Effect of Erythromycin on the Absorption, Metabolism and Elimination of CHF6001 in Healthy Volunteers

Inclusion Criteria:

1. Subject's written informed consent obtained prior to any study-related procedure;

2. Healthy male and female subjects aged 18-55 years inclusive;

3. Ability to understand the study procedures, the risks involved and ability to betrained to use the inhalers correctly and to generate sufficient peak inspiratoryflow (PIF) using the In Check device set as per NEXThaler® inhaler resistance;

4. Body mass index (BMI) between 18.0 and 35.0 kg/m2 extremes inclusive;

5. Non- or ex-smokers who smoked <5 pack-years (pack-years = the number of cigarettepacks per day times the number of years) and stopped smoking >1 year prior toscreening;

6. Good physical and mental status determined based on the medical history and ageneral clinical examination, at screening and before the first dosing;

7. Vital signs within normal limits at screening: diastolic blood pressure (DBP) 40-90mmHg, systolic blood pressure (SBP) 90 140 mmHg (two measures performed after atleast 5 min of resting; the mean value must be within the defined range);

8. A 12-lead digitalised electrocardiogram (ECG) considered as normal at screening: 40bpm ≤ heart rate (HR) ≤110 bpm; 120 ms ≤ time interval between the P and R wave inthe ECG (PR) ≤210 ms; 80 ms ≤ time interval between the Q and R and S wave in theECG (QRS) ≤120 ms; Fridericia-corrected time interval between the Q and T wave inthe ECG (QTcF) ≤450 ms for males and ≤470 ms for females;

9. Pulmonary function test within normal limits at screening: forced expiratory volumein the first second (FEV1) % predicted >80% and FEV1/forced vital capacity (FVC)ratio >0.70 (American Thoracic Society and European Respiratory Society [ATS/ERS]Task Force, 2019);

10. Female subjects:

11. Women of childbearing potential (WOCBP) fulfilling one of the followingcriteria: i. WOCBP with fertile male partners: they and/or their partner mustbe willing to use a highly effective birth control method preferably with lowuser dependency (with exception of combined or progestogen-only hormonalcontraception) from the signature of the informed consent and until thefollow-up contact, or ii.WOCBP with non-fertile male partners: contraception isnot required in this case;For the definition of WOCBP and of fertile men and the list of birth controlmethods with low user dependency, refer to Appendix 2 (or Section 4.1 of theClinical Trial Facilitation Group guidance for more detailed information);Or

12. Women of non-childbearing potential defined as physiologically incapable ofbecoming pregnant (i.e. postmenopausal, or permanently sterile as perdefinitions given in Appendix 2). Tubal ligation or partial surgicalinterventions are not acceptable. If indicated, as per Investigator's request,postmenopausal status may be confirmed by follicle-stimulating hormone (FSH)levels (according to local laboratory ranges).

Exclusion Criteria:

1. Participation in another clinical trial where investigational drug was received, andlast investigations were performed less than 8 weeks prior to screening;

2. Clinically relevant and uncontrolled respiratory, cardiac, hepatic,gastrointestinal, renal, endocrine, metabolic, neurologic or psychiatric disorders,gastric surgery recently or in the past, and/or impaired Inclusion criteria: gastricmotility that may interfere with successful completion of this protocol according tothe Investigator's judgment;

3. Clinically relevant abnormal laboratory values at screening suggesting an unknowndisease and requiring further clinical investigation or which may impact the safetyof the subject or the evaluation of the result of the study according to theInvestigator's judgment;

4. Abnormal liver enzymes at screening (alanine aminotransferase [ALT] or aspartateaminotransferase [AST] >1.5x upper limit of normal [ULN]), bilirubin >1.5x ULN);

5. Subjects with history of breathing problems (e.g. history of asthma). Allergicasthma diagnosis in childhood (until 12 years old) is allowed;

6. Positive human immunodeficiency virus 1 or 2 (HIV1 or HIV2) serology at screening;

7. Positive results from the hepatitis serology which indicates acute or chronichepatitis B (HB) or hepatitis C (HC) at screening (i.e. positive HB surface antigen [HBsAg], HB core antibody [IgM anti-HBc], HC antibody);

8. Blood donation or blood loss (equal or more than 450 mL) less than 8 weeks prior toscreening or before the first dosing;

9. Positive urine test for cotinine at screening and before the first dosing;

10. Documented history of alcohol abuse within 12 months prior to screening or apositive alcohol breath test at screening and before Treatment Period 1, Day -1;

11. Documented history of drug abuse within 12 months prior to screening or a positiveurine drug screen evaluated at screening and before the first dosing;

12. Intake of non-permitted concomitant medication in the predefined period prior toscreening or before the first dosing or the subject is expected to takenon-permitted concomitant medication during the study;

13. Presence of any current infection, or previous infection that resolved less than 7days prior to screening and before the first dosing;

14. Known intolerance and/or hypersensitivity to any of the excipients contained in theformulation used in the trial;

15. Unsuitable arm veins for repeated venipuncture;

16. Heavy caffeine drinker (>5 cups or glasses of caffeinated beverages, e.g. coffee,tea, cola per day);

17. For females only: pregnant or lactating women, where pregnancy is defined as thestate of a female after conception and until termination of the gestation, confirmedby a positive serum human chorionic gonadotropin laboratory test. Serum pregnancytest to be performed at screening and urine pregnancy test to be performed beforethe first dosing;

18. Subjects receiving treatment with any drug known to have a well defined potentialfor hepatotoxicity (e.g. isoniazide, nimesulide, fluconazole, itraconazole, etc.)within the 3 months preceding the screening visit;

19. Subjects using e-cigarettes within 6 months before screening;

20. Positive test for coronavirus disease 2019 (COVID-19) (antibody test or nucleic acidtest) within 14 days prior to screening and the associated complications/symptoms,which have not resolved within 14 days prior to screening.