E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Symptomatic neurogenic orthostatic hypotension |
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E.1.1.1 | Medical condition in easily understood language |
Patients that experience symptoms of low blood pressure when changing their posture |
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E.1.1.2 | Therapeutic area | Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10031127 |
E.1.2 | Term | Orthostatic hypotension |
E.1.2 | System Organ Class | 10047065 - Vascular 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 |
Evaluate the clinical efficacy of droxidopa versus placebo, as demonstrated by improvements in dizziness (OHSA Item #1) from randomization over a 12 week (maximum) treatment period in patients with symptomatic neurogenic orthostatic hypotension |
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E.2.2 | Secondary objectives of the trial |
Evaluate the clinical efficacy of droxidopa versus placebo using endpoints derived from the OHQ, Clinical Global Impression-Improvement (CGI-I), Clinical Global Impression-Severity (CGI-S) and Boston University Activity Measure For Post-Acute Care (AM-PAC) Basic Mobility Outpatient Short Form questionnaires, as well as assessment of patient-reported falls, and BP measurements during the orthostatic standing tests. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. 18 years or older and ambulatory (defined as able to walk at least 10 meters)
2. Clinical diagnosis of symptomatic orthostatic hypotension associated with Primary Autonomic Failure (PD, MSA, and PAF) or Dopamine Beta Hydroxylase Deficiency
3. At the Baseline visit (Visit 2), patients must demonstrate:
a. a score of at least 4 or greater on the Orthostatic Hypotension Symptom Assessment (OHSA) Item #1
b. a fall of at least 20 mmHg in their SBP, within 3 minutes of standing
4. 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 |
1. Score of 23 or lower on the mini-mental state examination (MMSE)
2. Concomitant use of vasoconstricting agents for the purpose of increasing blood pressure;
a. Patients taking vasoconstricting agents such as ephedrine, dihydroergotamine, or midodrine must stop taking these drugs at least 2 days or 5 half-lives (whichever is longer) prior to their baseline visit (Visit 2) and throughout the duration of the study
3. Known or suspected alcohol or substance abuse within the past 12 months
4. Women who are pregnant or breastfeeding
5. Women of childbearing potential (WOCP) who are not using at least one method of contraception with their partner
6. Sustained supine hypertension greater than or equal to 180 mmHg systolic or 110 mmHg diastolic, or have these measurements at their Baseline Visit (Visit 2). Sustained is defined as measurements persistently greater at 2 separate measurements at least 10 minutes apart with the subject supine and at rest for at least 5 minutes
7. Untreated closed angle glaucoma
8. Diagnosis of hypertension that requires treatment with antihypertensive medications (short-acting antihypertensives to treat nocturnal supine hypertension are allowed in this study)
9. Any significant uncontrolled cardiac arrhythmia
10. History of myocardial infarction, within the past 2 years
11. Current unstable angina
12. Congestive heart failure (NYHA Class 3 or 4)
13. Diabetic autonomic neuropathy
14. History of cancer within the past 2 years other than a successfully treated, non-metastatic cutaneous squamous cell or basal cell carcinoma or cervical cancer in situ
15. Gastrointestinal condition that may affect the absorption of study drug (e.g., ulcerative colitis, gastric bypass)
16. Any major surgical procedure within 30 days prior to the Baseline visit (Visit 2)
17. Previously treated with droxidopa within 30 days prior to the Baseline visit (Visit 2)
18. Currently receiving any other investigational drug or have received an investigational drug within 30 days prior to the Baseline visit (Visit 2)
19. Any condition or laboratory test result, which in the Investigator's judgment, might result in an increased risk to the patient, or would affect their participation in the study
20. The Investigator has the ability to exclude a patient if for any reason they feel the subject is not a good candidate for the study or will not be able to follow study procedures |
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E.5 End points |
E.5.1 | Primary end point(s) |
Relative mean change in OHSA Item #1 from Randomization (Visit 4) to Week 1 (Visit 5). |
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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. Relative mean change in OHSA Item #1 from Randomization (Visit 4) to Week 12 (Visit 8)
2. Patient reported falls from Randomization (Visit 4) to Week 12 (Visit 8)
3. Change in standing blood pressure (systolic and diastolic) from Randomization (Visit 4) to Week 12 (Visit 8)
4. Relative mean change in the OHQ Composite score and individual item scores from Randomization (Visit 4) to Week 12 (Visit 8)
5. Relative mean change in the Global assessment evaluations using the clinician-recorded and patient-recorded CGI-S scales from Randomization (Visit 4) to Week 12 (Visit 8)
6. Relative mean change in the Global assessment of improvement of disease status using the clinician recorded and patient-recorded CGI-I scales from Week 1 (Visit 5) to Week 12 (Visit 8)
7. Relative mean change in the AM-PAC Basic Mobility Outpatient Short Form score from Randomization (Visit 4) to Week 12 (Visit 8) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Relative mean change in OHSA Item #1 from Randomization to Week 12 - Visits 6, 7 and 8
2. Patient reported falls - Visits 6, 7 and 8
3. Change in standing blood pressure - Visits 6, 7 and 8
4. Relative mean change in the OHQ Composite score and individual item scores - Visits 6, 7 and 8
5. Relative mean change in the Global assessment evaluations - Visits 6, 7 and 8
6. Relative mean change in the Global assessment of improvement of disease status - Visits 6, 7 and 8
7. Relative mean change in the AM-PAC Basic Mobility Outpatient Short Form score - Visits 6, 7 and 8
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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 | Yes |
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.8.2.4 | 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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 41 |
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 |
Czech Republic |
France |
Germany |
Italy |
Spain |
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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |