A 12-week Study to Assess the Efficacy and Safety of Budesonide and Formoterol Fumarate Metered Dose Inhaler Relative to Budesonide Metered Dose Inhaler in Participants With Inadequately Controlled Asthma (LITHOS)

Asthma Clinical Trial

— LITHOS  

Official title:

A Randomized, Double-Blind, Parallel Group, Multicenter 12 Week Study to Assess the Efficacy and Safety of Budesonide and Formoterol Fumarate Metered Dose Inhaler Relative to Budesonide Metered Dose Inhaler in Participants With Inadequately Controlled Asthma (LITHOS)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05755906
• Other study ID #: D5982C00005
• Secondary ID: 2021-003334-36
• Status: Recruiting
• Phase: Phase 3
• Start date: February 27, 2023
• Est. completion date: January 8, 2025

Study information

• Verified date: June 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a 12-week study to evaluate the efficacy and safety of budesonide and formoterol fumarate metered dose inhaler relative to budesonide metered dose inhaler in adults and adolescents with inadequately controlled asthma.

Description:

This is a Phase III, randomized, double-blind, parallel group, multicenter study comparing Budesonide and Formoterol Fumarate Metered Dose Inhaler (BFF MDI) 160/9.6 μg twice daily (BID) to Budesonide MDI 160 μg (BD MDI), over 12 weeks. The study population will consist of adult and adolescent participants with asthma who remain inadequately controlled, as demonstrated by an Asthma Control Questionnaire (ACQ)-7 total score ≥1.5, despite treatment with low dose inhaled corticosteroid (ICS) or ICS/long-acting beta2-agonist (LABA). This study is to assess the benefits and safety of BFF MDI on lung function and asthma health-related quality of life. This study will be conducted at approximately 90 sites worldwide and will randomize approximately 340 adult and adolescent participants.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 340
• Est. completion date: January 8, 2025
• Est. primary completion date: January 8, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 80 Years

Eligibility

Inclusion Criteria

1. 12 to 80 years of age, male and female, BMI <40 kg/m2; females of childbearing potential should be using highly effective birth control.

2. Participants who have a documented history of physician-diagnosed asthma = 6 months prior to Visit 1, according to GINA guidelines [GINA 2021]. Healthcare records for one year prior to Visit 1 must be provided for adolescent participants (12 to < 18 years of age) to ensure consistent evaluation and follow-up of treatment in those participants.

3. Participants who have been regularly using a stable daily ICS or an ICS/LABA regimen (including a stable ICS dose), with allowed ICS doses, for at least 8 weeks prior to Visit 1.

4. ACQ-7 total score = 1.5 at Visits 1 and 4.

5. A pre-bronchodilator/pre-dose FEV1 < 90% predicted normal value at Visits 1, 2, and 3 and a pre-dose FEV1 of 50% to 90% at Visit 4 (pre-randomization).

6. Reversibility to albuterol, defined as a post-albuterol increase in FEV1 of = 12% and = 200 mL for participants = 18 years of age OR a post-albuterol increase in FEV1 of = 12% for participants 12 to < 18 years of age either in the 12 months prior to Visit 1 or at Visit 2 or Visit 3, if repeat testing is necessary.

7. A pre-bronchodilator/pre-dose FEV1 at Visits 2, 3, and 4 that has not changed 20% or more (increase or decrease) from the pre-bronchodilator/pre-dose FEV1 recorded at the previous visit.

8. Asthma stability during run-in based on Investigator discretion using the symptom worsening assessment defined in Section 8.1.2.8 as a guideline.

9. Willing and, in the opinion of the Investigator, able to adjust current asthma therapy, as required by the protocol.

10. Demonstrate acceptable MDI administration technique.

11. eDiary compliance = 70% during screening, defined as completing the daily eDiary and answering "Yes" to taking 2 puffs of run-in BD MDI for any 10 mornings and 10 evenings in the last 14 days prior to randomization. Exclusion criteria

1. Life-threatening asthma as defined as a history of significant asthma episode(s) requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma related syncopal episode(s).

2. Any respiratory infection or asthma exacerbation treated with systemic corticosteroids and/or additional ICS treatment in the 8 weeks prior to Visit 1 and throughout the Screening Period.

3. Hospitalization for asthma within 8 weeks of Visit 1.

4. Historical or current evidence of a clinically significant disease including, but not limited to: cardiovascular, hepatic, renal, hematological, neurological, endocrine, gastrointestinal, or pulmonary (eg, active tuberculosis, bronchiectasis, pulmonary eosinophilic syndromes, and COPD). Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the participant at risk through participation, or that could affect the efficacy or safety analysis.

