- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05830071
A Thorough QT (TQT) Study of CHF5993 pMDI in Healthy Volunteers (HV)
October 30, 2023 updated by: Chiesi Farmaceutici S.p.A.
A Randomized, Double-blind, Positive and Placebo-controlled, Single-dose, Crossover Study of the Effects of CHF5993 pMDI (BDP/FF/GB) at the Proposed Therapeutic and Supratherapeutic Doses, on the Cardiovascular Safety in Healthy Subjects
The purpose of this study is to evaluate the potential for cardiac repolarization, according to electrocardiographic monitoring (including QT and QTc intervals), of two dose levels of CHF5993 pMDI (beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB)) and of one dose of CHF5259 (GB) in healthy subjects compared to moxifloxacin and placebo.
Study Overview
Status
Completed
Intervention / Treatment
Detailed Description
The main purpose of this study is to evaluate the effect of a single supratherapeutic dose of inhaled BDP/FF/GB on cardiovascular safety.
The secondary purposes of the study are to: 1) evaluate the effect of a single supratherapeutic dose of inhaled BDP/FF/GB and GB on cardiovascular safety; 2) establish assay sensitivity by demonstrating the effect of a single oral dose of 400 mg moxifloxacin on cardiovascular safety; 3) determine the pharmacokinetics (PK) of single, inhaled therapeutic and supratherapeutic BDP/FF/GB doses and supratherapeutic GB dose; 4) determine if there is a relationship between the duration of the QTc intervals and the plasma concentrations of the B17MP (beclomethasone 17monopropionate active metabolite of BDP), FF and GB following the administration of BDP/FF/GB and GB pMDIs; 5) generate additional safety and tolerability information.
Study Type
Interventional
Enrollment (Actual)
95
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Chiesi Clinical trial info
- Phone Number: +39 5021 2791
- Email: clinicaltrials_info@chiesi.com
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21225
- Parexel Baltimore Early Phase Clinical Unit
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Adult
Accepts Healthy Volunteers
Yes
Description
Key Inclusion Criteria:
- Subject's written informed consent;
- 18-55 years of age;
- Ability to understand the study procedures, the risks involved and ability to be trained to use the inhalers correctly;
- Body Mass Index (BMI) between 18 and 32 kg/m2 extremes inclusive;
- Non- or ex-smokers who smoked < 5 pack years and stopped smoking > 1 year prior to screening;
- Good physical and mental status, determined on the basis of the medical history and a general clinical examination;
- Vital signs within normal limits at screening and prior to randomization: Diastolic BP 40-89 mmHg, Systolic BP 90-139 mmHg extremes included (mean value of three measures). Body temperature < 37.5°C;
- 12 -lead digitized Electrocardiogram (12-lead ECG) in triplicate considered as normal (40 ≤ Heart rate ≤ 110bpm, 120 ms ≤ PR ≤ 220 ms, QRS ≤ 110 ms, QTcF ≤ 450 ms);
- Lung function measurements within normal limits (normal values: forced expiratory volume in the 1st second [FEV1]/forced vital capacity [FVC] > 0.70 and FEV1 > 80% predicted);
- Female subjects of non-child bearing potential or females of child bearing potential with negative pregnancy test; and acceptable contraceptive methods.
Key Exclusion Criteria:
- Participation in another clinical trial where investigational drug was received and last investigations within the last 8 weeks;
- Clinically significant abnormal standard ECG at screening;
- Clinically relevant and uncontrolled respiratory, cardiac, hepatic, gastrointestinal, renal, endocrine, metabolic, neurologic, or psychiatric disorders that may interfere with successful completion of this protocol;
- Subjects with medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the investigator would prevent use of anticholinergic;
- Subjects with history of breathing problems (i.e., history of asthma including childhood asthma);
- Positive urine test for cotinine;
- Intake of non-permitted concomitant medications in the predefined period prior to screening or prior to randomization, or the subject is expected to take non-permitted concomitant medications during the study;
- Presence of any current infection, or previous infection that resolved less than 7 days prior to screening or to randomization;
- Known intolerance and/or hypersensitivity to any of the excipients contained in the formulation used in the trial;
- Women who are pregnant or lactating;
- Use of any kind of smoking electronic devices within 6 months before Screening.
