Safety and Pharmacokinetics of Halix(TM) Albuterol Unit Dose Disposable Inhaler Versus Albuterol MDI

The study objective is to compare the safety of albuterol in a dry powder inhaler (DPI) and
albuterol in an HFA metered dose inhaler (MDI) after single albuterol doses of 90mcg and
180mcg delivered by the DPI and 180mcg delivered by the MDI. Another study objective is to
compare the pharmacokinetics (metabolism) of albuterol with the two inhalers in all subjects
treated. To participate in the study, subjects must provide written informed consent, washout
any prohibited medications and pass all the screening criteria. Once this is done, there will
be 3 treatment visits for each subject. At each of these visits, the subject will inhale from
either the DPI or the MDI. Assignment of subjects to one of six (6) unique sequences of
treatment will be according to a randomized scheme. The subject will inhale albuterol either
once from the DPI (90mcg), twice from the DPI (180mcg) and twice from the MDI (180mcg).
Following inhalation of the study drug, there will be a series of assessments taken at times
postdose with spirometry (FEV1) measured up to 2 hours postdose, vital signs measured up to
10 hours post dose, ECGs obtained up to 5 hours postdose, blood taken to measure potassium
and glucose up to 6 hours postdose, and blood for pharmacokinetic evaluation obtained up to
10 hours postdose. A washout period of 60 to 192 hours will separate each of the 3 treatment
visits. Following these visits, there will be a study concluding visit 3 to 10 days later.

Inclusion Criteria:Subjects are required to meet ALL of the following inclusion criteria to
be eligible for enrollment in the study.

1. Has provided written informed consent

2. Speaks and understands the English language

3. Males or females 18 to 55 years of age (inclusive) at the Consent Visit

4. Nonsmoker or ex-smoker who has abstained from smoking for at least 1 year prior to the
Consent Visit and who has a ≤ 15 pack/year history of lifetime cigarette use

5. Has no history of use of nicotine gum, nicotine patch, e-cigarettes/vaping
preparations in the 3 months before the Consent Visit

6. Has a body mass index (BMI) of 18.5 to 35.0 (calculated as kg/m2)

7. Has never had a diagnosis of asthma, exercise-induced bronchospasm, chronic
obstructive pulmonary disease, or other chronic respiratory disease or chronic upper
airway condition (seasonal or perennial allergic rhinitis is not exclusionary;
however, nasal polypectomy within the 12 months prior to the Screening Visit is
exclusionary

8. Has a FEV1 ≥ 80% of predicted normal for age, gender, height and ethnicity (percent of
predicted normal values for FEV1 will be calculated using National Health and
Nutrition Examination Survey III [NHANES III]) calculation at the Screening Visit

9. Has a FEV1/FVC ratio ≥ 0.70 at the Screening Visit

10. Ability to maintain a peak inspiratory flow rate of at least 60 L/min measured by the
In-check DIAL device at the medium resistance setting.

11. At the Screening Visit, demonstrates adequate understanding of and ability to
successfully inhale from an MDI as determined by the investigator and through
demonstrated successful use of the Vitalograph® aerosol inhalation monitor (AIM™)
(training/validation device for MDI) using a placebo MDI canister.

[Note: potential subjects who cannot demonstrate successful MDI technique using with the
AIM device (with placebo canister) after in-clinic training at the Screening Visit will not
be eligible for continued participation in the study.] 12. At the Screening Visit,
demonstrates adequate understanding of and ability to successfully inhale when using the
Halix™ UDDI [Note: a placebo UDDI not containing any drug powder will be supplied for each
potential subject to become familiar with the inhaler and practice inhalation technique]
[Note: potential subjects who cannot demonstrate successful inhalation technique using the
Halix™ UDDI after in-clinic training at the Screening Visit will not be eligible for
continued participation in the study].

13. Willing and able to comply with all aspects of the study protocol including avoiding
use of certain concomitant medications and attending the required clinic visits (ie, has no
conflicting plans that would prohibit attendance at scheduled study visits including each
of the threeTreatment Day Visits)

Exclusion Criteria:Subjects will be excluded from participation in the study if ANY of the
following criteria are present:

1. Female subjects of childbearing potential (CBP) who are not using reliable
contraception (eg, abstinence, double barrier method, oral/implantable/transdermal
contraception, Depo-Provera, intrauterine device); a woman is of CBP unless she is
premenarchal, is at least 2 years postmenopausal, is without a uterus and/or both
ovaries, has had a bilateral tubal ligation, or has undergone the Essure procedure
with confirmation of tubal blockage.