5. Known history of drug or alcohol abuse within 12 months of Visit 1.

6. Unresectable cancer that has not been in complete remission for at least 5 years prior to Visit 1. Note: Squamous cell and basal cell carcinomas of the skin are not exclusionary.

7. Participation in another clinical study with a study intervention administered in the last 30 days or 5 half-lives, whichever is longer. Any other study intervention that is not identified in this protocol is prohibited for use during study duration.

8. Previous or current randomization into studies within the AEROSPHERE program including KALOS, LOGOS, VATHOS, LITHOS, or any glycopyrronium studies (PT001).

9. Use of a nebulizer or a home nebulizer for receiving asthma medications. Note: Acute use of a nebulizer for an asthma exacerbation during hospitalization is allowed as long as there is no occurrence within 8 weeks of Visit 1.

10. Do not meet the stable dosing period prior to Visit 1 or unable to abstain from protocol-defined prohibited medications during Screening and Treatment Periods.

11. Receipt of COVID-19 vaccine (regardless of vaccine delivery platform, eg, vector, lipid nanoparticle) =7 days prior to Visit 1 (from last vaccination or booster dose).

12. Participants with known hypersensitivity to beta2-agonists, corticosteroids, or any component of the MDI.

13. Any clinically relevant abnormal findings in physical examination, clinical chemistry, hematology, vital signs, or ECG, which in the opinion of the Investigator, may put the participant at risk because of his/her participation in the study.

14. Current smokers, former smokers with > 10 pack-years history, or former smokers who stopped smoking < 6 months prior to Visit 1 (including all forms of tobacco, e-cigarettes or other vaping devices, and marijuana).

15. Planned hospitalization during the study.

16. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).

17. Study Investigators, sub-Investigators, coordinators, and their employees or immediate family members.

18. Judgment by the Investigator that the participant is unlikely to comply with study procedures, restrictions and requirements.

19. For women only - currently pregnant (confirmed with positive highly sensitive urine pregnancy test), breast-feeding, or planned pregnancy during the study or not using acceptable contraception measures, as judged by the Investigator.

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• BFF MDI 160/9.6 µg BID (320/19.2µg/day)
Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 160/9.6 µg BID (320/19.2µg/day)
• BD MDI 160 µg BID (320 µg/day)
Budesonide (BD) metered-dose inhaler (MDI), 160 µg BID (320 µg/day)