Other inclusion/exclusion criteria as defined by the protocol.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Single therapeutic dose of CHF5993 (BDP/FF/GB)
Dose: BDP/FF/GB 100/6/12.5
μg, single dose inhalation via pressurized metered dose inhaler (2 puffs from 1 BDP/FF/GB 100/6/12.5
μg pMDI + 2 puffs from 3 placebo pMDI)
|
BDP/FF/GB 100/6/12.5 μg pMDI
Other Names:
placebo pMDI
Other Names:
|
Experimental: Single supra-therapeutic dose of CHF5993 (BDP/FF/GB)
Dose: BDP/FF/GB 800/48/100 μg single dose inhalation, via pressurized metered dose inhaler (8 puffs from 4 BDP/FF/GB 100/6/12.5
μg pMDI)
|
BDP/FF/GB 100/6/12.5 μg pMDI
Other Names:
|
Experimental: Single supra-therapeutic dose CHF5259 (GB)
Dose: GB 100 μg single dose inhalation, via pressurized metered dose inhaler (8 puffs from 4 GB 12.5 μg pMDI)
|
GB 12.5 μg pMDI
Other Names:
|
Placebo Comparator: Single dose Placebo
Dose: placebo single dose inhalation, via pressurized metered dose inhaler 8 puffs from 4 CHF5993 placebo pMDI
|
placebo pMDI
Other Names:
|
Active Comparator: Moxifloxacin
Dose: moxifloxacin 400 mg single dose, for oral use - open label treatment (1 tablet of moxifloxacin 400 mg PO)
|
400 mg Oral Tablets
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Effect of BDP/FF/GB pMDI at therapeutic dose on the heart rate-corrected QT interval based on the Fridericia's correction (QTcF).
Time Frame: time 0 (pre-dose) to 24 hours
|
Placebo-adjusted change in QTc interval based on the Fridericia's correction (ΔΔQTcF) after dosing CHF5993 pMDI (200/12/25 μg).
Through digitised 12-lead ECG, extracted from 12-Lead Holter ECG.
|
time 0 (pre-dose) to 24 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Effect of BDP/FF/GB pMDI and GB pMDI at supra-therapeutic dose on the heart rate-corrected QT interval based on the Fridericia's correction (QTcF).
Time Frame: time 0 (pre-dose) to 24 hours
|
Placebo-adjusted change from baseline in QTc interval based on the Fridericia's correction (ΔΔQTcF) after dosing CHF5993 pMDI (800/48/100 μg) and GB pMDI (100 μg).
Through digitised 12-lead ECG, extracted from 12-Lead Holter ECG.
|
time 0 (pre-dose) to 24 hours
|
Assay sensitivity by demonstrating the effect of a single oral therapeutic dose of moxifloxacin on QTcF.
Time Frame: time 0 (pre-dose) to 6 hours
|
Placebo-adjusted change from baseline in QTc interval based on the Fridericia's correction (ΔΔQTcF) after dosing 400 mg of moxifloxacin.
Through digitised 12-lead ECG, extracted from 12-Lead Holter ECG
|
time 0 (pre-dose) to 6 hours
|
Effect of BDP/FF/GB pMDI at therapeutic and supra-therapeutic dose and of GB pMDI at supra-therapeutic dose on Hearth Rate (HR).
Time Frame: time 0 (pre-dose) to 24 hours
|
Placebo-adjusted change from baseline of HR (ΔΔHR) after dosing BDP/FF/GB pMDI (200/12/25 μg and 800/48/100 μg) and GB pMDI (100 μg) will be summarized by means of descriptive statistics at each analysis time point and by treatment.
Through digitised 12-lead ECG, extracted from 12-Lead Holter ECG.
|
time 0 (pre-dose) to 24 hours
|
Effect of BDP/FF/GB pMDI at therapeutic and supra-therapeutic dose and of GB pMDI at supra-therapeutic dose on PR interval (PR).
Time Frame: time 0 (pre-dose) to 24 hours
|
Placebo-adjusted change from baseline of PR (ΔΔPR) after dosing BDP/FF/GB pMDI (200/12/25 μg and 800/48/100 μg) and GB pMDI (100 μg) will be summarized by means of descriptive statistics at each analysis time point and by treatment.
