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

NCT03643874 | Completed Phase 2 FDA Drug

• 1 other identifier: CONX-201
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Asthma

Keywords

Single-dose disposable dry powder inhaler

Outcome Measures

Primary Outcomes (1)

• Analyses of baseline-adjusted FEV1 (liters) at 25 (+/- 2) minutes after each initial and cumulative dose of albuterol

  Change from treatment day baseline in forced expiratory volume in one second (FEV1) (liters) will be assessed at 25 minutes after each cumulative dose of albuterol and serially up to 360 minutes after the last dose

  At each of the treatment visits, FEV1 will be measured prior to initial drug administration and at 25 minutes after each cumulative and hourly up to 6 hours after last dose

Secondary Outcomes (8)

• Analyses of baseline-adjusted FEV1 at 5 (+2) minutes after each initial and cumulative dose of albuterol

  At each of the two treatment visits, FEV1 (forced expiratory volume in one second) will be measured prior to initial drug administration and at 5 minutes after each cumulative dose adminstered at 30 minute intervals and up to 6 hours after the last dose

• Baseline-adjusted FEV1 AUC0-6 (liter-hour) after the last cumulative dose of albuterol

  At each of the treatment visits, FEV1 will be measured hourly from after the last dose of albuterol until 6 hours post-dose

• Comparison of the FEV1 at the lowest dose of albuterol and the highest cumulative dose of albuterol for each drug/device

  At each of the treatment visits, FEV1 (liters) will be measured prior to the first dose of albuterol and at 5 and 25 minutes after each dose of albuterol

• Systolic and diastolic blood pressure (mmHg) before and after each dose of albuterol

  Serial measurements of systolic and diastolic blood pressure in mmHg will be taken at baseline on each treatment day, at 15 minutes after each dose of albuterol, and at each hour post-dose for 6 hours after the last dose of albuterol

• Heart rate (beats per minute) before and after each dose of albuterol

  Serial measurements of heart rate (beats per minute) will be taken at baseline on each treatment day, at 15 minutes after each dose of albuterol, and at each hour for 6 hours after the last dose of albuterol

Other Outcomes (2)

• Peak plasma concentrations of albuterol after oral inhalation on each of 2 treatment days

  PK samples will be collected at approximately 15 minutes after each dose of albuterol and at hourly intervals up to 720 minutes after the last dose of albuterol on each treatment day

• Area under the plasma concentration versus time (AUC0-t) for albuterol after inhalation of cumulative doses of albuterol at 30 min intervals

  PK samples will be collected at approximately 15 minutes after each dose of albuterol and at hourly intervals up to 720 minutes after the last dose of albuterol

Study Arms (2)

Halix albuterol 90 mcg

EXPERIMENTAL

Cumulative doses of albuterol administered by the Halix albuterol 90 mcg UDDI will given at intervals as: 1 inhalation, then 1 inhalation 30 min later, then 2 inhalations 30 min later, and then 4 inhalations 30 min later.

Drug: Halix albuterol 90 mcg

Albuterol HFA MDI 90 mcg

ACTIVE COMPARATOR

Cumulative doses of albuterol administered by the albuterol HFA albuterol 90 mcg MDI will given at intervals as: 2 inhalations, then 2 inhalations 30 min later, then 4 inhalations 30 min later, and then 8 inhalations 30 min later.

Drug: albuterol HFA MDI 90 mcg

Interventions

Halix albuterol 90 mcg DRUG

albuterol unit dose disposable DPI delivers 90 mcg of albuterol in the excipient lactose with each inhalation. Albuterol 90 mcg will be given on one of the treatment days in cumulative doses up to a total dose of 720 mcg

Also known as: Halix

Halix albuterol 90 mcg

albuterol HFA MDI 90 mcg DRUG

albuterol HFA MDI delivers 90 mcg of albuterol with each inhalation. Albuterol 90 mcg will be given on one of the treatment days in cumulative doses up to a total dose of 1440 mcg

Also known as: Ventolin

Albuterol HFA MDI 90 mcg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• 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 \< 10 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 40.0 (calculated as kg/m2)
• Has stable (for at least 6 months) physician-diagnosed asthma with historical documentation of the diagnosis
• 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
• Demonstrates acceptable spirometry performance (i.e., meets American Thoracic Society \[ATS\]/European Respiratory Society \[ERS\] acceptability/repeatability criteria
• 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
• 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
• 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.
• 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.
• \[Note: potential subjects who cannot demonstrate successful MDI technique using with the AIM device (with placebo canister) after in-clinic training at the Screening Visit will not be eligible for continued participation in the study.\]
• At the Screening Visit, demonstrates adequate understanding of and ability to successfully inhale when using the Halix™ UDDI \[Note: a placebo UDDI not containing any drug powder will be supplied for each potential subject to become familiar with the inhaler and practice inhalation technique\] \[Note: potential subjects who cannot demonstrate successful inhalation technique using the Halix™ UDDI after in-clinic training at the Screening Visit will not be eligible for continued participation in the study\].

You may not qualify if:

• 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.
• 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
• 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)
• Oral corticosteroid use at any dose within the 6 weeks prior to the Screening Visit
• 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
• 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
• 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)
• Emergency room visit or hospitalization for any acute respiratory condition in the 3 months prior to the Screening Visit
• Presence of cancer not in remission for at least 5 years prior to the Screening Visit (excludes non-melanomatous skin cancer)
• Hospitalized for psychiatric disorder in the previous 12 months or has a history of attempted suicide within 5 years prior to the Screening Visit
• Unable to abstain from protocol-defined prohibited medications during the study
• 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)

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

Interventions

Albuterol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 2-way cumulative dose crossover

Study Record Dates

• First Submitted: August 7, 2018
• First Posted: August 23, 2018
• Study Start: June 30, 2018
• Primary Completion: August 31, 2018
• Study Completion: September 30, 2018
• Last Updated: January 30, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)