Ignite Creation Date:
2025-12-24 @ 4:01 PM
Ignite Modification Date:
2025-12-29 @ 11:46 PM
Study NCT ID:
NCT01327066
Status:
COMPLETED
Last Update Posted:
2012-03-07
First Post:
2011-03-30
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Electrocardiographic (ECG) Safety Study of Droxidopa at Clinical and Supratherapeutic Dose
Sponsor:
Chelsea Therapeutics
Organization:
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2012-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
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.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: