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

NCT04756960 | Completed Phase 1 Results

• 2 other identifiers: CLI-06001AA1-022020-004201-31
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of the study is to evaluate the bioavailability of CHF6001 after inhaled administration, to characterize the mass balance and route of elimination of CHF6001 along with its relevant metabolites, in healthy male subjects.

Conditions

Chronic Obstructive Pulmonary Disease (COPD); COPD

Keywords

Chronic Obstructive Pulmonary Disease; COPD; Healthy subjects; Phase I; CHF6001; Tanimilast; Chiesi Farmaceutici S.p.A

Outcome Measures

Primary Outcomes (27)

• PK Parameter -- AUC(0-t_iv) -- Plasma -- [14^C] Total

  AUC(0-t\_iv) for \[14\^C\] total in plasma. AUC(0-t\_iv)=Area Under the curve, from 0 to the last quantifiable concentration, after intravenous (iv) infusion administration.

  Pre-dose (within 60 min from inhaled dosing) and at the following timepoints relative to the start of the IV infusion: 5, 10, 15 [end of infusion], 20, 25, 30, 45, 60 min, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours.

• PK Parameter -- C(max_iv) -- Plasma -- [14^C] Total

  C(max\_iv) for \[14\^C\] total in plasma. C(max\_iv)=Peak plasma concentration after intravenous (iv) infusion administration

  Pre-dose (within 60 min from inhaled dosing) and at the following timepoints relative to the start of the IV infusion: 5, 10, 15 [end of infusion], 20, 25, 30, 45, 60 min, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours.

• PK Parameter -- t(max_iv) -- Plasma -- [14^C] Total

  t(max\_iv) for \[14\^C\] total. t(max\_iv)=Time to reach the Cmax, after intravenous (iv) infusion administration

  Pre-dose (within 60 min from inhaled dosing) and at the following timepoints relative to the start of the IV infusion: 5, 10, 15 [end of infusion], 20, 25, 30, 45, 60 min, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours.

• PK Parameter -- AUC(0-∞_iv) -- Plasma -- [14^C] Total

  Area under curve extrapolated to infinity (AUC(0-∞\_iv) for \[14\^C\] total in plasma. AUC(0-∞\_iv)=Area under curve extrapolated to infinity, after intravenous (iv) infusion administration

  Pre-dose (within 60 min from inhaled dosing) and at the following timepoints relative to the start of the IV infusion: 5, 10, 15 [end of infusion], 20, 25, 30, 45, 60 min, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours.

• PK Parameter -- t(1/2_iv) -- Plasma -- [14^C] Total

  Terminal half-life t(1/2\_iv) for \[14\^C\] total and CHF6001. t1/2\_iv=Terminal half-life, after intravenous (iv) infusion administration

  Pre-dose (within 60 min from inhaled dosing) and at the following timepoints relative to the start of the IV infusion: 5, 10, 15 [end of infusion], 20, 25, 30, 45, 60 min, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours.

• PK Parameter -- (Blood to Plasma Ratio) -- Blood, Plasma -- [14^C] Total

  Blood to plasma ratio for \[14\^C\] total.

  Pre-dose (within 60 min from inhaled dosing) and at 20 min after the start of IV infusion.

• PK Parameter -- AUC(0-t_iv) -- Plasma -- [14^C] CHF6001

  AUC(0-t\_iv) for \[14\^C\] CHF6001 in plasma. AUC(0-t\_iv)=Area Under the curve, from 0 to the last quantifiable concentration, after intravenous (iv) infusion administration

  Pre-dose (within 60 min from inhaled dosing) and at the following timepoints relative to the start of the IV infusion: 5, 10, 15 [end of infusion], 20, 25, 30, 45, 60 min, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours.

• PK Parameter -- C(max_iv) -- Plasma -- [14^C] CHF6001

  C(max\_iv) for \[14\^C\] CHF6001 in plasma. C(max\_iv)=Peak plasma concentration, after intravenous (iv) infusion administration

  Pre-dose (within 60 min from inhaled dosing) and at the following timepoints relative to the start of the IV infusion: 5, 10, 15 [end of infusion], 20, 25, 30, 45, 60 min, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours.

• PK Parameter -- t(max_iv) -- Plasma -- [14^C] CHF6001

  t(max\_iv) for \[14\^C\] CHF6001. t(max\_iv)=Time to reach the Cmax, after intravenous (iv) infusion administration

  Pre-dose (within 60 min from inhaled dosing) and at the following timepoints relative to the start of the IV infusion: 5, 10, 15 [end of infusion], 20, 25, 30, 45, 60 min, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours.

• PK Parameter -- AUC(0-∞_iv) -- Plasma -- [14^C] CHF6001

  Area under curve extrapolated to infinity (AUC0-∞\_iv) for \[14\^C\] CHF6001 in plasma. AUC(0-∞\_iv)=Area under curve extrapolated to infinity, after intravenous (iv) infusion administration

  Pre-dose (within 60 min from inhaled dosing) and at the following timepoints relative to the start of the IV infusion: 5, 10, 15 [end of infusion], 20, 25, 30, 45, 60 min, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours.

