Long-term Study of AIR001 in Subjects With WHO Group 1 Pulmonary Arterial Hypertension Who Completed AIR001-CS05

NCT01725269 | Terminated Phase 2 DMC

• 1 other identifier: AIR001-CS06
• Study Type: interventional
• Target: 17
• Locations: 3 countries
• Sites: 25

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.

Conditions

Pulmonary Arterial Hypertension

Keywords

AIR001; sodium nitrite; PAH; Pulmonary Arterial Hypertension; inhaled sodium nitrite

Outcome Measures

Primary Outcomes (1)

• To evaluate the intermediate/long-term safety of inhaled nebulized AIR001

  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.

  minimum of 6 months

Secondary Outcomes (1)

• To assess the effect of inhaled AIR001 on Time to Clinical Worsening, 6MWD, Functional Class, and Quality of Life

  minimum of 6 months

Study Arms (3)

80mg AIR001, nebulized four times daily

EXPERIMENTAL

AIR001, 80 mg into nebulizer

Drug: AIR001

46 mg AIR001, nebulized four times daily

EXPERIMENTAL

AIR001, 46 mg into nebulizer

Drug: AIR001

80mg AIR001, nebulized once daily

EXPERIMENTAL

AIR001, 80 mg into nebulizer

Drug: AIR001

Interventions

AIR001 DRUG

All doses specified are the amount loaded into the I-neb AAD System nebulizer.

Also known as: (sodium nitrite inhalation soution)

46 mg AIR001, nebulized four times daily; 80mg AIR001, nebulized four times daily; 80mg AIR001, nebulized once daily

Eligibility Criteria

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

You may qualify if:

• 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.
• Is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Has completed the 16-week AIR001-CS05study as planned.
• 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.
• 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.

You may not qualify if:

• 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.
• 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.
• Systolic blood pressure \< 90 mmHg at Baseline/Day 1.
• Diagnosis of Down syndrome.
• Moderate to severe hepatic impairment classified as a Child-Pugh Class B or C at Baseline/Day 1.
• 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.
• Has a hemoglobin (Hgb) concentration \< 8.5 g/dL at Baseline/Day 1.
• Personal or family history of the following:
• Congenital or acquired methemoglobinemia;
• RBC CYPB5 reductase deficiency.
• History of glucose-6-phosphate dehydrogenase (G6PD) deficiency or any contraindication to receiving methylene blue.
• For subjects with Human immunodeficiency virus (HIV) associated PAH, requirement for the use of inhaled pentamidine.
• 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.
• Known or suspected hypersensitivity or allergic reaction to sodium nitrite or sodium nitrate.
• 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.

Sponsors & Collaborators

• Aires Pharmaceuticals, Inc.: lead

Study Sites (25)

UCSD Medical Center

La Jolla, California, 92037, United States

Location

UCLA Medical Center

Torrance, California, 90509, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Kentuckiana Pulmonary Associates

Louisville, Kentucky, 40202, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Boston University School of Medicine

Boston, Massachusetts, 02118, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110-1093, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

The Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Adaani Frost, M.D.

Houston, Texas, 77030, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

St. Vincent's Hospital

Darlinghurst, New South Wales, 2010, Australia

Location

The Prince Charles Hospital

Chermside, Queensland, 4032, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Gottsegen Gyorgy Hungarian

Budapest, 1083, Hungary

Location

Semmelweis University

Budapest, 1125, Hungary

Location

University of Debrecen

Debrecen, 4012, Hungary

Location

University of Szeged

Szeged, 6720, Hungary

Location

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MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Adaani E Frost, M.D.

  Baylor College of Medicine, Houston

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2012
• First Posted: November 12, 2012
• Study Start: March 1, 2013
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: April 9, 2014

Record last verified: 2014-04

Locations

HU (4); US (17); AU (4)