A clinical trial to investigate the safety and tolerability of single and multiple intranasal (through the nose) dosing with the study drug CHF6467 in 68 healthy adult subjects. The study will investigate also how CHF6467 moves and behaves in the blood and in the fluid around the brain and spinal cord (cerebrospinal fluid) and if the drug CHF6467 causes an immune response by looking for specific molecules, called antibodies that may form against it. The study will be divided into two parts - Part 1 (testing single ascending doses of the study drug, SAD, lasting 4 days) and Part 2 (testing repeated or multiple ascending doses of the study drug, MAD, lasting 11 days). Each part of the study consists of a screening period, when eligible healthy volunteers will be selected, a treatment period, during which the study drug administration will take place and a follow-up period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
68
Intranasal administration of single ascending doses of CHF6467 in 4 different cohorts
Intranasal administration of multiple ascending doses of CHF6467 in 3 different cohorts
Intranasal administration of matched-placebo of CHF6467 in Part 1 and Part 2
Bulgaria MC Comac Medical Ltd.
Sofia, Bulgaria
RECRUITINGAdverse Events (AEs) and Adverse Drug Reactions (ADRs)
Number of events and number and percentage of subjects experiencing treatment-emergent AEs (TEAEs), treatment-emergent ADRs, serious TEAEs, non-serious TEAEs, severe TEAEs, TEAEs leading to discontinuation of study treatment and TEAEs leading to death
Time frame: From screening (3 to 21 days prior to Day 1) to the last follow-up visit (29 ±3 days after Day 1 for Part 1; 85 ±3 days after Day 1 for Part 2)
Vital signs: heart rate (HR)
Mean absolute value
Time frame: From Day 1 pre-dose to the first follow-up visit (15 ±3 days after Day 1 for Part 1; between 7 and 14 days after Day 10 for Part 2)
Vital signs: body temperature (BT)
Mean absolute value
Time frame: From Day 1 pre-dose to the first follow-up visit (15 ±3 days after randomisation for Part 1; between 7 and 14 days after last administration for Part 2)
Vital signs: systolic blood pressure (SBP), diastolic blood pressure (DBP)
* Mean absolute value * Mean change from baseline
Time frame: From Day 1 pre-dose to the first follow-up visit (15 ±3 days after Day 1 for Part 1; between 7 and 14 days after Day 10 for Part 2)
Bedside 12-lead ECG intervals (HR, PR, QRS, QT, QTcF)
Mean absolute value
Time frame: From Day 1 pre-dose to the first follow-up visit (15 ±3 days after Day 1 for Part 1; between 7 and 14 days after Day 10 for Part 2)
Bedside 12-lead ECG intervals (HR, PR, QRS, QT, QTcF)
Mean change from baseline
Time frame: From Day 1 pre-dose to the first follow-up visit (15 ±3 days after Day 1 for Part 1; between 7 and 14 days after Day 10 for Part 2)
Bedside 12-lead ECG intervals (HR, PR, QRS, QT, QTcF)
Mean difference vs. placebo in change from baseline
Time frame: From Day 1 pre-dose to the first follow-up visit (15 ±3 days after Day 1 for Part 1; between 7 and 14 days after Day 10 for Part 2)
Bedside 12-lead ECG intervals (HR, PR, QRS, QT, QTcF)
Number and percentage of subjects with: * QTcF \> 450 ms, \> 480 ms and \> 500 ms; * Change from baseline in QTcF \> 30 ms and \> 60 ms
Time frame: From Day 1 pre-dose to the first follow-up visit (15 ±3 days after Day 1 for Part 1; between 7 and 14 days after Day 10 for Part 2)
12-lead ECG parameters extracted from Holter (HR, PR, QRS, QTcF and QT)
Mean absolute value
Time frame: From Day 1 pre-dose to 24 hours post-dose (Day 2 in Part 1; Day 11 in Part 2)
12-lead ECG parameters extracted from Holter (HR, PR, QRS, QTcF and QT)
Mean change from baseline
Time frame: From Day 1 pre-dose to 24 hours post-dose (Day 2 in Part 1; Day 11 in Part 2)
12-lead ECG parameters extracted from Holter (HR, PR, QRS, QTcF and QT)
Mean difference vs. placebo in change from baseline.
