Asthma
Conditions
Keywords
Asthma, Budesonide, Formoterol, Umeclidinium, Inhalation Powder, Triple Therapy, Phase II
Brief summary
The goal of this clinical trial is to evaluate whether two different doses of an investigational drug (CP006 Inhalation Powder, a triple combination of budesonide, formoterol, and umeclidinium) improve lung function in adults with asthma compared to an active comparator (budesonide/formoterol inhalation powder, a marketed two-component product). The main questions it aims to answer are: Does CP006 produce a greater change in lung function (measured by trough FEV₁ before morning dose) after 28 days of treatment compared to the comparator? What medical problems do participants experience when taking CP006? Researchers will compare two dose levels of CP006 against the active comparator in a 1:1:1 ratio. Participants will: Complete a screening visit (up to 7 days) to confirm eligibility, including medical history, physical exam, and lung function tests Enter a 14-day run-in period during which they take the comparator medication (budesonide/formoterol) twice daily Be randomly assigned to one of three treatment groups: CP006 Dose 1, CP006 Dose 2, or the comparator Take their assigned treatment twice daily for 28 days Visit the clinic at Day 0 (baseline), Day 8, Day 15, and Day 29 for lung function tests, safety checks, and questionnaires (ACQ-5 and AQLQ) Measure their morning and evening peak expiratory flow (PEF) daily using a handheld device and record the results in a diary Return for a follow-up safety visit or phone call at Day 43 (±2 days) The total duration of participation is approximately 58 to 65 days.
Interventions
DRUGBudesonide, Formoterol Fumarate, and Umeclidinium Bromide
CP006 Inhalation Powder, 195 μg/5.5 μg/27.5 μg per inhalation. Administered as 1 inhalation twice daily for 28 days. Contains budesonide 195 μg, formoterol fumarate 5.5 μg, and umeclidinium bromide (equivalent to umeclidinium 27.5 μg) per inhalation.
Budesonide and formoterol fumarate inhalation powder (Symbicort® Turbuhaler®), 160 μg/4.5 μg per inhalation. Administered as 2 inhalations twice daily for 28 days.
DRUGPlacebo for CP006 Inhalation Powder
Placebo matching CP006 Inhalation Powder. Contains no active pharmaceutical ingredients. Administered as 1 inhalation twice daily for 28 days to maintain blinding.
DRUGPlacebo for Budesonide and Formoterol Fumarate
Placebo matching budesonide and formoterol fumarate inhalation powder (Symbicort® Turbuhaler®). Contains no active pharmaceutical ingredients. Administered as 2 inhalations twice daily for 28 days to maintain blinding.
Albuterol sulfate inhalation aerosol (Ventolin®), 100 μg per actuation. Used as rescue medication on an as-needed basis for asthma symptoms during the run-in and treatment periods.
Sponsors
Shanghai Xin Huanghe Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
This is a randomized, double-blind, double-dummy, parallel-group, active-controlled, multicenter Phase II study. Participants are assigned in a 1:1:1 ratio to one of three parallel treatment arms.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Ability to understand and comply with study procedures, willing to complete the study as per protocol, and provide written informed consent. 2. Age 18 to 75 years (inclusive), both sexes, BMI \< 40 kg/m². 3. Diagnosis of bronchial asthma per Chinese Guidelines for the Prevention and Management of Asthma (2024 edition) with documented medical history ≥ 3 months, and currently inadequately controlled asthma as defined by ACQ-5 score ≥ 1.5. 4. Regular daily use of medium/high-dose ICS/LABA regimen (including stable ICS dose) for at least 4 weeks prior to Visit 1. 5. Non-smoker, or smoking cessation for at least 6 months (including cigarettes, cigars, pipe tobacco), with smoking history ≤ 30 pack-years. 6. Positive bronchodilator reversibility test within 1 year prior to screening; or, if not available, meet the reversibility criteria of FEV₁ increase ≥ 12% and absolute increase ≥ 200 mL during screening. 7. Pre-bronchodilator FEV₁ ≥ 40% and ≤ 85% of predicted normal value at screening. 8. Agree to have no fertility plan (including sperm or egg donation) and voluntarily use effective contraception (including partner) during the study and for 3 months after the last dose.