• PK Parameter -- t(1/2_iv) -- Plasma -- [14^C] CHF6001

  Terminal half-life t(1/2\_iv) for \[14\^C\] CHF6001 in plasma. t(1/2\_iv)=Terminal half-life, after intravenous (iv) infusion administration

  Pre-dose (within 60 min from inhaled dosing) and at the following timepoints relative to the start of the IV infusion: 5, 10, 15 [end of infusion], 20, 25, 30, 45, 60 min, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours.

• PK Parameter -- Volume of Distribution During the Terminal Phase (Vz_iv) -- Plasma -- [14^C] CHF6001

  Volume of distribution during the terminal phase (Vz\_iv) of \[14\^C\] CHF6001 in plasma. Vz\_iv=Volume of distribution during the terminal phase, after intravenous (iv) infusion administration

  Pre-dose (within 60 min from inhaled dosing) and at the following timepoints relative to the start of the IV infusion: 5, 10, 15 [end of infusion], 20, 25, 30, 45, 60 min, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours.

• PK Parameter -- Vdss_iv -- Plasma -- [14^C] CHF6001

  Vdss\_iv=Volume of distribution is calculated at steady-state for \[14\^C\] CHF6001 in plasma, after intravenous (iv) infusion administration.

  Pre-dose (within 60 min from inhaled dosing) and at the following timepoints relative to the start of the IV infusion: 5, 10, 15 [end of infusion], 20, 25, 30, 45, 60 min, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours.

• PK Parameter -- Clearance (CL_iv) -- Plasma -- [14^C] CHF6001

  Systemic plasma clearance for \[14\^C\] CHF6001.

  Pre-dose (within 60 min from inhaled dosing) and at the following timepoints relative to the start of the IV infusion: 5, 10, 15 [end of infusion], 20, 25, 30, 45, 60 min, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours.

• PK Parameter -- Blood to Plasma Ratio -- Blood, Plasma -- [14^C] CHF6001

  Blood to plasma ratio for \[14\^C\] CHF6001.

  Pre-dose (within 60 min from inhaled dosing) and at 20 min after the start of IV infusion.

• PK Parameter -- AUC(0-t)_inh -- Plasma -- CHF6001

  AUC(0-t)\_inh for CHF6001 in plasma. AUC(0-t)\_inh=Area Under the curve, from 0 to the last quantifiable concentration after inhalation of CHF6001

  At baseline (pre-dose) (within 60 min from inhaled dosing) and at the following timepoints post inhaled dose: 15, 30, 60, 90 min, 2, 3.75, 5.75, 7.75, 9.75, 11.75, 13.75, 25.75, 49.75, 73.75, 97.75, 121.75, 145.75, 169.75, 193.75, 217.75, and 241.75 hours

• PK Parameter -- C(max_inh) -- Plasma -- CHF6001

  C(max\_inh) for CHF6001 in plasma. C(max\_inh)=Peak plasma concentration after inhalation of CHF6001

  Pre-dose (within 60 min from inhaled dosing) and at the following timepoints post inhaled dose: 15, 30, 60, 90 min, 2, 3.75, 5.75, 7.75, 9.75, 11.75, 13.75, 25.75, 49.75, 73.75, 97.75, 121.75, 145.75, 169.75, 193.75, 217.75, and 241.75 hours.

• PK Parameter -- t(max_inh) -- Plasma -- CHF6001

  t(max\_inh) for CHF6001 in plasma. t(max\_inh)=Time to reach the Cmax after inhalation of CHF6001

  Pre-dose (within 60 min from inhaled dosing) and at the following timepoints post inhaled dose: 15, 30, 60, 90 min, 2, 3.75, 5.75, 7.75, 9.75, 11.75, 13.75, 25.75, 49.75, 73.75, 97.75, 121.75, 145.75, 169.75, 193.75, 217.75, and 241.75 hours.

• PK Parameter -- AUC(0-∞_inh) -- Plasma -- CHF6001

  AUC(0-∞\_inh) for CHF6001 in plasma. AUC(0-∞\_inh)=Area under curve extrapolated to infinity after inhalation of CHF6001

  At baseline (pre-dose) (within 60 min from inhaled dosing) and at the following timepoints post inhaled dose: 15, 30, 60, 90 min, 2, 3.75, 5.75, 7.75, 9.75, 11.75, 13.75, 25.75, 49.75, 73.75, 97.75, 121.75, 145.75, 169.75, 193.75, 217.75, and 241.75 hours

• PK Parameter -- t(1/2_inh) -- Plasma -- CHF6001

  t(1/2\_inh) for CHF6001 in plasma. t(1/2\_inh)=Terminal half-life, after inhalation of CHF6001

  Pre-dose (within 60 min from inhaled dosing) and at the following timepoints post inhaled dose: 15, 30, 60, 90 min, 2, 3.75, 5.75, 7.75, 9.75, 11.75, 13.75, 25.75, 49.75, 73.75, 97.75, 121.75, 145.75, 169.75, 193.75, 217.75, and 241.75 hours.

