Safety and Tolerability of Inhaled CHF 6001 in Healthy Volunteers (HV)

Study Overview
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Brief Summary
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This study is designed to investigate the safety, tolerability and pharmacokinetics of inhaled CHF 6001 after single and multiple doses in healthy volunteers.

Detailed Description
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The study will be conducted in a single centre and will consist of a single dose part and a multiple dose part. Seven single doses of CHF 6001 will be administered according to an escalation, alternate cross over scheme. Five multiple doses of CHF 6001 will be administered for 7 days according to a sequential escalation scheme.

Official Title
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A Placebo-controlled Double-blind Single and Repeated Ascending Dose Study to Investigate the Safety and Tolerability of Inhaled CHF 6001 in Healthy Volunteers

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: CHF 6001 SD or placebo
* Drug: CHF 6001 MD or placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject's written informed consent obtained prior to any study-related procedure Male healthy volunteers aged 18-55 years; Able to understand the study procedures, the risks involved and ability to be trained to use the devices correctly. Body Mass Index (BMI) between 18.0 and 28.0 kg/m2; Non- or ex-smokers who smoked < 5 pack years (pack-years = the number of cigarette packs per day times the number of years) and stopped smoking > 1 year; Results of laboratory tests within the normal ranges. Minor deviations are acceptable provided that they are not judged clinically significant by the investigator. A reliable method of contraception for the subjects and their partner. Exclusion Criteria: Blood donation or blood loss less than 8 weeks before inhalation of the study medication; Positive HIV1 or HIV2 serology; Positive results from the Hepatitis serology which indicates acute or chronic Hepatitis B or Hepatitis C; History of substance abuse or drug abuse within 12 months prior to screening visit or with a positive urine drug screen at screening; Clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further clinical investigation; Clinically significant and uncontrolled cardiac, hepatic, renal, gastrointestinal, endocrine, metabolic, neurologic, or psychiatric disorder that may interfere with successful completion of this protocol; Treatment within the previous 3 months with any drug known to have a well defined potential for hepatotoxicity (e.g. isoniazide, nimesulide, ketoconazole). Subjects who refuse to abstain from alcohol or caffeine containing foods or beverages or grapefruit containing foods or beverages from 48 hour prior to each intake of study medication until the end of confinement at the clinical centre. Heavy caffeine drinker (> 5 cups or glasses of caffeinated beverages e.g., coffee, tea, cola per day).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CHF 6001 SD or placebo<br>Single administration of CHF 6001 dose levels 1 to 7 or placebo | Drug: CHF 6001 SD or placebo<br>* Dry Powder Inhaler<br>* Other names: CHF 6001 DPI;|
| Experimental: CHF 6001 MD or placebo<br>Multiple administration of CHF 6001 dose levels 1 to 5 or placebo | Drug: CHF 6001 MD or placebo<br>* Dry Powder Inhaler<br>* Other names: CHF 6001 DPI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events, adverse drug reactions, serious adverse events. | The number and percentage of subjects with adverse events, adverse drug reactions, serious adverse events | After 7 days of treatment | 
| Vital signs | Blood pressure and Heart rate | After 7 days of treatment | 
| 12-lead ECG | Heart rate, RR, PR, QRS, QT, QTcB, QTcF | After 7 days of treatment | 
| 24h ECG Holter | Number and percentages of subjects with arrhythmias ( e.g ventricular tachycardia, supra ventricular tachycardia,..) | After 7 days of treatment | 
| FEV1 |  | After 7 days of treatment | 
| Blood and urine Laboratory tests |  | After 7 days of treatment | 
| Body weight |  | After 7 days of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of CHF 6001 and its metabolite | AUC; Cmax and tmax; t½ | After 7 days of treatment |