Clincosm LogoSign in Get a demo

A Study to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Dose in Healthy Volunteers, Repeat Doses in Asthmatic Patients and of Single Dose in COPD Patients of CHF6366

Sponsor
Chiesi Farmaceutici S.p.A. (Industry)
Overall Status
Completed
CT.gov ID
NCT03378648
Collaborator
(none)
118
Enrollment
1
Location
3
Arms
15.6
Actual Duration (Months)
7.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

CHF6366 is a novel bifunctional compound displaying both muscarinic receptor antagonist and β2-adrenergic receptor agonist properties (MABA), with the potential to deliver optimal bronchodilation after inhalation dosing via two validated mechanisms in one molecule.

The study will consist of three parts:

Part 1 will consit of two cohorts of healthy male subjects to assess the safety, tolerability and pharmacokinetics of Single Ascending Dose (SAD) of CHF 6366

Part 2 will consist of four cohorts of asthmatic subjects to assess the saftey, tolerability and pharmacokinetics of Multiple Ascending Dose (MAD) of CHF6366

Part 3 will consist of one cohort of COPD patients to asess safety, tolerability of a single dose of CHF6366 in an active and placebo controlled design

Condition or Disease Intervention/Treatment Phase
  • Drug: CHF6366
  • Drug: Placebo CHF6366
  • Drug: umeclidinium bromide and vilanterol trifenatate
 Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
118 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
Part 1 alternating cross-over design Part 2 parallel group design Part 3 3-way cross-over designPart 1 alternating cross-over design Part 2 parallel group design Part 3 3-way cross-over design
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Part 1 double-blind Part 2 double-blind Part 3 placebo-controlled (double-blind), active-controlled (open labelled)
Primary Purpose:
Treatment
Official Title:
A First In Human Randomised, Double-Blind, Placebo-Controlled Study Of Single Ascending Doses In Healthy Male Volunteers And Repeated Ascending Dose In Asthmatic Patients Followed By A 3-Way Cross-Over, Placebo-Controlled, Single-Dose In Copd Patients To Investigate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of CHF6366
Actual Study Start Date :
Dec 28, 2017
Actual Primary Completion Date :
Apr 16, 2019
Actual Study Completion Date :
Apr 16, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: CHF6366 active

Drug: CHF6366
Drug: CHF6366 (Part 1 - SAD) Single doses of CHF6366 at each period (for up to 3 periods per subject) Drug: CHF6366 (Part 2 - MAD) Once daily doses of CHF6366 for 7 days Drug: CHF6366 (Part 3) Single dose of CHF6366
Placebo Comparator: CHF6366

Drug: Placebo CHF6366
Drug: Placebo (Part 1 - SAD) Single doses of placebo matching CHF6366 at each period (for up to 3 periods per subjects) Drug: Placebo (Part 2 - MAD) Once daily dose of placebo matching CHF6366 for 7 days Drug: Placebo (Part 3) Single dose of placebo matching CHF6366
Active Comparator: Comparator

Drug: umeclidinium bromide and vilanterol trifenatate
Part 3 Single dose

Outcome Measures

Primary Outcome Measures

  1. Adverse Events [Part 1 from Day 1 until day 3, Part 2 from Day 1 until day 8, Part 3 from Day 1 until Day 3 (per each period)]

  2. Vital signs [Part 1 from Day 1 until Day 3, Part 2 from Day 1 until day 8, Part 3 from Day 1 until Day 3 (per each period)]

    Systolic, diastolic Blood Pressure

  3. Change in Holter ECG parameters [Part 1 from Day 1 until Day 3, Part 2 from Day 1 until day 8, Part 3 from Day 1 until Day 3 (per each period)]

    HR, PR, QRS, QTcF, QT

  4. Change in Holter parameters [Part 1 from Day 1 until Day 3, Part 2 from Day 1, until Day 8, Part 3 from Day 1 until Day 3(per each period)]

