Study Evaluating 5 Doses of RPL554 and Placebo in COPD Patients Via a Dry Powder Inhaler
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Pulmonary Disease, Chronic Obstructive
Intervention: Part A: RPL554; Part B: RPL554; Placebos
Intervention description: 1 dose of either 50mcg/100mcg/1500mcg/3000mcg/6000mcg or placebo via dry powder inhaler; Patients will receive 4 or 5 repeat dose treatments in crossover fashion - doses will be confirmed after Part A; Part A: 1 dose of either 50ncg/100ncg/1500ncg/3000ncg/6000ncg or placebo via dry powder inhaler.
Part B: Patients will receive 4 or 5 repeat dose treatments in crossover fashion - doses will be confirmed after Part A.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Double (Participant, Investigator)
Enrollment: 37.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to investigate 5 doses of RPL554 and placebo, administered by
      dry powder inhaler (DPI), in patients with moderate to severe chronic obstructive pulmonary
      disease (COPD).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Sign an informed consent document indicating they understand the purpose of and
             procedures required for the study and are willing to participate in the study.

          2. For males, not to donate sperm and either be sexually abstinent or use contraception
             as specified by the protocol. For females, be of non-childbearing potential or use a
             highly effective form of contraception

          3. 12-lead ECG with heart rate between 45 and 90 beats per minute, QTcF ≤450 msec for
             males, and ≤ 470 msec for females, QRS interval ≤120 msec and no clinically
             significant abnormality including morphology

          4. Capable of complying with all study restrictions and procedures including ability to
             use the DPI correctly.

          5. Body mass index (BMI) between 18 and 35 kg/m2 (inclusive) with a minimum weight of 45
             kg.

          6. COPD diagnosis for 1 year [prior to screening

          7. Ability to perform acceptable and reproducible spirometry.

          8. Post-bronchodilator (four puffs of albuterol) spirometry at Screening demonstrating
             the following:

               -  FEV1/Forced Vital Capacity (FVC) ratio of ≤0.70

               -  FEV1 ≥40 % and ≤80% of predicted normal

               -  ≥150 mL increase from pre-bronchodilator FEV1

          9. Clinically stable COPD in the 4 weeks prior to Screening and during the period between
             Screening and Part A.

         10. A chest X-ray showing no abnormalities, which are both clinically significant and
             unrelated to COPD.

         11. Meet the concomitant medication restrictions and be expected to do so for the rest of
             the study.

         12. Current and former smokers with smoking history of ≥10 pack years. 14. Capable of
             withdrawing from long acting bronchodilators for the duration of the study, and short
             acting bronchodilators for 8 hours prior to dosing.

        Exclusion Criteria:

          1. A history of life-threatening COPD including Intensive Care Unit admission and/or
             requiring intubation.

          2. COPD exacerbation requiring oral or parenteral steroids, or lower respiratory tract
             infection requiring antibiotics, within 3 months of Screening or prior to Part A.

          3. A history of one or more hospitalizations for COPD or pneumonia within 6 months of
             Screening or prior to Part A.

          4. Intolerance or hypersensitivity to tiotropium, olodaterol, atropine, ipratropium, or
             RPL554.

          5. Evidence of cor pulmonale or clinically significant pulmonary hypertension.

          6. Other respiratory disorders

          7. Previous lung resection or lung reduction surgery.

          8. Use of immunosuppressive therapy, including oral corticosteroids

          9. Pulmonary rehabilitation, unless such treatment has been stable from 4 weeks prior to
             Screening and remains stable during the study.

         10. History of, or reason to believe a patient has, drug or alcohol abuse within the past
             5 years.

         11. Received an experimental drug within 30 days or five half lives, whichever is longer.

         12. Patients with uncontrolled disease including, but not limited to, endocrine, active
             hyperthyroidism, neurological, hepatic, gastrointestinal, renal, hematological,
             urological, immunological, psychiatric, or ophthalmic diseases that the Investigator
             believes are clinically significant.

         13. Documented cardiovascular disease, including any history of arrhythmias, angina,
             recent (<1 year) or suspected myocardial infarction, congestive heart failure,
             unstable or uncontrolled hypertension, or diagnosis of hypertension within 3 months
             prior to Screening

         14. Use of non-selective oral β-blockers.

         15. Major surgery (requiring general anesthesia) within 6 weeks prior to Screening, lack
             of full recovery from surgery at Screening, or planned surgery through the end of the
             study.

         16. A disclosed history or one known to the Investigator, of significant non compliance in
             previous investigational studies or with prescribed medications.

         17. Required use of oxygen therapy, even on an occasional basis.

         18. History of malignancy of any organ system within 5 years, with the exception of
             localized skin cancers (basal or squamous cell).

         19. Clinically significant abnormal values for safety laboratory tests (hematology,
             biochemistry, viral serology or urinalysis) at Screening, as determined by the
             Investigator. In particular, alanine aminotransferase or aspartate aminotransferase
             cannot be more than twice the upper limit of normal.

         20. Any other reason that the Investigator considers makes the patient unsuitable to
             participate.