Investigation of the Effect of Inhibition of CYP3A4/5 by Itraconazole on the PK of CHF6001 (Tanimilast)
Primary Purpose
Chronic Obstructive Pulmonary Disease
Status
Completed
Phase
Phase 1
Locations
Belgium
Study Type
Interventional
Intervention
CHF6001 DPI
Itraconazole
Sponsored by
About this trial
This is an interventional other trial for Chronic Obstructive Pulmonary Disease
Eligibility Criteria
Inclusion Criteria:
- 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 PIF using the In-Check device.
- Body Mass Index (BMI) between 18,0 and 35,0 kg/m2 extremes inclusive;
- Non- or ex-smokers who smoked < 5 pack years and stopped smoking > 1 year prior to screening;
- Good physical and mental status
- Vital signs within normal limits
- 12 -lead digitalized Electrocardiogram (12-lead ECG) considered as normal
- Pulmonary function test within normal limits
- Women of Childbearing Potential (WOCBP) with fertile male partners: they and/or their partner must be willing to use a highly effective birth control method in addition to a barrier contraception method from the signature of the informed consent and until the follow-up visit. Males with non-pregnant WOCBP partners: they and or/ their partner 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 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 the follow-up visit
Exclusion Criteria:
- Participation to another clinical trial where investigational drug was received, and last investigations were performed less than 8 weeks prior to screening;
- Clinically relevant and uncontrolled respiratory, cardiac, hepatic, gastrointestinal, renal, endocrine, metabolic, neurologic, or psychiatric disorders, gastric surgery recent or in the past, and/or impaired gastric motility
- Clinically relevant abnormal laboratory values
- Abnormal liver enzymes at screening
- Subjects with history of breathing problems
- Positive HIV1 or HIV2 serology
- Positive results from the Hepatitis serology
- Blood donation or blood loss (equal or more than 450 ml) less than 2 months prior to screening or before the first dosing;
- 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 the first dosing;
- Known intolerance and/or hypersensitivity to any of the excipients contained in the formulation used in the trial;
- Known allergy to antifungal medicines;
- Unsuitable veins for repeated venipuncture;
- Heavy caffeine drinker
- For females only: pregnant or lactating women. Serum pregnancy test to be performed at screening and urine pregnancy test to be performed before the first dosing;
- Subjects receiving treatment with any drug known to have a well-defined potential for hepatotoxicity (e.g. isoniazide, nimesulide, ketoconazole) within the previous 3 months before the screening visit
- Subjects using e-cigarettes within 6 months before screening.
- Positive documented COVID-19 test before admission
Sites / Locations
- SGS Life Sciences - Clinical Pharmacology Unit Antwerpen
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Treatment R
Treatment T
Arm Description
Single dose of CHF6001
Single dose of CHF6001 administered after repeated doses of oral Itraconazole
Outcomes
Primary Outcome Measures
Pharmacokinetic parameter (Cmax)
Peak Plasma Concentration (Cmax) for CHF6001
Pharmacokinetic parameter (AUCt)
Area under the plasma concentration versus time curve (AUCt) for CHF6001
Secondary Outcome Measures
Pharmacokinetic parameter (AUC0-96)
Area under plasma concentration from 0 to 96 hours (AUC0-96) for CHF6001, CHF5956 and CHF6095
Pharmacokinetic parameter (AUC0-∞)
Area under curve extrapolated to infinity (AUC0-∞) for CHF6001, CHF5956 and CHF6095
Pharmacokinetic parameter (tmax)
Time of the maximum plasma concentration (tmax) for CHF6001, CHF5956 and CHF6095
Pharmacokinetic parameter (t1/2)
Terminal half-life (t1/2) for CHF6001, CHF5956 and CHF6095
Pharmacokinetic parameter (CL/F)
Apparent systemic clearance (CL/F) for CHF6001
Pharmacokinetic parameter (AUCt)
Area under the plasma concentration versus time curve (AUCt) for CHF5956 and CHF6095
Pharmacokinetic parameter (Cmax)
Peak Plasma Concentration (Cmax) for CHF5956 and CHF6095
Full Information
NCT ID
NCT04739774
First Posted
January 29, 2021
Last Updated
May 4, 2021
Sponsor
Chiesi Farmaceutici S.p.A.
1. Study Identification
Unique Protocol Identification Number
NCT04739774
Brief Title
Investigation of the Effect of Inhibition of CYP3A4/5 by Itraconazole on the PK of CHF6001 (Tanimilast)
Official Title
Open-label, Non-randomized, One Sequence Cross-over Study to Investigate the Effect of Inhibition of CYP3A4/5 by Itraconazole on the Pharmacokinetics of CHF6001 in Healthy Subjects
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
February 22, 2021 (Actual)
Primary Completion Date
April 20, 2021 (Actual)
Study Completion Date
April 26, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chiesi Farmaceutici S.p.A.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The objective of this proposed study is to investigate the pharmacokinetics interaction between CHF6001 as substrate and Itraconazole as inhibitor of CYP3A4/5 in a drug-drug interaction study.
Detailed Description
This clinical trial is a single centre, single dose Phase I study, with a non-randomized, open label, one sequence cross-over design.