  5. Change in FEV1 [Part 1 drom Day 1 until Day 3, Part 2 from Day 1 until Day 8]

    Forced expiratory capacity in the first second

  6. Change in Laboratiry parameters [Part 1 Day -1 and Day 3, Part 2 Day -2 and Day 8, Part 3 Day -1 and Day 2]

    clinical chemistry, haematology and urinanalysis

  7. Change in serum potassium level [Part 1 Day 1, Part 2 Day 1 and Day 7, Part 3 Day 1]

Secondary Outcome Measures

  1. Area under the plasma concentration vs time curve [Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)]

  2. Peak plasma concentration (Cmax) [Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)]

    maximum plasma concentration of CHF6366

  3. Time to reach the maximum plasma concentration (tmax) [Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)]

  4. Elimination half-life (t1/2) [Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)]

  5. Clearance (CL/F) [Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)]

  6. Volume of distribution (Vz/F) [Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)]

  7. Area under the plasma concentration vs time curve during selected dosing interval [Part 2 Day 7]

  8. Peak plasma concentration during selected dosing (Cmaxss) [Part 2 Day 7]

  9. Value of minimum plasma concentration post dosing at selected dosing interval (Cminss) [Part 2 Day 7]

  10. Time of minimum plasma concentration post dosing at selected dosing interval (Tminss) [Part 2 Day 7]

  11. Time to reach the maximum plasma concentration at selected dosing interval(tmaxss) [Part 2 Day 7]

  12. Clearance at selected dosing interval (CL/Fss) [Part 2 Day 7]

  13. Volume of distribution at selected dosing interval (Vz/Fss) [Part 2 Day 7]

  14. Accumulation ratio (Rac) [Part 2 Day 7]

  15. Steady state concentration (Css) [Part 2 Day 7]

  16. Urinary excretion (Ae) [Part 1 from Day 1 until Day 3, Part 2 Day 1 and Day 7, Part 3 from Day 1 until Day 3 (per each period)]

  17. fraction excreted (fe) [Part 1 from Day 1 until Day 3, Part 2 Day 1 and Day 7, Part 3 from Day 1 until Day 3 (per each period)]

  18. Clearance (CLr) [Part 1 from Day 1 until Day 3, Part 2 Day 1 and Day 7, Part 3 from Day 1 until Day 3 (per each period)]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:

Part 1

  • male subjects aged 18-55 years inclusive;

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

  • Body Mass Index (BMI) between 18.5 and 32.0 kg/m2 extremes inclusive

  • 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;

  • Good physical and mental status, determined on the basis of the medical history and a general clinical examination;

  • Lung function equal to or more than 80% of predicted normal value and FEV1/FVC ratio > 0.70;

Part 2

  • Adult male and female subjects aged 18 to 75 years

  • Clinical diagnosis of mild persistent asthma

  • FEV1 reversibility of ≥ 12% or 200 ml over the baseline value starting within 30 mins after inhalation of 400 micrograms of salbutamol

  • Patients who are otherwise healthy as determined by medical history, physical examination, 12-lead ECG findings

Part 3

  • Male aged between 40 and 75 years

  • Stable patients with a post-bronchodilator 40% ≤ FEV1 < 80% of the predicted normal value, post-bronchodilator FEV1/FVC < 0.7 with salbutamol

  • Current smokers and ex-smokers

  • Response to ipratropium bromide defined as an increase in FEV1 of > 7 % starting 30 minutes after inhalation of 80 micrograms ipratropium bromide

  • Response to salbutamol defined an increase in FEV1 of > 7 % starting 15 minutes to 30 min following inhalation of 400 micrograms salbutamol MDI

Exclusion Criteria:

Part1

  • Any clinically relevant abnormabilites and/or uncontrolled diseases

  • Abnormal laboratory values

  • Recent respiratory tract infection

  • Hypersensitivity to the drug excipients

  • Positive serology results

  • Positive cotinine, alcohol, drug of abuse tests

Part 2

  • Pregnant and/or breast-feeding women

  • Subjects with a medical history or current diagnosis of COPD or any other pulmonary disease other than asthma

  • Subjects who have cardiovascular condition

  • Clinically significant laboratory abnormalities

  • Subject with serum potassium level below the lower limit of the laboratory reference range

  • History of alcohol, substance or drug abuse

  • Hypersensitivity to the drug excipients

Part 3

  • Female patients

  • Current diagnosis of asthma or allergic rhinitis or other atopic disease

  • Recent COPD exacerbations or a lower respiratory tract infection

  • Hypersensitivity to drug excipients;

  • Abuse of substance or drug t or with a positive urine drug screen

  • Unstable concurrent disease

  • Subjects who have cardiovascular condition

  • Clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease

  • Patients with serum potassium levels below the lower limit of the laboratory normal range

Contacts and Locations

Locations

Site City State Country Postal Code
1 Medicines Evaluation Unit Manchester United Kingdom

Sponsors and Collaborators

  • Chiesi Farmaceutici S.p.A.

Investigators

  • Principal Investigator: Dave Singh, MD, Medicines Evaluation Unit

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Chiesi Farmaceutici S.p.A.
ClinicalTrials.gov Identifier:
NCT03378648
Other Study ID Numbers:
  • CCD-06366AA1-01
  • 2015-005551-27
First Posted:
Dec 20, 2017
Last Update Posted:
May 7, 2020
Last Verified:
May 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Bromides

Study Results

No Results Posted as of May 7, 2020