Asthma, Chronic Obstructive Pulmonary Disease
Conditions
Keywords
Lung deposition, Gamma scintigraphy
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
Interventions
DRUGBeclometasone dipropionate Formoterol Fumarate Glycopyrronium Bromide
single inhalation of 99mTc radiolabelled TRIMBOW pMDI (4 puffs for a total dose of 400mcg BDP, 24mcg FF, 50 mcg GB)
Sponsors
Chiesi Farmaceutici S.p.A.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
28 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
Inclusion criteria for all subjects: 1. Subject's written informed consent obtained prior to any study-related procedure; 2. 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® 3. Body Mass Index (BMI) between 18 and 32 kg/m2 extremes inclusive; 4. Good physical status, determined on the basis of the medical history and a general clinical examination, at screening; 5. Vital signs within normal limits: Diastolic BP 40-90 mmHg, Systolic BP 90-140 mmHg or 90-160 mmHg if \>45 yrs 6. Males fulfilling one of the following criteria: 1. 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 2. 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 3. Non-fertile male subjects (contraception is not required in this case) or 4. Males with partner not of childbearing potential (contraception is not required in this case). 7. WOCBP fulfilling one of the following criteria: 1. 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 2. WOCBP with non-fertile male partners (contraception is not required in this case). 8. 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) 9. 12 -lead digitised Electrocardiogram (12-lead ECG) considered as normal at screening and at Day -1 Additional Criteria only for Healthy Volunteers and Asthmatic patients: 1. Male and female subjects aged 28-55 years inclusive; 2. 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 \> 6 months prior to screening; Additional Inclusion Criteria only for Healthy Volunteers: 1\. Lung function measurements within normal limits at screening: FEV1 equal to or more than 80% of predicted Additional Inclusion Criteria only for Asthmatic patients: 1. Diagnosis of asthma: Established diagnosis of permanent asthma for at least 12 months according to GINA guidelines 2. Patients with a pre-bronchodilator 60%≤ FEV1 \< 80% of the predicted normal value 3. Patients with a documented reversibility defined as an increase ≥ 12% and 200mL over baseline within 30 min after inhalation of 400µg salbutamol pMDI Additional Inclusion Criteria only for COPD patients: 1. Male and female patients aged 40-80 years inclusive 2. A smoking history of at least 10 pack-years 3. Current or ex-smokers are eligible. 4. Established diagnosis of COPD 5. A post-bronchodilator FEV1 ≤ 50% of the predicted normal value and a post-bronchodilator FEV1/FVC \< 0.7 10-15 minutes after 4 puffs (4x100 µg) of Salbutamol pMDI.
Exclusion criteria
Inclusion criteria for all subjects: 1. Pregnant or lactating women; 2. Clinically relevant and uncontrolled respiratory, cardiac, hepatic, gastrointestinal, renal, endocrine, metabolic, neurologic, or psychiatric disorders 3. Clinically relevant abnormal laboratory values at screening suggesting an unknown disease and requiring further clinical investigation 4. Subjects with medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction 5. Positive HIV1 or HIV2 serology at screening 6. Blood donation or blood loss less than 2 months prior screening 7. Participation to another clinical trial where investigational drug was received and last investigations were performed less than 90 days prior to screening; 8. Documented history of alcohol abuse within 12 months prior to screening or a positive alcohol breath test 9. Documented history of drug abuse within 12 months prior to screening 10. Positive results from the Hepatitis serology which indicates acute or chronic Hepatitis B or Hepatitis C at screening 11. 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 12. Unsuitable veins for repeated venepuncture/cannulation 13. Intake of non-permitted concomitant medications in the predefined period prior to screening 14. Radiation exposure, including that from the present study, in the last 12 months 15. Known intolerance/hypersensitivity or contra-indication to treatment Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| intrapulmonary lung deposition | immediately after dosing | calculated using individual Gamma camera images |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| extrathoracic deposition | immediately after dosing | — |
| amount of exhaled drug | immediately after dosing | — |
| TRIMBOW pharmacokinetics - (AUC0-t) | up to 24 hours post dose | Area Under plasma Concentration from 0 to last quantifiable concentration (AUC0-t) for BDP, B17MP, FF and GB |
| lung function assessment - FEV1, FVC, FEV1/FVC, FEF25%, FEF50%, FEF75% | up to 24 hours post dose | FEV1, FVC, FEV1/FVC, FEF25%, FEF50%, FEF75% |
| Intrapulmonary lung distribution of deposition: C/P ratio | immediately after dosing | — |
| TRIMBOW pharmacokinetics - (Cmax) | up to 24 hours post dose | Maximum plasma concentration (Cmax) for BDP, B17MP, FF and GB |
| TRIMBOW - (tmax) | up to 24 hours post dose | time of the maximum plasma concentration (tmax) for BDP, B17MP, FF and GB |
| TRIMBOW pharmacokinetics - (AUC0-∞) | up to 24 hours post dose | area under curve extrapolated to infinity (AUC0-∞) for B17MP, FF and GB |
| TRIMBOW pharmacokinetics - (t1/2) | up to 24 hours post dose | terminal half-life (t1/2) for B17MP, FF and GB |
| TRIMBOW pharmacokinetics - (AUC0-30) | up to 24 hours post dose | area under plasma concentration from 0 to 30 min (AUC0-30) for B17MP, FF and GB |
Countries
United Kingdom
Outcome results
None listed