Table 3.

Phase 3 clinical studies with droxidopa (L-DOPS) in patients with neurogenic OH

Study	Subjects (N)	Design	Enrichment design	L-DOPS dosage	Length	Titration	Primary efficacy endpoints	Results
NOH301 [67]	162 (PD, MSA, PAF, NDAN, DBHD)	Multicenter, multinational, double blind, randomized controlled trial parallel group induction design	Yes	100–600 mg three times daily	Initial open label titration, 1-week washout, 7-day randomized placebo controlled phase	Open label – before randomization	OHQ composite score at 1 week	Compared with placebo, patients on droxidopa had a significant improvement in overall OHQ scores (p<0.003); and standing BP that was 7 mmHg higher (p<0.001)
NOH302 [62]	101 (PD, MSA, PAF, NDAN, DBHD)	Multicenter, double blind, randomized controlled trial with withdrawal design	Yes	100–600 mg three times daily	Initial open label titration, 7-day open label treatment, 2-week of double blind placebo controlled phase	Open label – before randomization	OHQ Item 1 (dizziness / lightheadedness) at 2 weeks	No differences in the OHQ item 1. Significant improvement of the overall OHQ composite score on droxidopa than placebo (p=0.013). Standing systolic BP was not different between the two groups. Patient self-reported symptom severity showed a significant improvement with droxidopa (p=0.008).
NOH306A [69] NOH306B [101]	51 PD (306A) 171 PD (306 B)	Multicenter, double blind, randomized controlled trial parallel group induction design	No	100–600 mg three times daily	2-week double-blind titration; 8 weeks double blind maintenance treatment	Double blind – after randomization	OHQ composite score at 8 weeks (306A) OHQ Item 1 at 1 week (306B)	For the initial 51 subjects (Study 306A), the primary efficacy measure (OHQ composite score) did not show significant change versus placebo at week 8. For the subsequent 171 subjects (Study 306B) patients taking droxidopa had a significant improvement in symptoms of dizziness/lightheadedness (OHQ item 1) compared to placebo after 1 week (p = 0.018); and higher systolic BP standing (p=0.032).
NOH303 (Unpublished)	75 (PD, MSA, PAF, NDAN, DBHD)	Multicenter, open-label extension to 301 and 302 studies	No	100–600 mg three times daily	3-month open label treatment; 2 week placebo-controlled withdrawal phase; after the controlled phase of the trial some patients continued on open-label droxidopa for up to 2 years	No	OHQ composite score	No significant differences between treatment arms.
NOH304 (Unpublished)	255 (PD, PAF, NDAN, DBHD)	Long term, open-label safety extension to 301, 302 and 306 studies	No	100–600 mg three times daily	Up to 1–2 years	No	Safety measures	N/A
NOH305 [48]	18 (PD, PAF, NDAN, DBHD)	Multicenter, open-label extension to 301 and 304 studies	No	100–600 mg three times daily	An off drug 24-hour ambulatory BP assessment was compared to a 4–6 week on-drug 24-hour ambulatory BP assessment	No	Mean 24-hour systolic and diastolic BP	Overall mean 24-hour SBP and DBP were higher compared to off drug (137/81 mm Hg vs. 129/76 mmHg; p=0.017/0.002). Mean daytime SBP was significantly higher with droxidopa (8.4 ± 3.1 mmHg; p=0.014). Nocturnal BP was not significantly higher on droxidopa versus off treatment (p= 0.122).