AsthmaPhase 1/2NCT03378648
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
A Phase 1/2 study testing CHF6366 and umeclidinium bromide and vilanterol trifenatate in people with Asthma and Chronic Obstructive Pulmonary Disease, run by Chiesi Farmaceutici S.p.A. at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Asthma, Chronic Obstructive Pulmonary Disease
- What is being tested?
- CHF6366 and umeclidinium bromide and vilanterol trifenatate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 118 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 28 Dec 2017to 16 Apr 2019
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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;
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- 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
Who cannot join
- Part1
- Any clinically relevant abnormabilites and/or uncontrolled diseases
- Abnormal laboratory values
- Recent respiratory tract infection
- Hypersensitivity to the drug excipients
- Positive serology results
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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:
Read more
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
- Conditions
- Asthma, Chronic Obstructive Pulmonary Disease
- Being tested
- CHF6366, Placebo CHF6366, umeclidinium bromide and vilanterol trifenatate
- Medical subject headings
- Asthma, Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CHF6366Drug
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 CHF6366Drug
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
umeclidinium bromide and vilanterol trifenatateDrug
Part 3 Single dose
| Study group | Role | What they receive |
|---|---|---|
| CHF6366 active | Experimental | Not described Receives: Drug: CHF6366 |
| CHF6366 | Placebo comparator | Not described Receives: Drug: Placebo CHF6366 |
| Comparator | Active comparator | Not described Receives: Drug: umeclidinium bromide and vilanterol trifenatate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events
Measured: 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)
Vital signs
Systolic, diastolic Blood Pressure
Measured: 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)
Change in Holter ECG parameters
HR, PR, QRS, QTcF, QT
Measured: 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)
Change in Holter parameters
Measured: 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)
Change in FEV1
Forced expiratory capacity in the first second
Measured: Part 1 drom Day 1 until Day 3, Part 2 from Day 1 until Day 8
Change in Laboratiry parameters
clinical chemistry, haematology and urinanalysis
Measured: Part 1 Day -1 and Day 3, Part 2 Day -2 and Day 8, Part 3 Day -1 and Day 2
Change in serum potassium level
Measured: Part 1 Day 1, Part 2 Day 1 and Day 7, Part 3 Day 1
Secondary outcomes (18)
Area under the plasma concentration vs time curve
Measured: Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)
Peak plasma concentration (Cmax)
maximum plasma concentration of CHF6366
Measured: Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)
Time to reach the maximum plasma concentration (tmax)
Measured: Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)
Elimination half-life (t1/2)
Measured: Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)
Clearance (CL/F)
Measured: Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)
Volume of distribution (Vz/F)
Measured: Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)
Area under the plasma concentration vs time curve during selected dosing interval
Measured: Part 2 Day 7
Peak plasma concentration during selected dosing (Cmaxss)
Measured: Part 2 Day 7
Value of minimum plasma concentration post dosing at selected dosing interval (Cminss)
Measured: Part 2 Day 7
Time of minimum plasma concentration post dosing at selected dosing interval (Tminss)
Measured: Part 2 Day 7
Time to reach the maximum plasma concentration at selected dosing interval(tmaxss)
Measured: Part 2 Day 7
Clearance at selected dosing interval (CL/Fss)
Measured: Part 2 Day 7
Volume of distribution at selected dosing interval (Vz/Fss)
Measured: Part 2 Day 7
Accumulation ratio (Rac)
Measured: Part 2 Day 7
Steady state concentration (Css)
Measured: Part 2 Day 7
Urinary excretion (Ae)
Measured: 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)
fraction excreted (fe)
Measured: 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)
Clearance (CLr)
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2017
- Study start28 Dec 2017
- Primary completion16 Apr 2019
- Study completion16 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by Chiesi Farmaceutici S.p.A.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Part 1 alternating cross-over design Part 2 parallel group design Part 3 3-way cross-over design