[Note: If a female is identified as less than 2 years postmenopausal, a serum
follicle-stimulating hormone (FSH) determination will be performed as a part of
screening laboratory assessments. If a FSH result of < 40 mIU/mL is obtained, the
female will be determined to be of CBP and her unwillingness to use reliable
contraception as defined above will be exclusionary for the study.]

2. A woman who is pregnant (has a positive serum pregnancy test at Screening), is
lactating, or is likely/planning to become pregnant during the study

3. Vital signs at the Screening Visit (after at least 2 minutes seated at rest) showing
SBP either < 80 mmHg or >150 mmHg; DBP > 90 mmHg; or HR either < 40 bpm or > 100 bpm
(vital signs outside these criteria may be repeated once after an additional seated
rest period of at least 2 minutes- if vital signs exclusion criteria are not met after
the repeat measurements of SBP, DBP, or HR, screening may continue)

4. Emergency room visit or hospitalization for any acute respiratory condition in the 3
months prior to the Screening Visit

5. Currently receiving pharmacologic treatment for diabetes or hypertension

6. History of any acute or chronic hepatobiliary disorder or documented elevation of
alanine transaminase (ALT) or aspartate transaminase (AST) 2 or more times the upper
limit of the normal (ULN) laboratory reference range in the 12 months prior to the
Consent Visit,

7. Clinical laboratory results (after ≥4 hours fasting) at the Screening Visit that show
any one or more of the following:

- hemoglobin < 13.5 g/dL in male subjects; < 12 g/dL in female subjects

- hematocrit < 38 % in male subjects; <35% in female subjects

- total white blood cell count (WBC) < 2500 cells/mm3

- platelet count < 150,000 cells/mm3

- serum glucose < 80 mg/dL or > 120 mg/dL

- serum potassium < 3.5 mmol/L or > 5.2 mmol/L

- ALT or AST > 2.0 times ULN

- alkaline phosphatase (ALP) > 1.5 times ULN

- serum creatinine > 1.5 times ULN

- positive serum hCG (female subjects only)

- positive serologic test for HBsAg, anti-HCV antibody, or HIV antibody

- in the opinion of the investigator, a urinalysis result showing medically
significant abnormality

- positive urine drug screen [Exception: urine drug screen detects evidence of an
authorized prescribed medication]

- positive urine cotinine test

8. Presence of any uncontrolled (in the Investigator's medical opinion) systemic disease,
including, but not limited to renal, hepatic, hematologic, gastrointestinal,
endocrine, pulmonary, cardiac, neurologic, or psychiatric disease

9. Electrocardiogram obtained at Screening Visit that shows medically significant
abnormalities (e.g., left bundle branch block, frequent premature ventricular
contractions, chronic atrial fibrillation, or QTc interval prolongation > 450 msec for
males and > 470 msec for females)

10. Has a FEV1 < 80% of that predicted for age, gender, height, and ethnicity at the
Screening Visit based on NHANES III calculation.

11. Has a FEV1 / FVC ratio < 0.70

12. Inability to maintain a peak inspiratory flow rate of 60 L/min or higher

13. Presence of a current condition (e.g., alcoholism [or consumption of substantial
quantities of alcohol], drug abuse, or psychiatric condition) making it unlikely that
the requirements of the subject's participation in the protocol will be met

14. History of allergic reaction (known hypersensitivity) to albuterol sulfate and/or
lactose, in any formulation, or history of severe hypersensitivity to milk proteins

15. Current participation in a drug, drug/device or biologic investigational research
study or participation in a drug, drug/device or biologic investigational research
study within the 30 days prior to the Screening Visit

16. An elective surgical or medical procedure currently is planned or scheduled to be
performed during the study (this excludes routine immunotherapy/desensitization
procedures that are being performed on a regular schedule and have been unchanged for
at least 3 months prior to the Screening Visit)

17. Presence of a clinically diagnosed upper respiratory tract infection within the 14
days prior to the Screening Visit

18. Has undergone nasal polypectomy within the 12 months prior to the Screening Visit