E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-anaemic iron deficient patients with restless legs syndrome |
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E.1.1.1 | Medical condition in easily understood language |
Non-anaemic iron deficient patients with restless legs syndrome |
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E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10022970 |
E.1.2 | Term | Iron deficiency |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 efficacy of FCM versus placebo in the improvement of symptom severity of restless legs syndrome (RLS) as measured by the International Restless Legs Scale (IRLS) rating after 4 weeks |
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E.2.2 | Secondary objectives of the trial |
1. To demonstrate the efficacy of FCM versus placebo in the improvement of symptom severity of RLS as measured by the IRLS rating after 12 weeks.
2. To demonstrate the efficacy of FCM versus placebo according to time to the need for additional non-FCM RLS treatment due to lack or loss of efficacy.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with RLS
2. Patients with moderate to severe intensity of symptoms (IRLS total score ≥15)
3. Female or male patients 18 years of age or over
4. Patients must weigh ≥50 kg
5. Patients with normal haemoglobin levels, defined as ≥11.5 g/dL (females) or ≥12.5 g/dL (males)
6. Patients with serum ferritin <75 mcg/L
7. Patients who are naïve to RLS medication, or who will have taken no RLS medication for at least 7 days before baseline |
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E.4 | Principal exclusion criteria |
1. History or presence of severe psychiatric disorder with the exception of RLS-related mild to moderate depressive symptoms
2. Patients with current augmentation of RLS
3. Patients who were treated for RLS with the following within 4 weeks of baseline:
− Medication approved for RLS used in doses higher than as per current prescribing information (Summary of Product Characteristics).
− Any combination treatment for RLS.
− Medication not approved to treat RLS.
4. History of severe systemic diseases or clinically relevant hepatic dysfunction.
5. Acute or chronic infection, clinically relevant active inflammatory disease, at screening.
6. Known relevant cardiac dysfunction and/or arrhythmias
7. Known history or presence of moderate or severe pain disorders
8. Haemoglobinopathy or haemochromatosis or other iron storage disorders.
9. Use of erythropoietin stimulating agent within 3 months of screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in the IRLS total score (gold standard for efficacy evaluation in RLS) between baseline and Week 4 (Day 29). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Change in the IRLS total score (gold standard for efficacy evaluation in RLS) between baseline and Week 12 (Day 85).
2. Time to the need for additional non-FCM RLS treatment due to lack or loss of efficacy between Day 1 and Week 12 (Day 85) (time-to-event analysis).
3. Change between baseline and Weeks 1 (Day 7), 4 (Day 29), 8 (Day 57) and 12 (Day 85) in the severity of RLS as measured by the 6 items of the RLS-6 scales.
4. Change between baseline and Weeks 1 (Day 7), 4 (Day 29), 8 (Day 57) and 12 (Day 85) in CGI evaluation (Item 1).
5. Analysis of the CGI ratings (Items 2 and 3) at Weeks 1 (Day 7), 4 (Day 29), 8 (Day 57) and 12 (Day 85) and of the PGI-I efficacy rating at Weeks 4 (Day 29) and 12 (Day 85).
6. Proportion of patients with at least 50% improvement from baseline in the IRLS total score at Weeks 1 (Day 7), 4 (Day 29), 8 (Day 57) and 12 (Day 85) (Responder A).
7. Proportion of patients with an improvement by at least 6 points in the IRLS from baseline at any time during the treatment period (Responder B).
8. Change in disease-specific QoL-RLS between baseline and Weeks 4 (Day 29) and 12 (Day 85). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Week 12
2. Week 12
3. Weeks 4, 8, 12
4. Weeks 4, 8, 12
5. Weeks 1, 4, 8, 12
6. Weeks 1, 4, 8, 12
7. Week 12
8. Weeks 4, 12 |
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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 | No |
E.6.7 | Pharmacodynamic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | 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 | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
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 | No |
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 |
Finland |
Germany |
Switzerland |
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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
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Last Visit of Last Subject |
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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 | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 9 |