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 118 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chiesi Farmaceutici S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dave Singh, MD, Principal investigator, Medicines Evaluation Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03378648
- Sponsor's protocol ID
- CCD-06366AA1-01
- Other IDs
- 2015-005551-27, 2015
- Status last verified
- May 2020
- First submitted
- 14 Dec 2017
- Last updated
- 7 May 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03378648
- Acronym / sponsor ID
- CCD-06366AA1-01
- Conditions
- Asthma, Chronic Obstructive Pulmonary Disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 118 participants (actual)
- Lead sponsor
- Chiesi Farmaceutici S.p.A.Industry (pharma, biotech, devices)
- Study start
- 28 Dec 2017 (actual)
- Primary completion
- 16 Apr 2019 (actual)
- Study completion
- 16 Apr 2019 (actual)
- First posted
- 20 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Part 1 alternating cross-over design Part 2 parallel group design Part 3 3-way cross-over design
| Arm | Type | Receives |
|---|---|---|
| CHF6366 active | Experimental | Drug: CHF6366 |
| CHF6366 | Placebo comparator | Drug: Placebo CHF6366 |
| Comparator | Active comparator | Drug: umeclidinium bromide and vilanterol trifenatate |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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;
Key exclusion criteria (25 listed)
- Part1
- Any clinically relevant abnormabilites and/or uncontrolled diseases
- Abnormal laboratory values
- Recent respiratory tract infection
- Hypersensitivity to the drug excipients
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CHF6366Drug: 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 | Drug | CHF6366 active |
| Placebo CHF6366Drug: 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 | Drug | CHF6366 |
| umeclidinium bromide and vilanterol trifenatatePart 3 Single dose | Drug | Comparator |
Primary outcome
Adverse Events
Time frame: 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)
Vital signs
Time frame: 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
Change in Holter ECG parameters
Time frame: 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
Change in Holter parameters
Time frame: 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)
Change in FEV1
Time frame: Part 1 drom Day 1 until Day 3, Part 2 from Day 1 until Day 8
Forced expiratory capacity in the first second
Change in Laboratiry parameters
Time frame: 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
Change in serum potassium level
Time frame: Part 1 Day 1, Part 2 Day 1 and Day 7, Part 3 Day 1
18 secondary outcomes
Area under the plasma concentration vs time curve
Time frame: Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)
Peak plasma concentration (Cmax)
Time frame: Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)
Time to reach the maximum plasma concentration (tmax)
Time frame: Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)
Elimination half-life (t1/2)
Time frame: Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)
Clearance (CL/F)
Time frame: Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)
Volume of distribution (Vz/F)
Time frame: Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)
Area under the plasma concentration vs time curve during selected dosing interval
Time frame: Part 2 Day 7
Peak plasma concentration during selected dosing (Cmaxss)
Time frame: Part 2 Day 7
Value of minimum plasma concentration post dosing at selected dosing interval (Cminss)
Time frame: Part 2 Day 7
Time of minimum plasma concentration post dosing at selected dosing interval (Tminss)
Time frame: Part 2 Day 7
Time to reach the maximum plasma concentration at selected dosing interval(tmaxss)
Time frame: Part 2 Day 7
Clearance at selected dosing interval (CL/Fss)
Time frame: Part 2 Day 7
Volume of distribution at selected dosing interval (Vz/Fss)
Time frame: Part 2 Day 7
Accumulation ratio (Rac)
Time frame: Part 2 Day 7
Steady state concentration (Css)
Time frame: Part 2 Day 7
Urinary excretion (Ae)
Time frame: 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)
fraction excreted (fe)
Time frame: 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)
Clearance (CLr)
Time frame: 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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2020.
- Study Record on EU Clinical Trials Register including resultsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dave Singh, MD principal investigator
Medicines Evaluation Unit
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CHF6366 and umeclidinium bromide and vilanterol trifenatate in people with Asthma and Chronic Obstructive Pulmonary Disease, run by Chiesi Farmaceutici S.p.A. at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Events (time frame: 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)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2020.