Change From Baseline to Week 24 in Hemodynamics Parameters: Pulmonary Vascular Resistance Index (PVRI) (mmHg*Min*m^2/L)
Pulmonary Vascular Resistance Index (PVRI) is calculated using Mean Pulmonary Arterial Pressure(PAPm), Pulmonary Capillary Wedge Pressure (PCWP) and Cardiac Index (CI ), to provide information about right ventricular overload. The PVRI values and their respective changes from Baseline to Week 24 at peak exercise was measured by Swan-Ganz right heart catheterization.
Measured: Baseline and week 24
Change From Baseline to Week 24 in Hemodynamics Parameters: Pulmonary Vascular Resistance (PVR) (mmHg*Min/L)
pulmonary vascular resistance (PVR) is the resistance the right ventricle must overcome to pump blood into the pulmonary arteries. The change in PVR values from Baseline to Week 24 at peak exercise were measured by Swan-Ganz right heart catheterization.
Measured: Baseline and week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2012 (estimated)
- Study startApr 2012
- Primary completionJul 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- United Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Cynthia Madden, MD, MPH, Study chair, Senior Clinical Research Physician
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01588405
- Sponsor's protocol ID
- TDE-PH-205
- Status last verified
- Apr 2016
- First submitted
- 6 Jan 2012
- Last updated
- 16 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-Label Study of the Safety and Tolerability of Transitioning From Remodulin® to Oral Treprostinil in Subjects With Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT01588405
- Acronym / sponsor ID
- TDE-PH-205
- Conditions
- Pulmonary Arterial Hypertension
- Keywords
- Pulmonary Arterial Hypertension, UT-15C SR, PAH
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- United TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Apr 2012
- Primary completion
- Jul 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 1 May 2012 (estimated)
- Results
- Posted 16 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This multi-center, open-label study will assess the tolerability and safety of transitioning subjects with stable Pulmonary Arterial Hypertension (PAH) from continuous intravenous (IV) or subcutaneous (SC) Remodulin infusion to oral treprostinil (UT-15C sustained release (SR) tablets).
This study will consist of an in-hospital transition phase, dose optimization/evaluation phase, and follow up phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| UT-15C SR | Experimental | Drug: UT-15C SR |
Who may qualify
- Ages
- 15 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Between 15 and 80 years of age, inclusive, weigh at least 40 kg and have a diagnosis of PAH
- Have stable disease as confirmed by recent right heart catheterization and a Baseline 6MWD of at least 250 meters
- Have been receiving Remodulin for at least 90 days and at a stable dose for at least 30 days prior to the Baseline visit; the dose of Remodulin must be between 25-75 ng/kg/min, inclusive
- Must be also receiving an endothelin receptor antagonist (ERA) and/or a phosphodiesterase-5 inhibitor (PDE-5i) for at least 90 days and have been at a stable dose for at least 30 days prior to Baseline
Key exclusion criteria (1 listed)
- WHO functional class III and IV subjects will be excluded
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UT-15C SRSubjects will transition in the hospital from Remodulin to UT-15C SR within 5 days of the start of the transition. The dose of Remodulin will be decreased as the dose of UT-15C SR is increased over the 5 days. Once subjects have been transitioned from Remodulin, the dose of UT-15C SR will continue to be modified / titrated to the appropriate optimal dose for that subject throughout the rest of the study. | Drug | UT-15C SR |
Primary outcome
Number of Participants That Were Succesfully Transitioned From Parenteral Remodulin to UT-15C.
Time frame: Up to 24 weeks
Successful transition was based on the number of participants that completely transitioned to oral treprostinil by the week 4 study visit and clinically maintained on oral treprostinil treatment through Week 24.
14 secondary outcomes
Change From Baseline in Six-minute Walk Distance at Week 24
Time frame: Baseline and week 24
Change in Borg Dyspnea Score (Following 6MWT) From Baseline to Week 24
Time frame: Baseline and week 24
Change in Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) From Baseline to Week 24
Time frame: Baseline and week 24
Change in World Health Organization (WHO) Functional Classification From Baseline to Week 24
Time frame: Baseline and Week 24
Change in Dyspnea-fatigue Index From Baseline to Week 24
Time frame: Baseline and Week 24
Change From Baseline to Week 24 in Pharmacokinetic Parameters: Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), and Trough Plasma Concentration (Cmin)
Time frame: Baseline and Week 24
Change From Baseline to Week 24 in Pharmacokinetics Parameter: Peak Time to Reach Peak Plasma Concentration [Tmax (h)]
Time frame: Baseline and Week 24
Change From Baseline to Week 24 in Pharmacokinetics Parameters: Area Under the Plasma Concentration Curve (AUC) [h(ng/mL)]
Time frame: Baseline and Week 24
Change From Baseline to Week 24 in Hemodynamics Parameters: Mean Pulmonary Artery Pressure (PAPm), Mean Right Atrial Pressure (RAPm) and Mean Pulmonary Capillary Wedge Pressure (PCWPm)
Time frame: Baseline and week 24
Change From Baseline to Week 24 in Hemodynamics Parameters: Arterial Oxygen Saturation (SaO2) (%) and Mixed Venous Oxygen Saturation (SvO2) (%)
Time frame: Baseline and Week 24
Change From Baseline to Week 24 in Hemodynamics Parameters: Cardiac Output (CO) (L/Min)
Time frame: Baseline and week 24
Change From Baseline to Week 24 in Hemodynamics Parameters: Cardiac Index (CI) (L/Min/m^2)
Time frame: Baseline and week 24
Change From Baseline to Week 24 in Hemodynamics Parameters: Pulmonary Vascular Resistance Index (PVRI) (mmHg*Min*m^2/L)
Time frame: Baseline and week 24
Change From Baseline to Week 24 in Hemodynamics Parameters: Pulmonary Vascular Resistance (PVR) (mmHg*Min/L)
Time frame: Baseline and week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cynthia Madden, MD, MPH study chair
Senior Clinical Research Physician
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing UT-15C SR in people with Pulmonary Arterial Hypertension, run by United Therapeutics at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants That Were Succesfully Transitioned From Parenteral Remodulin to UT-15C. (time frame: Up to 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2016.