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)

• Sponsor: AstraZeneca (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05755906
• Collaborator: (none)
• Enrollment: 340
• Locations: 53
• Arms: 2
• Anticipated Duration (Months): 18
• Patients Per Site: 6.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: BFF MDI 160/9.6 μg BID (320/19.2μg/day); Drug: BD MDI 160 μg BID (320 μg/day)	Phase 3

Detailed 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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 340 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: Feb 27, 2023
• Anticipated Primary Completion Date: Aug 27, 2024
• Anticipated Study Completion Date: Aug 27, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BFF MDI 160/9.6 μg BID (320/19.2μg/day) 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); Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 160/9.6 μg BID (320/19.2μg/day); Other Names: BFF
Active Comparator: BD MDI 160 μg BID (320 μg/day) Budesonide (BD) metered-dose inhaler (MDI), 160 μg BID (320 μg/day)	Drug: BD MDI 160 μg BID (320 μg/day); Budesonide (BD) metered-dose inhaler (MDI), 160 μg BID (320 μg/day); Other Names: BD

Outcome Measures

Primary Outcome Measures

1. 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]

   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

Secondary Outcome Measures

1. US (Key secondary): Change from baseline in morning pre-dose trough FEV1 at Week 12 [at week 12]

   US (Key secondary): Change from baseline in morning pre-dose trough FEV1 at Week 12

2. Change from baseline in the mean number of puffs of rescue medication use (puffs/day) over 12 Weeks [over 12 Weeks]

   Change from baseline in the mean number of puffs of rescue medication use (puffs/day) over 12 Weeks

3. Percentage of responders in ACQ-7 (≥ 0.5 decrease equals response) at Week 12 [at Week 12]

   Percentage of responders in ACQ-7 (≥ 0.5 decrease equals response) at Week 12

4. Percentage of responders in ACQ-5 (≥ 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

5. 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]

   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

6. Onset of action on Day 1: Absolute change in FEV1 at 5 minutes on Day 1 [on Day 1]

   Onset of action on Day 1: Absolute change in FEV1 at 5 minutes on Day 1 (within group comparison)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 1 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 of 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 an Investigational Product administered in the last 30 days or 5 half-lives, whichever is longer. Any other Investigational Product that is not identified in this protocol is prohibited for use during study duration.

8. Previous or current randomization in any budesonide and formoterol fumarate or budesonide, glycopyrronium, and formoterol fumarate studies (PT009 or PT010).

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 electrocardiogram (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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Huntington Beach	California	United States	92647
2	Research Site	Los Angeles	California	United States	90017
3	Research Site	Los Angeles	California	United States	90025
4	Research Site	Los Angeles	California	United States	90048
5	Research Site	Newport Beach	California	United States	92663
6	Research Site	San Diego	California	United States	92123
7	Research Site	San Jose	California	United States	95117
8	Research Site	Cutler Bay	Florida	United States	33189
9	Research Site	DeBary	Florida	United States	32713
10	Research Site	Lexington	Kentucky	United States	40509
11	Research Site	White Marsh	Maryland	United States	21162
12	Research Site	North Dartmouth	Massachusetts	United States	02747
13	Research Site	Ann Arbor	Michigan	United States	48109
14	Research Site	Farmington Hills	Michigan	United States	48336
15	Research Site	Rolla	Missouri	United States	65401
16	Research Site	Saint Louis	Missouri	United States	63141
17	Research Site	Missoula	Montana	United States	59808
18	Research Site	Bellevue	Nebraska	United States	68123
19	Research Site	Skillman	New Jersey	United States	08558
20	Research Site	Hastings-on-Hudson	New York	United States	10706
21	Research Site	Gastonia	North Carolina	United States	28054
22	Research Site	Raleigh	North Carolina	United States	27607
23	Research Site	Columbus	Ohio	United States	43215
24	Research Site	Edmond	Oklahoma	United States	73034
25	Research Site	Oklahoma City	Oklahoma	United States	73120
26	Research Site	Boerne	Texas	United States	78006
27	Research Site	El Paso	Texas	United States	79903
28	Research Site	San Antonio	Texas	United States	78229
29	Research Site	Waco	Texas	United States	76712
30	Research Site	Milwaukee	Wisconsin	United States	53228
31	Research Site	Ajax	Ontario	Canada	L1S 2J5
32	Research Site	Toronto	Ontario	Canada	M9V 4B4
33	Research Site	Winchester	Ontario	Canada	K0C 2K0
34	Research Site	Windsor	Ontario	Canada	N8X 2G1
35	Research Site	Montreal	Quebec	Canada	H3M 1L3
36	Research Site	Quebec		Canada	G1G 3Y8
37	Research Site	Quebec		Canada	G1V 4W2
38	Research Site	Jindrichuv Hradec		Czechia	377 01
39	Research Site	Kralupy nad Vltavou		Czechia	278 01
40	Research Site	Novy Bor		Czechia	473 01
41	Research Site	Praha 9		Czechia	190 00
42	Research Site	Rudná		Czechia	252 19
43	Research Site	Teplice		Czechia	415 01
44	Research Site	Varnsdorf		Czechia	407 47
45	Research Site	Berlin		Germany	10787
46	Research Site	Berlin		Germany	12159
47	Research Site	Geesthacht		Germany	21502
48	Research Site	Hamburg		Germany	22143
49	Research Site	Hannover		Germany	30449
50	Research Site	Landsberg		Germany	86899
51	Research Site	Leipzig		Germany	04207
52	Research Site	Schleswig		Germany	24837
53	Research Site	Wiesbaden		Germany	65189

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT05755906
• Other Study ID Numbers: D5982C00005; 2021-003334-36
• First Posted: Mar 6, 2023
• Last Update Posted: Mar 10, 2023
• Last Verified: Mar 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Asthma

Study Results

No Results Posted as of Mar 10, 2023