Evaluation of the Absolute Bioavailability and Mass Balance of CHF6001 (Tanimilast)

Study Overview
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Brief Summary
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The objective of the proposed study is to evaluate the bioavailability of CHF6001 after inhaled administration and to characterize the mass balance and route of elimination of CHF6001 in human along with its relevant metabolites.

Detailed Description
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This clinical trial is a single centre Phase I study, with a single dose, non-randomized, open-label, uncontrolled design. A total of 8 subjects will be included in the study. It will aim to assess the absolute bioavailability, the mass balance and routes of elimination of CHF6001 in male healthy volunteers, using [14C]-radiolabelled drug substance administered as an intravenous (IV) infusion concomitantly to an inhaled non-radiolabelled dose. Standard safety assessments will be conducted during the Study, including safety blood and urine laboratory tests, vital signs, physical examinations, ECGs and observations of any adverse events. Blood, urine and feces samples will be also collected for PK analysis.

Official Title
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Evaluation of the Absolute Bioavailability and Mass Balance of CHF6001 Following a Single Inhaled Dose Co-administered With an Intravenous Radiolabelled Microtracer Dose in Healthy Volunteers

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: CHF6001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject's written informed consent obtained prior to any study-related procedure; Able to understand the study procedures, the risks involved and ability to be trained to use correctly the inhalers and to generate sufficient PIF using the In-Check device and Placebo inhaler; Male subjects aged 30 to 55 years inclusive; Body mass index (BMI) within the range of 18 to 35 kg/m2 inclusive; Non- or ex-smoker who smoked < 5 pack years and who stopped smoking > 1 year prior to screening; Good physical and mental status; Vital signs at screening within limits; 12-lead digitised Electrocardiogram (12-lead ECG) in triplicate considered as normal; Lung function measurements within normal limits at screening; Regular bowel movements at screening; Males with non-pregnant Women of Childbearing Potential (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. 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. Exclusion Criteria: Participation in another clinical trial with an investigational drug in the 3 months or 5 half-lives of that investigational drug (whichever is longer) preceding the administration of the study drug; Clinically relevant and uncontrolled respiratory, cardiac, hepatic (including Gilbert syndrome), gastrointestinal, renal, endocrine, metabolic, neurologic, or psychiatric disorder; Clinically relevant abnormal laboratory values; Subjects with history of breathing problems; Positive to HIV1 or HIV2 serology at screening; Positive results from the Hepatitis serology which indicates acute or chronic Hepatitis B or Hepatitis C at screening; Blood donation or blood loss (equal or more than 450 mL) less than 2 months prior screening or prior to treatment; Positive urine test for cotinine; Documented history of alcohol abuse within 12 months prior to screening or a positive alcohol breath test; Documented history of drug abuse within 12 months prior to screening or a positive urine drug screen; Intake of non-permitted concomitant medications in the predefined period; Presence of any current infection, or previous infection that resolved less than 7 days prior to screening or before treatment; Known intolerance and/or hypersensitivity to any of the excipients contained in the formulation used in the trial; Unsuitable veins for repeated venipuncture; Heavy caffeine drinker; Abnormal haemoglobin level at screening; Subjects using e-cigarettes within 6 months prior to screening; Subjects been involved in a study involving a 14C-labeled drug within the 12 months prior to enrollment; Subjects with exposure to significant diagnostic or therapeutic radiation or current employment in a job requiring radiation exposure monitoring within 12 months prior to Day-1; Documented COVID-19 diagnosis within the last 8 weeks or which has not resolved within 14 days prior to screening and before treatment.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CHF6001<br>single dose of CHF6001 DPI co-administered with an intravenous microdose of [14C]-labelled CHF6001 | Drug: CHF6001<br>* 4 inhalations of CHF6001 800µg/20mg NEXThaler® DPI (total dose of 3200µg) co-administered with an intravenous microdose (18.5µg (18.5kBq)) of [14C]-labelled CHF6001<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameter (AUC0-t) | Area under the plasma concentration versus time curve (AUC0-t) for [14C] CHF6001, [14C] total and CHF6001 | Over 240 hours after administration | 
| Pharmacokinetic parameter (Cmax) | Peak Plasma Concentration (Cmax) for [14C] CHF6001, [14C] total and CHF6001 | Over 240 hours after administration | 
| Pharmacokinetic parameter (tmax) | Time of the maximum plasma concentration (tmax) for [14C] CHF6001, [14C] total and CHF6001 | Over 240 hours after administration | 
| Pharmacokinetic parameter (AUC0-∞) | Area under curve extrapolated to infinity (AUC0-∞) for [14C] CHF6001, [14C] total and CHF6001 | Over 240 hours after administration | 
| Pharmacokinetic parameter (t1/2) | Terminal half-life (t1/2) for [14C] CHF6001, [14C] total and CHF6001 | Over 240 hours after administration | 
| Pharmacokinetic parameter (volume of distribution) | Volume of distribution calculated at steady state and during the terminal phase for [14C] CHF6001 | Over 240 hours after administration | 
| Pharmacokinetic parameter (clearance) | Systemic and renal blood and plasma clearance for [14C] CHF6001 | Over 240 hours after administration | 
| Pharmacokinetic parameter (excreted fraction) | Urine and feces excreted fraction for [14C] CHF6001 and [14C] total | Over 240 hours after administration | 
| Pharmacokinetic parameter (fraction of metabolites) | Fraction of the relevant metabolites in plasma, and fraction of the relevant metabolites recovered in urine and feces | Over 240 hours after administration | 
| Pharmacokinetic parameter (blood to plasma ratio) | Blood to plasma ratio for [14C] CHF6001 and [14C] total | Over 240 hours after administration | 
| Pharmacokinetic parameter (Eh) | Hepatic extraction for [14C] CHF6001 | Over 240 hours after administration | 
| Pharmacokinetic parameter (F) | Absolute inhaled bioavailability for CHF6001 | Over 240 hours after administration |