A Dose Ranging Study With CHF 1531 in Subjects With Asthma (FLASH)

NCT03086460 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CCD-05993AA3-03
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 10

Brief Summary

To evaluate the dose-response of different doses of CHF 1531 pressurized metered dose inhaler (pMDI) containing formoterol fumarate, on lung function and other clinical outcomes and to identify the optimal dose(s) with regard to benefit/ risk ratio for further development in the target subject population.

Conditions

Asthma

Outcome Measures

Primary Outcomes (4)

• FEV1 Area Under the Curve Between 0 and 12 h [AUC(0-12h)], Normalized by Time -- Change From Baseline to Post Dose Day 14

  Spirometry used to measure FEV1, was performed according to internationally accepted standards. Results show the change from baseline in FEV1 AUC(0-12h), normalized by time on Day 14; it was calculated by using the linear trapezoidal rule, based on the changes in FEV1 from the baseline values. Patients receiving the same treatment during two periods are considered twice in the ANCOVA model (once for each period attended). Definitions: AUC=Area under the curve; AUC(0-12h)=AUC between 0 and 12 h; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose) on Day 1 of the treatment period; FEV1=Forced expiratory volume in the 1st second;

  Baseline, Day 14 post-dose

• Sensitivity Analysis 1: FEV1 AUC(0-12h), Normalized by Time -- Change From Baseline to Post Dose Day 14

  The primary analysis was repeated, considering patients "as randomized" and including only the first instance of each treatment. Patients receiving the same treatment in more than one period were included in the analysis with only data from the first instance of each treatment.

  Baseline, Day 14 post-dose

• Sensitivity Analysis 2: FEV1 AUC(0-12h), Normalized by Time -- Change From Baseline to Post Dose Day 14

  The primary analysis was repeated, considering only patients and treatment periods for which treatment was assigned on or after the randomization error occurred. The number of patients shown represents those with at least one post-baseline assessment available.

  Baseline, Day 14 post-dose

• Sensitivity Analysis 3: FEV1 AUC(0-12h), Normalized by Time -- Change From Baseline to Post Dose Day 14

  Patients receiving the same treatment during two treatment periods are considered twice in the ANCOVA model (once for each period attended). Patients considered in this analysis are those with at least one available post-baseline assessment.

  Baseline, Day 14 post-dose

Secondary Outcomes (20)

• FEV1 AUC(0-12h), Normalized by Time -- Change From Baseline to Post Dose Day 1

  Baseline, Day 1 post-dose

• FEV1 AUC(0-4h), Normalized by Time -- Change From Baseline to Post Dose Day 1 and Day 14

  Baseline, Day 1, Day 14 post-dose

• FEV1 Peak(0-4h), Normalized by Time -- Change From Baseline to Post Dose Day 1 and Day 14

  Baseline, Day 1, Day 14 post-dose

• FVC AUC(0-12h), Normalized by Time -- Change From Baseline to Post Dose Day 1 and Day 14

  Baseline, Day 1, Day 14 post-dose

• FVC AUC(0-4h), Normalized by Time -- Change From Baseline to Post Dose Day 1 and Day 14

  Baseline, Day 1, Day 14 post-dose

Study Arms (6)

Treatment A

EXPERIMENTAL

Treatment A, CHF 1531 pMDI: CHF 1531 pMDI 6 μg total daily dose (TDD): 1 inhalation of CHF 1531 pMDI 3 μg/actuation plus 1 inhalation of CHF 1531 matched Placebo BID.

Drug: CHF 1531 pMDI

Treatment B

EXPERIMENTAL

Treatment B, CHF 1531 pMDI: CHF 1531 pMDI 12 μg TDD: 1 inhalation of CHF 1531 pMDI 6 μg/actuation plus 1 inhalation of CHF 1531 matched Placebo BID.

Drug: CHF 1531 pMDI

Treatment C

EXPERIMENTAL

Treatment C, CHF 1531 pMDI: CHF 1531 pMDI 24 μg TDD: 2 inhalations of CHF 1531 pMDI 6 μg/actuation BID.

Drug: CHF 1531 pMDI

Treatment D

EXPERIMENTAL

Treatment D, CHF 1531 pMDI CHF 1531 pMDI 48 μg TDD: 2 inhalations of CHF 1531 pMDI 12 μg/actuation BID.

Drug: CHF 1531 pMDI

Treatment E

EXPERIMENTAL

Treatment E, Matched placebo Placebo: 2 inhalations of CHF 1531 pMDI matched Placebo BID.

Drug: Placebo pMDI

Treatment F

ACTIVE COMPARATOR

Treatment F, Formoterol fumarate inhalation solution (IS) Perforomist® IS (active comparator, open-label) 40 μg TDD: 1 inhalation, 20 μg/ 2 mL vial, 1 vial BID.

