Long-term Study of AIR001 in Subjects With WHO Group 1 Pulmonary Arterial Hypertension Who Completed AIR001-CS05
Primary Purpose
Pulmonary Arterial Hypertension
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AIR001
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring AIR001, sodium nitrite, PAH, Pulmonary Arterial Hypertension, inhaled sodium nitrite
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- 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.
- 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.
- Is currently pregnant or breastfeeding or intends to become pregnant during the duration of the study.
- Investigators, study staff or their immediate families.
Sites / Locations
- UCSD Medical Center
- UCLA Medical Center
- University of Colorado Denver
- Kentuckiana Pulmonary Associates
- University of Maryland Medical Center
- Tufts Medical Center
- Brigham and Women's Hospital
- Boston University School of Medicine
- Washington University School of Medicine
- Duke University Medical Center
- University of Cincinnati
- The Ohio State University Medical Center
- University of Pittsburgh Medical Center
- University of Texas Southwestern Medical Center
- Adaani Frost, M.D.
- Inova Fairfax Hospital
- Aurora St. Luke's Medical Center
- St. Vincent's Hospital
- The Prince Charles Hospital
- Royal Hobart Hospital
- The Alfred Hospital
- Gottsegen Gyorgy Hungarian
- Semmelweis University
- University of Debrecen
- University of Szeged
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
80mg AIR001, nebulized four times daily
46 mg AIR001, nebulized four times daily
80mg AIR001, nebulized once daily
Arm Description
AIR001, 80 mg into nebulizer
AIR001, 46 mg into nebulizer
AIR001, 80 mg into nebulizer
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
To assess the effect of inhaled AIR001 on Time to Clinical Worsening, 6MWD, Functional Class, and Quality of Life
The secondary objectives of this study are to evaluate the effect of inhaled nebulized AIR001 administered according to 3 different treatment arms (80 mg 4 times daily, 46 mg 4 times daily, or 80 mg once daily) in subjects with WHO Group 1 PAH who completed the 16-week AIR001-CS05 study, as determined by time to the first morbidity/mortality event as defined in Time to Clinical Worsening (TTCW) assessments and by change from Baseline in AIR001-CS05 to the 40th week from the start of AIR001 nebulization in AIR001-CS05 (Week 24 of AIR001-CS06) and End of Study (EOS) or Termination visit of AIR001-CS06 in the following:6-Minute Walk Distance (6MWD) assessed at peak, WHO/NYHA Functional Class, Quality of Life (QOL) as measured by SF-36,Borg Dyspnea Index,6MWD assessed at trough
Full Information
NCT ID
NCT01725269
First Posted
November 8, 2012
Last Updated
April 7, 2014
Sponsor
Aires Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01725269
Brief Title
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
2. Study Status
Record Verification Date
April 2014
Overall Recruitment Status
Terminated
Why Stopped
Terminated early dt acquisition of Sponsor and change in corporate priorities
Study Start Date
March 2013 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
April 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aires Pharmaceuticals, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension
Keywords
AIR001, sodium nitrite, PAH, Pulmonary Arterial Hypertension, inhaled sodium nitrite
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
17 (Actual)
8. Arms, Groups, and Interventions
Arm Title
80mg AIR001, nebulized four times daily
Arm Type
Experimental
Arm Description
AIR001, 80 mg into nebulizer
Arm Title
46 mg AIR001, nebulized four times daily
Arm Type
Experimental
Arm Description
AIR001, 46 mg into nebulizer
Arm Title
80mg AIR001, nebulized once daily
Arm Type
Experimental
Arm Description
AIR001, 80 mg into nebulizer
Intervention Type
Drug
Intervention Name(s)
AIR001
Other Intervention Name(s)
(sodium nitrite inhalation soution)
Intervention Description
All doses specified are the amount loaded into the I-neb AAD System nebulizer.
Primary Outcome Measure Information:
Title
To evaluate the intermediate/long-term safety of inhaled nebulized AIR001
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.
Time Frame
minimum of 6 months
Secondary Outcome Measure Information:
Title
To assess the effect of inhaled AIR001 on Time to Clinical Worsening, 6MWD, Functional Class, and Quality of Life
Description
The secondary objectives of this study are to evaluate the effect of inhaled nebulized AIR001 administered according to 3 different treatment arms (80 mg 4 times daily, 46 mg 4 times daily, or 80 mg once daily) in subjects with WHO Group 1 PAH who completed the 16-week AIR001-CS05 study, as determined by time to the first morbidity/mortality event as defined in Time to Clinical Worsening (TTCW) assessments and by change from Baseline in AIR001-CS05 to the 40th week from the start of AIR001 nebulization in AIR001-CS05 (Week 24 of AIR001-CS06) and End of Study (EOS) or Termination visit of AIR001-CS06 in the following:6-Minute Walk Distance (6MWD) assessed at peak, WHO/NYHA Functional Class, Quality of Life (QOL) as measured by SF-36,Borg Dyspnea Index,6MWD assessed at trough
Time Frame
minimum of 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
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.
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.
Is currently pregnant or breastfeeding or intends to become pregnant during the duration of the study.
Investigators, study staff or their immediate families.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adaani E Frost, M.D.
Organizational Affiliation
Baylor College of Medicine, Houston
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCSD Medical Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
UCLA Medical Center
City
Torrance
State/Province
California
ZIP/Postal Code
90509
Country
United States
Facility Name
University of Colorado Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Kentuckiana Pulmonary Associates
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
University of Maryland Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Boston University School of Medicine
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Washington University School of Medicine
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110-1093
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
The Ohio State University Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Adaani Frost, M.D.
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Inova Fairfax Hospital
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22042
Country
United States
Facility Name
Aurora St. Luke's Medical Center
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53215
Country
United States
Facility Name
St. Vincent's Hospital
City
Darlinghurst
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
The Prince Charles Hospital
City
Chermside
State/Province
Queensland
ZIP/Postal Code
4032
Country
Australia
Facility Name
Royal Hobart Hospital
City
Hobart
State/Province
Tasmania
ZIP/Postal Code
7000
Country
Australia
Facility Name
The Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
Gottsegen Gyorgy Hungarian
City
Budapest
ZIP/Postal Code
1083
Country
Hungary
Facility Name
Semmelweis University
City
Budapest
ZIP/Postal Code
1125
Country
Hungary
Facility Name
University of Debrecen
City
Debrecen
ZIP/Postal Code
4012
Country
Hungary
Facility Name
University of Szeged
City
Szeged
ZIP/Postal Code
6720
Country
Hungary
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Long-term Study of AIR001 in Subjects With WHO Group 1 Pulmonary Arterial Hypertension Who Completed AIR001-CS05
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