E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 evaluate the efficacy by ACR20 response rates of 3 dose levels of TAK-715 in combination with methotrexate versus placebo plus methotrexate in the treatment of the signs and symptoms of rheumatoid arthritis at the end of 6 weeks in subjects with a partial response to methotrexate.
To evaluate the safety of the combination of TAK-715 at each of the 3 dose levels in combination with methotrexate versus placebo plus methotrexate over 6 weeks. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy by ACR50 and ACR70 response rates of 3 dose levels of TAK-715 in combination with methotrexate versus placebo plus methotrexate in the treatment of the signs and symptoms of rheumatoid arthritis over 6 weeks. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Men and women, who are capable of understanding and willing to sign the informed consent, are 18 years or older, with a diagnosis of rheumatoid arthritis for at least 6 months with partial response to methotrexate are to be included in this study.
Subjects must have active rheumatoid arthritis using American College of Rheumatology (ACR) criteria (defined as ≥6 swollen joints and ≥9 tender joints, and a CRP ≥1.2 mg/dL or ESR ≥28 mm/hr) despite methotrexate therapy.
All subjects must have been treated with methotrexate for at least 6 months and have been on a stable dose for at least 4 weeks prior to the Baseline Visit.
Subjects on non-steroidal anti-inflammatory drugs (NSAIDs) must remain on a stable dose of their NSAIDs (throughout the study) and subjects on prednisone (or its equivalent) must remain on a stable maintenance dose (throughout the study) not to exceed 10 mg/day.
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E.4 | Principal exclusion criteria |
Subjects who have hypersensitivity to TAK-715 or its constituents, with a significant history of uncontrolled hypertension, secondary, non-inflammatory type of arthritis, severe liver disease, or any significant results from physical exams, electrocardiograms (ECGs), chest x-ray, purified protein derivative (PPD) skin test for tuberculosis, or clinical laboratory and diagnostic screening tests as determined by the investigator.
The subject has failed therapy due to lack of efficacy with any anti-TNF agent or 2 or more disease-modifying antirheumatic drugs (DMARDs) other than methotrexate.
Excluded medication are:
• All DMARDs and biologics other than methotrexate used to treat rheumatoid arthritis (including tetracycline when used as a DMARD).
• Tetracyclines cannot be used for any reason during the study.
• All systemic (non-DMARD) immunosuppressants with the exception of prednisone or its equivalent.
• Controlled-release oxycodone (OxyContin) and other non-NSAID long-acting analgesics.
• Aspirin and aspirin-containing combination products used for analgesia. (Aspirin ≤325 mg/day for cardiac prophylaxis is permitted.)
• CYP3A4 inhibitors, which include: grapefruit juice, itraconazole, ketoconazole, macrolide antibiotics (not azithromycin) and nefazodone.
• Intra- or peri-articular joint injections are not allowed during the study.
• Any investigational drugs within 30 days prior to enrollment and throughout the trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary safety endpoints will include the following parameters: • Adverse events • Hematology, chemistry and urinalysis laboratory test results • Vital signs • Physical examination findings • Weight • ECG findings
The primary efficacy endpoint for this study is the composite ACR20 response rates at Week 6 for the 3 TAK-715 groups versus the response rate for the placebo group.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 8 |