Pulmonary HypertensionPhase 2NCT01104870
A Dose Response Study of UT-15C SR in Patients With Exercise-Induced Pulmonary Hypertension
A Phase 2 study testing UT-15C in people with Pulmonary Hypertension, run by United Therapeutics at 9 sites in United States.
Trial summary
This is a prospective, randomized, parallel group study to assess the hemodynamic effect of three different dose regimens of a sustained release (SR) tablet of UT-15C in patients with exercise-induced pulmonary hypertension (PH), as measured by the change in peak total pulmonary resistance index (TPRI) during exercise… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pulmonary Hypertension
- What is being tested?
- UT-15C
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 9 sitesUnited States
- Study dates
- Apr 2010to Jan 2013
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A subject was eligible for inclusion in this study if all of the following criteria applied:
- Was between the ages of 18 and 75 years of age at Screening
- Weighed a minimum of 40 kilograms with a body mass index less than 40 kg/m2 at Screening
- Agreed to have right heart catheterization with exercise performed at Baseline and Week 12, or at the time of early discontinuation of study drug
- Had exercise-induced PH at Baseline (defined as a PAPm ≥ 30 mmHg during exercise).
- Note: eligible subjects may or may not have had a PAPm ≥ 25 mmHg at rest
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- Exercise-induced PH may have been:
- Idiopathic, heritable, drug- or toxin-induced PAH, or PAH associated with connective tissue diseases or HIV infection
- Due to ILD
- Due to sarcoidosis
- Had a Baseline pulmonary function tests as follows:
- Forced vital capacity (FVC) ≥ 50% (predicted)
- If FVC <50% (predicted), total lung capacity (TLC) must be ≥ 50% (predicted)
- Forced expiratory volume / forced vital capacity (FEV / FVC) ratio ≥ 50%
- Had a Baseline 6MWD between 150 and 450 meters, inclusive
- Was optimally treated with conventional pulmonary hypertension therapy (e.g. oral vasodilators, oxygen, digoxin, etc) with no additions, discontinuations, or dose changes for at least 14 days prior to Baseline (excluding anticoagulants). Oral diuretics may have been adjusted, but not discontinued or added, within 14 days of Baseline
- May or may not have been receiving an approved PDE-5 inhibitor OR an approved ERA.
- Subjects receiving an approved ERA or an approved PDE-5 inhibitor must have been on a stable dose for 30 days prior to Baseline, and were willing to remain on a PDE-5 inhibitor or an ERA and at the same dose for the duration of the 12-week Treatment Phase. If a subject chose to discontinue their PDE-5 or ERA prior to entering this study, they must have had a ≥30 day washout period between the last dose of the PDE-5 or ERA and start of the screening phase.
- If female, was physiologically incapable of childbearing or practicing an acceptable method of birth control as deemed appropriate by the physician or institution. Women of childbearing potential had a negative serum pregnancy test at Screening
- Was able to communicate effectively with study personnel, and considered reliable, willing and likely to be cooperative with protocol requirements, including attending all study visits, in the opinion of the Principal Investigator
- Voluntarily gave informed consent to participate in the study.
