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

NCT03373409 | Completed Phase 1 FDA Drug

• 1 other identifier: CONX-101
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Healthy male and female volunteers without asthma will be recruited to enroll in a single dose 3-way crossover study of the safety and pharmacokinetics of albuterol when administered using the Halix (TM) albuterol unit dose disposable dry powder inhaler (DPI) and the albuterol HFA (hydrofluoroalkane) MDI inhaler.

Conditions

Asthma

Keywords

Dry Powder Inhaler

Outcome Measures

Primary Outcomes (1)

• Forced Expiratory Volume in 1 second (FEV1) before and after oral inhalation of albuterol on 3 different treatment days

  Change from treatment day baseline in forced expiratory volume in one second (FEV1) will be assessed serially up to 120 minutes after each of 3 single doses of inhaled albuterol

  At each of the 3 treatment visits, FEV1 (forced expiratory volume in one second) will be measured prior to drug administration and 6 times after dose- at 5 min, 15 min, 30 min, 45 min, 60 min and 120 min.

Secondary Outcomes (4)

• Systolic and diastolic blood pressure before and after oral inhalation of albuterol on 3 different treatement days

  Serial measurements of systolic and diastolic blood pressure will be taken at baseline (15-40 mnutes pre-dose) and at 15, 30, 45, 60, 120 minutes post dose and at 3, 4, 5, 6, 10, 12, and 14 hours post-dose

• Serum potassium before and after oral inhalation of albuterol on 3 different treatment days

  Serial measurments of serum potassium will be obtained at 10, 20, 30, 45, 60 and 120 minutes post-dose and 3 and 4 hours post-dose

• Serum glucose before and after oral inhalation of albuterol on 3 different treatment days

  Serial measurments of serum potassium will be obtained at 10, 20, 30, 45, 60 and 120 minutes post-dose and 3 and 4 hours post-dose

• Electrocardiographic QTc interval before and after oral inhalation of albuterol on 3 different treatment days

  Serial ECGs (electrocardiograms) will be taken at baseline (5-40 minutes pre-dose), 10 min post-dose, 50 min post-dose, and 5 hours post-dose.

Other Outcomes (6)

• Peak plasma concentration (Cmax) of albuterol after oral inhalation on 3 different treatment days

  PK samples to be collected postdose at 5, 10, 20, 30, 45, 60, and 120 minutes, and at 3, 4, 5, 6, 10, 12, and 14 hours post-dose

• Area under the plasma concentration versus time (AUC0-t) of albuterol after oral inhalation on 3 different treatment days

  PK samples to be collected postdose at 5, 10, 20, 30, 45, 60, and 120 minutes, and at 3, 4, 5, 6, 10, 12, and 14 hours post-dose

• Area under the plasma concentration versus time to infinity (AUC0-inf) of albuterol after oral inhalation on 3 different treatment days

  PK samples to be collected postdose at 5, 10, 20, 30, 45, 60, and 120 minutes, and at 3, 4, 5, 6, 10, 12, and 14 hours post-dose

Study Arms (3)

Albuterol DPI 90mcg

EXPERIMENTAL

Participants will receive albuterol 90mcg via the albuterol DPI

Drug: Albuterol DPI 90mcg

Albuterol DPI 180mcg

EXPERIMENTAL

Participants will receive albuterol 180mcg via the albuterol DPI

Drug: Albuterol DPI 180mcg

Albuterol HFA MDI

ACTIVE COMPARATOR

Participants will receive albuterol 180mcg via the HFA MDI inhaler

Drug: Albuterol HFA MDI

Interventions

Albuterol DPI 90mcg DRUG

Albuterol unit dose disposable DPI delivers 90mcg of albuterol in the excipient lactose with each inhalation. Albuterol 90mcg will be given on one of the 3 treatment days. One inhalation from the DPI will be used.

Also known as: Halix (TM) albuterol unit dose disposable inhaler

Albuterol DPI 90mcg

Albuterol DPI 180mcg DRUG

Albuterol unit dose disposable DPI delivers 90mcg of albuterol in the excipient lactose with each inhalation. Albuterol 180mcg will be given on one of the 3 treatment days. Two inhalations from the DPI will be used to deliver the 180mcg dose

Also known as: Halix (TM) albuterol unit dose disposable inhaler

Albuterol DPI 180mcg

Albuterol HFA MDI DRUG

Albuterol HFA MDI delivers 90mcg of albuterol with each inhalation. Albuterol 180mcg will be given on one of the 3 treatment days. Two inhalations from the MDI will be used to deliver the 180mcg dose

Also known as: Ventolin HFA MDI

Albuterol HFA MDI

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Has provided written informed consent
• Speaks and understands the English language
• Males or females 18 to 55 years of age (inclusive) at the Consent Visit
• 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
• Has no history of use of nicotine gum, nicotine patch, e-cigarettes/vaping preparations in the 3 months before the Consent Visit
• Has a body mass index (BMI) of 18.5 to 35.0 (calculated as kg/m2)
• 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
• Has a FEV1/FVC ratio ≥ 0.70 at the Screening Visit
• 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.
• 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 \[Note: a placebo UDDI not containing any drug powder will be supplied for each potential subject to become familiar with the inhaler and practice inhalation technique\] \[Note: potential subjects who cannot demonstrate successful inhalation technique using the Halix™ UDDI after in-clinic training at the Screening Visit will not be eligible for continued participation in the study\].
• \. 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)

You may not qualify if:

• 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.
• 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
• Emergency room visit or hospitalization for any acute respiratory condition in the 3 months prior to the Screening Visit
• Currently receiving pharmacologic treatment for diabetes or hypertension
• 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,
• 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

Sponsors & Collaborators

• Concentrx Pharmaceuticals, Inc.: lead
• PharPoint Research, Inc.: collaborator
• Kramer Consulting, LLC: collaborator

Study Sites (1)

North Carolina Clinical Research

Raleigh, North Carolina, 27607, United States

Location

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• William J Alexander, MD

  Concentrx Pharmaceuticals

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3-way single dose crossover

Study Record Dates

• First Submitted: October 3, 2017
• First Posted: December 14, 2017
• Study Start: November 30, 2017
• Primary Completion: May 28, 2018
• Study Completion: July 25, 2018
• Last Updated: January 30, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)