Evaluation of the Absolute Bioavailability and Mass Balan... | NCT04756960

NCT04756960

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
2020-004201-31	EudraCT Number

Status Module

Description Module

Label	Type	Description	Intervention Names
CHF6001	Experimental	single dose of CHF6001 dry-powder inhaler (DPI) co-administered with an intravenous microdose of [14^C]-labelled CHF6001	Drug: CHF6001

Name	Type	Description	Arm Group Labels	Other Names
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

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Eligibility Module

Eligibility Criteria

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 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;
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 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;
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.

Facility	Status	City	State	ZIP	Country	Contacts
Covance - Clinical Research Unit		Leeds		LS2 9LH	United Kingdom

ID	Title	Description
FG000	CHF6001	Single dose of CHF6001 dry-powder inhaler (DPI) co-administered with an intravenous microdose of [14^C]-labelled CHF6001 CHF6001: 4 inhalations of CHF6001 800µg/20mg NEXThaler® DPI (total dose of 3200µg) co-administered with an intravenous microdose (18.5µg (18.5kBq)) of [14^C]-labelled CHF6001

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	CHF6001	Single dose of CHF6001 DPI co-administered with an intravenous microdose of [14^C]-labelled CHF6001 CHF6001: 4 inhalations of CHF6001 800µg/20mg NEXThaler® DPI (total dose of 3200µg) co-administered with an intravenous microdose (18.5µg (18.5kBq)) of [14^C]-labelled CHF6001

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Pharmacokinetic Population: all subjects from the safety population excluding subjects without any valid pharmacokinetic (PK) measurement or with major protocol deviations significantly affecting PK, for example: incorrect inhalation, change in subject condition (cold), failure in delivery of the device, use of non-permitted medications.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ngEq/mL

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.

ID	Title	Description
OG000	CHF6001

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	CHF6001	Single dose of CHF6001 DPI co-administered with an intravenous microdose of [14C]-labelled CHF6001 CHF6001: 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

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Oct 19, 2020	Jul 22, 2022	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Mar 15, 2022	Jul 22, 2022	SAP_001.pdf

ID	Term
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002908	Chronic Disease