CHF6333 FIH: A Study to Investigate Safety, Tolerability and Pharmacokinetics of Single and Repeat Doses of CHF6333 in Healthy Subjects

• Sponsor: Chiesi Farmaceutici S.p.A. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03056326
• Collaborator: (none)
• Enrollment: 72
• Location: 1
• Arms: 2
• Duration (Months): 8
• Patients Per Site Per Month: 9.1

Study Details

Study Description

Brief Summary

Human Neutrophil Elastase (HNE) plays a pivotal role in innate immunity and in neutrophilic lung inflammation that characterized many diseases. CHF 6333 is a potent and 24h-durable inhibitor of HNE, developed as Dry Powder Inhaler (DPI) formulation. This study is designed to investigate the tolerability, safety and pharmacokinetics of inhaled CHF6333 DPI in healthy male subjects.

The study will comprise two parts:

Part 1 will consist of two alternated cohorts of healthy male subjects to assess the safety, tolerability and pharmacokinetics of Single Ascending Dose (SAD) of CHF6333.

Part 2 will consist of four sequential cohorts of healthy male subjects to assess the safety, tolerability and pharmacokinetics of Multiple Ascending Dose (MAD) of CHF6333

Condition or Disease	Intervention/Treatment	Phase
Non-Cystic Fibrosis Bronchiectasis; Cystic Fibrosis	Drug: CHF6333 (Part 1 - SAD); Drug: Placebo (Part 1 - SAD); Drug: CHF6333 (Part 2 - MAD); Drug: Placebo (Part 2 - MAD)	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model Description: Part 1: alternating cross-over design Part 2: parallel designPart 1: alternating cross-over design Part 2: parallel design
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase I, Randomised, Double-blind, Placebo-controlled Study to Investigate the Safety, Tolerability and Pharmacokinetics of Inhaled CHF 6333 After Single and Repeated Ascending Doses in Healthy Male Subjects
• Study Start Date: Nov 1, 2016
• Actual Primary Completion Date: Jul 1, 2017
• Actual Study Completion Date: Jul 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CHF6333 Active	Drug: CHF6333 (Part 1 - SAD); Single doses of CHF6333 at each period; Drug: CHF6333 (Part 2 - MAD); once daily multiple doses of CHF6333 for 14 days
Placebo Comparator: Placebo	Drug: Placebo (Part 1 - SAD); Single doses of placebo matching CHF6333 at each period; Drug: Placebo (Part 2 - MAD); once daily multiple doses of placebo matching CHF6333 for 14 days

Outcome Measures

Primary Outcome Measures

1. Adverse events [Part 1 from Day 1 to 5, Part 2 from Day 1 to 15]

   Treatment-related Adverse events

2. Change in Vital signs [Part 1 from Day 1 to 5, Part 2 from Day 1 to 15]

   Blood pressure

3. Heart Rate [Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15]

   Change in Heart Rate (from ECG)

4. QTcF interval [Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15]

   Change in QTcF interval (from ECG)

5. PR interval [Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15]

   Change in PR interval (from ECG)

6. QRS interval [Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15]

   Change in QRS interval (from ECG)

7. Holter recording abnormalities [Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15]

   24h-holter ECG recording

8. FEV1 [Part 1 Day 1-2, Part 2 Day 1-14-15]

   Change in FEV1 (Forced exhalation volume in the first second)

9. Clinical chemistry and haematology [Part 1 Day 1-5, Part 2 Day 1-15]

   change in Clinical chemistry and haematology parameters

10. Urinalysis [Part 1 Day 1-5, Part 2 Day 1-15]

    Change in urinalysis parameters

Secondary Outcome Measures

1. Area under the plasma concentration [Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15]

2. Peak plasma concentration (Cmax) [Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15]

   maximum plasma concentration of CHF6333

3. Time to reach the maximum plasma concentration (tmax) [Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15]

4. Elimination half-life (t1/2) [Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15]

5. Clearance (CL/F) [Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15]

   Absolute plasma clearance

6. Volume of distribution (Vz/F) [Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15]

   plasma volume of distribution

7. Urinary excretion (Ae) [Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15]

   Amount of CHF6333 excreted in urine

8. fraction excreted (fe) [Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15]

   Percentage of drug excreted in urine

9. Renal clearance (CLr) [Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Male subjects aged 18-55 years

• BMI between 18-30 kg/m2

• Non smokers

• Lung function above 80% of predicted normal value

• Healthy subjects based on medical evaluation including medical history, physical examination, laboratory tests and cardiac testing

Exclusion Criteria:

• Any clinically relevant abnormalities and/or uncontrolled diseases

• Abnormal laboratory values

• Recent respiratory tract infection

• Hypersensitivity to the drug or excipients

• Positive serology results

• Positive cotinine, alcohol, drug of abuse tests

• Unsuitable veins for repeated venepuncture

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	SGS Life Sciences	Antwerpen		Belgium	2060

Sponsors and Collaborators

• Chiesi Farmaceutici S.p.A.

Investigators

• Principal Investigator: Frédéric Vanhoutte, SGS Life Sciences, a division of SGS Belgium NV

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Chiesi Farmaceutici S.p.A.
• ClinicalTrials.gov Identifier: NCT03056326
• Other Study ID Numbers: CCD-06333AA1-01; 2015-005552-94
• First Posted: Feb 17, 2017
• Last Update Posted: Nov 7, 2017
• Last Verified: Nov 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Additional relevant MeSH terms: Cystic Fibrosis; Bronchiectasis; Fibrosis

Study Results

No Results Posted as of Nov 7, 2017