A Dose Response Study of UT-15C SR in Patients With Exercise-Induced Pulmonary Hypertension

NCT01104870 | Completed Phase 2 Results

• 1 other identifier: TDE-PH-202
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 9

Brief 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 from Baseline to Week 12.

Conditions

Pulmonary Hypertension

Outcome Measures

Primary Outcomes (1)

• 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).

  Baseline and Week 12

Secondary Outcomes (7)

• Change in Mean Pulmonary Artery Pressure (PAPm) From Baseline to Week 12

  Baseline and Week 12

• Change in Cardiac Index (CI) From Baseline to Week 12

  Baseline and Week 12

• Change in 6-minute Walk Distance (6MWD) From Baseline to Week 12

  Baseline and Week 12

• Change in Borg Dyspnea Score (Following 6MWT) From Baseline to Week 12

  Baseline and Week 12

• Change in PH Symptoms From Baseline to Week 12

  Change from Baseline at 12 Weeks

Study Arms (3)

Dose Group 1

ACTIVE COMPARATOR

UT-15C 0.25 mg twice daily

Drug: UT-15C

Dose Group 2

ACTIVE COMPARATOR

UT-15C 1.25 mg twice daily

Drug: UT-15C

Dose Group 3

ACTIVE COMPARATOR

UT-15C individual Maximum Tolerated Dose

Drug: UT-15C

Interventions

UT-15C DRUG

oral

Also known as: treprostinil diethanolamine, sustained release

Dose Group 1; Dose Group 2; Dose Group 3

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• United Therapeutics: lead

Study Sites (9)

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

University of Arizona

Tucson, Arizona, 87524, United States

Location

University of California Los Angeles Pulmonary Division

Los Angeles, California, 90095, United States

Location

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

University of Rochester Medical Center, Mary Parkes Center

Rochester, New York, 14623, United States

Location

The Carl and Edyth Lindner Research Center at The Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

The Ohio State University Medical Center

Columbus, Ohio, 43221, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Hypertension, Pulmonary

Interventions

treprostinil

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Kevin Laliberte, PharmD
• Organization: United Therapeutics, Corp.

KLaliberte@unither.com

919-425-8176

Study Officials

• Rajan Saggar, MD

  UCLA Pulmonary Division

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2010
• First Posted: April 16, 2010
• Study Start: April 1, 2010
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: May 27, 2016
• Results First Posted: December 30, 2015

Record last verified: 2016-05

Locations

US (9)