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)

NCT05755906 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: D5982C000052021-003334-36
• Study Type: interventional
• Target: 374
• Locations: 7 countries
• Sites: 104

Brief 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.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve 0 to 3 Hours (AUC0-3) at Week 12

  Change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve 0 to 3 hours (AUC0-3) at Week 12. FEV1 AUC0-3 is calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time to report the result in liters. Treatment policy is implemented to handle all intercurrent events with the exception of initiation of new asthma therapy or administration of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of randomised study intervention, for which the composite strategy is implemented.

  At Week 12

Secondary Outcomes (8)

• Change From Baseline in Morning Pre-dose Trough FEV1 at Week 12

  At Week 12

• Onset of Action on Day 1: Absolute Change in FEV1 at 5 Minutes on Day 1

  On Day 1

• Change From Baseline in the Mean Number of Puffs of Rescue Medication Use (Puffs/Day) Over 12 Weeks

  Over 12 Weeks

• Percentage of Responders in ACQ-7 (≥ 0.5 Decrease Equals Response) at Week 12

  At Week 12

• Percentage of Responders in ACQ-5 (≥ 0.5 Decrease Equals Response) at Week 12

  At Week 12

Study Arms (2)

BFF MDI 160/9.6 μg BID (320/19.2μg/day)

EXPERIMENTAL

Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), BDI (320/19.2μg/day)

Drug: BFF MDI 160/9.6 μg BID (320/19.2μg/day)

BD MDI 160 μg BID (320 μg/day)

ACTIVE COMPARATOR

Budesonide (BD) metered-dose inhaler (MDI), 160 μg BID (320 μg/day)

Drug: BD MDI 160 μg BID (320 μg/day)

Interventions

BD MDI 160 μg BID (320 μg/day) DRUG

Budesonide (BD) metered-dose inhaler (MDI), 160 μg BID (320 μg/day)

Also known as: BD

BD MDI 160 μg BID (320 μg/day)

BFF MDI 160/9.6 μg BID (320/19.2μg/day) DRUG

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

Also known as: BFF

BFF MDI 160/9.6 μg BID (320/19.2μg/day)

Eligibility Criteria

• Age: 12 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• to 80 years of age, male and female, BMI \<40 kg/m2; females of childbearing potential should be using highly effective birth control.
• 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.
• 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.
• ACQ-7 total score ≥ 1.5 at Visits 1 and 4.
• 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).
• 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.
• 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.
• Asthma stability during run-in based on Investigator discretion using the symptom worsening assessment defined in Section 8.1.2.8 as a guideline.
• Willing and, in the opinion of the Investigator, able to adjust current asthma therapy, as required by the protocol.
• Demonstrate acceptable MDI administration technique.
• 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.

You may not qualify if:

• 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).
• 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.
• Hospitalization for asthma within 8 weeks of Visit 1.
• 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.
• Known history of drug or alcohol abuse within 12 months of Visit 1.
• 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.
• Previous or current randomization into studies within the AEROSPHERE program including KALOS, LOGOS, VATHOS, LITHOS, or any glycopyrronium studies (PT001).
• 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.
• 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.
• 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).
• Participants with known hypersensitivity to beta2-agonists, corticosteroids, or any component of the MDI.
• 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.
• 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).
• Planned hospitalization during the study.
• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (104)

Research Site

Chandler, Arizona, 85224, United States

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Mesa, Arizona, 85213, United States

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Tucson, Arizona, 85745, United States

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Bakersfield, California, 93301, United States

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Encinitas, California, 92024, United States

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Fresno, California, 93720, United States

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Huntington Beach, California, 92647, United States

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Los Angeles, California, 90017, United States

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Los Angeles, California, 90025, United States

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Los Angeles, California, 90048, United States

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Newport Beach, California, 92663, United States

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Northridge, California, 91324, United States

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Sacramento, California, 95823, United States

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San Diego, California, 92123, United States

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San Jose, California, 95117, United States

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Ventura, California, 93003, United States

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Walnut Creek, California, 94598, United States

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Cutler Bay, Florida, 33189, United States

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DeBary, Florida, 32713, United States

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DeLand, Florida, 32720, United States

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Miami, Florida, 33155, United States

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Miami, Florida, 33173, United States

