Lung Deposition of TRIMBOW® pMDI in Healthy Volunteers, Asthmatic and COPD Patients
Lung Deposition of TRIMBOW® pMDI in Healthy Volunteers, Asthmatic and COPD Patients
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
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 exclusion Criteria only for Healthy volunteers and Asthmatic patients:

 1. Positive urine test for cotinine at screening or prior Day 1

 2. Current use of any nicotine or nicotine replacement product

 Additional exclusion criteria only for Asthmatic and COPD patients:

 1. Use of systemic corticosteroids medication within 4 weeks prior to the screening or
 slow release corticosteroids within 12 weeks before the screening or prior Day 1

 2. A diagnosis of lung cancer or a history of lung cancer

 3. A history of lung volume reduction surgery

 4. Lower respiratory tract infection that requires use of antibiotics

 Additional exclusion Criteria only for Healthy volunteers:

 1. Subjects with history of breathing problems

 Additional exclusion Criteria only for Asthmatic patients:

 1. History of near fatal asthma, hospitalization for asthma in intensive care unit

 2. Any change in dose, schedule or formulation in the treatment of asthma in the 4 weeks
 prior to the screening visit or prior Day 1

 3. Non-persistent asthma:

 4. Treatment with chronic systemic corticosteroids or anti IgE or other monoclonal
 antibodies

 5. Known respiratory disorders other than asthma

 Additional exclusion Criteria only for COPD patients:

 1. Any change in dose, schedule or formulation in the treatment for COPD in the 4 weeks
 prior to the screening

 2. A concurrent diagnosis of asthma, in the opinion of the investigator

 3. Known respiratory disorder other than COPD that in the Investigator's opinion would
 affect efficacy and safety evaluation or place the patient at risk.

 4. Oxygen therapy: patients requiring long term (at least 12 hours daily) oxygen therapy
 for chronic hypoxemia.

 5. Change in dose or type of any medications for COPD within 4 weeks prior to the
 screening visit.