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Chronic Obstructive Pulmonary Disease (COPD)Phase 1NCT04756960

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

A Phase 1 study testing CHF6001 in people with Chronic Obstructive Pulmonary Disease (COPD) and COPD, run by Chiesi Farmaceutici S.p.A. at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 30 to 55 years, men onlyHealthy volunteers can take part
What is being tested?
CHF6001
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteUnited Kingdom
Study dates
10 Mar 2021to 29 Apr 2021
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 30 to 55 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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;
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  • 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.

Who cannot join

  • 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;
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  • 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 14^C-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 coronavirus disease 2019 (COVID-19) diagnosis within the last 8 weeks or which has not resolved within 14 days prior to screening and before treatment.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site
  • Covance - Clinical Research Unit

    Leeds, LS2 9LH

Other trials in United Kingdom

About this study

Official title: 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

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.

Read the detailed description

This clinical trial is a single centre Phase I study, with a single dose, non-randomized, open-label, uncontrolled design. A total of 8 healthy male subjects were included in the study.

The aim was to assess the absolute bioavailability, the mass balance, and routes of elimination of CHF6001 (Tanimilast) in healthy male subjects, using [14^C]-radiolabelled drug substance, administered as an intravenous (iv) infusion concomitantly with an inhaled (inh) non-radiolabelled dose of CHF6001.

Standard safety assessments were conducted during the study, including safety blood and urine laboratory tests, vital signs, physical examinations, ECGs, and assessment of any adverse events (AE). Blood, urine, and feces samples were collected for pharmacokinetic (PK) analyses.

Being tested
CHF6001
Keywords
Chronic Obstructive Pulmonary Disease, COPD, Healthy subjects, Phase I, CHF6001, Tanimilast, Chiesi Farmaceutici S.p.A
Medical subject headings
Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CHF6001Drug

    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

Study groups in NCT04756960
Study groupRoleWhat they receive
CHF6001Experimentalsingle dose of CHF6001 dry-powder inhaler (DPI) co-administered with an intravenous microdose of [14^C]-labelled CHF6001
Receives: Drug: CHF6001

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 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.

  2. 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

    Measured: 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.

  3. 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

    Measured: 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.

  4. 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

    Measured: 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.

  5. 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

    Measured: 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.

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

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

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

  7. 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

    Measured: 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.

  8. 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

    Measured: 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.

  9. 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

    Measured: 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.

  10. 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

    Measured: 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.

  11. 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

    Measured: 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.

  12. 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

    Measured: 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.

  13. 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.

    Measured: 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.

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

    Systemic plasma clearance for [14^C] CHF6001.

    Measured: 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.

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

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

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

  16. 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

    Measured: 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

  17. PK Parameter -- C(max_inh) -- Plasma -- CHF6001

    C(max_inh) for CHF6001 in plasma.

    C(max_inh)=Peak plasma concentration after inhalation of CHF6001

    Measured: 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.

  18. 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

    Measured: 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.

  19. 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

    Measured: 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

  20. 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

    Measured: 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.

  21. 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).

    Measured: 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

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

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

    Measured: 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.

  23. 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.

    Measured: 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.

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

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

    Measured: 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.

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

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

    Measured: 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.

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

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

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

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

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

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Feb 2021
  2. Study start10 Mar 2021
  3. Primary completion29 Apr 2021
  4. Study completion29 Apr 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04756960
Sponsor's protocol ID
CLI-06001AA1-02
Other IDs
2020-004201-31
Status last verified
Sep 2023
First submitted
8 Feb 2021
Last updated
18 Mar 2024
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CHF6001 in people with Chronic Obstructive Pulmonary Disease (COPD) and COPD, run by Chiesi Farmaceutici S.p.A. at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PK Parameter -- AUC(0-t_iv) -- Plasma -- [14^C] Total (time frame: 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.). The study lists 27 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2024.

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