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Droxidopa in patients with neurogenic orthostatic hypotension associated with Parkinson's disease (NOH306A).
J Parkinsons Dis. 2014; 4(1):57-65.JP

Abstract

BACKGROUND

Neurogenic orthostatic hypotension (nOH) is common in Parkinson's disease (PD), and represents a failure to generate norepinephrine responses appropriate for postural change. Droxidopa (L-threo-3,4-dihydroxyphenylserine) is an oral norepinephrine prodrug.

OBJECTIVE

Interim analyses of the initial patients enrolled in a multicenter, randomized, double-blind, placebo-controlled phase 3 trial of droxidopa for nOH in PD (ClinicalTrials.gov Identifier: NCT01176240).

METHODS

PD patients with documented nOH underwent ≤ 2 weeks of double-blind droxidopa or placebo dosage optimization followed by 8 weeks of maintenance treatment (100-600 mg t.i.d.). The primary efficacy measure was change in Orthostatic Hypotension Questionnaire (OHQ) composite score from baseline to Week 8. Key secondary variables included dizziness/lightheadedness score (OHQ item 1) and patient-reported falls.

RESULTS

Among 24 droxidopa and 27 placebo recipients, mean OHQ composite-score change at Week 8 was -2.2 versus -2.1 (p = 0.98); in response to this pre-planned futility analysis, the study was temporarily stopped and all data from these patients were considered exploratory. At Week 1, mean dizziness/lightheadedness score change favored droxidopa by 1.5 units (p = 0.24), with subsequent numerical differences favoring droxidopa throughout the observation period, and at Week 1, mean standing systolic blood-pressure change favored droxidopa by 12.5 mmHg (p = 0.04). Compared with placebo, the droxidopa group exhibited an approximately 50% lower rate of reported falls (p = 0.16) and fall-related injuries (post-hoc analysis).

CONCLUSIONS

This exploratory analysis of a small dataset failed to show benefit of droxidopa, as compared with placebo by the primary endpoint. Nonetheless, there were signals of potential benefit for nOH, including improvement in dizziness/lightheadedness and reduction in falls, meriting evaluation in further trials.

Authors+Show Affiliations

University of South Florida, Tampa, FL, USA.Chelsea Therapeutics, Inc., Charlotte, NC, USA.Parkinson's Disease and Movement Disorders Center of Boca Raton, Boca Raton, FL, USA.

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24326693

Citation

Hauser, Robert A., et al. "Droxidopa in Patients With Neurogenic Orthostatic Hypotension Associated With Parkinson's Disease (NOH306A)." Journal of Parkinson's Disease, vol. 4, no. 1, 2014, pp. 57-65.
Hauser RA, Hewitt LA, Isaacson S. Droxidopa in patients with neurogenic orthostatic hypotension associated with Parkinson's disease (NOH306A). J Parkinsons Dis. 2014;4(1):57-65.
Hauser, R. A., Hewitt, L. A., & Isaacson, S. (2014). Droxidopa in patients with neurogenic orthostatic hypotension associated with Parkinson's disease (NOH306A). Journal of Parkinson's Disease, 4(1), 57-65. https://doi.org/10.3233/JPD-130259
Hauser RA, Hewitt LA, Isaacson S. Droxidopa in Patients With Neurogenic Orthostatic Hypotension Associated With Parkinson's Disease (NOH306A). J Parkinsons Dis. 2014;4(1):57-65. PubMed PMID: 24326693.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Droxidopa in patients with neurogenic orthostatic hypotension associated with Parkinson's disease (NOH306A). AU - Hauser,Robert A, AU - Hewitt,L Arthur, AU - Isaacson,Stuart, PY - 2013/12/12/entrez PY - 2013/12/12/pubmed PY - 2014/10/15/medline KW - Hypotension KW - Parkinson's disease KW - droxidopa KW - falls KW - orthostatic KW - treatment SP - 57 EP - 65 JF - Journal of Parkinson's disease JO - J Parkinsons Dis VL - 4 IS - 1 N2 - BACKGROUND: Neurogenic orthostatic hypotension (nOH) is common in Parkinson's disease (PD), and represents a failure to generate norepinephrine responses appropriate for postural change. Droxidopa (L-threo-3,4-dihydroxyphenylserine) is an oral norepinephrine prodrug. OBJECTIVE: Interim analyses of the initial patients enrolled in a multicenter, randomized, double-blind, placebo-controlled phase 3 trial of droxidopa for nOH in PD (ClinicalTrials.gov Identifier: NCT01176240). METHODS: PD patients with documented nOH underwent ≤ 2 weeks of double-blind droxidopa or placebo dosage optimization followed by 8 weeks of maintenance treatment (100-600 mg t.i.d.). The primary efficacy measure was change in Orthostatic Hypotension Questionnaire (OHQ) composite score from baseline to Week 8. Key secondary variables included dizziness/lightheadedness score (OHQ item 1) and patient-reported falls. RESULTS: Among 24 droxidopa and 27 placebo recipients, mean OHQ composite-score change at Week 8 was -2.2 versus -2.1 (p = 0.98); in response to this pre-planned futility analysis, the study was temporarily stopped and all data from these patients were considered exploratory. At Week 1, mean dizziness/lightheadedness score change favored droxidopa by 1.5 units (p = 0.24), with subsequent numerical differences favoring droxidopa throughout the observation period, and at Week 1, mean standing systolic blood-pressure change favored droxidopa by 12.5 mmHg (p = 0.04). Compared with placebo, the droxidopa group exhibited an approximately 50% lower rate of reported falls (p = 0.16) and fall-related injuries (post-hoc analysis). CONCLUSIONS: This exploratory analysis of a small dataset failed to show benefit of droxidopa, as compared with placebo by the primary endpoint. Nonetheless, there were signals of potential benefit for nOH, including improvement in dizziness/lightheadedness and reduction in falls, meriting evaluation in further trials. SN - 1877-718X UR - https://www.unboundmedicine.com/medline/citation/24326693/Droxidopa_in_patients_with_neurogenic_orthostatic_hypotension_associated_with_Parkinson's_disease__NOH306A__ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JPD-130259 DB - PRIME DP - Unbound Medicine ER -