A four part study to investigate the safety, tolerability and blood levels of single and repeat doses of CHF6297 in healthy volunteers, repeat doses of CHF6297 in patients with COPD and to investigate the anti-inflammatory effect of CHF 6297 after healthy volunteers have been given a challenge agent.

Phase 1

• Conditions: Chronic Obstructive Pulmonary Disease; MedDRA version: 20.0Level: LLTClassification code 10010952Term: COPDSystem Organ Class: 100000004855; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2015-003075-30-GB
• Lead Sponsor: Chiesi Farmaceutici S.p.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-06-07
• Last Update Posted: 11 June 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 136

Inclusion Criteria

All Parts
1.Subject’s written informed consent obtained prior to any study-related procedure;
2.Ability to understand the study procedures, the risks involved and ability to be trained to use the devices correctly and to generate sufficient PIF (at least 40 L/min) using the In-Check device set as per Plastiape RS-01 inhaler resistance or similar;
3.Vital signs within normal range at screening and prior to randomisation:
4.Males fulfilling one of the following criteria:
a. Males with non-pregnant WOCBP partners: they and/or their partner of childbearing potential must be willing to use a highly effective birth control method in addition to the male condom from the signature of the informed consent and until 90 days after the follow-up visit. Subjects must not donate sperm during the study and for 90 days after the follow-up visit or
b. Males with pregnant WOCBP partner: they must be willing to use male contraception (condom) from the signature of the informed consent and until 90 days after the follow-up visit. Subjects must not donate sperm during the study and for 90 days after the follow-up visit or
c. Non-fertile male subjects (contraception is not required in this case) or
d. Males with partner not of childbearing potential (contraception is not required in this case).

Parts 1, 2 and 4
1. Healthy male subjects aged 18-55 years inclusive;
2.Body Mass Index (BMI) between 18 and 32 kg/m2 extremes inclusive;
3.Non- or ex-smokers who smoked < 5 pack years (pack-years = the number of cigarette packs per day times the number of years) and stopped smoking > 1 year;
4.Good physical and mental status, determined on the basis of the medical history and a general clinical examination;
5.12-lead digitised Electrocardiogram (12-lead ECG) considered as normal
6.Lung function measurements within normal limits at screening and prior to randomisation:

Part 3
1.Male or female of non-childbearing potential aged between 40 and 75 years inclusive;
2.BMI in the range of 18-35 Kg/m2;
3.Current or past smoker (from at least 6 months) of at least 10 pack/years, where one pack-year is equivalent to 20 cigarettes per day for 1 year;
4.Inclusion of female patients is only acceptable if they are of non-childbearing potential defined as physiologically incapable of becoming pregnant (i.e. post-menopausal or permanently sterile).
5.COPD patients as defined by the GOLD guidelines with a post- bronchodilator FEV1 between 40-80% of the predicted value and a ratio FEV1/FVC <0.70 at screening. Patients taking stable doses of their current therapy for COPD since at least 3 months prior to screening and no change is expected during the study conduction;
6.At screening, subjects must be able to produce an adequate induced sputum sample defined as a load of at least 75mg with a viability factor of not less than 40%, (with less than 30 % epithelial cells). The patients may be re-challenged after at least 48 hours, once if the first sputum sample does not meet these criteria;

Part 4
1.At screening, subjects must be able to produce an adequate induced sputum sample defined as a load of at least 75mg with a viability factor of not less than 40%, (with less than 30 % epithelial cells) and neutrophil % differential count < 50%. The subjects may be re-challenged once by induction after at least 48 hours, if the first sputum sample did not meet these criteria. The subject will be enrolled only after an adequate sputum sample is produced;

Are the tr

Exclusion Criteria

All Parts
1.Positive HIV1 or HIV2 serology at screening;
2.Positive results from the Hepatitis serology which indicates acute or chronic Hepatitis B or Hepatitis C at screening;
3.Any clinically relevant abnormal laboratory value at screening suggesting an unknown disease and requiring further clinical investigation;
4.Abnormal liver enzymes at screening;
5.History of substance abuse or drug abuse within 12 months prior to screening visit or with a positive urine drug screen evaluated at screening and prior to randomisation;
6.History of hypersensitivity to any of the excipients contained in the formulation used in the trial;
7.Subjects who refuse to agree to abstain from alcohol or caffeine containing foods or beverages or grapefruit containing foods or beverages from 48 hour prior to each intake of study medication until the end of confinement at the clinical centre;

Parts 1, 2 and 4
1.Subjects with history of sustained and non-sustained cardiac arrhythmias (ECG demonstrated) and subjects with a family history of sudden cardiac death;
2.Blood donation or blood loss (equal or more than 450 ml) less than 8 weeks prior to screening or prior to randomisation;
3.Clinically relevant and uncontrolled hepatic, gastrointestinal, endocrine, metabolic, neurologic, or psychiatric disorder that may interfere with successful completion of this protocol;
4.The subject has taken non-permitted concomitant medications in the predefined period prior to screening or prior to randomisation;
5.Participation to another clinical trial where investigational drug was received less than 3 months prior to screening;
6.Subjects with any current infection, or who have a previous respiratory tract infection that resolved less than 4 weeks prior to screening or to randomisation, or any other previous infection that resolved less than 7 days prior to screening or to randomisation;
7.Heavy caffeine drinker (> 5 cups or glasses of caffeinated beverages e.g., coffee, tea, cola per day);
8.Subjects who have a positive urine test for cotinine at screening or prior to randomisation;

Parts 1 and 2
1.Clinically significant abnormal 24h Holter ECG at screening;
2.Unsuitable veins for repeated venepuncture;

Part 3
1.An abnormal and clinically significant 12-lead ECG at screening or prior to randomisation that results in active medical problem. Patients whose 12-lead ECG shows QTcF >450 ms for males or QTcF >470 ms for females at screening or prior to randomisation;
2.Blood draws or loss of 250 mL or more within 45 days prior to randomisation;
3.Current or chronic history of liver disease or known hepatic or biliary abnormalities;
4.Recent (less than 1 year) history of alcohol dependency, or substance abuse;
5.Female patients of childbearing potential;
6.Past or current history of asthma (NOT childhood asthma);
7.History or symptoms of significant neurological disease;
8.Unstable concurrent disease or patients who have clinically significant cardiovascular condition or patients with atrial fibrillation. Or the need for chronic use of any other medication for treatment of lung disease during the study period; Or patients requiring long term (at least 12 hours daily) oxygen therapy for chronic hypoxemia; Or known respiratory disorders other than COPD;
9.A worsening of COPD or a lower respiratory tract infection requiring use of oral or systemic corticosteroids, oral and/or nebulised ß2 agonists and/or antibiotics within 6 weeks preceding the screeni

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified