A Study of Ranolazine Acute Administration and Short Term Administration in Pulmonary Arterial Hypertension

NCT01757808 | Completed Phase 1 DMC

• 1 other identifier: 11-0301
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the safety of ranolazine in people with pulmonary arterial hypertension (PAH) and who are receiving 1 or more background PAH therapies: ambrisentan, sildenafil,tadalafil, epoprostenol, treprostinil (IV, SC, inhaled), or iloprost. The primary objective is:

• To estimate the effect of ranolazine administration on acute hemodynamics.
• To assess safety of ranolazine acutely over 6 hrs in the catheterization lab and after 12 weeks of therapy
• To assess changes in right ventricular function after 12 weeks of therapy.

Conditions

Pulmonary Arterial Hypertension

Keywords

PAH; Ranolazine; right ventricle; Safety; cardiopulmonary exercise testing

Outcome Measures

Primary Outcomes (1)

• Change in pulmonary vascular resistance (PVR)

  12 weeks

Secondary Outcomes (4)

• Change in CPET (VE/VCO2, PETCO2, peak VO2, peak HR, peak RER, work max (MET or Watt), sub maximum exercise time

  12 weeks

• Change in RV echo parameters: 2D, 3D

  12 weeks

• Change in 6MWD

  12 weeks

• Safety/SAE

  12 weeks

Study Arms (2)

Ranolazine

EXPERIMENTAL

Drug: Ranolazine

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Ranolazine DRUG

ranolazine sustained release at a dose of 500mg for one month followed by a dose of 1000mg.

Also known as: GS-9668

Ranolazine

Placebo DRUG

placebo at a dose of 500mg for one month followed by a dose of 1000mg.

Also known as: sugar pill

Placebo

Eligibility Criteria

• Age: 18 Years - 72 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects age 18-72 yrs will have a diagnosis of PAH. PAH as defined as idiopathic PAH, heritable PAH or PAH associated with collagen vascular disease, congenital heart disease (repaired), or anorexigen use. A history of PAH as defined by hemodynamics at diagnosis by right heart catheterization defined as: mean PAP \>25 mmHg with a normal PCWP \< 15 mm Hg at rest and a PVR \>3 Wood units.
• Baseline 6MW \>150 meters
• Patients will be receiving FDA approved PAH monotherapy or dual therapy medications: including, ambrisentan (5,10mg), sildenafil (60-240mg), tadalafil (40mg), epoprostenol, treprostinil, or iloprost at stable doses for \>90days.
• Receiving conventional therapy as clinically indicated (oxygen, calcium channel blockers, digoxin) with dose that is unchanged in the preceding 30 days prior to enrollment. This is excluding anticoagulants (warfarin) as the patient's dose may not be stable if the patient is having a cardiac catheterization at baseline within 30 days of enrollment and warfarin is being held.

You may not qualify if:

• PAH Category II-IV and Category I associated with all other etiologies: HIV, portopulmonary disease
• All subjects on monotherapy calcium blockers as "calcium blocker responders" irrespective of therapy
• All subjects receiving CY3P4 inducer (i.e. bosentan)
• Subjects with pulmonary hypertension due to significant interstitial lung disease, chronic obstructive pulmonary disease, congestive heart failure, valvular heart disease
• Subjects with (World Health Organization (WHO) functional Class I or Class IV
• Subjects with total lung capacity (TLC) \< 60% of predicted
• Subjects with significant obstructive lung disease with FEV1/FVC ratio \< 70% of predicted
• Subjects with hypotension defined as systolic arterial pressure \< 90 mmHg at baseline
• Subjects with hypertension defined as systolic arterial pressure \>140 mmHg at baseline and a diastolic arterial pressure \> 90 mmHg despite adequate medical therapy.
• Subjects with impaired renal function as defined as estimated glomerular filtration rate (eGFR) less than 45 mL/min/BSA (where BSA=1.73m2) as calculated by the Modification of Diet in Renal Disease (MDRD) equation:
• Patients with eGFR 45-50 mL/min/BSA may be enrolled only after discussion with data safety monitoring board. Patients with eGFR ≥ 50 mL/min/BSA may be enrolled without such a discussion.
• Subjects with liver function tests (transaminases (AST/ALT), total bilirubin, and alkaline phosphatase) \>2X normal values
• Subjects with acutely decompensated heart failure requiring hospitalization or medication adjustment or hospitalization for any cause within the previous 30 days prior to screening
• Subjects may not be receiving any other investigational agents
• Subjects with left ventricular ejection fraction \<45% or left ventricular shortening fraction \<0.2

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University of Chicago

Chicago, Illinois, 60637, United States

Location

Related Publications (1)

• Gomberg-Maitland M, Schilz R, Mediratta A, Addetia K, Coslet S, Thomeas V, Gillies H, Oudiz RJ. Phase I safety study of ranolazine in pulmonary arterial hypertension. Pulm Circ. 2015 Dec;5(4):691-700. doi: 10.1086/683813.

  PMID: 26697176 DERIVED

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

Ranolazine; Sugars

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbohydrates

Study Officials

• Mardi Gomberg-Maitland, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2012
• First Posted: December 31, 2012
• Study Start: August 1, 2011
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: March 3, 2017

Record last verified: 2017-03

Locations

US (1)