Locations

Country	Name	City	State
Canada	Research Site	Ajax	Ontario
Canada	Research Site	Kamloops	British Columbia
Canada	Research Site	Kelowna	British Columbia
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Penticton	British Columbia
Canada	Research Site	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Winchester	Ontario
Canada	Research Site	Windsor	Ontario
Canada	Research Site	Winnipeg	Manitoba
Czechia	Research Site	Jindrichuv Hradec
Czechia	Research Site	Kralupy nad Vltavou
Czechia	Research Site	Louny
Czechia	Research Site	Lovosice
Czechia	Research Site	Miroslav
Czechia	Research Site	Praha 11
Czechia	Research Site	Praha 9
Czechia	Research Site	Rudná
Czechia	Research Site	Teplice
Czechia	Research Site	Varnsdorf
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Geesthacht
Germany	Research Site	Hamburg
Germany	Research Site	Hannover
Germany	Research Site	Landsberg
Germany	Research Site	Leipzig
Germany	Research Site	Schleswig
Germany	Research Site	Wiesbaden
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Guri-si
Korea, Republic of	Research Site	Jeonju
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Ulsan
Malaysia	Research Site	Alor Setar
Malaysia	Research Site	George Town
Malaysia	Research Site	Ipoh
Malaysia	Research Site	Kajang
Malaysia	Research Site	Kota Bharu
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Kuala Terengganu
Malaysia	Research Site	Sarawak Miri
Malaysia	Research Site	Seremban
Philippines	Research Site	Iloilo City
Philippines	Research Site	Manila
Philippines	Research Site	Manila
Philippines	Research Site	Marilao
South Africa	Research Site	Durban
South Africa	Research Site	Durban
South Africa	Research Site	Newton
South Africa	Research Site	Pretoria
South Africa	Research Site	Tygervalley
United States	Research Site	Amarillo	Texas
United States	Research Site	American Fork	Utah
United States	Research Site	Andrews	Texas
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Annapolis	Maryland
United States	Research Site	Atlanta	Georgia
United States	Research Site	Atlanta	Georgia
United States	Research Site	Austin	Texas
United States	Research Site	Bakersfield	California
United States	Research Site	Beaumont	Texas
United States	Research Site	Bellevue	Nebraska
United States	Research Site	Boerne	Texas
United States	Research Site	Bountiful	Utah
United States	Research Site	Chandler	Arizona
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Cheney	Washington
United States	Research Site	Chicago Ridge	Illinois
United States	Research Site	Choctaw	Oklahoma
United States	Research Site	Columbus	Ohio
United States	Research Site	Cutler Bay	Florida
United States	Research Site	Dallas	Texas
United States	Research Site	DeBary	Florida
United States	Research Site	DeLand	Florida
United States	Research Site	Detroit	Michigan
United States	Research Site	Edmond	Oklahoma
United States	Research Site	El Paso	Texas
United States	Research Site	Encinitas	California
United States	Research Site	Farmington Hills	Michigan
United States	Research Site	Fayetteville	North Carolina
United States	Research Site	Forney	Texas
United States	Research Site	Fresno	California
United States	Research Site	Gastonia	North Carolina
United States	Research Site	Gilroy	California
United States	Research Site	Glendale	Arizona
United States	Research Site	Hatboro	Pennsylvania
United States	Research Site	Henderson	Nevada
United States	Research Site	Hialeah	Florida
United States	Research Site	Huntington Beach	California
United States	Research Site	Huntington Beach	California
United States	Research Site	Kalispell	Montana
United States	Research Site	Kansas City	Missouri
United States	Research Site	Katy	Texas
United States	Research Site	Kernersville	North Carolina
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lexington	Kentucky
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Marrero	Louisiana
United States	Research Site	Mesa	Arizona
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	Missoula	Montana
United States	Research Site	New Windsor	New York
United States	Research Site	Newport Beach	California
United States	Research Site	North Dartmouth	Massachusetts
United States	Research Site	North Las Vegas	Nevada
United States	Research Site	Northridge	California
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Omaha	Nebraska
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Plantation	Florida
United States	Research Site	Portsmouth	New Hampshire
United States	Research Site	Raleigh	North Carolina
United States	Research Site	Rolla	Missouri
United States	Research Site	Sacramento	California
United States	Research Site	Saint Louis	Missouri
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Diego	California
United States	Research Site	San Jose	California
United States	Research Site	Schenectady	New York
United States	Research Site	Skillman	New Jersey
United States	Research Site	South Bend	Indiana
United States	Research Site	Tampa	Florida
United States	Research Site	Teaneck	New Jersey
United States	Research Site	Thousand Oaks	California
United States	Research Site	Tucson	Arizona
United States	Research Site	Ventura	California
United States	Research Site	Victoria	Texas
United States	Research Site	Waco	Texas
United States	Research Site	Walnut Creek	California
United States	Research Site	Wheat Ridge	Colorado
United States	Research Site	White Marsh	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Germany,  Korea, Republic of,  Malaysia,  Philippines,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	United States (US): Change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve 0 to 3 hours (AUC0-3) at Week 12	United States (US): Change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve 0 to 3 hours (AUC0-3) at Week 12	at week 12
Secondary	US (Key secondary): Change from baseline in morning pre-dose trough FEV1 at Week 12	US (Key secondary): Change from baseline in morning pre-dose trough FEV1 at Week 12	at week 12
Secondary	Change from baseline in the mean number of puffs of rescue medication use (puffs/day) over 12 Weeks	Change from baseline in the mean number of puffs of rescue medication use (puffs/day) over 12 Weeks	over 12 Weeks
Secondary	Percentage of responders in ACQ-7 (= 0.5 decrease equals response) at Week 12	Percentage of responders in ACQ-7 (= 0.5 decrease equals response) at Week 12	at Week 12
Secondary	Percentage of responders in ACQ-5 (= 0.5 decrease equals response) at Week 12	Percentage of responders in ACQ-5 (= 0.5 decrease equals response) at Week 12	at Week 12
Secondary	Percentage of responders in the Asthma Quality of Life Questionnaire for 12 years and older (AQLQ(s) +12) (= 0.5 increase equals response) at Week 12	Percentage of responders in the Asthma Quality of Life Questionnaire for 12 years and older (AQLQ(s) +12)(= 0.5 increase equals response) at Week 12	at Week 12
Secondary	Onset of action on Day 1: Absolute change in FEV1 at 5 minutes on Day 1	Onset of action on Day 1: Absolute change in FEV1 at 5 minutes on Day 1 (within group comparison)	on Day 1