Pharmacokinetics, Safety and Tolerability of Twice-Daily Aclidinium Bromide/Formoterol Fumarate Fixed Dose Combination in Chinese Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: Aclidinium Bromide/Formoterol Fumarate 400/12μg BID
Intervention description: Aclidinium bromide/formoterol fumarate 400/12μg administered by inhalation via the Genuair® multidose dry powder inhaler, twice daily (morning and evening) for 5 days
Intervention MeSH terms: Bromides; Formoterol Fumarate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 40 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: COPD

Summary:

      A Phase IIa, open-label, repeat-dose trial to investigate the pharmacokinetics (PK), safety
      and tolerability of single and multiple twice daily doses of inhaled Aclidinium
      Bromide/Formoterol Fumarate 400/12 μg in 20 Chinese male and female patients with stable
      moderate to severe COPD.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ability to communicate with medical team and staff, willing to participate in the
             trial, willing to give written informed consent, and comply with the trial procedures
             and restrictions.

          -  Chinese men or non-pregnant, non-lactating women, aged ≥40 years old at Visit 1
             (Screening).

          -  Patients with a diagnosis of COPD (GOLD guidelines) for a period of at least 6 months
             prior to Visit 1 (screening).

          -  Current or former smokers with a smoking history of ≥10 pack-years.

          -  Patients with moderate to severe stable COPD (Stage II or Stage III, according to GOLD
             Guidelines) at Visit 1: post-bronchodilator FEV1 ≥30% and <80% and post-bronchodilator
             FEV1/FVC <70%.

          -  Must be able to perform repeatable pulmonary function testing for FEV1 according to
             ATS/ERS 2005 criteria at Visit 1 (Screening).

        Exclusion Criteria:

          -  Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff
             and/or site staff) or patients employed by or relatives of the employees of the site
             or sponsor.

          -  Previous enrolment or randomisation in the present study.

          -  History or current diagnosis of asthma.

          -  Any respiratory tract infection (including the upper respiratory tract) or COPD
             exacerbation (including the mild COPD exacerbation) within 6 weeks prior to screening
             or during the run-in period.

          -  Patients hospitalized for COPD exacerbation (an emergency room visit for longer than
             24 hours will be considered a hospitalization) within 3 months prior to screening and
             during the run-in period.

          -  Use of long-term oxygen therapy ≥15 hours per day.

          -  Patient with a history of hypersensitivity reaction to inhaled anticholinergics,
             sympathomimetic amines, inhaled medication, or any component thereof.

          -  Patients with known narrow-angle glaucoma, symptomatic bladder neck obstruction, acute
             urinary retention, or patients with symptomatic nonstable prostatic hypertrophy.

          -  Patients with Type I or uncontrolled Type II diabetes, uncontrolled hypothyroidism or
             hyperthyroidism, hypokalaemia, hyperadrenergic state, or uncontrolled or untreated
             hypertension.

          -  Clinically significant cardiovascular conditions.

          -  Patient with resting systolic blood pressure ≥160 mmHg, a resting diastolic blood
             pressure ≥100 mmHg, or a resting heart rate ≤50 bpm or ≥100 bpm at Visit 1 (Screening)
             or/and at Visit 2 (Day -1 to Day 7).

          -  Have a body mass index (BMI) ≥40 kg/m2

          -  Electrocardiogram (ECG) at Screening or Day -1 showing corrected QT interval (QTc)
             using Fridericia's correction (QTcF) >470 msec.

          -  Patients with clinically relevant abnormalities in the results of the laboratory
             tests, ECG parameters (other than QTcF), or in the physical examination at Visit 1,
             except those related to COPD.

          -  Positive results for drugs of abuse in the urine at Visit 1 (Screening).

          -  Positive test for hepatitis B surface antigen (HBsAg), hepatitis C antibody and/or
             human immunodeficiency virus (HIV) I antibodies at Visit 1 (Screening).

          -  History of malignancy of any organ system (including lung cancer), treated or
             untreated, within the past 5 years other than basal or squamous cell skin cancer.

          -  Any other serious or uncontrolled physical or mental condition/disease.

          -  Patient with a history (within 2 years prior to Visit 1 [Screening]) of drug and/or
             alcohol abuse that may prevent trial compliance based on investigator judgment.

          -  Taken any medication within 14 days before the first dose of IP, or hormonal drug
             products and traditional Chinese medicines within 30 days before the first dose of IP,
             with the exception of allowed medications listed in the study protocol.

          -  Participation in any other clinical investigation using an experimental drug requiring
             repeated blood or plasma drawn within 60 days of Day 1 at Visit 2.

          -  Have participated in a blood/plasma donation or blood loss greater than 400 mL within
             90 days or greater than 200 mL within 30 days prior to Visit 1 (Screening).

          -  Have any clinical condition that might affect the absorption, distribution,
             biotransformation, or excretion of Aclidinium Bromide/Formoterol Fumarate.

          -  Have consumed caffeine or any grapefruit-containing products within 48 hours or
             alcohol within 72 hours before Day -1 at Visit 2.

          -  Inability to be venipunctured or tolerate venous access as determined by the
             investigator or designee.

          -  Inability to use a multidose DPI.

          -  Subjects unable to give their consent, or subjects of consenting age but under
             guardianship, or vulnerable subjects.

          -  In the opinion of the PI, subjects who are unlikely to comply with the protocol
             requirements, instructions, and trial-related restrictions.

          -  Previously taken Aclidinium or previously participated in an investigational study of
             Aclidinium within 6 months of Day 1