Electrocardiographic (ECG) Safety Study of Droxidopa at Clinical and Supratherapeutic Dose
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Double-Blind Randomized Crossover Trial to Define the Ecg Effects of Droxidopa Using a Clinical and a Supratherapeutic Dose Compared With Placebo and Moxifloxacin (a Positive Control) in Healthy Men and Women: a Thorough ECG Trial|
- ECG Effects [ Time Frame: Baseline to End of Treatment (12 days) ] [ Designated as safety issue: Yes ]The primary ECG endpoint is the time matched, placebo adjusted change from Baseline in QT interval corrected using an individual correction method (QTcI) (ΔΔQTcI). The QTcI method provides an optimization of QT correction for HR as compared with fixed exponent approaches such as Bazett (QTcB) or Fridericia (QTcF).
- QTcF and QTcB (for historic reasons only), HR, and PR, QRS, and uncorrected QT intervals, change in ECG morphological patterns, and the correlation between the QTcI change and droxidopa plasma concentrations [ Time Frame: Baseline to End of Treatment (12 days) ] [ Designated as safety issue: Yes ]
|Study Start Date:||March 2011|
|Study Completion Date:||June 2011|
|Primary Completion Date:||April 2011 (Final data collection date for primary outcome measure)|
Experimental: Droxidopa - Therapeutic
Droxidopa 600 mg
600 mg, single oral dose
Experimental: Droxidopa - Supratherapeutic Dose
Droxidopa 2000 mg
2000 mg, single oral dose
Placebo Comparator: Placebo
400 mg, single oral dose
Other Name: AveloxDrug: Placebo
Placebo matching Droxidopa or Moxifloxacin
Active Comparator: Moxifloxacin
Moxifloxacin 400 mg dose
400 mg, single oral dose
Other Name: Avelox
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01327066
|United States, Texas|
|PPD Phase I Clinic|
|Austin, Texas, United States, 78744|
|Principal Investigator:||Thomas Hunt, MD||PPD Phase I Clinic|