Investors, however, didn’t seem to be buying Chelsea’s happy chatter, sending Chelsea shares lower by 11% to $5.47 in early trading. The stock was down 18% in the pre-market. Chelsea has now conducted three phase III studies of Northera, two of which failed, raising obvious concerns that the drug will not fare well under a stringent review by U.S. drug regulators. Northera is being developed as a treatment for patients with neurogenic orthostatic hypotension (NOH), a disease characterized by a chronic drop in blood pressure upon standing. The phase III study announced Wednesday, which enrolled Parkinson’s disease patients suffering from NOH, was a failure with Northera unable to demonstrate a benefit over placebo based on patient-reported results from a questionnaire specifically designed to rate the severity of symptoms resulting from low blood pressure and the degree those symptoms interfere with a patient’s ability to perform activities of daily living. Chelsea, however, insisted that investors focus on secondary endpoints of the study, one of which showed that patients treated with Northera suffered fewer falls than patients treated with a placebo. The analysis of the phase III study released Wednesday came from an interim analysis, so Chelsea now plans to change the study’s primary endpoint to assess fall prevention and enroll additional patients with NOH. in December, Chelsea said FDA agreed to allow the company to file for approval of Northera based on two previously conducted clinical trials. Wednesday, Chelsea said the failure of this most recent phase III trial would have no adverse effect on its plans to seek FDA approval of Northera as a treatment for NOH. yet, the phase III study that failed Wednesday used the same NOH symptom questionnaire for the primary endpoint that was used in a previous positive phase III study announced last year. Chelsea used this NOH symptom questionnaire to measure the benefit provided by Northera because a past attempt at using dizziness as a primary endpoint in a phase III study resulted in disappointing, failed outcome.