Who cannot join
- A subject was not eligible for inclusion in this study if any of the following criteria applied:
- Had received epoprostenol, treprostinil, iloprost, beraprost, or any other prostacyclin therapy within 30 days of Baseline (except if used during acute vasoreactivity testing)
- Had previous intolerance or significant lack of efficacy to an oral or parenteral prostacyclin or prostacyclin analogue that resulted in discontinuation or inability to effectively titrate that therapy
- Had a concurrent injury, illness (other than PH or a PH related condition), or other confounding factor that would prevent the accurate assessment of the subject's exercise capacity
- Had a musculoskeletal disorder (e.g. recent hip replacement, artificial leg, etc.) or any other disease that was likely to limit ambulation, or was connected to a machine that was not portable
- Had portal hypertension
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- Had congenital heart disease (repaired or unrepaired)
- Had a history or current evidence of left-sided heart disease including myocardial infarction in the previous 3 years or mitral valve stenosis, or evidence of current left-sided heart disease as defined by mean resting pulmonary capillary wedge pressure (PCWPm) or left ventricular end diastolic pressure (LVEDP) > 15 mmHg or left ventricular ejection fraction (LVEF) < 45% (as assessed by either multigated acquisition [MUGA] scan, angiography or echocardiography), or symptomatic coronary artery disease (i.e., demonstrable ischemia either at rest or during exercise)
- Had acute pulmonary embolism (less than 6 months), chronic thromboembolic disease, pulmonary veno-occlusive disease, or pulmonary capillary hemangiomatosis
- Had an atrial septostomy
- Had a current diagnosis of uncontrolled sleep disordered breathing
- Had PH associated with:
- chronic obstructive lung disease (COPD), cystic fibrosis, emphysema, alveolar hypoventilation disorders, chronic exposure to high altitude, developmental abnormalities, schistosomiasis, or chronic hemolytic anemia
- hematologic disorders (myeloproliferative disorders, splenectomy)
- metabolic disorders (glycogen storage disease, Gaucher disease, thyroid disorders
- pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, neurofibromatosis, vasculitis
- tumoral obstruction, fibrosing mediastinitis, or extensive loss of lung tissue from surgery or trauma
- Had chronic renal insufficiency as defined by either a Screening creatinine value greater than 2.5 mg/dL (221 μmol/L) or the requirement for dialysis.
- Had liver function tests (AST or ALT) greater than three times the upper limit of normal at Screening.
- Had anemia as defined by a Screening hemoglobin value of less than 10 g/dL, active infection, or any other condition that would interfere with the interpretation of study assessments.
- Had uncontrolled systemic hypertension as evidenced by systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg.
- Was pregnant or nursing.
- Had an unstable psychiatric condition or was mentally incapable of understanding the objectives, nature, or consequences of the trial, or had any condition which in the Investigator's opinion would constitute an unacceptable risk to the subject's safety.
- Was receiving an investigational drug, had an investigational device in place or had participated in an investigational drug or device study within 30 days prior to Screening.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
The Carl and Edyth Lindner Research Center at The Christ Hospital
Cincinnati, Ohio, 45219
University of Cincinnati
Cincinnati, Ohio, 45267
The Ohio State University Medical Center
Columbus, Ohio, 43221
University of California Los Angeles Pulmonary Division
Los Angeles, California, 90095
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, 85013
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
University of Rochester Medical Center, Mary Parkes Center
Rochester, New York, 14623
University of California Davis Medical Center
Sacramento, California, 95817
University of Arizona
Tucson, Arizona, 87524
About this study
Official title: A 12-Week, Randomized, Dose Response Study of UT-15C (Treprostinil Diethanolamine) SR in Patients With Exercise-Induced Pulmonary Hypertension
This is a prospective, randomized, parallel group study to assess the hemodynamic effect of three different dose regimens of a sustained release (SR) tablet of UT-15C in patients with exercise-induced pulmonary hypertension (PH), as measured by the change in peak total pulmonary resistance index (TPRI) during exercise from Baseline to Week 12.
Read the detailed description
Prospective, randomized, parallel group study with two periods: a 10 week, dose titration period, followed by a 2 week, dose maintenance period in patients with exercise-induced PH.
The study population will be randomized into Dose Group 1, Dose Group 2, or an Individual Maximum Tolerated Dose (iMTD) of UT-15C SR by Week 10 and maintained through Week 12. Patients may be either currently receiving an approved oral background therapy for their PH (phosphodiesterase-5 [PDE-5] inhibitor, OR endothelin receptor antagonist [ERA]) (no dual background therapy), or not currently receiving therapy for PH.
- Conditions
- Pulmonary Hypertension
- Being tested
- UT-15C
- Medical subject headings
- Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UT-15CDrug
Also called treprostinil diethanolamine, sustained release
oral
| Study group | Role | What they receive |
|---|---|---|
| Dose Group 1 | Active comparator | UT-15C 0.25 mg twice daily Receives: Drug: UT-15C |
| Dose Group 2 | Active comparator | UT-15C 1.25 mg twice daily Receives: Drug: UT-15C |
| Dose Group 3 | Active comparator | UT-15C individual Maximum Tolerated Dose Receives: Drug: UT-15C |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Peak Total Pulmonary Resistance Index (TPRI) During Exercise From Baseline to Week 12
The effects of 12-week treatment with different doses of UT-15C on peak TPRI during exercise will be evaluated by comparing the change from Baseline to Week 12 at peak wattage on a pairwise basis between treatment groups.