Through digitised 12-lead ECG, extracted from 12-Lead Holter ECG.
|
time 0 (pre-dose) to 24 hours
|
Effect of BDP/FF/GB pMDI at therapeutic and supra-therapeutic dose and of GB pMDI at supra-therapeutic dose on QRS interval (QRS).
Time Frame: time 0 (pre-dose) to 24 hours
|
Placebo-adjusted change from baseline of QRS (ΔΔQRS) after dosing BDP/FF/GB pMDI (200/12/25 μg and 800/48/100 μg) and GB pMDI (100 μg) will be summarized by means of descriptive statistics at each analysis time point and by treatment.
Through digitised 12-lead ECG, extracted from 12-Lead Holter ECG.
|
time 0 (pre-dose) to 24 hours
|
Effect of BDP/FF/GB pMDI at therapeutic and supra-therapeutic dose and of GB pMDI at supra-therapeutic dose on individual-corrected QT interval (QTcI)
Time Frame: time 0 (pre-dose) to 24 hours
|
Placebo-adjusted change from baseline in individual-corrected QT interval (ΔΔQTcI) after dosing BDP/FF/GB pMDI (200/12/25 μg and 800/48/100 μg) and GB pMDI (100 μg).
Through digitised 12-lead ECG, extracted from 12-Lead Holter ECG.
|
time 0 (pre-dose) to 24 hours
|
Effect of moxifloxacin at therapeutic dose on individual-corrected QT interval.
Time Frame: time 0 (pre-dose) to 6 hours
|
Placebo-adjusted change from baseline in individual-corrected QT interval (ΔΔQTcI) after dosing 400 mg of moxifloxacin.
Through digitised 12-lead ECG, extracted from 12-Lead Holter ECG.
|
time 0 (pre-dose) to 6 hours
|
Changes in T-wave morphology and U-wave presence.
Time Frame: time 0 (pre-dose) to 24 hours
|
Frequency of treatment-emergent changes in T-wave morphology and U-wave presence after dosing BDP/FF/GB pMDI (200/12/25 μg and 800/48/100 μg) and GB pMDI (100 μg).
Through digitised 12-lead ECG, extracted from 12-Lead Holter ECG.
|
time 0 (pre-dose) to 24 hours
|
Analysis of categorical outliers of Hearth Rate (HR), PR interval (PR), QRS interval (QRS) and QTcF interval (QTcF), after BDP/FF/GB pMDI dosing at therapeutic and supra-therapeutic dose, and after GB dosing at supra-therapeutic dose.
Time Frame: time 0 (pre-dose) to 24 hours
|
Results of categorical outliers will be summarized by treatment in frequency tables reporting: counts and percentages for number of subjects and number of time points with 1) abnormal actual QTcF values, and 2) abnormal change from baseline of HR, PR, QRS and QTcF.
Through digitised 12-lead ECG, extracted from 12-Lead Holter ECG.
|
time 0 (pre-dose) to 24 hours
|
Analysis of Maximum plasma concentration (Cmax), pharmacokinetic parameter of FF, GB, BDP and B17MP
Time Frame: time 0 (pre-dose) to 24 hours
|
Analysis of Cmax after dosing BDP/FF/GB pMDI (200/12/25 μg and 800/48/100 μg) and GB pMDI (100 μg).
|
time 0 (pre-dose) to 24 hours
|
Analysis of Area under the curve from 0 to 12 hours post-dose (AUC0-12), pharmacokinetic parameter of FF, GB, BDP and B17MP
Time Frame: time 0 (pre-dose) to 24 hours
|
Analysis of AUC0-12, after dosing BDP/FF/GB pMDI (200/12/25 μg and 800/48/100 μg) and GB pMDI (100 μg).
|
time 0 (pre-dose) to 24 hours
|
Analysis of Area under the plasma concentration-time curve from time 0 to time t (AUC0 t), pharmacokinetic parameter of FF, GB, BDP and B17MP
Time Frame: time 0 (pre-dose) to 24 hours
|
Analysis of AUC0-t after dosing BDP/FF/GB pMDI (200/12/25 μg and 800/48/100 μg) and GB pMDI (100 μg).
