Phase 1 PK Study of AERO-007, an Inhaled LABA+LAMA Combination for Nebulization Delivery in COPD Patients

Comparison of Pharmacokinetics of Glycopyrrolate (AERO-002) in AERO-007 Combination Product Versus Active Comparator Inhalation Glycopyrrolate Product in Healthy Volunteers

This is a phase 1, single-dose, 2-period crossover study in healthy volunteers to compare the systemic pharmacokinetic (PK) profile of inhaled AERO-002 versus inhaled active comparator product.

AERO-007 is a propriety inhalation solution formulation of fixed-dose combination of LABA+LAMA (indacaterol and glycopyrrolate) for delivery using a general-purpose nebulizer device.

Combination of a long-acting beta-agonist (LABA) bronchodilator and a long-acting muscarinic antagonist (LAMA) bronchodilator is the preferred choice for initial pharmacotherapy for COPD patients with high symptom severity, frequently experiencing breathlessness, and patients with high exacerbation risk.

Although there are currently multiple LABA+LAMA combination bronchodilators available in handheld inhalers, a significant number of COPD patients, generally high risk and older patients, do not receive optimal benefit from inhalers. Nebulized delivery provides an effective alternative where disease management is sub optimal. To date there are no approved LABA+LAMA combinations available by nebulization.

In this phase 1 study, 24 healthy volunteers will be randomized to receive single doses of two study treatments (AERO-002 and active comparator) in a crossover design administered by random sequence. Study assessments will be performed pre- and post-dose for 24 hours. Treatment visits will be separated by a washout period of 7 days.

Inclusion Criteria:

• Male or female aged 18 to 55 years, inclusive, at the time of informed consent
• Forced expiratory volume in 1 second (FEV1) > 80% of predicted normal at the Screening Visit (using the Global Lung Function Initiative [GLI] 2012 reference values)
• Body mass index > 18 and < 32 kg/m2 at the Screening Visit
• Able to abstain from alcohol for 24 hours prior to the Screening Visit, and prior to and after each dosing visit
• Female participants of childbearing potential must not be pregnant, breast feeding, or lactating, and heterosexual female participants of childbearing potential must agree to use, with their partner, a male condom plus an approved method of highly effective birth control from the time of informed consent and for 30 days following the last administered dose
• Female participants of childbearing potential must have a negative serum or urine pregnancy test at the Screening Visit and a negative urine pregnancy test prior to dosing at each Treatment Visit
• Male participants who are sexually active with a female partner of childbearing potential must use, with their partner, a male condom plus an approved method of highly effective contraception from the time of informed consent and for 30 days following the last administered dose
• Participants must agree not to donate semen or ova/oocytes from the time of informed consent and for 30 days following the last administered dose
• Participants must be in good health as determined by medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory assessments at the time of screening, as judged by the Investigator
• Willing and able to provide written informed consent

Exclusion Criteria:

• Any condition or abnormality (including medical history, clinical laboratory, ECG, physical examination, or vital sign abnormalities), current or past, that, in the opinion of the Investigator or Medical Monitor, would compromise the safety of the participant, or would interfere with or complicate study procedures or assessments
• Lower respiratory tract infection within 6 weeks prior to the Screening Visit
• History of malignancy of any organ system, except for localized skin cancers, within 5 years prior to the Screening Visit
• Major surgery (requiring general anaesthesia) within 6 weeks prior to the Screening Visit, or planned surgery through the end of the study
• Positive serum hepatitis B surface antigen (HbsAg), hepatitis C virus antibodies (HCV Ab) or human immunodeficiency virus (HIV) 1 and/or 2 antibodies at the Screening Visit
• Chronic viral infection or immunodeficiency condition
• History of any drug and/or alcohol abuse in the past 2 years prior to the Screening Visit
• Current or previous use of tobacco, nicotine products, or e-cigarettes within 6 months prior to the Screening Visit through the End of Study Visit
• Smoking history of > 5 pack years
• Positive urine cotinine test at the Screening Visit or prior to dosing at each Treatment Visit
• Regular alcohol consumption in males >21 units per week and females >14 units per week
• Positive urine drugs of abuse test and/or alcohol breath test at the Screening Visit or prior to dosing at each Treatment Visit that cannot be accounted for by concomitant medication, in the opinion of the Investigator
• Donation of ≥ 450 mL of blood within 8 weeks of the Screening Visit
• History of intolerance or hypersensitivity to any of the ingredients in the formulation for AERO-002 or other aerosol medications
• Participation in another investigational drug study within 30 days of the last dose, 5 average terminal elimination half-lives (T1/2) or twice the duration of the biological effect, whichever is longer, prior to the Screening Visit
• History or high risk of noncompliance with study visits and procedures or unsuitable for entry into the study, at the discretion of the Investigator