Lung Deposition of Beclometasone Dipropionate/Formoterol Fumarate/Glycopyrronium Bromide Administered Via pMDI in Healthy, Asthmatic and COPD Patients

NCT02975843 | Completed Phase 1

• 2 other identifiers: CCD-05993AA1-152016-001088-35
• Study Type: interventional
• Target: 28
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to investigate the lung deposition and distribution pattern of Beclometasone dipropionate/Formoterol Fumarate/Glycopyrronium Bromide using a Gamma-scintigraphic technique after inhalation of a single dose of 99mTc radiolabelled CHF 5993 Administered via pMDI in healthy volunteers, asthmatic and COPD patients.

Conditions

Chronic Obstructive Pulmonary Disease; Asthma

Outcome Measures

Primary Outcomes (1)

• Intrapulmonary Lung deposition expressed as % of nominal dose

  Calculated using the individual Gamma camera images

  Immediately after dosing

Secondary Outcomes (10)

• Distribution of lung deposition

  Immediately after dosing

• Extrathoracic deposition

  Immediately after dosing

• Exhaled activity

  Immediately after dosing

• BDP/B17MP, Formoterol, and GB Area under curve (AUC) 0-t

  the area under the plasma concentration-time curve from 0 to the last quantifiable concentration. Over 24h

• BDP/B17MP, Formoterol, and GB Area under curve (AUC) 0-30min

  area under the plasma concentration-time curve from 0 to 30 min post-dose

Study Arms (1)

CHF5993

EXPERIMENTAL

99mTc Radiolabelled Beclometasone dipropionate/Formoterol Fumarate/Glycopyrronium Bromide administered via pMDI

Drug: Beclometasone dipropionate/Formoterol Fumarate/Glycopyrronium

Interventions

Beclometasone dipropionate/Formoterol Fumarate/Glycopyrronium DRUG

single inhalation of 99mTc radiolabelled CHF 5993 pMDI (4 puffs for a total dose of: Beclometasone diproprionate (BDP) 400 μg, Formoterol fumarate (FF) 24 μg, Glycopirronium bromide (GB) 50 μg)

Also known as: CHF5993 pMDI

CHF5993

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject's written informed consent obtained prior to any study-related procedure
• Body mass index (BMI) between 18 and 32 kg/m2
• Ability to understand the study procedures and the risks involved and ability to be trained to use the devices correctly at screening and pre-dose.
• Normal vital signs (Diastolic BP 60-90 mmHg, Systolic BP 90-140 mmHg or 90-150 if \>45 yrs) at screening and pre-dose.
• lead digitalised ECG considered as normal: 60 ≤ heart rate ≤ 100 bpm, 120 ms ≤ PR ≤210 ms, QRS ≤ 120 ms, QTcF ≤ 450 ms (male) and ≤ 470 ms (female) at screening and pre-dose
• Males fulfilling one of the following criteria:
• Males with non-pregnant Women of childbearing potential (WOCBP) partners: they and/or their partner of childbearing potential must be willing to use a highly effective birth control method in addition to the male condom from the signature of the informed consent and until 90 days after the follow-up visit. Subjects must not donate sperm during the study and for 90 days after the follow-up visit or
• Males with pregnant WOCBP partner: they must be willing to use male contraception (condom) from the signature of the informed consent and until 90 days after the follow-up visit. Subjects must not donate sperm during the study and for 90 days after the follow-up visit or
• Non-fertile male subjects (contraception is not required in this case) or
• Males with partner not of childbearing potential (contraception is not required in this case).
• WOCBP fulfilling one of the following criteria:
• WOCBP with fertile male partners: they and/or their partner must be willing to use a highly effective birth control method with low user dependency from the signature of the informed consent and until 30 days after the follow-up visit or
• WOCBP with non-fertile male partners (contraception is not required in this case).
• Female patients of non-childbearing potential defined as physiologically incapable of becoming pregnant (i.e. post-menopausal or permanently sterile). Tubal ligation or partial surgical interventions are not acceptable. If indicated, as per investigator's request, post-menopausal status may be confirmed by follicle-stimulating hormone levels (according to local laboratory ranges)
• Males and females aged 18-55

You may not qualify if:

• Pregnant or lactating women
• Documented history of drug abuse (within 12 months before screening) and/or positive urine drug test at screening and/or at treatment period
• History of hypersensitivity to M3 Antagonists, β2-agonist, corticosteroids or any of the excipients contained in any of the formulations used in the trial;
• Any clinically relevant abnormal laboratory value at screening suggesting an unknown disease and requiring further clinical investigation or which may impact the safety of the subject or the evaluation of the result of the study according to the investigator's judgment
• Clinically relevant and uncontrolled hepatic, gastrointestinal, renal, genitourinary, endocrine, metabolic neurologic, or psychiatric disorder that may interfere with successful completion of this protocol
• Serology at the screening positive to HIV1 or HIV2 and positive results for Hepatitis which indicates acute or chronic Hepatitis B (i.e. positive HB surface antigen HBsAg positive and/or positive HB core antibody anti-HBc) or Hepatitis C (HCV antibody);
• Subjects with history of sustained and non-sustained cardiac arrhythmias (ECG demonstrated) and subjects with a family history of sudden cardiac death
• Subjects who have cardiovascular condition such as, but not limited to unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, acute ischemic heart disease in the last year prior to study screening, which may impact the safety of the subject or the evaluation of the result of the study according to the investigator's judgment
• Medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the investigator would prevent use of anticholinergic agents"
• Significant blood loss ≥ 400 ml within 3 months prior screening and between screening and Day 1;
• Participation in another clinical trial with an investigational drug in the previous 3 months before the administration of the study drug; a longer and more appropriate time could be considered by the principal investigator based on the elimination of the half-life and/or long term toxicity of the previous investigational drug;
• Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 1999, shall participate in the study.
• Unsuitable veins for repeated venipuncture
• Any not allowed concomitant medication
• Current use of any nicotine or nicotine replacement product

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Asthma

Interventions

Beclomethasone

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bronchial Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Chlorinated

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2016
• First Posted: November 29, 2016
• Study Start: November 21, 2016
• Primary Completion: March 21, 2017
• Study Completion: April 11, 2017
• Last Updated: June 23, 2017

Record last verified: 2017-06