E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039073 |
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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 demonstrate the clinical efficacy of L-000883191 1.25 mg twice daily in the treatment of rheumatoid arthritis.
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E.2.2 | Secondary objectives of the trial |
To demonstrate the safety and tolerability of L-000883191 in RA patients. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Patient understands the study procedures and agrees to participate in the study by giving written informed consent. Patient has satisfied (for RA diagnosis) at least 4 of 7 ARA 1987 revised criteria for the diagnosis of RA sometime in the past (see Appendix 2). Patient has active RA with a minimum level ofdisease activity at both Visit I and Visit 2, including at least 10 swollen joints and 10 tender or painful joints, a Patient Giobal Assessment of Disease Activity of >40 mm (on a 100-mm Visual Analog Scale [VAS]), an Investigator Global Assessment of Disease Activity of fair, poor, or very poor (on a 5-point Likert scale), and 1 of the following: an ESR greater than or equal to 28, a CRP of at least 2.0 mg/dL (Sl units: 20.0 mgIL) or morning stiffness that lasts at least 45 minutes.
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E.4 | Principal exclusion criteria |
Patient has any history of conduction system abnormality or arrhythmia, including but not limited to an abnormal QTc (>440 msec) or prolonged QRS (QRS >120 msec) or prolonged PR (>200 msec) interval on the Visit 1.0 ECG. Patients noted to have a QTc interval of> 440 msec at any later point in the study will be removed from the study. For patients who do not have a history of tuberculosis, an intradermal PPD test will be administered at the screening visit. A patient with a PPD test result of<l0 mm diameter induration will be considered eligible to participate in the study if there is no evidence of prior or active TB on chest x ray. Patients with a PPD of>10 mm will be excluded from the study regardless of radiographic findings. For patients on immunosuppressive therapy (e.g., methotrexate, leflunomide or steroids) at the time of testing, a cutoff of 5 mm should be used. Patients who have had a PPD result of<5 mm within the previous 3 months (prior to enrollment) and have had no pulmonary symptoms since the time of this test, need not repeat this test. It is acknowledged that screening procedures for TB vary from region to region worldwide. In regions where published local guidelines for the screening of patients for TB exist, those guidelines should be reviewed and the most conservative approach (either that outlined in this study or those recommended by published local guidelines) should be followed. Except for patients with a recent chest x-ray (3 months [which has been read as negative and is available for review]; and have had no pulmonary symptorns since the time of the film), all patients should have a chest x-ray at the time of screening. Patient has evidence of any acute or chronic gastrointestinal disease documented by history, physical examination, radiography or scans, and / or laboratory values. This includes a history of complicated peptic ulcer disease, Crohn disease, ulcerative colitis, proctitis, mesenteric arteritis or enteritis as well as unexplained diarrhea, bloody or mucoid stools, loose stools, nausea, vomiting, dyspepsia, or abdominal pain. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Swollen joint counts based on the average responses across Weeks 8,10 and 12 including discontinuation visits.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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 | Yes |
E.8.1.6 | Cross over | No |
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 | Yes |
E.8.2.3.1 | Comparator description |
paracetamol for rescue medication |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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
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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 | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 10 |