Cold Challenge With C21 in RP

Exclusion Criteria

• •1. Smoking (including E-cigarettes) or use of nicotine replacement therapy for three months prior to Visit 1 and during the trial.
• •2. BMI \>30
• •3. Mixed connective tissue disease or "overlap" (i.e. those who satisfy more than one set of ACR criteria for a rheumatic disease).
• •4. Concurrent serious medical condition with special attention to cardiac or ophthalmic conditions which in the opinion of the investigator makes the patient inappropriate for this study
• •5. Malignancy within the past 5 years with the exception of in situ removal of basal cell carcinoma and cervical intraepithelial neoplasia grade I
• •6. Planned major surgery within the duration of the study
• •7. Subjects who forsake any alcohol intake or have known uncontrolled allergic conditions or allergy/hypersensitivity to any components of the trial drug or placebo excipients (see Section 7.1)
• •8. Blood donation (or corresponding blood loss) within three months prior to Visit 1
• •9. Treatment with any of the medications listed below within 4 weeks prior to Visit 1:
• •* Any dose-change or initiation of vasoactive substances
• •, and not able or willing to withhold these medications for 3 days preceding Visit 2 and Visit 3, respectively
• •* Iloprost
• •* Any treatment with CYP3A4 inducers (e.g. rifampicin, phenytoin, St John's Wort)
• •* Any treatment with CYP3A4 inhibitors (e.g. clarithromycin, ketoconazole, nefazodone, itraconazole, ritonavir)
• •* Any treatment with medicines that are substrates of CYP1A2, CYP3A4 or CYP2C9 with a narrow therapeutic range
• •* Any experimental drug
• •* Any systemic immunosuppressive therapy other than:
• •* Inhaled corticosteroids which can be used throughout the trial period
• •* The continuation of stable doses of \<10 mg prednisolone
• •* Mycophenolate mofetil (MMF) which must be withheld for 3 days preceding Visit 2 and Visit 3
• •10. Any of the following findings at the time of screening:
• •* Finger temperature below 27°C after acclimatising at an ambient temperature of 23°C for a period of 20 minutes
• •* Prolonged QTcF (\>450 ms), cardiac arrhythmias or any clinically significant abnormalities in the resting ECG, as judged by the Investigator
• •* Positive results for HBsAg, HCVAb or HIV 1+2 Ag/Ab
• •* Positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG)
• •* Clinically significant abnormal laboratory value at Visit 1 indicating a potential risk for the subject if enrolled in the trial as evaluated by the Investigator
• •11. Pregnant or breast-feeding female subjects.
• •12. Female subjects of childbearing potential not willing to use contraceptive methods described in Section 5.3.1.
• •13. Male subjects not willing to use contraceptive methods described in Section 5.3.1.
• •14. Participation in any other interventional trial during the trial period
• •15. Subjects known or suspected of not being able to comply with this trial protocol (e.g. due to alcoholism, drug dependency or psychological disorder)