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Integrated Analysis of Droxidopa for the Treatment of Neurogenic Orthostatic Hypotension in Patients with Parkinson Disease.

ABSTRACT: Introduction:Neurogenic orthostatic hypotension (nOH) is associated with neurodegenerative conditions, may cause symptoms of end-organ hypoperfusion, increases fall risk, and can negatively impact quality of life. Droxidopa is approved for the treatment of symptomatic nOH in adults. As the largest subpopulation of patients with nOH has a diagnosis of Parkinson disease (PD), the efficacy and tolerability of droxidopa in patients with PD and nOH were examined using integrated clinical trial data. Methods:Post hoc analyses included data from the phase 3, randomized, placebo-controlled clinical trials of droxidopa (two short-term [1-2 weeks] trials and one medium-term [8-10 weeks] trial) in the subset of participants with PD and symptomatic nOH. Efficacy was assessed using standing blood pressure (BP) measurements and the Orthostatic Hypotension Questionnaire (OHQ), a patient-reported evaluation of nOH symptoms (Orthostatic Hypotension Symptom Assessment [OHSA]), and their impact (Orthostatic Hypotension Daily Activity Scale [OHDAS]). Results:The analysis included 307 patients with PD (droxidopa, n?=?150; placebo, n?=?157). Compared with placebo, droxidopa significantly improved the OHQ composite score (P?=?0.014), the OHSA composite score (P?=?0.022), and the OHDAS composite score (P?=?0.029) from baseline to end of study/week one. We found significant increases in standing mean systolic/diastolic BP for droxidopa versus placebo (P?=?0.003/0.002). Adverse event (AE) rates were qualitatively similar between groups; the most frequently reported AEs in the droxidopa groups included headache, dizziness, nausea, and hypertension. Conclusions:These post hoc analyses suggest that droxidopa provides meaningful clinical benefits and is well tolerated in the treatment of symptomatic nOH in patients with PD.

SUBMITTER: Hauser RA

PROVIDER: S-EPMC6277368 | biostudies-literature | 2018 Nov-Dec

REPOSITORIES: biostudies-literature

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Integrated Analysis of Droxidopa for the Treatment of Neurogenic Orthostatic Hypotension in Patients with Parkinson Disease.

Hauser Robert A RA Biaggioni Italo I Hewitt L Arthur LA Vernino Steven S

Movement disorders clinical practice 20181108 6

<h4>Introduction</h4>Neurogenic orthostatic hypotension (nOH) is associated with neurodegenerative conditions, may cause symptoms of end-organ hypoperfusion, increases fall risk, and can negatively impact quality of life. Droxidopa is approved for the treatment of symptomatic nOH in adults. As the largest subpopulation of patients with nOH has a diagnosis of Parkinson disease (PD), the efficacy and tolerability of droxidopa in patients with PD and nOH were examined using integrated clinical tria ...[more]

PMID: 30637284

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Project description:BackgroundDroxidopa, a prodrug of norepinephrine, was approved for treatment of neurogenic orthostatic hypotension (nOH) due to primary autonomic disorders based on 3 randomized double-blind studies. We performed safety and efficacy analyses of this pooled dataset (n = 460).MethodsEfficacy was assessed using Orthostatic Hypotension Questionnaire (OHQ) scores (composite and individual items). Safety and tolerability were also examined.ResultsDroxidopa improved virtually all nOH symptom scores compared with placebo, significantly reducing OHQ composite score (-2.68 ± 2.20 vs -1.82 ± 2.34 units; P < 0.001), dizziness/lightheadedness score (-3.0 ± 2.9 vs -1.8 ± 3.1 units; P < 0.001), and 3 of 5 other symptom assessments (visual disturbances, weakness, and fatigue [P ≤ 0.010]). Droxidopa significantly improved 3 of 4 measures of activities of daily living (standing a long time, walking a short time, and walking a long time [P ≤ 0.003]) and significantly increased upright systolic blood pressure (11.5 ± 20.5 vs 4.8 ± 21.0 mmHg for placebo; P < 0.001). Droxidopa was effective in patients using inhibitors of dopa decarboxylase (DDCI; the enzyme that converts droxidopa to norepinephrine), but its efficacy was numerically greater in non-DDCI users. Droxidopa was well-tolerated. Rates of most adverse events were similar between groups. Supine hypertension rates were low, but slightly higher in patients receiving droxidopa (≤7.9% vs ≤4.6% for placebo); patients with severe hypertension at screening were excluded from these studies.ConclusionsDroxidopa is effective for the treatment of nOH in patients with primary autonomic disorders and is generally well-tolerated. A longer trial is underway to confirm efficacy beyond the ≤2 to 10 - week period assessed in the current trials.Trial registrationClinicalTrials.gov identifiers: NCT00782340 , first received October 29, 2008; NCT00633880 , first received March 5, 2008; and NCT01176240 , first received July 30, 2010.

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Integrated Analysis of Droxidopa for the Treatment of Neurogenic Orthostatic Hypotension in Patients with Parkinson Disease.

Publications

Integrated Analysis of Droxidopa for the Treatment of Neurogenic Orthostatic Hypotension in Patients with Parkinson Disease.

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