Electrocardiographic (ECG) Safety Study of Droxidopa at Clinical and Supratherapeutic Dose
Condition: QTc Interval
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is define the electrocardiographic (ECG) effects of Droxidopa at
      clinical (600 mg) and supratherapeutic (2000 mg) doses compared with placebo and moxifloxacin
      in healthy male and female subjects.
    

Detailed description: 
      This will be a randomized, double blind, single-site, 4 period crossover study in healthy
      male and female subjects to determine if droxidopa administered as a single therapeutic (600
      mg) and a single supratherapeutic (2000 mg) dose delays cardiac repolarization as determined
      by the measurement of QTc interval. Study drug (droxidopa, placebo, and moxifloxacin) will be
      administered in a double blind, double dummy manner. The central ECG laboratory (eResearch
      Technology, Inc, Philadelphia, Pennsylvania) will be blinded to treatment.

      A total of 52 healthy subjects (approximately 26 women and 26 men) will be enrolled and
      randomly assigned to a treatment sequence. Subjects will cross over into 4 treatment periods
      where each subject will receive single doses of the following treatments under fasting
      conditions separated by a minimum 3 day washout period (from Day 1):

        -  Droxidopa 600 mg (therapeutic dose), oral capsules

        -  Droxidopa 2000 mg (supratherapeutic dose), oral capsules

        -  Placebo (matched to droxidopa), oral capsules

        -  Moxifloxacin 400 mg (positive control; over encapsulated), oral Subjects will be
           screened for study participation from Days -21 to -2 and admitted to the clinic on Day
           -2 of Period 1 for prestudy assessments. On Day -1 of each period, subjects will undergo
           a full day of continuous 12 lead Holter monitoring; 4 ECGs will be extracted from the H
           12+ flash card approximately 1 minute apart at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, and
           23 hours.

      On the morning of Day 1 of each period, after at least an 8 hour fast, subjects will receive
      a single dose of study drug according to the randomly assigned treatment sequence. After
      dosing, subjects will be monitored for 23 hours using a continuous 12 lead ECG Holter
      monitor. At the ECG core laboratory, 4 ECGs will be extracted approximately 1 minute apart at
      0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, and 23 hours (Day 2) after dosing. The ECGs will be
      extracted from Holter recording flashcards during a 10 minute ECG extraction window that will
      end at the onset of each pharmacokinetic (PK) collection nominal time point. Each ECG
      extraction window will be preceded by a 10 minute supine rest period.

      A single 12 lead ECG will be performed at Screening for inclusion/exclusion in the study, and
      a baseline safety 12 lead ECG will be performed at Check in. In addition, a safety 12 lead
      ECG will be recorded and reviewed by the investigator on Day 1 of each period at 2 hours
      after dosing.

      Pharmacokinetic blood samples will be collected on Day 1 of each period before dosing and
      0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, and 23 hours (Day 2) after dosing. Subjects will be
      supine for at least 10 minutes before each of the time points for PK samples. The ECG
      extractions will be time matched to the PK samples, but will be obtained before the actual
      sampling time to avoid changes in autonomic tone associated with the psychological aspects of
      blood collection as well as the reduction in blood volume subsequent to blood collection.

      Meal timing and components, activity levels, and general conditions in the Phase I unit will
      be as similar as possible on Day -1 and Day 1 of each treatment period. Subjects will be
      discharged on Day 2 of Period 4 (ie, 24 hours after the last dose is administered). The total
      study duration will be approximately 34 days.
    

Intervention name(s): Droxidopa; Droxidopa; Moxifloxacin; Placebo
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 600 mg, single oral dose; 2000 mg, single oral dose; 400 mg, single oral dose; Placebo matching Droxidopa or Moxifloxacin
Other intervention name(s): L-DOPS; Northera; L-DOPS; Northera; Avelox; sugar pill; sham
Intervention MeSH terms: Moxifloxacin; Droxidopa
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: QTc; ECG Effects