The primary measure of efficacy was the change from Baseline to Week 12 in peak TPRI during exercise assessed 3 to 6 hours after the subject's morning dose of UT-15C to obtain measurements at peak concentrations of treprostinil. The equation used to determine the Total Pulmonary Resistance Index (TPRI) (mmHg/[L/min/m^2]) is Mean Pulmonary Artery Pressure (PAPm)/ Cardiac Index (CI).
Measured: Baseline and Week 12
Secondary outcomes (7)
Change in Mean Pulmonary Artery Pressure (PAPm) From Baseline to Week 12
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. The PAPm values and their respective changes from Baseline to Week 12 at peak exercise will be summarized by treatment group and measured by Swan-Ganz right heart catheterization.
Measured: Baseline and Week 12
Change in Cardiac Index (CI) From Baseline to Week 12
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 12 at peak exercise will be summarized by treatment group and measured by Swan-Ganz right heart catheterization.
Measured: Baseline and Week 12
Change in 6-minute Walk Distance (6MWD) From Baseline to Week 12
The intent of the 6MWD test is to evaluate exercise capacity associated with carrying out activities of daily living. Change in 6MWD from Baseline to Week 12, correlates with the current clinical standard for assessing patient functional status in the treatment of PH and is considered an objective measure of patient functional status by the American Thoracic Society (ATS). Subjects were instructed to walk down a corridor at a comfortable speed as far as they could manage for six minutes. 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 12
Change in Borg Dyspnea Score (Following 6MWT) From Baseline to Week 12
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 12
Change in PH Symptoms From Baseline to Week 12
Symptoms of PH including fatigue, dyspnea, edema, dizziness, syncope, chest pain and orthopnea were assessed and severity grade values (i.e., 0, 1, 2 or 3) for each symptom were assigned for subjects. A severity of 0 indicated no symptoms, the maximum severity was 3, indicating severe symptoms. Median change in symptom severity from Baseline to Week 12 is described.
Measured: Change from Baseline at 12 Weeks
Number of Participants With a Change From Baseline World Health Organization (WHO) Functional Classification at Week 12
The WHO Functional Class of pulmonary hypertension is a physical activity rating scale as follows: 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. Only participants who experienced a change in WHO functional classification from Baseline to Week 12 are described by class change below; all other participants maintained their Baseline WHO functional classification at Week 12.
Measured: Change from Baseline at Week 12
Change in N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Concentrations From Baseline to Week 12
The N-terminal pro-BNP (NT-proBNP) serum concentration was assessed to compare the severity of heart failure at Baseline and Week 12.
Measured: Baseline and Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2010 (estimated)
- Study startApr 2010
- Primary completionJan 2013
- Study completionJan 2013
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 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- United Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Rajan Saggar, MD, Principal investigator, UCLA Pulmonary Division
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01104870
- Sponsor's protocol ID
- TDE-PH-202
- Status last verified
- May 2016
- First submitted
- 4 Jan 2010
- Last updated
- 27 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 27 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 12-Week, Randomized, Dose Response Study of UT-15C (Treprostinil Diethanolamine) SR in Patients With Exercise-Induced Pulmonary Hypertension
- ClinicalTrials.gov ID
- NCT01104870
- Acronym / sponsor ID
- TDE-PH-202
- Conditions
- Pulmonary Hypertension
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- United TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Apr 2010
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 16 Apr 2010 (estimated)
- Results
- Posted 30 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a prospective, randomized, parallel group study to assess the hemodynamic effect of three different dose regimens of a sustained release (SR) tablet of UT-15C in patients with exercise-induced pulmonary hypertension (PH), as measured by the change in peak total pulmonary resistance index (TPRI) during exercise from Baseline to Week 12.
Detailed description
Prospective, randomized, parallel group study with two periods: a 10 week, dose titration period, followed by a 2 week, dose maintenance period in patients with exercise-induced PH.
