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

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

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

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: CHF 6001 SD or placebo; Drug: CHF 6001 MD or placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham, United Kingdom
    • Quotient Clinical

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CHF 6001 SD or placebo; Single administration of CHF 6001 dose levels 1 to 7 or placebo	Drug: CHF 6001 SD or placebo; Dry Powder Inhaler; Other Names: CHF 6001 DPI
Experimental: CHF 6001 MD or placebo; Multiple administration of CHF 6001 dose levels 1 to 5 or placebo	Drug: CHF 6001 MD or placebo; Dry Powder Inhaler; Other Names: CHF 6001 DPI

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Chiesi Farmaceutici S.p.A.

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: April 2, 2012
• First Submitted That Met QC Criteria: October 8, 2012
• First Posted (Estimate): October 10, 2012

Study Record Updates

• Last Update Posted (Actual): July 31, 2020
• Last Update Submitted That Met QC Criteria: July 30, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: CCD-1006-PR-0048