Clinical trial NCT01703052: Safety and Tolerability of Inhaled CHF 6001 in Healthy Volunteers (HV)
Official title: A Placebo-controlled Double-blind Single and Repeated Ascending Dose Study to Investigate the Safety and Tolerability of Inhaled CHF 6001 in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Lead sponsor: Chiesi Farmaceutici S.p.A.
Sponsor class: INDUSTRY
First posted: 2012-10-10
Enrollment: 74
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Adverse events, adverse drug reactions, serious adverse events.
timeFrame: After 7 days of treatment
measure: Vital signs
timeFrame: After 7 days of treatment
measure: 12-lead ECG
timeFrame: After 7 days of treatment
measure: 24h ECG Holter
timeFrame: After 7 days of treatment
measure: FEV1
timeFrame: After 7 days of treatment
measure: Blood and urine Laboratory tests
timeFrame: After 7 days of treatment
measure: Body weight
timeFrame: After 7 days of treatment
Secondary outcomes:
measure: Pharmacokinetics of CHF 6001 and its metabolite
timeFrame: After 7 days of treatment
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Quotient Clinical
Study officials:
affiliation: Quotient Clinical
name: Stuart Mair, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ferrari A, Compagnoni A, Nandeuil A, Maison-Blanche P. Evaluation of the Effects of CHF6001, an Inhaled PDE4 Inhibitor, on Cardiac Repolarization and Cardiac Arrhythmias in Healthy Volunteers. J Cardiovasc Pharmacol. 2016 Jul;68(1):41-8. doi: 10.1097/FJC.0000000000000384.
citation: Jolling K, Abelo A, Luyckx N, Nandeuil MA, Govoni M, Cella M, Lindauer A. Concentration-QT Modeling Following Inhalation of the Novel Inhaled Phosphodiesterase-4 Inhibitor CHF6001 in Healthy Volunteers Shows an Absence of QT Prolongation. CPT Pharmacometrics Syst Pharmacol. 2019 Jul;8(7):460-468. doi: 10.1002/psp4.12405. Epub 2019 May 11.
citation: Mariotti F, Govoni M, Lucci G, Santoro D, Nandeuil MA. Safety, tolerability, and pharmacokinetics of single and repeat ascending doses of CHF6001, a novel inhaled phosphodiesterase-4 inhibitor: two randomized trials in healthy volunteers. Int J Chron Obstruct Pulmon Dis. 2018 Oct 18;13:3399-3410. doi: 10.2147/COPD.S174156. eCollection 2018.