E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037917 |
E.1.2 | Term | Raynauds |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the severity of secondary Raynaud’s disease-related attacks during the 14-day SLx-2101 dosing period. |
|
E.2.2 | Secondary objectives of the trial |
- To investigate the frequency and total daily duration of secondary Raynaud’s disease-related attacks during the 14-day SLx-2101 dosing period. - To determine the safety and tolerability of repeat oral doses of SLx-2101 in patients with secondary Raynaud’s disease over 14 days dosing. - To explore the effect of SLx-2101 on capillary blood flow velocity and vasospastic symptoms in patients with secondary Raynaud’s disease. - To determine the pharmacokinetic profile of repeat oral doses of SLx 2101 in patients with secondary Raynaud’s disease. - To assess changes in pulmonary artery systolic pressure (PASP) using Doppler echocardiography. - To investigate the effects of SLx-2101 on inflammatory parameters (CRP, IL-6) and on brain natriuretic peptide (BNP).
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female subjects aged between 18 and 65 years, inclusive. Female subjects must be of non-childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy, double oophrectomy or tubal ligation or postmenopausal defined as 12 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and E2 level less than or equal to 25 pg/mL or Females, who are of childbearing potential, must use adequate contraception with double protection prior to and during the trial: double barrier methods (condom, diaphragm, coil or intrauterine device (IUD) in combination with spermicide) or hormonal contraception (oral. depot or implants) in combination with a barrier method. 2. Able to provide written informed consent prior to the performance of any study specific procedures. 3. Body weight within a body mass index range of 17 – 30 kg/m2 (inclusive). 4. History of secondary Raynaud’s disease of at least 1 year since diagnosis. 5. A 12-lead ECG at the pre-study medical, which in the opinion of the Investigator has no abnormalities that will compromise safety in this study. 6. No known positive pre-study urine drugs of abuse screen. 7. Subject able and prepared to withdraw from all vasoactive agents (e.g., calcium channel blockers, nitrates, etc.) at least 1 week before initiating in the study. 8. No known positive pre-study hepatitis B antigen, hepatitis C test and human immunodeficiency virus tests. 9. Secondary Raynaud’s disease due to sclerodermia and / or connective tissue disease. 10. Available to complete all study measurements.
|
|
E.4 | Principal exclusion criteria |
1. Past or present disease that is judged by the Investigator to have the potential to interfere with the study procedures, compromise safety, or affect the pharmacokinetic and pharmacodynamic evaluations. 2. Subjects with a hypertension stage 2 (JNC7/NIH, 2004): SBP >=160 mmHg and DBP >=100 mmHg. 3. Subjects with hypotension (systolic blood pressure <95 mmHg and diastolic blood pressure <45 mmHg). 4. Hypersensitivity to the active substance of SLx-2101or to any of the excipients. 5. Moderate and severe hepatic impairment according to Child-Pugh class B and C (documented in the medical record). (Child-Pugh criteria are described in the appendix.) 6. Screening liver function tests exceeding 1.5 times the upper limit of the normal range. 7. Abuse of alcohol, defined as a maximum weekly intake of greater than 21 units or an average daily intake of greater than 3 units for males or an average weekly intake of greater than 14 units or an average intake of greater than 2 units for females (1 unit is equivalent to a half pint of beer or 1 measure of spirits or 1 glass of wine, which is equivalent to 10 mg alcohol). 8. History or presence of gastro-intestinal, hepatic or renal disease (serum creatinine > 2.0 mg/dl) or other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs. 9. History or presence of cardiovascular disease that is judged by the Investigator to have the potential to interfere with the study procedures, compromise safety, or affect the pharmacokinetic and pharmacodynamic evaluations. 10. Recent (last 12 months) history of stroke or myocardial infarction. 11. Intake of any vasoactive agents (e.g., calcium channel blockers, nitrates, etc.) less than 1 week before the start of dosing until the end of the study (follow-up visit). 12. Concomitant treatment with potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir) or inducers (e.g., bosentan, carbamazepine, phenytoin, phenobarbital, St John’s wort and rifamipicine) less than 1 week before start of dosing until the end of the study. 13. Intake of any selective serotonin-reuptake-inhibitors (SSRI). 14. History or presence of loss of vision in one eye caused by a vascular problem. 15. Pregnant or nursing females. 16. Exposure to a new chemical entity within 3 months prior to the first dosing day. 17. Participation in a trial with any investigational drug within 30 days before the start of the study. 18. If participation in the study will result in the subject having donated more than 500 mL blood (males) or 400 mL blood (females) in the previous 6 months.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Daily Raynaud’s condition scores derived from patient questionnaires on scaled ratings (0 points - subject had no difficulties with the Raynaud’s condition; 10 points - subject had extreme difficulties). |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |