A Phase II, Randomised, Double-Blind, Placebo-Controlled Pilot Efficacy Study of ADC4022 (Theophylline Solution for Inhalation) on Markers of Pulmonary Inflammation in Subjects with Moderate to Severe COPD
- Conditions
- Chronic Obstructive Pulmonary Disease (COPD)MedDRA version: 9.1 Level: LLT Classification code 10009033 Term: Chronic obstructive pulmonary disease
- Registration Number
- EUCTR2007-001968-78-GB
- Lead Sponsor
- Argenta Discovery Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 130
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 <80% and FEV1/FVC ratio =70% and
b.post-bronchodilator FEV1 predicted: =40% and <80% and FEV1/FVC ratio =70%
5.The subject can produce an adequate sputum specimen after induction
6.The subject has a history of = 10-pack years of cigarette smoking
7.The subject has either a =15% increase or =200ml increase in FEV1 from pre-dose following a fixed dose of inhaled salbutamol administered by pressurised metered dose inhaler (pMDI, 2 puffs [2x 100 µg])
8.If the subject is currently being treated with inhaled corticosteroids, they have been on a fixed dose for at least 1 month prior to screening
9.The subject has a height =152 cm
10.The subject who is also a woman of child-bearing potential (WOCBP) has a negative serum pregnancy test at screening. WOCBP include: any female who has experienced menarche and is not post-menopausal [defined as amenorrhea for >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
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method