Lung Deposition of TRIMBOW® pMDI in Healthy Volunteers, Asthmatic and COPD Patients

NCT03795350 | Terminated Phase 1

• 2 other identifiers: CLI-05993AA1-202017-005030-29
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the lung deposition and distribution pattern of TRIMBOW using a Gamma-scintigraphic technique after inhalation of a single dose of 99mTc radiolabelled TRIMBOW administered via pMDI in healthy volunteers, asthmatic and COPD patients

Conditions

Chronic Obstructive Pulmonary Disease; Asthma

Keywords

Lung deposition; Gamma scintigraphy

Outcome Measures

Primary Outcomes (1)

• intrapulmonary lung deposition

  calculated using individual Gamma camera images

  immediately after dosing

Secondary Outcomes (10)

• Intrapulmonary lung distribution of deposition: C/P ratio

  immediately after dosing

• extrathoracic deposition

  immediately after dosing

• amount of exhaled drug

  immediately after dosing

• TRIMBOW pharmacokinetics - (AUC0-t)

  up to 24 hours post dose

• lung function assessment - FEV1, FVC, FEV1/FVC, FEF25%, FEF50%, FEF75%

  up to 24 hours post dose

Study Arms (1)

TRIMBOW

EXPERIMENTAL

Experimental: BDP/FF/GB 4 puffs of 99mTc Radiolabelled Beclometasone dipropionate/Formoterol Fumarate/Glycopyrronium Bromide administered via pMDI

Drug: Beclometasone dipropionate Formoterol Fumarate Glycopyrronium Bromide

Interventions

Beclometasone dipropionate Formoterol Fumarate Glycopyrronium Bromide DRUG

single inhalation of 99mTc radiolabelled TRIMBOW pMDI (4 puffs for a total dose of 400mcg BDP, 24mcg FF, 50 mcg GB)

TRIMBOW

Eligibility Criteria

• Age: 28 Years - 80 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;
• Ability to understand the study procedures, the risks involved and ability to demonstrate correct use of the inhaler using the AIM™ (Aerosol Inhalation Monitor) Vitalograph®
• Body Mass Index (BMI) between 18 and 32 kg/m2 extremes inclusive;
• Good physical status, determined on the basis of the medical history and a general clinical examination, at screening;
• Vital signs within normal limits: Diastolic BP 40-90 mmHg, Systolic BP 90-140 mmHg or 90-160 mmHg if \>45 yrs
• 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).
• Females 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)
• lead digitised Electrocardiogram (12-lead ECG) considered as normal at screening and at Day -1

You may not qualify if:

• Pregnant or lactating women;
• Clinically relevant and uncontrolled respiratory, cardiac, hepatic, gastrointestinal, renal, endocrine, metabolic, neurologic, or psychiatric disorders
• Clinically relevant abnormal laboratory values at screening suggesting an unknown disease and requiring further clinical investigation
• Subjects with medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction
• Positive HIV1 or HIV2 serology at screening
• Blood donation or blood loss less than 2 months prior screening
• Participation to another clinical trial where investigational drug was received and last investigations were performed less than 90 days prior to screening;
• Documented history of alcohol abuse within 12 months prior to screening or a positive alcohol breath test
• Documented history of drug abuse within 12 months prior to screening
• Positive results from the Hepatitis serology which indicates acute or chronic Hepatitis B or Hepatitis C at screening
• 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
• Unsuitable veins for repeated venepuncture/cannulation
• Intake of non-permitted concomitant medications in the predefined period prior to screening
• Radiation exposure, including that from the present study, in the last 12 months
• Known intolerance/hypersensitivity or contra-indication to treatment

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (1)

Simbec Research Ltd

Merthyr Tydfil, United Kingdom

Location

Related Publications (1)

• Usmani OS, Baldi S, Warren S, Panni I, Girardello L, Rony F, Taylor G, DeBacker W, Georges G. Lung Deposition of Inhaled Extrafine Beclomethasone Dipropionate/Formoterol Fumarate/Glycopyrronium Bromide in Healthy Volunteers and Asthma: The STORM Study. J Aerosol Med Pulm Drug Deliv. 2022 Aug;35(4):179-185. doi: 10.1089/jamp.2021.0046. Epub 2022 Feb 4.

  PMID: 35128939 RESULT

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Asthma

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

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: December 18, 2018
• First Posted: January 7, 2019
• Study Start: January 14, 2019
• Primary Completion: April 3, 2020
• Study Completion: April 3, 2020
• Last Updated: May 6, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)