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New Medical Therapies™

Orthostatic Hypotension

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January 24, 2011

Chelsea Therapeutics reported positive results from a phase III trial of Northera for the treatment of symptomatic neurogenic orthostatic hypotension (NOH). This long-term safety and efficacy study, 303, enrolled 102 subjects with NOH who previously demonstrated a symptomatic benefit from Northera treatment in either of two previous studies. Following the initial three-month open-label treatment period with Northera at doses from 100 mg up to 600 mg three times daily, subjects were randomized to either continue Northera treatment or be withdrawn to placebo for a blinded two-week period. After six months of open-label treatment, subjects taking Northera reported a mean Orthostatic Hypotension Questionnaire (OHQ) composite reduction of 2.9 units (p<0.001) from the mean baseline score. By month 12, the mean OHQ composite score showed a 2.8 unit (p<0.001) improvement from baseline. In a subset of subjects with Parkinsons disease (n≡38), the six-month mean OHQ composite score reflected a statistically significant (p<0.001) 3.3 unit improvement. At 12 months, the PD subgroup had sustained a 50% percent improvement from baseline (p<0.001). Northera also resulted in durable increases in blood pressure, achieving a statistically significant mean improvement of 12.4 mmHg (p<0.01) in standing SBP after 12 months of therapy compared with baseline. In the Parkinsons subgroup there was a 10.8 mmHg improvement (p<0.05) in standing SBP after 12 months of treatment. Safety and tolerability data continued to be positive.

September 27, 2010

Chelsea Therapeutics issued positive results from a phase III trial of Northera for neurogenic orthostatic hypotension. This randomized, placebo-controlled trial enrolled 160 subjects with neurogenic orthostatic hypotension and primary autonomic failure. The subjects initially entered a seven day open-label washout period during which they were titrated to an optimal therapeutic dose of Northera (up to 600 mg three times daily). Subjects were required to demonstrate both a blood pressure and symptomatic improvement to be eligible to move forward. The eligible subjects then entered into a seven day, double-blind, randomized, placebo-controlled treatment period and received either placebo or Northera for one week. Northera provided statistically significant improvement over placebo on composite Orthostatic Questionnaire Score (p≡0.003) . The study also showed statistically significant benefits in all three composite scores and 8 out of 10 Individual Items of the Orthostatic Hypotension Questionnaire. In addition, Northera resulted in significant improvement in standing blood pressure (P<0.001).

May 24, 2010

Chelsea Therapeutics released positive results from a phase III trial of Northera for neurogenic orthostatic hypotension (NOH). This long-term safety extension study (303) was designed to provide long-term, open-label treatment for subjects who had previously demonstrated a symptomatic benefit from Northera treatment in earlier phase III studies. Following the initial three-month open-label treatment period with doses of 100 mg up to 600 mg of Northera three times daily, 75 subjects were randomized to either continue Northera treatment or be withdrawn to placebo for a blinded two-week period to assess the comparative safety and durability-of-effect of Northera against placebo. After three months of open-label treatment, the subjects taking Northera reported a mean decrease of 3.2 units in their Orthostatic Hypotension Questionnaire composite score, representing a greater than 50% reduction in the signs and symptoms of NOH when compared with baseline (p<0.001). By the end of the treatment period, minimal or no orthostatic hypotension was reported by 47% of the subjects, compared with 1% at baseline. In addition, a statistically significant mean improvement of 13.4 mmHg in standing blood pressure was observed after three months of therapy compared with baseline (p<0.001). Northera was safe and well tolerated throughout the extended dosing period.

November 10, 2008

Chelsea Therapeutics reported positive interim data from a phase III trial of droxidopa for the treatment of neurogenic orthostatic hypotension (NOH). This randomized, placebo-controlled, induction-design, four-week trial planned to enroll 118 subjects across international sites. Prior to randomization, all subjects were to be undergo a two-week, open-label dose titration period, during which they would receive up to 600 mg of droxidopa three times daily (tid). All subjects who responded to treatment subsequently underwent a seven day washout period, followed by double-blind randomization to droxidopa or placebo treatment for one week. Results are from the first 35 subjects to complete the open label dose titration phase. Data revealed a clear improvement across all doses of Droxidopa up to 600 mg tid. The average Orthostatic Hypotension Symptom Assessment Scale (OHSA) baseline score for responders prior to treatment was 6.4 and the average score at the end of the titration was 1.8. In addition, a mean improvement in standing systolic blood pressure (SBP) of 27 mmHg was observed. This improvement was achieved with only a modest impact on supine blood pressure, with mean standing SBP increasing 32.4% compared to only a 13.8% increase in mean supine SBP. The double-blind, randomized portion of the study is currently underway.

Chelsea Therapeutics reported positive interim data from a phase III trial of droxidopa for the treatment of neurogenic orthostatic hypotension (NOH). This randomized, placebo-controlled, induction-design, four-week trial planned to enroll 118 subjects across international sites. Prior to randomization, all subjects were to be undergo a two-week, open-label dose titration period, during which they would receive up to 600 mg of droxidopa three times daily (tid). All subjects who responded to treatment subsequently underwent a seven day washout period, followed by double-blind randomization to droxidopa or placebo treatment for one week. Results are from the first 35 subjects to complete the open label dose titration phase. Data revealed a clear improvement across all doses of Droxidopa up to 600 mg tid. The average Orthostatic Hypotension Symptom Assessment Scale (OHSA) baseline score for responders prior to treatment was 6.4 and the average score at the end of the titration was 1.8. In addition, a mean improvement in standing systolic blood pressure (SBP) of 27 mmHg was observed. This improvement was achieved with only a modest impact on supine blood pressure, with mean standing SBP increasing 32.4% compared to only a 13.8% increase in mean supine SBP. The double-blind, randomized portion of the study is currently underway.

January 15, 2007

Chelsea reported positive preliminary results from a phase II trial of droxidopa for the treatment of neurogenic orthostatic hypotension. This double-blind, randomized, placebo-controlled, parallel group trial enrolled 125 subjects in Europe under the direction of Christopher Mathias, D Phil, DSc, FRCP, Professor of Neurovascular Medicine, Imperial College School of Medicine at St. Mary's Hospital, London. Subjects received either placebo or Droxidopa three times daily (tid) in doses ranging from 100 mg to 300 mg, for 28 days. The primary endpoint was to determine the optimal dose of Droxidopa in the treatment of orthostatic hypotension in subjects with multiple system atrophy (MSA) or Parkinson's Disease (PD). Treatment was well tolerated with little difference in adverse events between the droxidopa and placebo groups. Statistical significance in reducing the fall in orthostatic systolic blood pressure (SBP) was demonstrated at 300 mg tid with the difference in SBP being 11.6 mm Hg between the groups. Based on these results, phase III trials are undergoing development.

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