The study population will be randomized into Dose Group 1, Dose Group 2, or an Individual Maximum Tolerated Dose (iMTD) of UT-15C SR by Week 10 and maintained through Week 12. Patients may be either currently receiving an approved oral background therapy for their PH (phosphodiesterase-5 [PDE-5] inhibitor, OR endothelin receptor antagonist [ERA]) (no dual background therapy), or not currently receiving therapy for PH.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose Group 1 | Active comparator | Drug: UT-15CUT-15C 0.25 mg twice daily |
| Dose Group 2 | Active comparator | Drug: UT-15CUT-15C 1.25 mg twice daily |
| Dose Group 3 | Active comparator | Drug: UT-15CUT-15C individual Maximum Tolerated Dose |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- A subject was eligible for inclusion in this study if all of the following criteria applied:
- Was between the ages of 18 and 75 years of age at Screening
- Weighed a minimum of 40 kilograms with a body mass index less than 40 kg/m2 at Screening
- Agreed to have right heart catheterization with exercise performed at Baseline and Week 12, or at the time of early discontinuation of study drug
- Had exercise-induced PH at Baseline (defined as a PAPm ≥ 30 mmHg during exercise).
Key exclusion criteria (24 listed)
- A subject was not eligible for inclusion in this study if any of the following criteria applied:
- Had received epoprostenol, treprostinil, iloprost, beraprost, or any other prostacyclin therapy within 30 days of Baseline (except if used during acute vasoreactivity testing)
- Had previous intolerance or significant lack of efficacy to an oral or parenteral prostacyclin or prostacyclin analogue that resulted in discontinuation or inability to effectively titrate that therapy
- Had a concurrent injury, illness (other than PH or a PH related condition), or other confounding factor that would prevent the accurate assessment of the subject's exercise capacity
- Had a musculoskeletal disorder (e.g. recent hip replacement, artificial leg, etc.) or any other disease that was likely to limit ambulation, or was connected to a machine that was not portable
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-15CAlso: treprostinil diethanolamine, sustained releaseoral | Drug | Dose Group 1, Dose Group 2, Dose Group 3 |
Primary outcome
Change in Peak Total Pulmonary Resistance Index (TPRI) During Exercise From Baseline to Week 12
Time frame: Baseline and Week 12
The effects of 12-week treatment with different doses of UT-15C on peak TPRI during exercise will be evaluated by comparing the change from Baseline to Week 12 at peak wattage on a pairwise basis between treatment groups. The primary measure of efficacy was the change from Baseline to Week 12 in peak TPRI during exercise assessed 3 to 6 hours after the subject's morning dose of UT-15C to obtain measurements at peak concentrations of treprostinil. The equation used to determine the Total Pulmonary Resistance Index (TPRI) (mmHg/[L/min/m^2]) is Mean Pulmonary Artery Pressure (PAPm)/ Cardiac Index (CI).
7 secondary outcomes
Change in Mean Pulmonary Artery Pressure (PAPm) From Baseline to Week 12
Time frame: Baseline and Week 12
Change in Cardiac Index (CI) From Baseline to Week 12
Time frame: Baseline and Week 12
Change in 6-minute Walk Distance (6MWD) From Baseline to Week 12
Time frame: Baseline and Week 12
Change in Borg Dyspnea Score (Following 6MWT) From Baseline to Week 12
Time frame: Baseline and Week 12
Change in PH Symptoms From Baseline to Week 12
Time frame: Change from Baseline at 12 Weeks
Number of Participants With a Change From Baseline World Health Organization (WHO) Functional Classification at Week 12
Time frame: Change from Baseline at Week 12
Change in N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Concentrations From Baseline to Week 12
Time frame: Baseline and Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 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.
Rajan Saggar, MD principal investigator
UCLA Pulmonary Division
9 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 in people with Pulmonary Hypertension, run by United Therapeutics at 9 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 21 inclusion and 24 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 27 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 9 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 30 Dec 2015). 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?
Change in Peak Total Pulmonary Resistance Index (TPRI) During Exercise From Baseline to Week 12 (time frame: Baseline and Week 12). 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 27 May 2016.