Safety and Efficacy of Albuterol Administered by the Halix™ Dry Powder Inhaler in Subjects With Asthma

• Status: Completed
• Trial end date: 2018-09-30
• Target enrollment: 0
• Participant gender: All

Summary

Male and female subjects with mild to moderate asthma will be recruited to enroll in a 2-way crossover during which escalating doses of albuterol will be administered at 30 minute intervals on a single treatment day. Albuterol will be administered by the Halix albuterol unit dose disposable inhaler on one day and by Ventolin albuterol HFA MDI on the other day. Assignment to device for albuterol delivery will be by random allocation.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Concentrx Pharmaceuticals, Inc.
• Collaborators: Kramer Consulting, LLC; PharPoint Research, Inc.
• Treatments: Albuterol

Criteria

Inclusion Criteria:

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 < 10 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 40.0 (calculated as kg/m2)

7. Has stable (for at least 6 months) physician-diagnosed asthma with historical documentation of the diagnosis

8. Must be receiving one (1) of the following required inhaled asthma therapies listed below for at least 30 days prior to the Screening Visit: (1) only SABA, which is used for rescue, or (2) low to medium doses of ICS (alone or in combination with SABA and/or LABA), used regularly as maintenance asthma therapy

9. Demonstrates acceptable spirometry performance (i.e., meets American Thoracic Society [ATS]/European Respiratory Society [ERS] acceptability/repeatability criteria

10. Has a pre-bronchodilator FEV1 of ≥50 to <85% of predicted normal value after withholding SABA ≥ 8 hours and (if applicable) LABA for 48 hours

11. Has confirmed FEV1 reversibility to inhaled Ventolin HFA aerosol 180 mcg, defined as a post-Ventolin increase in FEV1 of ≥15 % at or before 30 minutes postdose - NOTE: only 2 reversibility attempts are allowed and, if applicable, a second attempt must occur at least 24 hours after the first attempt and within the 21-day Screening Period

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

13. 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® (Lenexa, KS) 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.]

14. 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].

15. 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 (i.e., has no conflicting plans that would prohibit attendance at scheduled study visits including each of the 2 Treatment Day Visits)

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Exclusion Criteria:

1. Female subjects of childbearing potential (CBP) who are not using reliable contraception (e.g., abstinence, double barrier method, oral/implantable/transdermal contraception, Depo-Provera, intrauterine device, having one male sexual partner who has undergone vasectomy); 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 an 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 Visit), 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. Chronic obstructive pulmonary disease or other significant lung disease (e.g. chronic bronchitis, emphysema, bronchiectasis with a need for treatment, cystic fibrosis, or bronchopulmonary dysplasia)

5. Oral corticosteroid use at any dose within the 6 weeks prior to the Screening Visit

6. Receipt of any marketed (e.g. omalizumab, mepolizumab, reslizumab) or investigational biologic within 3 months of the date of the Screening Visit or within 5 half-lives of the drug, whichever is longer

7. Currently a smoker, or a former smoker with > 10 pack-year history, or a former smoker who stopped smoking <1 year before the Screening Visit

8. A history of life-threatening asthma defined as any history of significant asthma episodes(s) requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma-related syncopal episode(s)

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

10. Current history of uncontrolled hypertension or uncontrolled diabetes, in the opinion of the Investigator (NOTE: controlled hypertension and/or controlled diabetes are not exclusionary)

11. Presence of cancer not in remission for at least 5 years prior to the Screening Visit (excludes non-melanomatous skin cancer)

12. Hospitalized for psychiatric disorder in the previous 12 months or has a history of attempted suicide within 5 years prior to the Screening Visit

13. Unable to abstain from protocol-defined prohibited medications during the study

14. Clinical laboratory tests (after ≥4 hours fasting) at the Screening Visit that show results outside the normal ranges for the following clinical laboratory tests that, in the Investigator's opinion, are judged to be clinically significant:

• hemoglobin

• hematocrit

• total white blood cell count (WBC)

• platelet count

• serum glucose

• serum potassium

• ALT

• AST

• alkaline phosphatase

• serum creatinine

15. Clinical laboratory tests at the Screening Visit that show any of the following:

• positive serum hCG (female subjects only)

• positive urine drug screen (exception is evidence of authorized prescribed medications)

• positive urine cotinine test

16. 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

17. Electrocardiogram obtained at Screening Visit that shows (in the Investigator's medical opinion) medically significant abnormalities (e.g., left bundle branch block, frequent premature ventricular contractions, chronic atrial fibrillation, or QTcB interval prolongation > 450 msec for males and > 470 msec for females)

18. Presence of current drug or alcohol abuse, in the Investigator's opinion, making it unlikely that the requirements of the subject's participation in the protocol will be met

19. History of allergic reaction (known hypersensitivity) to albuterol sulfate and/or lactose, in any formulation

20. History of intolerance to aerosolized β2-adrenergic agonists

21. Receipt of a drug or biologic in an investigational research study within the 30 days prior to the Screening Visit

22. 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)

23. Presence of a clinically diagnosed upper respiratory tract infection within the 7 days prior to the Screening Visit

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