Clinical trial NCT03071081 (phase 1, status: completed)
Conditions: ulcerative colitis
ICD codes: K51.80, K51.813, K51.814, K51.90, K51.913, K51.914, K51.811
Drugs: top1288, placebo to top1288
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. Subject is a healthy male, aged between 18 and 55 years of age (inclusive) at
             Screening.

          2. Subject has a body mass index (BMI) of between 18.0 and 29.9 kg/m2 (inclusive), with a
             body weight of at least 50 kg at Screening.

          3. Subject is in good physical and mental health in the opinion of the Investigator.

          4. Subject has clinical laboratory test results within the reference ranges of the
             testing laboratory unless results outside the reference ranges are deemed not
             clinically significant by the Investigator at Screening and Day -1.

          5. Subject has a supine blood pressure and pulse rate within the normal range after 5
             minutes' rest (systolic blood pressure: 90 to 140 mmHg, diastolic blood pressure: 40
             to 90 mmHg, pulse rate: 40 to 90 beats per minute) at Screening and Day -1.

          6. Subjects must be willing to comply with the contraception restrictions of the protocol
             for this study.

          7. Subject has regular bowel opening of usually 1 motion per day of normal consistency.

        Exclusion Criteria:

          1. Subject has participated in another study of an investigational medication (or a
             medical device) within the last 3 months or 5 half-lives of the investigational
             medication, whichever is longer, prior to the first day or dosing.

          2. Subject has made a blood donation (> 400 mL) or had a comparable blood loss (> 350 mL)
             within the last 3 months prior to first administration of study drug.

          3. Subject tests positive for human immunodeficiency virus (HIV)-1/2 antibodies,
             hepatitis B surface antigen, or hepatitis C antibodies at Screening.

          4. Subject has a history of alcohol and/or drug abuse.

          5. Subject has an alcohol consumption of more than 21 units of alcohol per week.

          6. Subject tests positive for alcohol and/or drugs (urine tests) at Screening or
             admission.

          7. Subject has received any prescription or non-prescription medications, including
             over-the-counter medications, nutraceuticals (e.g., St. John's Wort, ginseng, kava
             kava, Ginkgo biloba and melatonin), foods or beverages containing grapefruit and
             vitamin supplements within 14 days prior to admission (Day -1) or nutraceuticals
             containing caffeine- or xanthine-related substances within 72 hours prior to admission
             (Day -1). Foods or beverages containing Seville-type (sour) oranges, or poppy seeds
             are also excluded within this time period.

          8. The subject has a history of daily consumption of 5 or more cups of coffee or tea.

          9. Subject has a known hypersensitivity to any components of the study drug.

         10. Subject has any history of any clinically significant acute or chronic condition
             affecting the colon and/or rectum and/or anus, including haemorrhoids and irritable
             bowel syndrome, sufficient to cause symptoms and/or that in the judgement of the PI
             and the Sponsor's study Physician/Medical Monitor would interfere with the subject's
             participation in the study.

         11. Any findings on pre-dose endoscopy that in the PI's judgement would interfere with
             subject participation in the study.

         12. Subject has acute or chronic condition affecting GI motility such as constipation or
             diarrhoea that would, in the judgement of the PI and the Sponsor's study
             Physician/Medical Monitor, interfere with the subject's participation in the study

         13. Subject has cardiovascular or cerebrovascular disease, including hypertension, angina,
             ischaemic heart disease, transient ischaemic attacks, stroke and peripheral arterial
             disease sufficient to cause symptoms and/or require therapy to maintain stable status.

         14. Subject has an active infection (e.g., sepsis, pneumonia, abscess) or has had a
             serious infection (resulting in hospitalisation or requiring parenteral antibiotic
             treatment) within 6 weeks prior to study drug administration.

         15. Subject has a history of positive tuberculosis test or evidence of possible
             tuberculosis or latent tuberculosis infection at Screening (interferon gamma release
             assay testing) that cannot be attributed to a prior Bacillus Calmette-Guérin
             inoculation.

         16. Subject has received live attenuated vaccination within 6 weeks prior to Screening or
             intends to have such a vaccination during the course of the study.

         17. Subject has any of the following haematology values at Screening or Day -1:

               -  Haemoglobin, < 13 g/dL.

               -  Absolute neutrophil count < 1.5 x 109/L (< 1500/μL).

         18. Subject has a 12-lead electrocardiogram (ECG) with results considered to be
             potentially clinically significant, e.g., QTcF > 450 ms, bundle branch block, evidence
             of myocardial ischaemia, at Screening or Day -1.

         19. Subject has an abnormality in the ECG that, in the opinion of the Investigator,
             increases the risks associated with participating in the study.

         20. Subject has renal or liver impairment at Screening or Day -1, defined as:

               -  Serum creatinine level ≥ 135 μmol/L, or

               -  Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≥2 x upper
                  limit of normal, or

               -  Alkaline phosphate and/or bilirubin > 1.5 x upper limit of normal (an isolated
                  bilirubin 1.5 x upper limit of normal is acceptable if bilirubin is fractionated
                  and direct bilirubin is < 35%).

         21. Subject has active neoplastic disease or history of any neoplastic disease within 5
             years of Screening (except for basal or squamous cell carcinoma of the skin or
             carcinoma in situ that has been definitively treated with standard of care).

         22. Subject has any other acute or chronic illness which, in the opinion of the
             Investigator or Sponsor's study Physician/Medical Monitor, could pose a threat or harm
             to the subject's participation in the study.

         23. The subject has used nicotine-containing products (including, but not limited to,
             cigarettes, pipes, cigars, chewing tobacco, nicotine patch, or nicotine gum) within 2
             weeks prior to admission to the study centre (Day -1).