| Eligibility |
Inclusion Criteria (A subject will be eligible for inclusion in this study only if all of
the following criteria are met):
1. An Institutional Review Board (IRB) approved informed consent is signed and dated by
the subject prior to any study related activities.
2. The subject is 18 years of age or older.
3. If the subject is a female of childbearing potential, then the subject has a negative
pregnancy test at the Day 1 Visit (tests performed within 2 days before Day 1 are
accepted) and agrees to practice a highly effective (failure rate of less than 1% per
year when used consistently and correctly) method of birth control until 24 hours
after completion of all study assessments defined in Appendix 1. If the subject is
postmenopausal or has documented surgical sterilization, a pregnancy test and birth
control is not necessary. It is the Investigator's responsibility for determining
whether the subject has adequate birth control for study participation.
4. The subject has been diagnosed with PAH belonging to one of the following subgroups of
the updated Nice Clinical Classification Group 1, which includes:
1. Idiopathic PAH (1.1), or
2. Heritable PAH (1.2), or
3. Drug and toxin induced PAH (1.3), or
4. PAH associated with connective tissue disease (1.4.1), HIV infection (1.4.2), or
congenital heart disease (1.4.4) with simple systemic-to-pulmonary shunt at least
1 year after surgical repair
5. The subject is NYHA Functional Class II - IV at Screening and:
1. has not previously been treated for PAH, or
2. has documented stable doses of no more than 2 approved non prostacyclin
PAH-disease specific therapies for at least 3 months prior to Screening, is
willing and able to add LIQ861 to their treatment regimen and is willing to hold
the dosing of these therapies for at least 12 hours prior to study-mandated right
heart catheterization procedures.
6. The subject can complete a baseline six-minute walk distance (6MWD) =150 m.
7. The subject has had evidence of Forced Expiratory Volume in 1 Second (FEV1) and Forced
Vital Capacity (FVC) =60% of predicted values and FEV1/FVC ratio =60% during the 6
month period prior to consent.
Exclusion Criteria (A subject is not eligible for inclusion in the study if any of the
following criteria apply):
1. The subject's clinical condition is such that, in the opinion of the Investigator,
they are not expected to remain clinically stable for the duration of the study.
2. Subjects with pulmonary hypertension (PH) in the Updated Nice Classification Groups
2-5, or PAH Group 1 subgroups not covered by the inclusion criteria (e.g., associated
with portal hypertension [1.4.3] or with schistosomiasis [1.4.5]).
3. The subject is currently taking prostacyclin analogues or agonists, including
treprostinil, iloprost, epoprostenol or selexipag.
4. The subject has discontinued any medication (except for anticoagulants, but otherwise
including but not limited to oxygen, a different class of vasodilator, diuretic,
digoxin, and digitalis) for pulmonary hypertension within 14 days prior to Day 1.
5. The subject has had a new type of therapy (including but not limited to oxygen, a
different class of vasodilator, diuretic, digoxin, and digitalis) for pulmonary
hypertension added within 30 days prior to Day 1.
6. The subject has uncontrolled systemic hypertension as evidenced by systolic blood
pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg at
the time of screening.
7. The subject has a history of hemodynamically significant left-sided heart disease
including, but not limited to: aortic or mitral valve disease, pericardial
constriction, restrictive or congestive cardiomyopathy, or symptomatic coronary artery
disease (CAD).
8. The subject has had an atrial septostomy.
9. The subject has a history of prolongation of QT interval on ECG as follows: Male
subjects with a corrected QT interval using Fridericia's formula (QTcF) >450 msec and
female subjects with QTcF >470 msec.
10. The subject has any serious or life-threatening disease other than conditions
associated with PAH.
11. The subject is taking any excluded medications listed in the Investigator's Brochure,
namely inhibitors and inducers of CYP2C8 (see Appendix 3).
12. The subject has a hypersensitivity or allergy to any of the ingredients of LIQ861, NO,
or other clinically relevant allergies (clinical relevance per Investigator judgment).
13. The subject has had an acute pulmonary embolus within 6 months prior to Baseline.
14. The subject has had a stroke or transient ischemic attack within 6 months prior to
Baseline.
15. The subject has evidence of an active uncontrolled sepsis or systemic infection in the
period after informed consent up to Baseline.
16. The subject is pregnant or lactating.
17. The subject has any musculoskeletal disease or any other disease that limits
evaluation of 6MWD.
18. The subject has participated in an investigational product or device study within the
30 days prior to Baseline.
19. The subject has current evidence of drug abuse in the opinion of the Investigator.
20. The subject has severe hepatic impairment as evidenced by any history of ascites AND
encephalopathy.
21. The subject has severe renal impairment (estimated glomerular filtration rate [eGFR]
<35 mL/min utilizing the Modification of Diet in Renal Disease (MDRD) study equation
or requires dialytic support.
22. The subject is an employee or an immediate family member to an employee of the Sponsor
or the Investigator.
23. The subject is not a member or beneficiary of a social security scheme.
24. The subject lacks a legal protection measure.
25. The subject has been deprived of their liberty by a judicial or administrative
decision.
26. The subject has a known Hepatitis B or Hepatitis C infection with active viral
replication.
27. The subject has a known HIV infection with CD4 count less than 200 and more than
undetectable viral load, defined as less than 50 copies /mL.
28. The subject required use of intravenous inotropes including, but not limited to,
Levosimendan, Dopamine, Dobutamine, Dopexamine, Epinephrine, Isoprenaline
(isoproterenol), Norepinephrine (noradrenaline), Milrinone, or Amrinone, within 30
days prior to Baseline.
29. The subject required intravenous diuretic therapy within 30 days prior to Baseline.
30. Subjects taking vitamin K antagonist therapy with a known INR =3.5 (assessed per local
care standards) at the time of screening assessments or at Baseline.
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