|
time 0 (pre-dose) to 24 hours
|
Analysis of Area under the curve from time 0 to infinity (AUC0-∞), pharmacokinetic parameter of FF, GB, BDP and B17MP
Time Frame: time 0 (pre-dose) to 24 hours
|
Analysis of AUC0-∞ after dosing BDP/FF/GB pMDI (200/12/25 μg and 800/48/100 μg) and GB pMDI (100 μg).
|
time 0 (pre-dose) to 24 hours
|
Analysis of Time to maximum plasma concentration (tmax), pharmacokinetic parameter of FF, GB, BDP and B17MP
Time Frame: time 0 (pre-dose) to 24 hours
|
Analysis of tmax, after dosing BDP/FF/GB pMDI (200/12/25 μg and 800/48/100 μg) and GB pMDI (100 μg).
|
time 0 (pre-dose) to 24 hours
|
Analysis of Terminal half-life (t1/2), pharmacokinetic parameter of FF, GB, BDP and B17MP
Time Frame: time 0 (pre-dose) to 24 hours
|
Analysis of t1/2, after dosing BDP/FF/GB pMDI (200/12/25 μg and 800/48/100 μg) and GB pMDI (100 μg).
|
time 0 (pre-dose) to 24 hours
|
Incidence of Adverse events
Time Frame: from study start through study completion, an average of 4 months
|
Number and percentage of subjects with at least one event and number of treatment emergent events
|
from study start through study completion, an average of 4 months
|
Incidence of Adverse Drug Reactions
Time Frame: from study start through study completion, an average of 4 months
|
Number and percentage of subjects with at least one event and number of treatment emergent events
|
from study start through study completion, an average of 4 months
|
Change of systolic and diastolic blood pressure
Time Frame: from study start through study completion, an average of 4 months
|
Number and percentage of subjects with with abnormal changes from baseline
|
from study start through study completion, an average of 4 months
|
Body temperature abnormal values
Time Frame: from study start through study completion, an average of 4 months
|
Number and percentage of subjects with at least one event and number of treatment emergent events
|
from study start through study completion, an average of 4 months
|
Abnormal results of physical examinations
Time Frame: from study start through study completion, an average of 4 months
|
Number and percentage of subjects with at least one event and number of treatment emergent events
|
from study start through study completion, an average of 4 months
|
Abnormal clinical chemistry and haematology laboratory tests
Time Frame: from study start through study completion, an average of 4 months
|
Number and percentage of subjects with at least one event and number of treatment emergent events
|
from study start through study completion, an average of 4 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Ronald Goldwater, MDCM/M.SC(A), Parexel Baltimore Early Phase Clinical Unit
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 29, 2023
Primary Completion (Actual)
October 13, 2023
Study Completion (Actual)
October 13, 2023
Study Registration Dates
First Submitted
March 28, 2023
First Submitted That Met QC Criteria
April 13, 2023
First Posted (Actual)
April 26, 2023
Study Record Updates
Last Update Posted (Actual)
October 31, 2023
Last Update Submitted That Met QC Criteria
October 30, 2023
Last Verified
October 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Respiratory Tract Diseases
- Lung Diseases
- Disease Attributes
- Chronic Disease
- Lung Diseases, Obstructive
- Pulmonary Disease, Chronic Obstructive
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Muscarinic Antagonists
- Cholinergic Antagonists
- Cholinergic Agents
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Adrenergic Agonists
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Anti-Bacterial Agents
- Adjuvants, Anesthesia
- Anticonvulsants
- Bronchodilator Agents
- Anti-Asthmatic Agents
- Respiratory System Agents
- Contraceptive Agents, Hormonal
- Contraceptive Agents
- Reproductive Control Agents
- Contraceptives, Oral, Combined
- Contraceptives, Oral
- Contraceptive Agents, Female
- Adrenergic beta-2 Receptor Agonists
- Adrenergic beta-Agonists
- Moxifloxacin
- Norgestimate, ethinyl estradiol drug combination
- Beclomethasone
- Glycopyrrolate
- Bromides
- Formoterol Fumarate
Other Study ID Numbers
- CLI-05993AB7-03
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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