Clinical trial NCT01725269: Long-term Study of AIR001 in Subjects With WHO Group 1 Pulmonary Arterial Hypertension Who Completed AIR001-CS05
Official title: A Phase 2, Multicenter, Open-Label Study to Evaluate the Intermediate/Long Term Safety and Efficacy of AIR001 in Subjects With WHO Group 1 Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pulmonary Arterial Hypertension
Keywords: AIR001
sodium nitrite
PAH
Pulmonary Arterial Hypertension
inhaled sodium nitrite
Lead sponsor: Aires Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2012-11-12
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The AIR001-CS05 study evaluated the safety and efficacy (effectiveness) of AIR001 over 16 weeks in subjects who have PAH. The purpose of the AIR001-CS06 study is to evaluate the intermediate / long-term safety of AIR001 in subjects who have completed the AIR001-CS05 study. Assessments to evaluate the effectiveness of the study drug will include measurements of exercise ability and evaluations of PAH disease symptoms.

Detailed description: The primary objective of this study is to evaluate the intermediate/long-term safety of inhaled nebulized AIR001 administered according to 3 treatment arms (80 milligrams (mg) 4 times daily, 46 mg 4 times daily, or 80 mg once daily) in subjects with World Health Organization (WHO) Group 1 Pulmonary Arterial Hypertension (PAH) who have completed the 16-week AIR001-CS05 study.

Eligibility criteria: Inclusion Criteria:

1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study prior to initiation of any subject-mandated procedures.
2. Is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Has completed the 16-week AIR001-CS05study as planned.
4. If on corticosteroids, has been receiving a stable dose of less than or equal to 20 mg/day of prednisone (or equivalent dose, if other corticosteroid) for at least 1 month (30 days) prior to the AIR001-CS05 study Baseline/Day 1 visit. If receiving treatment for Connective Tissue Disease (CTD) with any other drugs, doses should remain stable, if clinically feasible, for the duration of the AIR001-CS06 study.
5. Women of childbearing potential must be using at least one form of medically acceptable contraception (i.e. either oral, topical, implanted hormonal contraceptives, or an intrauterine device) or two barrier methods; have a negative pregnancy test at Screening and Baseline/Day 1 and agree to use reliable methods of contraception until at least 24-hours after the last dose of study drug. Women who are surgically sterile (i.e. hysterectomy, bilateral oophorectomy, or tubal ligation) or those who are post-menopausal for at least 2 years are not considered to be of childbearing potential. Men who are not sterile (i.e. have not had a vasectomy) must also agree to use contraception until at least 24-hours after the last dose of study drug.

Exclusion Criteria:

1. Participation in a device or other interventional clinical studies (other than AIR001-CS05), within 1 month (30 days) of Baseline/Day 1 and/or during study participation.
2. Has uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure \> 160 mmHg or sitting diastolic blood pressure \> 100 mmHg during Baseline/Day 1 visit.
3. Systolic blood pressure \< 90 mmHg at Baseline/Day 1.
4. Diagnosis of Down syndrome.
5. Moderate to severe hepatic impairment classified as a Child-Pugh Class B or C at Baseline/Day 1.
6. Has chronic renal insufficiency as defined by serum creatinine \> 2.5 mg/dL or has an estimated Glomerular Filtration Rate (eGFR) \< 30 mL/min at Baseline/Day 1, or requires dialytic support.
7. Has a hemoglobin (Hgb) concentration \< 8.5 g/dL at Baseline/Day 1.
8. Personal or family history of the following:

   1. Congenital or acquired methemoglobinemia;
   2. RBC CYPB5 reductase deficiency.
9. History of glucose-6-phosphate dehydrogenase (G6PD) deficiency or any contraindication to receiving methylene blue.
10. For subjects with Human immunodeficiency virus (HIV) associated PAH, requirement for the use of inhaled pentamidine.
11. The use of oral or topical nitrates (nitroglycerin, glyceryl trinitrate (GTN), isosorbide dinitrate, and isosorbide mononitrate) within 1 month (30 days) prior to Baseline/Day 1 or throughout the AIR001-CS06 study until EOS or Termination visit. Note: Intravenous GTN in an emergency setting may be administered by starting with a low dose and titrating upward, while the subject is being monitored closely for changes in blood pressure and heart rate.
12. Known or suspected hypersensitivity or allergic reaction to sodium nitrite or sodium nitrate.
13. History of malignancy within 5-years prior to Baseline/Day 1 of the AIR001-CS05 study, with the exception of localized non-metastatic basal cell carcinoma of the skin and in situ carcinoma of the cervix.
14. Other severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
15. Has a psychiatric, addictive or other disorder that compromises the ability to give informed consent for participating in this study. This includes subjects with a recent history of abusing alcohol or illicit drugs 1 month (30 days) prior to study Baseline/Day 1 of the AIR001-CS05 study and for the duration of the study.
16. Is currently pregnant or breastfeeding or intends to become pregnant during the duration of the study.
17. Investigators, study staff or their immediate families.

Primary outcomes:
measure: To evaluate the intermediate/long-term safety of inhaled nebulized AIR001
timeFrame: minimum of 6 months
Secondary outcomes:
measure: To assess the effect of inhaled AIR001 on Time to Clinical Worsening, 6MWD, Functional Class, and Quality of Life
timeFrame: minimum of 6 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UCSD Medical Center
state: California
city: Torrance
country: United States
facility: UCLA Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Louisville
country: United States
facility: Kentuckiana Pulmonary Associates
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University School of Medicine
state: Massachusetts
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Adaani Frost, M.D.
state: Texas
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
city: Darlinghurst
country: Australia
facility: St. Vincent's Hospital
state: New South Wales
city: Chermside
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Budapest
country: Hungary
facility: Gottsegen Gyorgy Hungarian
city: Budapest
country: Hungary
facility: Semmelweis University
city: Debrecen
country: Hungary
facility: University of Debrecen
city: Szeged
country: Hungary
facility: University of Szeged
Study officials:
affiliation: Baylor College of Medicine, Houston
name: Adaani E Frost, M.D.
role: PRINCIPAL_INVESTIGATOR
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