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

NCT06395610 | Completed Phase 1

• 2 other identifiers: CLI-06001AA1-142023-507300-30-00
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to investigate the effect of the interaction of Erythromycin (CYP3A4/5 moderate inhibitor) on the pharmacokinetic of CHF6001 (CYP3A4/5 substrate) in Healthy Volunteers.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

Drug-drug Interaction study; CYP3A4/5 inhibitor; CYP3A4/5 substrate

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetic parameter (AUC0-t)

  Area under the curve from time 0 to the last quantifiable concentration (AUC0-t)

  Over 96 hours after administration in blood

• Pharmacokinetic parameter (Cmax)

  Maximum plasma concentration (Cmax) of CHF6001 without and with the concomitant administration of Erythromycin

  Over 96 hours after administration in blood

Secondary Outcomes (7)

• Pharmacokinetic parameter (AUC0-96)

  Over 96 hours after administration in blood

• Pharmacokinetic parameter (AUC0-∞)

  Over 96 hours after administration in blood

• Pharmacokinetic parameter (tmax)

  Over 96 hours after administration in blood

• Pharmacokinetic parameter (CL/F)

  Over 96 hours after administration in blood

• Pharmacokinetic parameter (t1/2)

  Over 96 hours after administration in blood

Study Arms (2)

Treatment R

EXPERIMENTAL

Single dose of CHF6001

Drug: CHF6001 DPI

Treatment T

EXPERIMENTAL

Single dose of CHF6001 administered after repeated doses of oral Erythromycin

Drug: CHF6001 DPI; Drug: Erythromycin

Interventions

CHF6001 DPI DRUG

Single dose of CHF6001

Treatment R; Treatment T

Erythromycin DRUG

Repeated doses of oral Erythromycin

Treatment T

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject's written informed consent obtained prior to any study-related procedure;
• Healthy male and female subjects aged 18-55 years inclusive;
• Ability to understand the study procedures, the risks involved and ability to be trained to use the inhalers correctly and to generate sufficient peak inspiratory flow (PIF) using the In Check device set as per NEXThaler® inhaler resistance;
• Body mass index (BMI) between 18.0 and 35.0 kg/m2 extremes inclusive;
• 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 prior to screening;
• Good physical and mental status determined based on the medical history and a general clinical examination, at screening and before the first dosing;
• Vital signs within normal limits at screening: diastolic blood pressure (DBP) 40-90 mmHg, systolic blood pressure (SBP) 90 140 mmHg (two measures performed after at least 5 min of resting; the mean value must be within the defined range);
• A 12-lead digitalised electrocardiogram (ECG) considered as normal at screening: 40 bpm ≤ heart rate (HR) ≤110 bpm; 120 ms ≤ time interval between the P and R wave in the ECG (PR) ≤210 ms; 80 ms ≤ time interval between the Q and R and S wave in the ECG (QRS) ≤120 ms; Fridericia-corrected time interval between the Q and T wave in the ECG (QTcF) ≤450 ms for males and ≤470 ms for females;
• Pulmonary function test within normal limits at screening: forced expiratory volume in 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);
• Female subjects:
• Women of childbearing potential (WOCBP) fulfilling one of the following criteria: i. WOCBP with fertile male partners: they and/or their partner must be willing to use a highly effective birth control method preferably with low user dependency (with exception of combined or progestogen-only hormonal contraception) from the signature of the informed consent and until the follow-up contact, or ii.WOCBP with non-fertile male partners: contraception is not required in this case;
• For the definition of WOCBP and of fertile men and the list of birth control methods with low user dependency, refer to Appendix 2 (or Section 4.1 of the Clinical Trial Facilitation Group guidance for more detailed information);
• Women of non-childbearing potential defined as physiologically incapable of becoming pregnant (i.e. postmenopausal, or permanently sterile as per definitions given in Appendix 2). Tubal ligation or partial surgical interventions 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).

You may not qualify if:

• Participation in another clinical trial where investigational drug was received, and last investigations were performed less than 8 weeks prior to screening;
• Clinically relevant abnormal laboratory values at screening suggesting an unknown disease and requiring further clinical investigation or which may impact the safety of the subject or the evaluation of the result of the study according to the Investigator's judgment;
• Abnormal liver enzymes at screening (alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\] \>1.5x upper limit of normal \[ULN\]), bilirubin \>1.5x ULN);
• Subjects with history of breathing problems (e.g. history of asthma). Allergic asthma diagnosis in childhood (until 12 years old) is allowed;
• Positive human immunodeficiency virus 1 or 2 (HIV1 or HIV2) serology at screening;
• Positive results from the hepatitis serology which indicates acute or chronic hepatitis B (HB) or hepatitis C (HC) at screening (i.e. positive HB surface antigen \[HBsAg\], HB core antibody \[IgM anti-HBc\], HC antibody);
• Blood donation or blood loss (equal or more than 450 mL) less than 8 weeks prior to screening or before the first dosing;
• Positive urine test for cotinine at screening and before the first dosing;
• Documented history of alcohol abuse within 12 months prior to screening or a positive alcohol breath test at screening and before Treatment Period 1, Day -1;
• Documented history of drug abuse within 12 months prior to screening or a positive urine drug screen evaluated at screening and before the first dosing;
• Intake of non-permitted concomitant medication in the predefined period prior to screening or before the first dosing or the subject is expected to take non-permitted concomitant medication during the study;
• Presence of any current infection, or previous infection that resolved less than 7 days prior to screening and before the first dosing;
• Known intolerance and/or hypersensitivity to any of the excipients contained in the formulation used in the trial;
• Unsuitable arm veins for repeated venipuncture;
• Heavy caffeine drinker (\>5 cups or glasses of caffeinated beverages, e.g. coffee, tea, cola per day);

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (1)

MC Comac Medical Ltd.

Sofia, 1618, Bulgaria

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Erythromycin

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2024
• First Posted: May 2, 2024
• Study Start: March 28, 2024
• Primary Completion: June 18, 2024
• Study Completion: June 18, 2024
• Last Updated: July 3, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

BU (1)