A total of 24 healthy male and female are planned to be included.
Participants will be dosed with CHF6001 before and during co-administration of Itraconazole and will act as their own control. The study will be run with a one-sequence crossover design, where all subjects will be treated with CHF6001 in the first treatment period and CHF6001+Itraconazole in the second treatment period in order to avoid the need of a very long washout from the CYP3A4/5 inhibitor.
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 samples will be also collected for PK analysis.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Model Description
one sequence cross-over design
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment R
Arm Type
Experimental
Arm Description
Single dose of CHF6001
Arm Title
Treatment T
Arm Type
Experimental
Arm Description
Single dose of CHF6001 administered after repeated doses of oral Itraconazole
Intervention Type
Drug
Intervention Name(s)
CHF6001 DPI
Intervention Description
Single dose of CHF6001
Intervention Type
Drug
Intervention Name(s)
Itraconazole
Intervention Description
Repeated doses of oral Itraconazole
Primary Outcome Measure Information:
Title
Pharmacokinetic parameter (Cmax)
Description
Peak Plasma Concentration (Cmax) for CHF6001
Time Frame
Over 96 hours after administration in blood
Title
Pharmacokinetic parameter (AUCt)
Description
Area under the plasma concentration versus time curve (AUCt) for CHF6001
Time Frame
Over 96 hours after administration in blood
Secondary Outcome Measure Information:
Title
Pharmacokinetic parameter (AUC0-96)
Description
Area under plasma concentration from 0 to 96 hours (AUC0-96) for CHF6001, CHF5956 and CHF6095
Time Frame
Over 96 hours after administration in blood
Title
Pharmacokinetic parameter (AUC0-∞)
Description
Area under curve extrapolated to infinity (AUC0-∞) for CHF6001, CHF5956 and CHF6095
Time Frame
Over 96 hours after administration in blood
Title
Pharmacokinetic parameter (tmax)
Description
Time of the maximum plasma concentration (tmax) for CHF6001, CHF5956 and CHF6095
Time Frame
Over 96 hours after administration in blood
Title
Pharmacokinetic parameter (t1/2)
Description
Terminal half-life (t1/2) for CHF6001, CHF5956 and CHF6095
Time Frame
Over 96 hours after administration in blood
Title
Pharmacokinetic parameter (CL/F)
Description
Apparent systemic clearance (CL/F) for CHF6001
Time Frame
Over 96 hours after administration in blood
Title
Pharmacokinetic parameter (AUCt)
Description
Area under the plasma concentration versus time curve (AUCt) for CHF5956 and CHF6095
Time Frame
Over 96 hours after administration in blood
Title
Pharmacokinetic parameter (Cmax)
Description
Peak Plasma Concentration (Cmax) for CHF5956 and CHF6095
Time Frame
Over 96 hours after administration in blood
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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 PIF using the In-Check device.
Body Mass Index (BMI) between 18,0 and 35,0 kg/m2 extremes inclusive;
Non- or ex-smokers who smoked < 5 pack years and stopped smoking > 1 year prior to screening;
Good physical and mental status
Vital signs within normal limits
12 -lead digitalized Electrocardiogram (12-lead ECG) considered as normal
Pulmonary function test within normal limits
Women of Childbearing Potential (WOCBP) with fertile male partners: they and/or their partner must be willing to use a highly effective birth control method in addition to a barrier contraception method from the signature of the informed consent and until the follow-up visit. Males with non-pregnant WOCBP partners: they and or/ their partner 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 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 the follow-up visit
Exclusion Criteria:
Participation to another clinical trial where investigational drug was received, and last investigations were performed less than 8 weeks prior to screening;
Clinically relevant and uncontrolled respiratory, cardiac, hepatic, gastrointestinal, renal, endocrine, metabolic, neurologic, or psychiatric disorders, gastric surgery recent or in the past, and/or impaired gastric motility
Clinically relevant abnormal laboratory values
Abnormal liver enzymes at screening
Subjects with history of breathing problems
Positive HIV1 or HIV2 serology
Positive results from the Hepatitis serology
Blood donation or blood loss (equal or more than 450 ml) less than 2 months prior to screening or before the first dosing;
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 the first dosing;
Known intolerance and/or hypersensitivity to any of the excipients contained in the formulation used in the trial;
Known allergy to antifungal medicines;
Unsuitable veins for repeated venipuncture;
Heavy caffeine drinker
For females only: pregnant or lactating women. Serum pregnancy test to be performed at screening and urine pregnancy test to be performed before the first dosing;
Subjects receiving treatment with any drug known to have a well-defined potential for hepatotoxicity (e.g. isoniazide, nimesulide, ketoconazole) within the previous 3 months before the screening visit
Subjects using e-cigarettes within 6 months before screening.
Positive documented COVID-19 test before admission
Facility Information:
Facility Name
SGS Life Sciences - Clinical Pharmacology Unit Antwerpen
City
Antwerp
ZIP/Postal Code
2060
Country
Belgium
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Investigation of the Effect of Inhibition of CYP3A4/5 by Itraconazole on the PK of CHF6001 (Tanimilast)
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