Clinical trial NCT02919995 (phase 2, status: completed)
Conditions: cystic fibrosis
ICD codes: E84.9, Z14.1, E84.0, E84.11, E84.8, E84.19, P09.4
Drugs: rpl554, placebo
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
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. Male or female aged ≥18 years at the time of informed consent. Females of
             childbearing potential must have been using a consistent and reliable form of
             contraception (see Appendix 1) from the last menses before the first study treatment
             administration, and must commit to continue to do so during the study and for 3 months
             after the last dose of study treatment.

             3. Have a 12-lead ECG recording at screening (Visit 1) and Visit 2 pre-dose showing
             the following:

               -  Heart rate between 45 and 90 beats per minute

               -  QT interval corrected for heart rate using Fridericia's formula (QTcF) interval
                  ≤450 msec

               -  QRS interval ≤120 msec

               -  PR interval ≤220 msec

               -  No clinically significant abnormality including morphology (e.g. left bundle
                  branch block, atrioventricular nodal dysfunction, ST segment abnormalities) 4.
                  Capable of complying with all study restrictions and procedures including ability
                  to use the study nebuliser correctly.

                  5. Body mass index (BMI) between 18 and 30 kg/m2 (inclusive) with a minimum
                  weight of 40 kg.

                  6. Patients with a genetic diagnosis of CF. 7. Spirometry at screening
                  demonstrating an FEV1 ≥40% and ≤80% of predicted normal.

                  8. Capable of withdrawing from long acting bronchodilators1 until the end of the
                  treatment period, and short acting bronchodilators for 8 hours prior to
                  administration of study treatment.

                  9. Clinically stable CF in the 2 weeks prior to randomisation (Visit 2).

        Exclusion Criteria:

          1. History of cirrhotic liver disease or portal hypertension.

          2. CF exacerbation requiring hospitalisation in the month prior to screening (Visit 1) or
             prior to randomisation (Visit 2).

          3. Use of oral or intravenous antibiotics (in additional to usual maintenance therapy) in
             the 2 weeks prior to screening (Visit 1) or randomisation (Visit 2).

          4. Other non-CF related respiratory disorders: Patients with a current diagnosis of
             active tuberculosis, lung cancer, sarcoidosis, sleep apnoea, known alpha-1 antitrypsin
             deficiency or other active pulmonary diseases.

          5. Previous lung resection or lung transplant.

          6. History of, or reason to believe a patient has, drug or alcohol abuse within the past
             3 years.

          7. Received an experimental drug within 3 months or five half-lives, whichever is longer.

          8. Patients with a history of chronic uncontrolled disease including, but not limited to,
             cardiovascular (including arrhythmias), endocrine, active hyperthyroidism,
             neurological, hepatic, gastrointestinal, renal, haematological, urological,
             immunological or ophthalmic diseases that the Investigator believes are clinically
             significant.

          9. Documented cardiovascular disease: angina, recent or suspected myocardial infarction,
             congestive heart failure, a history of unstable, or uncontrolled hypertension, or has
             been diagnosed with hypertension in last 3 months.

         10. Has had major surgery, (requiring general anaesthesia) in the 6 weeks prior to
             screening (Visit 1) or will not have fully recovered from surgery, or planned surgery
             through the end of the study.

         11. Infection with nontuberculous mycobacteria, methicillin-resistant Staphylococcus
             aureus (MRSA), or Burkholderia species.

         12. Use of immune-suppression; long term use of prednisolone ≥10 mg/day.

         13. History of malignancy of any organ system within 5 years with the exception of
             localised skin cancers (basal or squamous cell).

         14. Clinically significant abnormal values for safety laboratory tests (haematology,
             biochemistry or urinalysis) at screening (Visit 1), as determined by the Investigator.

         15. A disclosed history or one known to the Investigator, of significant non-compliance in
             previous investigational studies or with prescribed medications.

         16. Requires oxygen therapy, even on an occasional basis.

         17. Pregnancy or lactation (female subjects only).

         18. Any other reason that the Investigator considers makes the patient unsuitable to
             participate. -