E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Symptomatic Neurogenic Orthostatic Hypotension in Subjects with Primary Autonomic Failure |
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E.1.1.1 | Medical condition in easily understood language |
symptomatic neurogenic Orthostatic Hypotension (snOH) in people with Parkinson's disease (PD), multiple system atrophy (MSA) or pure autonomic failure (PAF) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
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 long-term safety of TD-9855 over a 182-week period. |
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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. Completion of Study 0170 and, in the opinion of the Investigator, would benefit from long-term treatment with TD-9855.
2. The subject must be able to understand the nature of the study and must provide written informed consent prior to the conduct of any study procedures (including any changes occurring in the subject’s current therapeutic regimen).
3. The subject must be willing to continue on treatment and must continue to meet all the inclusion criteria for the preceding study (Study 0170) except, a score of ≥4 in OHSA#1. |
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E.4 | Principal exclusion criteria |
1. Subjects may not be enrolled in another clinical trial, with the exception of purely observational studies, which are allowed.
2. Psychiatric, neurological, or behavioral disorders that may interfere with the ability of subjects to give informed consent, or interfere with the conduct of the study.
3. Medical, laboratory, or surgical issues deemed by the Investigator to be clinically significant.
4. Hypersensitivity to TD-9855 or the formulation excipients. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary safety and tolerability endpoints include:
• Physical examination
• Neurological examination
• Vital signs
• Resting ECGs
• Clinical laboratory tests including biochemistry, hematology, and urinalysis.
• Concomitant medication
• AEs
• Subject compliance to study treatment
• Incidence of falls
• Columbia Suicide Severity Rating Scale (C-SSRS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
• Physical examination evaluated at visits 1,4, 6
• Neurological examination evaluated at visits 1,4, 6
• Vital signs evaluated at visits 1, 2, 3, 4, 5, 6
• Resting ECGs evaluated at visits 1, 4, 6
• Clinical laboratory tests including biochemistry, hematology, and urinalysis evaluated at visits 1, 4 and 6
• Concomitant medication evaluated at all visits and at telephone contacts
• Subject compliance to study treatment evaluated at visits 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14
• Incidence of falls evaluated at visits 1, 2, 3, 4, 5 and 6
• Columbia Suicide Severity Rating Scale (C-SSRS) evaluated at visits 1, 2, 3, 4, 5 and 6 |
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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 | 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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
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 |
Argentina |
Australia |
Austria |
Bulgaria |
Canada |
Chile |
Denmark |
Estonia |
France |
Germany |
Hungary |
Israel |
Italy |
Mexico |
New Zealand |
Peru |
Poland |
Portugal |
Russian Federation |
Spain |
Ukraine |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 11 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 13 |