QTc Interval Clinical Trial
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
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.
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.
;
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
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