Time frame: From Day 1 pre-dose to 24 hours post-dose (Day 2 in Part 1; Day 11 in Part 2)
12-lead ECG parameters extracted from Holter (HR, PR, QRS, QTcF and QT)
The number and percentage of subjects with: * QTcF \> 450 ms, \> 480 ms and \> 500 ms; * Change from baseline in QTcF \> 30 ms and \> 60 ms
Time frame: From Day 1 pre-dose to 24 hours post-dose (Day 2 in Part 1; Day 11 in Part 2)
12-lead Holter abnormal findings (total pauses > 2.5 seconds, atrial fibrillation and atrial flutter, ventricular runs, premature atrial contractions (PAC) burden, premature ventricular contractions (PVC) burden, other aberrant morphologies
Time frame: From Day 1 pre-dose to 24 hours post-dose (Day 2 in Part 1; Day 11 in Part 2)
Mean 24-hour heart rate (HR0-24h, from 12-lead Holter recording) and mean hourly HR
Time frame: From Day 1 pre-dose to 24 hours post-dose
Blood laboratory tests evaluation: chemistry, haematology
Shift table will be presented by treatment at each post-dose time point
Time frame: From Day 1 pre-dose to the first follow-up visit (15 ±3 days after Day 1 for Part 1; between 7 and 14 days after Day 10 for Part 2)
Blood laboratory tests evaluation: chemistry, haematology
Mean absolute value will be presented by treatment
Time frame: From Day 1 pre-dose to the first follow-up visit (15 ±3 days after Day 1 for Part 1; between 7 and 14 days after Day 10 for Part 2)
Blood laboratory tests evaluation: chemistry, haematology
Mean change from baseline (Day -1) will be presented by treatment at each post-dose time point
Time frame: From Day 1 pre-dose to the first follow-up visit (15 ±3 days after Day 1 for Part 1; between 7 and 14 days after Day 10 for Part 2)
Urine laboratory tests evaluation (urine strip): urinalysis
Urinalysis values will be presented in the listings for each subject
Time frame: From Day 1 pre-dose to the first follow-up visit (15 ±3 days after Day 1 for Part 1; between 7 and 14 days after Day 10 for Part 2)
CHF6467 AUC0-24h
Area under the concentration-time curve from time 0 to 24 h
Time frame: From Day 1 pre-dose to the end of treatment (Day 1 in Part 1; Day 10 in Part 2)
CHF6467 AUC0-t
Area Under the Curve from time 0 to time t
Time frame: From Day 1 pre-dose to the end of treatment (Day 1 in Part 1; Day 10 in Part 2)
CHF6467 AUC0-∞
Area Under the Curve from time 0 Extrapolated to Infinity
Time frame: From Day 1 pre-dose to the end of treatment (Day 1 in Part 1; Day 10 in Part 2)
CHF6467 Cmax
Maximum Serum Concentration
Time frame: From Day 1 pre-dose to the end of treatment (Day 1 in Part 1; Day 10 in Part 2)
CHF6467 tmax
Time corresponding to maximum concentration
Time frame: From Day 1 pre-dose to the end of treatment (Day 1 in Part 1; Day 10 in Part 2)
CHF6467 t½
Terminal half-life
Time frame: From Day 1 pre-dose to the end of treatment (Day 1 in Part 1; Day 10 in Part 2)
CHF6467 CL/F
Total body clearance
Time frame: From Day 1 pre-dose to the end of treatment (Day 1 in Part 1; Day 10 in Part 2)
CHF6467 Vd/F
Apparent volume of distribution
Time frame: From Day 1 pre-dose to the end of treatment (Day 1 in Part 1; Day 10 in Part 2)
CHF6467 dose normalized AUC0-24h
Time frame: From Day 1 pre-dose to the end of treatment (Day 1 in Part 1; Day 10 in Part 2)
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CHF6467 dose normalized AUC0-t
Time frame: From Day 1 pre-dose to the end of treatment (Day 1 in Part 1; Day 10 in Part 2)
CHF6467 dose normalized AUC0-∞
Time frame: From Day 1 pre-dose to the end of treatment (Day 1 in Part 1; Day 10 in Part 2)
CHF6467 dose normalized Cmax
Time frame: From Day 1 pre-dose to the end of treatment (Day 1 in Part 1; Day 10 in Part 2)
CHF6467 concentration in Cerebrospinal fluid (CSF)
Time frame: At either 1, 2, 4 or 6 hours post-dose on Day 1 (Part 1) or Day 10 (Part 2)
CHF6467 Antidrug Antibodies (ADA) detection in serum
Time frame: From Day 1 pre-dose to last follow-up visit (29 ±3 days after Day 1 for Part 1; 85 ±3 days after Day 1 for Part 2)
CHF6467 Cmin
Minimum Serum Concentration
Time frame: Post-dose on Day 9
CHF6467 tmin
Time corresponding to minimum concentration
Time frame: Post-dose on Day 9
CHF6467 Cav
Average Serum Concentration
Time frame: Post-dose on Day 9
CHF6467 Rac Cmax
Accumulation Ratio considering Cmax
Time frame: Comparison Day 9 vs Day 1
CHF6467 Rac AUC0-24h
Accumulation Ratio considering AUC0-24h
Time frame: Comparison Day 9 vs Day 1