PK Linearity and Steady State PK of CHF 6532 in Healthy Subjects

NCT03942666 | Completed Phase 1

• 2 other identifiers: CLI-06532AA1-032019-000250-59
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this clinical pharmacology study is to evaluate the CHF 6532 linearity after single oral administrations of four doses of a tablet formulation and to evaluate the pharmacokinetic (PK) at steady state following the repeated open label b.i.d. administration at one dose.

Conditions

Asthma

Outcome Measures

Primary Outcomes (2)

• PK linearity of CHF 6532

  Assessment of CHF 6532 PK linearity in blood and urine depending on increasing doses of CHF 6532

  Over 12 hours after administration in urine, over 48 hours after administration in blood

• Steady state PK of CHF 6532

  Assessment of CHF 6532 PK in blood and urine after a repeated administration of CHF 6532

  Over 12 hours after administration at Day 1 and Day 10 in urine, over 12 hours after administration at Day 1 and over 24 hours after administration at Day 10 in blood

Secondary Outcomes (3)

• Cardiac Safety of CHF 6532

  Over 24 hours after single administration in Part I, Over 24 hours at Day 10 in Part II

• PK linearity of CHF 6532-AG

  Over 12 hours after administration in urine, over 48 hours after administration in blood

• Steady state PK of CHF 6532-AG

  Over 12 hours after administration at Day 1 and Day 10 in urine, over 12 hours after administration at Day 1 and over 24 hours after administration at Day 10 in blood

Study Arms (6)

Treatment A

EXPERIMENTAL

Single administration of CHF 6532 Dose #1

Drug: Treatment A

Treatment B

EXPERIMENTAL

Single administration of CHF 6532 Dose #2

Drug: Treatment B

Treatment C

EXPERIMENTAL

Single administration of CHF 6532 Dose #3

Drug: Treatment C

Treatment D

EXPERIMENTAL

Single administration of CHF 6532 Dose #4

Drug: Treatment D

Treatment E

PLACEBO COMPARATOR

Single administration of CHF 6532 Placebo

Drug: Treatment E

Treatment F

OTHER

Part II: Administration of tablet of CHF 6532 b.i.d. for 10 days at one dose.

Drug: Treatment F

Interventions

Treatment A DRUG

tablet of CHF 6532

Treatment A

Treatment B DRUG

tablet of CHF 6532

Treatment B

Treatment C DRUG

tablet of CHF 6532

Treatment C

Treatment D DRUG

tablet of CHF 6532

Treatment D

Treatment E DRUG

Placebo tablet of CHF 6532

Treatment E

Treatment F DRUG

tablet of CHF 6532

Treatment F

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject's written informed consent obtained prior to any study-related procedure;
• Healthy male or female subjects aged 18-60 years inclusive;
• Ability to understand the study procedures, the risks involved and willingness to follow the study procedures including intake of non-permitted concomitant medications;
• Body Mass Index (BMI) between 19.0 and 30.0 kg/m2 extremes inclusive;
• Non- or ex-smokers who smoked \< 5 pack years;
• Good physical and mental status, determined on the basis of the medical history and a general physical examination;
• Vital signs within normal limits;
• Body temperature 35.5-37.2ºC;
• lead digitised Electrocardiogram (12-lead ECG) considered as normal;
• Female subject of non-childbearing potential (WONCBP) defined as physiologically incapable of becoming pregnant (i.e. post-menopausal or permanently sterile) and female subjects of childbearing potential (WOCBP) fulfilling one of the following criteria: a/ WOCBP with fertile male partners: they and/or their partner must be willing to use a highly effective birth control method from the signature of the informed consent and until the follow-up visit or b/WOCBP with non-fertile male partners: (contraception is not required in this case).

You may not qualify if:

• Clinically significant abnormal 24 hours Holter ECG at screening;
• Subjects with history of sustained and non-sustained cardiac arrhythmias (ECG demonstrated) and subjects with a family history of sudden cardiac death;
• Blood donation or blood loss (equal or more than 450 ml) less than 8 weeks prior to randomisation;
• Abnormal haemoglobin level;
• Subjects with history of asthma, including childhood asthma, COPD or any other chronic pulmonary diseases or condition;
• Positive HIV1 or HIV2 serology;
• Positive results for the Hepatitis serology;
• Clinically relevant and uncontrolled hepatic, gastrointestinal, endocrine, metabolic (specially, subjects with deficiency in glucuronidation), neurologic, or psychiatric disorder that may interfere with successful completion of this protocol according to the Investigator's judgement;
• Any clinically relevant abnormal laboratory value suggesting an unknown disease and requiring further clinical investigation or which may impact the safety of the subject or the evaluation of the result of the study according to the Investigator's judgment;
• Abnormal liver enzymes;
• Unsuitable veins for repeated venepuncture;
• History of substance abuse or drug abuse within 12 months prior to screening;
• Subjects who have received an investigational drug or device within 1 month or 7 times the elimination half-life (whichever is longer) prior to screening visit or are currently participating in another clinical trial or have been previously randomised in this trial;
• History of hypersensitivity to any of the excipients contained in the formulation used in the trial;
• Known intolerance/hypersensitivity to quinolone-type antibiotics, e.g. moxifloxacin, norfloxacin, ciprofloxacin, nalidixic acid;

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (1)

SGS Life Sciences - Clinical Pharmacology Unit Antwerpen

Antwerp, 2060, Belgium

Location

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part II: double blind Part II: open label
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part I: 5-way, 5-period crossover Part II: single group

Study Record Dates

• First Submitted: May 6, 2019
• First Posted: May 8, 2019
• Study Start: May 10, 2019
• Primary Completion: November 22, 2019
• Study Completion: November 22, 2019
• Last Updated: July 22, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)