Exclusion criteria
1. Allergy to any sympathomimetic amines (e.g., formoterol or salbutamol), glucocorticoids, or excipient lactose. 2. Life-threatening asthma, defined as asthma exacerbation requiring non-invasive/invasive mechanical ventilation, and/or history of hypercapnia, respiratory arrest, hypoxic seizures, or asthma-related syncope within 1 year prior to screening or during run-in. 3. Acute upper or lower respiratory bacterial infection requiring systemic antibiotic therapy within 4 weeks prior to screening or during run-in, which leads to changes in asthma treatment or may affect study participation per investigator's judgment. 4. Concurrent respiratory diseases other than asthma, including but not limited to idiopathic pulmonary fibrosis, clinically significant atelectasis, active tuberculosis, COPD, bronchiectasis, etc., which may place the subject at undue risk or affect study outcome assessment per investigator's judgment. 5. History of malignancy in any organ system within the past 5 years, except for early-stage tumors with low metastatic and mortality risk that have been curatively treated. 6. Severe cardiovascular disease, including but not limited to NYHA Class III-IV, severe arrhythmias such as QTcF prolongation (QTcF \> 450 ms for males, \> 460 ms for females), myocardial infarction or unstable angina within 6 months prior to screening, or poorly controlled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg on 2 or more consecutive measurements). 7. Hepatic or renal impairment defined as ALT \> 2×ULN, AST \> 2×ULN, or serum creatinine \> 1.5×ULN. 8. History of familial hypokalemia or conditions predisposing to severe hypokalemia, or serum potassium below the lower limit of normal at screening. 9. Current or history of glaucoma, cataract, symptomatic prostatic hypertrophy, urinary retention, or bladder neck obstruction. 10. Poorly controlled diabetes mellitus (fasting blood glucose \> 10 mmol/L on 2 consecutive non-fasting days or HbA1c ≥ 8.0%). 11. History of drug abuse, substance abuse, or alcohol abuse within 1 year prior to screening (alcohol abuse defined as average daily alcohol intake \> 2 units; 1 unit = 360 mL beer, or 45 mL of 40% liquor, or 150 mL wine). 12. Use of inhaled short-acting anticholinergics, inhaled short-acting β₂-agonists (other than study drug), or combinations thereof within 24 hours prior to screening. 13. Use of LAMA or LAMA-containing combination products within 4 weeks prior to screening. 14. Use of any marketed or investigational biologic agents for asthma (e.g., omalizumab, mepolizumab, benralizumab, reslizumab) within 3 months or 5 half-lives (whichever is longer) prior to screening. 15. Use of theophyllines, oral sustained-release bronchodilators, antihistamines, or anti-allergic drugs for asthma within 1 week prior to screening. 16. Use of anti-leukotriene agents within 48 hours prior to screening. 17. Use of tricyclic antidepressants, MAOIs, or SSRIs (e.g., fluoxetine, sertraline) within 4 weeks prior to screening, except for stable SSRI use for at least 4 weeks prior to screening. 18. Use of CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, clarithromycin) within 2 weeks prior to screening. 19. Use of systemic corticosteroids at a dose ≥ 20 mg/day prednisone or equivalent for more than 1 week within 4 weeks prior to screening, or use of systemic corticosteroids at ≥ 20 mg/day prednisone or equivalent within 1 week prior to screening. 20. Initiation of allergen immunotherapy within 4 weeks prior to screening, except for those who have been on stable-dose treatment for at least 4 weeks prior to screening and will maintain stable dose during the study. 21. Oral candidiasis suspected or confirmed by investigator on oral examination. 22. Participation in another clinical trial and receipt of investigational drug/treatment within 2 months prior to enrollment. 23. Pregnant or lactating females, or positive pregnancy test in women of childbearing potential. 