E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Symptomatic neurogenic orthostatic hypotension (NOH) in patients with Primary Autonomic Failure (PD, MSA and PAF), DBH deficiency and Non-Diabetic Neuropathy. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of droxidopa in patients with symptomatic NOH as measured by the relative change in mean score of Item 1 of the Orthostatic Hypotension Symptom Assessment (OHSA) 7 days following randomization to treatment with droxidopa or placebo. |
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E.2.2 | Secondary objectives of the trial |
Evaluate efficacy of droxidopa as measured by changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements 3 minutes post standing; Evaluate efficacy of droxidopa using the clinician-recorded and patient-recorded Clinical Global Impressions-Severity (CGI-S) and Clinical Global Impressions-Improvement (CGI-I) scales; Evaluate efficacy of droxidopa by symptom and activity measurements using the composite scores of OHSA, OHDAS (the two subcomponents of the Orthostatic Hypotension Questionnaire (OHQ)); Evaluate the safety of droxidopa based on the occurrence of treatment-emergent adverse events and specific evaluation of blood pressure, heart rate, ECG, and laboratory findings across the study. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male or female and aged 18 years or over; Clinical diagnosis of orthostatic hypotension associated with Primary Autonomic Failure (PD, MSA and PAF), Dopamine Beta Hydroxylase Deficiency or Non-Diabetic Autonomic Neuropathies; A documented fall in systolic blood pressure of at least 20 mmHg, or in diastolic blood pressure of at least 10 mmHg, within 3 minutes after standing; Provide written informed consent to participate in the study and understand that they may withdraw their consent at any time without prejudice to their future medical care. |
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E.4 | Principal exclusion criteria |
Taking ephedrine or midodrine; - Patients taking ephedrine or midodrine must stop taking these drugs at least 2 days prior to their baseline visit (Visit 2). Taking anti-hypertensive medication; - the use of short-acting anti-hypertensive medications at bedtime is permitted. Current taking tri-cyclic antidepressant medication or other norepinephrine re-uptake inhibitors Have a history of more than moderate alcohol consumption; Women who are pregnant or lactating; Have a history of closed angle glaucoma; Have pre-existing sustained severe hypertension (BP  180/110 mmHg in the sitting position); Have atrial fibrillation or, in the investigators opinion, have any other significant cardiac arrhythmia; In the investigators opinion, have any other significant systemic, hepatic, cardiac or renal illness; Have diabetes mellitus or insipidus; Have a known or suspected malignancy; Have known gastrointestinal illness or other gastrointestinal disorder that may, in the investigators opinion, affect the absorption of study drug; In the investigators opinion, have clinically significant abnormalities on clinical examination or laboratory testing; Have a serum creatinine level > 130 µmol/L. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is the relative change in the mean score of Item 1 of the Orthostatic Hypotension Symptom Assessment (OHSA) 7 days following the randomization to treatment with droxidopa or placebo. |
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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) | Yes |
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 | 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 | 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 | 12 |
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 | 12 |