E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Worsening of symptoms of lung disease |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010953 |
E.1.2 | Term | COPD exacerbation |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To assess the efficacy of a single and repeated dose of BCT197 in COPD patients presenting with an exacerbation measured by the improvement in FEV1 over the first 5 days of treatment relative to placebo, and over the first 10 days in Parts III and IV. |
|
E.2.2 | Secondary objectives of the trial |
• To assess the safety & tolerability of a single and a repeated dose of BCT197 in this patient population
• To measure the time to recovery using the EXACT-PRO 14 point patient reported outcome
• To assess the time to the next exacerbation during the follow-up period
• To assess the proportion of patients responding to treatment with BCT197 at Day 30
• To assess dyspnea as measured by the Borg CR10 scale® at Day 5, as compared to baseline
• To assess Quality of Life as measured by SAS/IAS CRQ patient reported outcome at Day 14
• To assess length of hospitalization following initial admission (if appropriate – not all patients will be admitted)
• To determine the pharmacokinetics of BCT197 and its metabolites in plasma following a single (Day 1) and a two day dose (Day 1 & Day 6) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent must be obtained before any study related assessment is performed.
2. Males/females age ≥ 40 to ≤ 80 years
3. COPD diagnosed according to Global Initiative for Chronic Obstructive Lung Disease (GOLD 2009) as Stage II to IV and patient presenting with a COPD exacerbation
4. Smoking history of at least 10 pack years
5. Females must NOT be of child bearing potential (post-menopausal [according to protocol definition] or surgically sterilized). All female patients must have a negative pregnancy test result before randomization.
6. Be able to communicate well with the investigator, be able to understand and comply with the requirements of the study, and be able to perform acceptable spirometry.
|
|
E.4 | Principal exclusion criteria |
1.Use of any oral or iv corticosteroids within 30 days of randomization
2.Use of any calcium channel blockers within 48 hours of randomization
3.Use of macrolide containing antibiotics within 48 hours of randomization
4.Arterial blood pH <7.26 at randomization
5.History or presence of clinically significant uncontrolled left ventricular failure
6.Clinical or radiological evidence of pneumonia
7.Elevated liver enzymes (1.5 x ULN) at entry to the study, or history of liver toxicity with other drugs. If patients have a history of liver disease or liver injury as indicated by abnormal liver function tests, then the Investigator should be guided by the following criteria in such cases:
a.ALT will have to be strictly within the normal range before inclusion.
b.γ-GT, AST and alkaline phosphatase must not exceed twice the upper limit of normal
8.Participation in any ongoing clinical investigation within four (4) weeks prior to initial dosing or longer if required by local regulations, and for any other limitation of participation based on local regulations
9.Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer; or longer if required by local regulations, and for any other limitation of participation in an investigational trial based on local regulations.
10.History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
11.History of clinically significant ECG abnormalities.
12.History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
13.Pregnant or nursing (lactating) women.
14.Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study. The Investigator should make this determination in consideration of the subject’s medical history and/or clinical or laboratory evidence of any of the following:
•Inflammatory bowel disease, ulcers, gastrointestinal or rectal bleeding
•Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection
•Pancreatic injury or pancreatitis •Tuberculosis •Dermatitis •Long term oxygen therapy ( > 15 hours a day)
15.History or presence of impaired renal function as indicated by clinically significantly abnormal creatinine or BUN and/or urea values, or abnormal urinary constituents (e.g., albuminuria) as judged clinically significant by the attending physician.
16.History of immunodeficiency diseases.
17.History of Hepatitis B or C.
18.History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted at baseline.
19.Fertile males defined as all males physiologically capable of conceiving offspring UNLESS the patient agrees to one of the criteria below (for 10 days following study drug administration i.e.: for Days 1 to 10 inclusive in Part I & II, and for Days 1 to 20 inclusive in Parts III and IV)
a) Use two highly effective contraceptive methods comprising a barrier method (condom or occlusive cap) plus spermicide, if sexually active
OR
b) To be abstemious
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The improvement in FEV1 over the first 5 days of treatment relative to placebo.
Measure: FEV1, in Parts I and II, and improvement in FEV1 over the first 10 days in Parts III and IV.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 5 for parts I and II
Day 10 for parts III and IV |
|
E.5.2 | Secondary end point(s) |
Time to recovery using the EXACT-PRO 14 point patient reported outcome |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 14, 30 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 9 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Romania |
Russian Federation |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |