E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Dementia with Lewy bodies (DLB) |
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E.1.1.1 | Medical condition in easily understood language |
Dementia with Lewy bodies (DLB) is a type of dementia that shares symptoms with both Alzheimer's disease and Parkinson's disease. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067889 |
E.1.2 | Term | Dementia with Lewy bodies |
E.1.2 | System Organ Class | 10029205 - Nervous system 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 assess the long-term safety and tolerability of 35 mg and 70 mg RVT-101 in subjects with DLB |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female subjects who have completed the last on-treatment visit (Visit 12) of the lead-in study (RVT-101-2001). Subjects who were prematurely discontinued from the lead-in study may be enrolled in this study only after discussion with the Medical Monitor. The number of subjects enrolled in this study who did not complete the lead-in study (RVT-101-2001) will be capped at 12. 2. If the subject is currently receiving any of the following medications or non-medication therapies, the treatment regimen has been stable (i.e., no changes in the type of drug, dose or frequency of dosing) for at least 30 days prior to the Screening/Baseline Visit and there is no intent to change this treatment regimen up to Visit 4 of this study. • Acetylcholinesterase inhibitors (i.e., donepezil, galantamine, rivastigmine, tacrine) • Memantine • Axona® (caprylidene) • Antidepressants (other than MAO inhibitors) • Thyroid hormones • Atypical antipsychotics (e.g., quetiapine) • Benzodiazepines and other sedatives/hypnotics Note: Benzodiazepines or other sedatives/hypnotics (including antihistamines) with half-life less than 6 hours can be taken on an as needed basis. • Cognitive tasks for cognitive rehabilitation under medical supervision • Neurostimulation 3. Female subjects must be: a) Of non-childbearing potential (i.e., any female who is post-menopausal [greater than 1 year without menstrual period in the absence of hormone replacement therapy]) or surgically sterile; or, b) If pre-menopausal or menopausal for 1 year or less, must have a negative pregnancy test and must not be lactating at the Screening/Baseline visit. Female subjects of childbearing potential and who are sexually active are required to use a highly effective method of birth control during the course of the study. Female subjects for whom menopausal status is in doubt, in the opinion of the investigator, will be required to use a highly effective form of birth control. Highly effective forms of birth control are defined as methods that have a failure rate of less than 1% per year when used correctly and consistently and include: • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation; oral, intravaginal, or transdermal • progestogen-only hormonal contraception associated with inhibition of ovulation; oral, injectable, or implantable • intrauterine device (IUD) • intrauterine hormone-releasing system (IUS) • bilateral tubal occlusion • vasectomised partner • sexual abstinence • double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository) Subjects who have a positive pregnancy test during the study or become pregnant during the study will be discontinued. 4. Male subjects who are sexually active and whose partner is of child-bearing potential are required to use an adequate form of birth control, including at least 1 barrier method. 5. Subject continues to be able to ingest pills (in tablet form) whole. 6. Subject has a caregiver who has signed an agreement to oversee the subject’s compliance with IP and protocol-specified procedures and report on subject’s health status. 7. Subject has provided full written informed consent prior to the performance of any protocol-specified procedure; or, if unable to provide informed consent due to cognitive status, subject has provided assent and a legally acceptable representative (LAR) has provided full written informed consent on behalf of the subject. 8. Subject is able to comply with the study procedures in the opinion of the investigator. 9. The subject’s general health status is acceptable for participation in this study. |
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E.4 | Principal exclusion criteria |
1. Subject who, at Visit 1, is experiencing an ongoing, uncontrolled AE(s) from the lead-in study (RVT-101-2001) or did experience an uncontrolled AE in the lead-in study (RVT-101-2001) that might prevent the subject from safely participating in the study in the opinion of the investigator. Subjects who experienced an SAE that was deemed related, possibly related or probably related to IP during the lead-in study may be considered for participation in this study only after discussion with the Medical Monitor. 2. Subject who, in the opinion of the investigator, had a clinically significant vital sign or ECG abnormality at Visit 12 of the lead-in study, or at the Screening/Baseline visit for this study, that would prevent the subject from safely participating in this study. 3. Subject who, in the opinion of the investigator, had a clinically significant laboratory abnormality at Visit 11 or Visit 12 of the lead-in study, or at the Screening/Baseline visit for this study, that would prevent the subject from safely participating in this study. Investigators need not wait for laboratory results at Visit 12 of the lead-in study or the Screening/Baseline Visit of this study before enrolling the subject in this study. However, any clinically significant abnormality subsequently identified from Visit 12 of the lead-in study and/or at the Screening/Baseline visit for this study will be evaluated by the investigator and the subject assessed for continued participation. 4. Subject who, in the opinion of the investigator, has any confounding medical or psychiatric condition that would prevent the subject from safely participating in this study. 5. Significant suicide risk as defined by (a) suicidal ideation as endorsed on items 4 or 5 of the suicidal ideation section of the Since Last Visit version C-SSRS at the Screening/Baseline visit of this study or (b) any suicidal behaviour endorsed on the Since Last Visit version of the C-SSRS at the Screening/Baseline visit of this study, or (c) clinical assessment of significant suicidal risk. 6. Treatment with any concomitant medication detailed in Table 1. Prohibited medications as outlined in Table 1 unless otherwise specified, need to have been discontinued for 5 half-lives prior to the Screening/Baseline Visit and assessed as no longer clinically necessary for the subject. 7. Confirmed corrected QT interval (QTc) value ≥ 450 msec for males or ≥ 470 msec for females at the Screening/Baseline visit for this study. Subjects with a QRS value greater than 120 msec and subjects with a QTc value less than 500 msec may be eligible following discussion with the Medical Monitor. 8. Subject who, in the investigator’s opinion, is unable to take the IP product as directed throughout the study (with assistance is acceptable) or who has demonstrated significant non-compliance with IP in the lead-in study (RVT-101-2001). 9. Subject or caregiver is an immediate family member or employee of the participating investigator, any of the participating site staff, or of the sponsor study staff. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of AEs and changes in physical examinations, vital signs measurements (including measurements of orthostatic changes in BP and HR), ECGs, clinical laboratory assessments, QSO, and C-SSRS results |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Visit 1 (Screening/Baseline)
Treatment Period (V2 through V7): Visits 2 through 7 should be scheduled relative to Visit 1 with a visit window of ±3 days for Visits 2 and 3 and a visit window of ±7 days for Visits 4 to 7. If the visit window is used, the subsequent visit should remain according to the planned visit schedule (i.e., the subsequent visit date should not be re-calculated from the date of the previous visit but should remain relative to the Screening/Baseline visit).
Follow-Up Visit (Visit 8): All subjects who complete Visit 7 or the ET Visit will be required to attend a Safety Follow-up Visit (Visit 8) 14 to 19 days after Visit 7 or the ET Visit. |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 |
Different dosage of same product |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
Canada |
France |
Italy |
Netherlands |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 12 |