24. Any other condition that, per investigator's judgment, may affect the assessment of efficacy or safety, or makes the subject unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Morning Pre-dose Trough FEV₁ at Day 29 | Baseline (Day 0) and Day 29 | Forced expiratory volume in one second (FEV₁) measured before the morning dose of study medication (after at least 12 hours since the last dose) at Day 29. Change from baseline is calculated as the Day 29 value minus the baseline value (measured at Day 0 before the first dose). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Morning Pre-dose Trough FEV₁ at Day 8 and Day 15 | Baseline (Day 0), Day 8, and Day 15 | Forced expiratory volume in one second (FEV₁) measured before the morning dose of study medication at Day 8 and Day 15. Change from baseline is calculated as the value at each time point minus the baseline value (measured at Day 0 before the first dose). |
| Change from Baseline in Mean Morning and Evening Pre-dose PEF at Day 7, Day 14, and Day 28 | Baseline (7 days prior to randomization), Day 7, Day 14, and Day 28 | Peak expiratory flow (PEF) measured by a handheld peak flow meter before the morning and evening doses of study medication. The mean PEF value over the 7 days prior to each visit is calculated. Change from baseline is calculated as the mean value at each time point minus the baseline mean value (measured during the 7 days prior to randomization). |
| Change from Baseline in Mean Daily PEF Diurnal Variability at Week 4 | Baseline (7 days prior to randomization) and Week 4 | PEF diurnal variability is calculated as 2 × (highest PEF in a day - lowest PEF in a day) / (highest PEF in a day + lowest PEF in a day) × 100%. The mean daily PEF diurnal variability over 7 days at Week 4 is compared to baseline (the 7 days prior to randomization). |
| Change from Baseline in Asthma Quality of Life Questionnaire (AQLQ) Score at Day 15 and Day 29 | Baseline (Day 0), Day 15, and Day 29 | The AQLQ consists of 32 items covering symptoms, activity limitation, emotional function, and environmental stimuli. Each item is scored on a 7-point scale (1 = severely impaired, 7 = not impaired at all). The total score is the mean of all item scores. Change from baseline is calculated as the score at each time point minus the baseline score (measured at Day 0 before the first dose). |
| Change from Baseline in Asthma Control Questionnaire (ACQ-5) Score at Day 8, Day 15, and Day 29 | Baseline (Day 0), Day 8, Day 15, and Day 29 | The ACQ-5 consists of 5 questions assessing asthma symptoms, rescue medication use, and impact on daily activities over the past week. Each item is scored on a 0-6 scale. The total score is the mean of all item scores. Change from baseline is calculated as the score at each time point minus the baseline score (measured at Day 0 before the first dose). |
| Total Number of Actuations of Rescue Medication Used During the Treatment Period | Day 1 through Day 28 | Total actuations of albuterol sulfate inhalation aerosol (100 µg per actuation) used on an as-needed basis for asthma symptoms during the 28-day treatment period. |
| Total Number of Days with Rescue Medication Use During the Treatment Period | Day 1 through Day 28 | Number of days on which albuterol sulfate inhalation aerosol was used at least once during the 28-day treatment period. |
| Percentage of Days with No Rescue Medication Use During the Treatment Period | Day 1 through Day 28 | Percentage of days during the 28-day treatment period on which no albuterol sulfate inhalation aerosol was used, calculated as (number of days with no rescue medication use / total days in the treatment period) × 100%. |
| Time to First Asthma Exacerbation During the Treatment Period | Day 0 through Day 28 | Time from randomization (Day 0) to the first occurrence of an asthma exacerbation, measured in days. |
| Number of Participants with Moderate Asthma Exacerbations | Day 1 through Day 28 | Number of participants who experienced at least one moderate asthma exacerbation during the 28-day treatment period. |
| Number of Participants with Severe Asthma Exacerbations | Day 1 through Day 28 | Number of participants who experienced at least one severe asthma exacerbation during the 28-day treatment period. |
Countries
China
Outcome results
None listed