Chronic Obstructive Pulmonary Disease (COPD) MedDRA version: 9.1 Level: LLT Classification code 10009033 Term: Chronic obstructive pulmonary disease
Conditions
Interventions
Product Name: ADC4022
Product Code: ADC4022
Pharmaceutical Form: Nebuliser solution
INN or Proposed INN: theophylline
CAS Number: 58559
Sponsors
Argenta Discovery Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Screening and Washout Phase Subjects meeting all of the following inclusion criteria at Screening should be considered for admission to the study: 1. The subject is able to understand the requirements of the study and provide written informed consent to participate 2. The subject is male or female between the ages of 40 and 75 years, inclusive 3. The subject has a confirmed diagnosis of COPD and has been symptomatic for at least 2 years 4. The subject has moderate to severe COPD, as defined by the American Thoracic Society and the European Respiratory Society: a. Pre-bronchodilator FEV1 predicted =40% and 12 consecutive months], or has not undergone surgical sterilization (hysterectomy, bilateral oophorectomy, or bilateral tubal ligation). Even women who are using acceptable contraceptive medications or devices to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy) will be considered WOCBP. WOCBP must agree to avoid becoming pregnant for the duration of the 12-week study by using adequate contraception at study entry and throughout the trial. Adequate contraception is defined as appropriate and consistent use of 1 of the following: a. Oral contraception b. Injectable contraception c. Intrauterine device d. Implantable device e. Double-barrier method (e.g., condom and spermicide) WOCBP will be routinely monitored (review at each visit and testing if indicated by the principal investigator [PI]) during study participation for adherence to this criterion. 11. The subject is able to complete all aspects of the study, including all visits and tests, and is capable of self-administration of study medications (via Pari LC Plus nebuliser delivery systems) 12. The subject agrees to abide by the study protocol and its restrictions. Additional Inclusion Criteria for Run-In and Randomisation To be eligible to proceed to the run-in and randomisation periods, subjects must meet the following criteria: 1. The subject must continue to show evidence of disease stability with no change beyond the normal day-to day variations 2. The subject must show no evidence of exacerbation, including signs of sustained worsening of the subject’s condition from the
Exclusion criteria
Exclusion criteria: 1. The subject has experienced a respiratory tract infection and/or an exacerbation of COPD within 30 days prior to the screening visit. Exacerbation of COPD is defined as a change in symptoms that require: a. an increase in use or the addition of one or more of the following therapies: corticosteroids, antibiotics, or oxygen for >3 days; and/or b. hospitalization or an extension of a hospitalization within the past 3 months 2. The subject uses systemic corticosteroids (oral or parenteral) 3. The subject has received long term oxygen therapy, defined as the daily use of supplemental oxygen for > 12 hours/day, within 30 days prior to the Screening visit 4. The subject has a previous history or diagnosis of asthma as an adult. Note, subjects who have been diagnosed with asthma are eligible if further investigation and consultation confirms COPD as the correct diagnosis. 5. The subject has a chest x-ray within 12 months prior to Visit 1 which is diagnostic of an active or clinically significant disease other than COPD 6. The subject has a history or presence of active tuberculosis, cystic fibrosis, bronchiectasis, lung cancer or sarcoidosis or any other clinically important lung diseases 7. The subject has had a lobectomy 8. The subject has a history or presence of severe right sided heart failure (defined as NYHA class III-IV), myocardial infarction, or cor pulmonale within 6 months prior to Screening 9. The subject has evidence of any unstable or clinically significant, hematopoietic, malignant, cardiovascular, hepatic, renal, neurologic, psychiatric, autoimmune disorder, or condition or disease other than COPD that, in the opinion of the PI, could place the subject at increased risk of complications, interfere with study participation, or confound any of the study objectives 10. The subject has any clinically significant laboratory or ECG abnormalities which, per the Investigator’s judgment, could place the subject at increased risk of complications, interfere with study participation, or confound any of the study objectives. 11. The subject has had radiation or chemotherapy within the previous 12 months 12. The subject is unwilling to discontinue any of the prohibited medications as outlined within the protocol 13. The subject has a history of hypersensitivity to theophylline or budesonide or any of the excipients used in the preparation of Pulmicort Respules 1mg nebuliser suspension (disodium edetate, sodium chloride, polysorbate 80, citric acid anhydrous, sodium citrate) 14. The subject has a history of anaphylaxis associated with medicinal products 15. The subject is pregnant, intends to become pregnant, or is breast feeding 16. The subject’s alcohol intake is excessive. Excessive is defined as an average daily intake of greater than six units, or a maximum weekly intake of greater than 21 units for males and 14 for females (one unit equals half a pint of beer, one measure of spirits or one glass of wine) 17. The subject participated in another study (for a marketed drug) within 3 months before the start of this study or (for an investigational drug) within 4 months before the start of this study (prior participation at any time in n
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of ADC4022 (theophylline solution for inhalation), compared to placebo, on markers of pulmonary inflammation (percent neutrophils and absolute neutrophil counts) in induced sputum expressed as percent change from baseline to 4 weeks in subjects with moderate to severe COPD, when co-administered with inhaled budesonide. ; Secondary Objective: 1) Evaluation of ADC4022, compared to placebo, on the following: •IL-8 concentration in induced sputum •Total induced sputum cell count •Macrophages, eosinophils, and lymphocytes in induced sputum •Counts of CD8+ and CD68+ cells obtained from bronchial biopsy •Pulmonary function as measured by spirometry (FEV1, FVC, FEV1/FVC, and PEFR) •Disease control as measured by exacerbation rate and use of rescue medication •Symptoms and quality of life as measured by the SGRQ •Counts of CD45+, and CD4+ cells and cells expressing genes for TNFa and interferon gamma (IFN?) obtained from bronchial biopsy. 2) Evaluation of the tolerability of ADC4022. 3) Evaluation of the single dose and repeat dose (Day 28) pharmacokinetics of ADC4022. ; Primary end point(s): The primary endpoints for statistical comparison between treatment groups will be the percent neutrophils and absolute neutrophil counts in induced sputum. The effect of ADC4022, compared to placebo, will be expressed as percent change from baseline to end-of-study. The baseline neutrophils level in a subject is taken at Visit 3. The end-of-study neutrophils level is taken at Visit 7 (no more than 28 days of treatment). | — |
Countries
United Kingdom
Outcome results
None listed