• PK Parameter -- Absolute Inhaled Bioavailability (F_inh) -- Plasma -- CHF6001

  Absolute inhaled bioavailability for CHF6001. F\_inh=Inhaled absolute bioavailability based on AUC(0-∞) after inhalation of CHF6001 F\_inh=(AUC(0-∞)\_inh x Dose\_iv)/ (AUC(0-∞)\_iv x Dose\_inh).

  At baseline (pre-dose) (within 60 min from inhaled dosing) and at the following timepoints post inhaled dose: 15, 30, 60, 90 min, 2, 3.75, 5.75, 7.75, 9.75, 11.75, 13.75, 25.75, 49.75, 73.75, 97.75, 121.75, 145.75, 169.75, 193.75, 217.75, and 241.75 hours

• PK Parameter -- Cumulative Excreted Fraction (in %) -- Urine -- [14^C] Total

  Urine excreted fraction for cumulative \[14\^C\] total.

  Baseline (pre dose, -12-0h) and relative to the start of the IV infusion at: 0-4h, 4-8h, 8-12h, 12-24h, 24-48h, 48-72h, 72-96h, 96-120h, 120-144h, 144-168h, 168-192h, 192-216h, and 216-240h.

• PK Parameter -- Cumulative Excreted Fraction (in %) -- Urine -- [14^C]-CHF6001

  Urine excreted fraction for cumulative \[14\^C\]-CHF6001. Measurements in urine were performed. All measured values were below the limit of quantification of the bioanalytical method.

  Baseline (pre dose, -12-0h) and relative to the start of the IV infusion at: 0-4h, 4-8h, 8-12h, 12-24h, 24-48h, 48-72h, 72-96h, 96-120h, 120-144h, 144-168h, 168-192h, 192-216h, and 216-240h.

• PK Parameter -- Cumulative Excreted Fraction (in %) -- Fecal -- [14^C] Total

  Fecal excreted fraction for cumulative \[14\^C\] total.

  Baseline (pre dose, Day -1) and relative to the start of the IV infusion at: 0-24h, 24-48h, 48-72h, 72-96h, 96-120h, 120-144h, 144-168h, 168-192h, 192-216h, and 216 -240h.

• PK Parameter -- Cumulative Excreted Fraction (in %) -- Fecal -- [14^C]-CHF6001

  Fecal excreted fraction for cumulative \[14\^C\]-CHF6001.

  Baseline (pre dose, Day -1) and relative to the start of the IV infusion at: 0-24h, 24-48h, 48-72h, 72-96h, 96-120h, 120-144h, 144-168h, 168-192h, 192-216h, and 216 -240h.

• PK Parameter -- Cumulative Excreted Fraction (in %) -- Urine and Fecal -- [14^C] Total

  Urine and fecal excreted fraction for cumulative \[14\^C\] total.

  Over 240 h after administration; please see timepoints for outcome #22 (urine) and #24 (fecal).

• PK Parameter -- Cumulative Excreted Fraction (in %) -- Urine and Fecal -- [14^C]-CHF6001

  Urine and Fecal excreted fraction for cumulative \[14\^C\]-CHF6001.

  Over 240 h after administration; please see timepoints for outcome #22 (urine) and #24 (fecal).

Study Arms (1)

CHF6001

EXPERIMENTAL

single dose of CHF6001 dry-powder inhaler (DPI) co-administered with an intravenous microdose of \[14\^C\]-labelled CHF6001

Drug: CHF6001

Interventions

CHF6001 DRUG

4 inhalations of CHF6001 800 µg/20 mg NEXThaler® dry-powder inhaler (DPI), (total dose of 3200µg) co-administered with an intravenous microdose (18.5µg (18.5 kBq)) of \[14\^C\]-labelled CHF6001

CHF6001

Eligibility Criteria

• Age: 30 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 Peak Inspiratory Flow (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/m\^2 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;
• 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.

You may not qualify if:

• 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 Human Immunodeficiency Virus 1/Human Immunodeficiency Virus 2 (HIV1/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;

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (1)

Covance - Clinical Research Unit

Leeds, LS2 9LH, United Kingdom

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

tanimilast

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Clinical Trial Transparency
• Organization: Chiesi Farmaceutici S.p.A.

clinicaltrials_info@chiesi.com

+ 39 0521 2791

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2021
• First Posted: February 16, 2021
• Study Start: March 10, 2021
• Primary Completion: April 29, 2021
• Study Completion: April 29, 2021
• Last Updated: March 18, 2024
• Results First Posted: March 18, 2024

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)