Clinical Study Evaluating the Effects of First-line Oral cOmbination theraPy of maciTentan and tadalafIl in Patients With Newly Diagnosed pulMonary Arterial Hypertension (OPTIMA)

NCT02968901 | Terminated Phase 4

• 1 other identifier: AC-055-405
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 18

Brief Summary

The purpose of the study is to document the effect of first line dual oral combination therapy with macitentan 10mg and tadalafil 40mg on pulmonary vascular resistance (PVR) in treatment-naïve patients with newly diagnosed pulmonary arterial hypertension (PAH).

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (1)

• pulmonary vascular resistance (PVR)

  Change from Baseline to Week 16 in percentage of patients with clinically meaningful improvement of PVR (decrease of 30% from baseline to Week 16)

  16 weeks

Secondary Outcomes (9)

• mean right atrial pressure (mRAP)

  Week 16

• 6MWD

  Week 16

• level NT-proBNP

  Week 16

• mean pulmonary arterial pressure (mPAP)

  Week 16

• cardiac index (CI)

  Week 16

Study Arms (1)

bitherapy

EXPERIMENTAL

Macitentan and tadalafil

Drug: macitentan; Drug: tadalafil

Interventions

macitentan DRUG

used in open label

bitherapy

tadalafil DRUG

used in open label

bitherapy

Eligibility Criteria

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

You may qualify if:

• Signed informed consent prior to any study-mandated procedure.
• Male or female ≥ 18 and ≤ 75 years of age at screening.
• Initial PAH diagnosis \< 6 months prior to Day 1.
• Right heart catheterization (RHC) performed between Day -28 and Day 1 (RHC data obtained at the study site within this time frame, but before the study, i.e., before signed informed consent, are acceptable), meeting all the following criteria:
• Resting mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg.
• Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) ≤ 15 mmHg.
• PVR ≥ 400 dyn·sec/cm5 (≥ 5 Wood units) if PCWP \< 12 mmHg OR PVR ≥ 500 dyn·sec/cm5 (≥ 6.25 Wood units) if PCWP in \[12-15\] mmHg.
• Negative vasoreactivity test mandatory in idiopathic PAH (at this or a previous RHC).
• World Health Organization (WHO) Functional Class (FC) II to III.
• PAH etiology belonging to one of the following groups:
• Idiopathic.
• Heritable.
• Anorexigens induced.
• Associated with one of the following:
• Connective tissue disease

You may not qualify if:

• Any PAH-specific drug therapy \[e.g. any endothelin receptor antagonist, phosphodiesterase-5 inhibitors (PDE-5i), soluble guanylate cyclase stimulator, prostacyclin, prostacyclin analog, or prostacyclin receptor agonist\] at any time prior to Day 1 (single-dose administration for vasoreactivity testing is permitted; previous iloprost used intermittently for the treatment of digital ulcers or Raynaud's phenomenon is permitted if stopped \> 6 months prior to Day 1).
• Subjects who changed the dose or discontinued calcium channel blockers within 1 week prior to Day 1.
• Initiation of diuretics within 1 week prior to RCH.
• Subjects on oral diuretics in whom the dose has not been stable for at least 1 week prior to RHC.
• Treatment with other PDE-5i for erectile dysfunction.
• Treatment with strong inducers of CYP3A4 (e.g., carbamazepine, rifampin, rifampicin, rifabutin, rifapentin, phenobarbital, phenytoin, and St. John's wort) ≤ 28 days prior to Day 1.
• Treatment with strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, boceprevir, telaprevir, saquinavir, lopinavir, fosamprenavir, darunavir, tipranavir, atazanavir, nelfinavir, amprenavir, indinavir) ≤ 28 days prior to Day 1.
• History of priapism.
• Significant aortic and mitral valve disease requiring a specific treatment.
• Pericardial constriction.
• Life-threatening arrhythmia.
• Uncontrolled hypertension.
• Symptomatic coronary artery disease.
• Cardio-pulmonary rehabilitation program based on exercise (planned, or started ≤ 12 weeks prior to Day 1).
• Body mass index (BMI) \> 40 kg/m2 at screening.

Sponsors & Collaborators

• Actelion: lead

Study Sites (18)

Hôpital Jean Minjoz

Besançon, 25030, France

Location

Hôpital de Haut Levêque

Bordeaux, 33604, France

Location

Hôpital Côte de Nacre

Caen, 14033, France

Location

CHU Site du Bocage

Dijon, 21079, France

Location

Hôpital Albert Michallon

Grenoble, 38700, France

Location

Hôpital Bicètre

Le Kremlin-Bicêtre, 94270, France

Location

Hôpital Dupuytren

Limoges, 87042, France

Location

Hôpital Louis Pradel

Lyon, 69677, France

Location

Hôpital Timone Adultes

Marseille, 13005, France

Location

Hôpital Arnaud de Villeneuve

Montpellier, 34929, France

Location

CHR La Miletrie

Poitiers, 86021, France

Location

Hôpital Robert Debré

Reims, 51092, France

Location

Hôpital Pontchaillou

Rennes, 35033, France

Location

Hôpital Charles Nicolle

Rouen, 76031, France

Location

Hôpital Nord

Saint-Priest-en-Jarez, 42277, France

Location

Hôpital Civil

Strasbourg, 67091, France

Location

Hôpital Larrey

Toulouse, 31059, France

Location

Hôpital Bretonneau

Tours, 37044, France

Location

Related Links

• Clinical study evaluating the effects of first-line oral combination therapy of macitentan and tadalafil in patients with newly diagnosed pulmonary arterial hypertension (OPTIMA)

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

macitentan; Tadalafil

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2016
• First Posted: November 21, 2016
• Study Start: September 1, 2015
• Primary Completion: September 10, 2018
• Study Completion: September 10, 2018
• Last Updated: October 8, 2019

Record last verified: 2019-10

Locations

FR (18)