Drug: Formoterol Inhalation Solution

Interventions

CHF 1531 pMDI DRUG

Dose Response: Test one of five different doses of CHF 1531

Treatment A; Treatment B; Treatment C; Treatment D

Formoterol Inhalation Solution DRUG

Active Control

Also known as: PERFOROMIST® 20 μg/ 2 mL vial, 1 vial BID

Treatment F

Placebo pMDI DRUG

Matched Placebo

Treatment E

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects aged ≥18 and ≤75 years who have signed an Informed Consent Form prior to initiation of any study-related procedure.
• A diagnosis of asthma as defined in the Global Initiative for Asthma (GINA) Report, 2016, documented for at least 1 year prior to screening.
• Poorly controlled or uncontrolled asthma evidenced by a score ≥1.5 on the Asthma Control Questionnaire 7 © (ACQ-7)
• A pre-bronchodilator Forced Expiratory Volume in the 1st Second ( FEV1) ≥60% and \<85% of their predicted normal value, after appropriate washout from bronchodilators, at the screening and randomization visits
• Subjects with a positive response to a reversibility test at screening, defined as change in FEV1 (ΔFEV1) ≥12% and ≥200 mL over baseline within 30 minutes after inhaling 4 puffs of albuterol hydrofluoroalkane(HFA) 90 µg/actuation.
• Use of ICS (low/medium dose according to GINA Report, 2016) with or without a long-acting bronchodilator for 3 months (at a stable dose in the last 4 weeks) before screening visit.
• A cooperative attitude and ability to demonstrate correct use of the diary, peak flow meter, and pMDI inhaler.

You may not qualify if:

• Pregnant or lactating women and all women physiologically capable of becoming pregnant UNLESS they are willing to use a highly effective birth control methods
• Subjects who suffer from Chronic Obstructive Pulmonary Disease (COPD) as defined by the Global Strategy for Prevention, Diagnosis and Management of COPD (GOLD) Report, 2017, or are suspected of having Asthma COPD Overlap Syndrome (ACOS) as described in the GINA Report, 2016.
• Inability to carry out pulmonary function testing, to comply with study procedures or with study drug intake.
• Current smokers or ex-smokers (tobacco, vapor cigarettes, marijuana) with a smoking history of \>10 pack-years or having stopped smoking one year or less prior to screening visit.
• History of life-threatening asthma, clinically significant uncontrolled disease or respiratory infection.
• An asthma exacerbation requiring oral/intravenous corticosteroids ≤ 30 days, intramuscular depot corticosteroid ≤3 months or hospitalization within 6 months prior to screening.
• Subjects with unresolved bacterial or viral respiratory tract, sinus, or middle ear infection affecting asthma status within 2 weeks prior to screening.
• Subjects who received a vaccination within 2 weeks prior to screening or during the run-in.
• Subjects with oral candidiasis at screening and at randomization.
• Subjects with any clinically significant, uncontrolled condition.
• Subjects with serum potassium levels \<3.5 milliequivalents per litre (mEq/L) or (3.5 mmol/L) at screening.
• Subjects who have clinically significant cardiovascular condition.
• Subjects who have a clinically significant abnormal 12-lead ECG that results in active medical problem which may impact the safety of the patient according to Investigator's judgment.
• Subjects whose 12-lead ECG shows Fridericia's corrected QT interval (QTcF) \>450 ms for males or QTcF \>470 ms for females at screening or randomization visits.
• Subjects with known intolerance/hypersensitivity or contra-indication to treatment with inhaled β2-adrenergic receptor agonists, corticosteroids or propellant gases/excipients.

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (10)

Chiesi Investigational Site

Tucson, Arizona, 85710, United States

Location

Chiesi Investigational Site

Los Angeles, California, 90048, United States

Location

Chiesi Investigational Site

Lutherville, Maryland, 21093, United States

Location

Chiesi Investigational Site

St Louis, Missouri, 63141, United States

Location

Chiesi Investigational Site

Raleigh, North Carolina, 27607, United States

Location

Chiesi Investigational Site

Greenville, South Carolina, 29615, United States

Location

Chiesi Investigational Site

Orangeburg, South Carolina, 29118, United States

Location

Chiesi Investigational Site

Spartanburg, South Carolina, 29303, United States

Location

Chiesi Investigational Site

Knoxville, Tennessee, 37909, United States

Location

Chiesi Investigational Site

Richland, Washington, 99352, United States

Location

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Related Links

• Global Initiative for Chronic Obstructive Lung Disease, Inc. Global strategy for the diagnosis, management, and prevention of Chronic Obstructive Pulmonary Disease: 2017
• Global Initiative for Asthma. Global strategy for asthma management and prevention (2016 update). 2016.
• Centers for Disease Control and Prevention: Asthma
• Chiesi Farmaceutici S.p.A Respiratory
• Chiesi Farmaceutici S.p.A - Press Release: Chiesi Farmaceutifici is the first company to submit a marketing authorisation application to the European Medicine Agency for a triple combination for the treatment of COPD
• RT Magazine: Asthma-COPD Therapy Foradil Aerolizer to be Discontinued

MeSH Terms

Conditions

Asthma

Interventions

Formoterol Fumarate

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

Results Point of Contact

• Title: Clinical Trial Transparency
• Organization: Chiesi Farmaceutici S.p.A.

clinicaltrials_info@chiesi.com

+ 39 0521 2791

Study Officials

• Richard Sterling

  Sterling ENT, PA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2017
• First Posted: March 22, 2017
• Study Start: September 8, 2017
• Primary Completion: July 23, 2018
• Study Completion: July 28, 2018
• Last Updated: August 16, 2021
• Results First Posted: August 16, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)