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Pulmonary Arterial HypertensionPhase 4OPTIMANCT02968901

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

A Phase 4 study testing macitentan and tadalafil in people with Pulmonary Arterial Hypertension, run by Actelion at 18 sites in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Pulmonary Arterial Hypertension
What is being tested?
macitentan and tadalafil
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
18 sitesFrance
Study dates
1 Sep 2015to 10 Sep 2018
Phase
Phase 4
Are there results?
None posted in the registry

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

  • 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.
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  • 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
  • Congenital heart disease with simple systemic-to-pulmonary shunt (atrial septal defect, ventricular septal defect, patent ductus arteriosus) ≥1 year after surgical repair
  • HIV infection
  • 6MWD ≥ 50 m at screening.
  • Woman of childbearing potential [see definition in Section 4.5.1] must:
  • Have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test at the D1 visit, and
  • Agree to perform monthly pregnancy tests up to 30 days after EOT2, and
  • Agree to use reliable contraception [defined in Section 4.5.2] from screening up to 30 days after EOT2. Reliable contraception must be started at least 11 days prior to Day 1.

Who cannot join

  • 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.
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  • 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.
  • Acute myocardial infarction ≤ 12 weeks prior to Day 1.
  • Known permanent atrial fibrillation.
  • Low blood pressure < 90/50 mmHg at screening or Day 1.
  • Ongoing or planned treatment with nitrates and/or doxazosin.
  • DLCO < 40% of predicted value (eligible only if no sign of veno-occlusive disease according to adjudication committee);
  • Presence of ≥ 1 of the following signs of relevant lung disease at any time prior to Day 1:
  • FEV1/FVC < 70% and FEV1 < 65% of predicted after bronchodilator administration;
  • Total Lung Capacity (TLC) < 60% of predicted.
  • Known or suspicion of pulmonary veno-occlusive disease (PVOD).
  • Severe renal insufficiency (estimated creatinine clearance ≤ 30 mL/min/1.73m²) assessed by central laboratory at screening.
  • Ongoing or planned dialysis.
  • Documented severe hepatic impairment (with or without cirrhosis) according to National Cancer Institute organ dysfunction working group criteria, defined as total bilirubin > 3 x ULN accompanied by AST > ULN (assessed by central laboratory at screening) and/or Child-Pugh Class C.
  • Serum AST and/or ALT > 3 x ULN (assessed by central laboratory at screening).
  • Porto-pulmonary hypertension.
  • Hemoglobin < 100 g/L assessed by central laboratory at screening.
  • Hypersensitivity to any active substance or excipient of macitentan or tadalafil formulation.
  • Loss of vision in one eye because of non-arteritic anterior ischemic optic neuropathy (NAION), regardless of whether or not this episode was in connection with previous PDE-5i exposure.
  • Hereditary degenerative retinal disorders, including retinitis pigmentosa.
  • Pregnancy, breast-feeding, intention to become pregnant during the study or woman of childbearing potential not agree to use reliable method of contraception from screening up to 30 days after EOT2.
  • Hereditary problems of galactose intolerance, Lapp lactase deficiency, glucosegalactose malabsorption.
  • Any factor or condition likely to affect protocol compliance of the patient as judged by the investigator.
  • Treatment with another investigational drug (planned, or taken ≤ 12 weeks prior to Day 1).
  • Concomitant life-threatening disease with a life expectancy < 12 months.

Trial locations and contacts

18 sites in 1 country.

18 sites in 1 country

France18 sites

  • Hôpital Jean Minjoz

    Besançon, 25030

  • Hôpital de Haut Levêque

    Bordeaux, 33604

  • Hôpital Côte de Nacre

    Caen, 14033

  • CHU Site du Bocage

    Dijon, 21079

  • Hôpital Albert Michallon

    Grenoble, 38700

  • Hôpital Bicètre

    Le Kremlin-Bicêtre, 94270

  • Hôpital Dupuytren

    Limoges, 87042

  • Hôpital Louis Pradel

    Lyon, 69677

  • Hôpital Timone Adultes

    Marseille, 13005

  • Hôpital Arnaud de Villeneuve

    Montpellier, 34929

  • CHR La Miletrie

    Poitiers, 86021

  • Hôpital Robert Debré

    Reims, 51092

  • Hôpital Pontchaillou

    Rennes, 35033

  • Hôpital Charles Nicolle

    Rouen, 76031

  • Hôpital Nord

    Saint-Priest-en-Jarez, 42277

  • Hôpital Civil

    Strasbourg, 67091

  • Hôpital Larrey

    Toulouse, 31059

  • Hôpital Bretonneau

    Tours, 37044

Other trials in France

About this study

Official title: Prospective, Multicenter, Open-label Study Evaluating the Effects of First-line Oral Combination Therapy of Macitentan and Tadalafil in Patients With Newly Diagnosed Pulmonary Arterial Hypertension (OPTIMA).

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).

Being tested
macitentan, tadalafil
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.

  • macitentanDrug

    used in open label

  • tadalafilDrug

    used in open label

Study groups in NCT02968901
Study groupRoleWhat they receive
bitherapyExperimentalMacitentan and tadalafil
Receives: Drug: macitentan; Drug: tadalafil

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

    Measured: 16 weeks

Secondary outcomes (9)

  1. mean right atrial pressure (mRAP)

    Change from Baseline to Week 16 in mean right atrial pressure (mRAP)

    Measured: Week 16

  2. 6MWD

    Change from Baseline to Week 16 in 6MWD

    Measured: Week 16

  3. level NT-proBNP

    Change in NT-proBNP from baseline to Week 16

    Measured: Week 16

  4. mean pulmonary arterial pressure (mPAP)

    Change from Baseline to Week 16 in mean pulmonary arterial pressure (mPAP)

    Measured: Week 16

  5. cardiac index (CI)

    Change from Baseline to Week 16 in cardiac index (CI).

    Measured: Week 16

  6. total pulmonary resistance (TPR)

    Change from Baseline to Week 16 in total pulmonary resistance (TPR)

    Measured: Week 16

  7. mixed venous oxygen saturation (Sv02)

    Change from Baseline to Week 16 in mixed venous oxygen saturation (Sv02)

    Measured: Week 16

  8. WHO functional class

    Change from baseline to Week 16 in WHO functional class and Percentage of patients with improvement/worsening of WHO functional class from baseline to Week 16

    Measured: Week 16

  9. Number of treatment goals

    Number of treatment goals (score 0 or 1 per goal, i.e. total score 0-5) met at Week 16: WHO-FC I or II; Cardiac index > 2.8 L/min/m²; mRAP < 8 mmHg; 6MWD > 400 m; NT-proBNP < 3xULN

    Measured: Week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Nov 2016 (estimated)
  2. Study start1 Sep 2015
  3. Primary completion10 Sep 2018
  4. Study completion10 Sep 2018

Resources

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 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02968901
Sponsor's protocol ID
AC-055-405
Acronym
OPTIMA
Status last verified
Oct 2019
First submitted
14 Nov 2016
Last updated
8 Oct 2019
Results posted
No
Data monitoring committee
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing macitentan and tadalafil in people with Pulmonary Arterial Hypertension, run by Actelion at 18 sites in France.

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 22 inclusion and 38 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: stopped early, as of the sponsor's last update on 8 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in France. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early. Results are not available in the source record.

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?

pulmonary vascular resistance (PVR) (time frame: 16 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02968901.

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 8 Oct 2019.

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