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Miami, Florida, 33175, United States

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Miami, Florida, 33180, United States

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Plantation, Florida, 33324, United States

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Tampa, Florida, 33607, United States

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Atlanta, Georgia, 30361, United States

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South Bend, Indiana, 46617, United States

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Lexington, Kentucky, 40509, United States

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Annapolis, Maryland, 21401, United States

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White Marsh, Maryland, 21162, United States

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North Dartmouth, Massachusetts, 02747, United States

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Farmington Hills, Michigan, 48336, United States

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Rolla, Missouri, 65401, United States

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St Louis, Missouri, 63141, United States

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Kalispell, Montana, 59901, United States

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Missoula, Montana, 59808, United States

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Bellevue, Nebraska, 68123, United States

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Henderson, Nevada, 89052, United States

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Las Vegas, Nevada, 89102, United States

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North Las Vegas, Nevada, 89030, United States

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Portsmouth, New Hampshire, 03801, United States

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New Windsor, New York, 12553, United States

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Schenectady, New York, 12308, United States

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Fayetteville, North Carolina, 28314, United States

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Raleigh, North Carolina, 27607, United States

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Columbus, Ohio, 43215, United States

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Edmond, Oklahoma, 73034, United States

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Oklahoma City, Oklahoma, 73120, United States

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Hatboro, Pennsylvania, 19040, United States

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Pittsburgh, Pennsylvania, 15236, United States

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Austin, Texas, 78704, United States

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Beaumont, Texas, 77701, United States

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Boerne, Texas, 78006, United States

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El Paso, Texas, 79912, United States

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Forney, Texas, 75126, United States

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San Antonio, Texas, 78229, United States

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San Antonio, Texas, 78258, United States

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Victoria, Texas, 77901, United States

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Waco, Texas, 76712, United States

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American Fork, Utah, 84003, United States

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Bountiful, Utah, 84010, United States

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Milwaukee, Wisconsin, 53228, United States

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Kamloops, British Columbia, V2C 5T1, Canada

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Kelowna, British Columbia, V1Y 4N7, Canada

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Penticton, British Columbia, V2A 5L5, Canada

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Ajax, Ontario, L1S 2J5, Canada

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Toronto, Ontario, M9V 4B4, Canada

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Winchester, Ontario, K0C 2K0, Canada

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Windsor, Ontario, N8X 2G1, Canada

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Montreal, Quebec, H3M 1L3, Canada

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Québec, Quebec, G1G 3Y8, Canada

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Québec, Quebec, G1V 4W2, Canada

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Jindřichův Hradec, 377 01, Czechia

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Louny, 44 001, Czechia

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Lovosice, 410 02, Czechia

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Miroslav, 671 72, Czechia

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Prague, 148 00, Czechia

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Prague, 190 00, Czechia

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Teplice, 415 01, Czechia

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Varnsdorf, 407 47, Czechia

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Alor Star, 5460, Malaysia

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George Town, 10450, Malaysia

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Ipoh, 30990, Malaysia

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Kajang, 43000, Malaysia

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Kota Bharu, 15586, Malaysia

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Kuala Lumpur, 59100, Malaysia

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Kuala Terengganu, 20400, Malaysia

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Sarawak Miri, 98000, Malaysia

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Seremban, 70300, Malaysia

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Iloilo City, 5000, Philippines

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Manila, 1000, Philippines

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Manila, 1014, Philippines

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Marilao, 3019, Philippines

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Durban, 4001, South Africa

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Durban, 4450, South Africa

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Newton, 2113, South Africa

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Pretoria, 0186, South Africa

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Tygervalley, 7530, South Africa

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Daegu, 42415, South Korea

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Guri-si, 11923, South Korea

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Jeonju, 54907, South Korea

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Seoul, 03312, South Korea

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Ulsan, 44033, South Korea

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Related Links

• CSR Synopsis

MeSH Terms

Conditions

Asthma

Interventions

BID protein, human

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2023
• First Posted: March 6, 2023
• Study Start: February 27, 2023
• Primary Completion: November 19, 2024
• Study Completion: November 19, 2024
• Last Updated: January 28, 2026
• Results First Posted: January 28, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Locations

CA (10); KR (5); MY (9); ZA (5); US (63); CZ (8); PH (4)