A Phase 2, Multi-Center, unblinded study to evaluate the intermediate/long term safety and effectiveness of AIR001 in subjects with high blood pressure in the blood vessels in the lungs

• Register: EUCTR
• Last refreshed on: 10 March 2014
• Main ID: EUCTR2012-000153-31-HU
• Date of registration: 14/11/2012
• Prospective Registration: Yes
• Primary sponsor: Aires Pharmaceuticals, Inc
• Public title: A Phase 2, Multi-Center, unblinded study to evaluate the intermediate/long term safety and effectiveness of AIR001 in subjects with high blood pressure in the blood vessels in the lungs
• Scientific title: A Phase 2, Multi-Center, Open-Label study to evaluate the intermediate/long term safety and efficacy of AIR001 in subjects with WHO Group I Pulmonary Arterial Hypertension
• Date of first enrolment: 22/01/2013
• Target sample size: 90
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000153-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Different dosage of the same product Number of treatment arms in the trial: 3

Countries of recruitment

Australia, Czech Republic, France, Germany, Hungary, Italy, Poland, Serbia, United States

Contacts

• Name: Ed Parsley
• Affiliation: Aires Pharmaceuticals, Inc

• Name: Ed Parsley
• Affiliation: Aires Pharmaceuticals, Inc

Key inclusion & exclusion criteria

Inclusion criteria:
1. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study prior to initiation of any study-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-CS05 study as planned.
4. If on corticosteroids, has been receiving a stable dose of = 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 last dose of study drug.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 81
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 9

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. Sitting 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 Glomular 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:
a. Congenital or acquired methemoglobinemia;
b. 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 (or intends to father a child) during the study.
17. Investigators, study staff or their immediate families.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Pulmonary Arterial Hypertension

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Name: AIR001 Inhalation Solution
Product Code: AIR001
Pharmaceutical Form: Nebuliser solution
INN or Proposed INN: sodium nitrite
CAS Number: 7632-00-0
Current Sponsor code: AIR001
Other descriptive name: SODIUM NITRITE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 80-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Not applicable

Primary end point(s): Intermediate/long-term safety

Main Objective: 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 Objective: 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 immediately post completion of AIR001 nebulization (peak) , but no more than 40-minutes after completion of AIR001 nebulization
• WHO/NYHA Functional Class (FC)
• QOL as measured by SF-36 health survey instrument
• Borg Dyspnea Index
• 6MWD assessed prior to AIR001 nebulization (trough)

Secondary Outcome(s)

Secondary end point(s): Secondary efficacy endpoints will be evaluated by assessments of TTCW and 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 EOS or Termination visit of AIR001-CS06 in the following:
• 6MWD assessed immediately post completion of AIR001 nebulization (peak) , but no more than 40-minutes after completion of AIR001 nebulization
• WHO/NYHA FC
• QOL as measured by SF-36 health survey instrument
• Borg Dyspnea Index
• 6MWD assessed prior to AIR001 nebulization (trough)
The safety of AIR001 will be monitored throughout the study. The safety endpoints will be as follows:
• Changes in oxygenation status as measured by pulse oximetry from Baseline in AIR001-CS05 to EOS or Termination of AIR001- CS06.
• Assessment for the development of clinically significant methemoglobinemia from Baseline in AIR001-CS05 to EOS or Termination of AIR001- CS06.
• Treatment-emergent adverse events up to 28-days following discontinuation of the study drug.
• Treatment-emergent serious adverse events up to 28-days following discontinuation of the study drug.

Timepoint(s) of evaluation of this end point: Baseline to EOS/Termination visit

Secondary ID(s)

AIR001-CS06

77272

Source(s) of Monetary Support

Aires Pharmaceuticals, Inc