Guanfacine Immediate-release Electrocardiogram Results (QTc) Study

A Phase I, Randomized, Gender Stratified, Double-Blind, Placebo- and Positive-Controlled, Three Period Crossover Trial to Assess the Effect of Guanfacine Hydrochloride on QT/QTc Interval in Healthy Men and Women

To assess the effect of immediate-release guanfacine hydrochloride, administered at therapeutic and supratherapeutic doses, on QT/QTc in healthy normal males and females

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: immediate release guanfacine hydrochloride; Drug: moxifloxacin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Tacoma, Washington, United States
      • Charles River Clinical Services Northwest, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy Normal Subjects

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Subjects will receive placebo on Day 1. Subjects will receive placebo on Day 6.
Experimental: Immediate-release Guanfacine HCl	Drug: immediate release guanfacine hydrochloride; Subjects will receive 2x2mg immediate-release guanfacine on day 1. Subjects will receive 4x2mg immediate-release guanfacine on day 6.; Other Names: Tenex
Active Comparator: Moxifloxacin HCl	Drug: moxifloxacin; Subjects will receive 400mg of moxifloxacin on day 1. Subjects will receive 400mg of moxifloxacin on day 6.; Other Names: Avelox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Electrocardiogram Results (QTcNi) at Time of Maximum Plasma Concentration (Tmax) on Day 1	QTcNi is the QT interval using a subject-specific correction formula. QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). The QT interval has to be corrected in order to aid interpretation.	Baseline, Tmax (time of subject-specific maximum plasma concentration)
Change From Baseline in Electrocardiogram Results (QTcNi) at Tmax on Day 6	QTcNi is the QT interval using a subject-specific correction formula. QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). The QT interval has to be corrected in order to aid interpretation.	Baseline and Tmax (time of subject-specific maximum plasma concentration)
Change From Baseline in Electrocardiogram Results (QTcF) at Tmax on Day 1	QTcF is the QT interval using Fridericia's correction formula. QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). The QT interval has to be corrected in order to aid interpretation.	Baseline and Tmax (time of subject-specific maximum plasma concentration)
Change From Baseline in Electrocardiogram Results (QTcF) at Tmax on Day 6	QTcF is the QT interval using Fridericia's correction formula. QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). The QT interval has to be corrected in order to aid interpretation.	Baseline and Tmax (time of subject-specific maximum plasma concentration)
Change From Baseline in Heart Rate (HR) at Tmax on Day 1		Baseline and Tmax (time of subject-specific maximum plasma concentration)
Change From Baseline in Heart Rate (HR) at Tmax on Day 6		Baseline and Tmax (time of subject-specific maximum plasma concentration)
Change From Baseline in Electrocardiogram Results (QT) Interval at Tmax on Day 1	QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval).	Baseline and Tmax (time of subject-specific maximum plasma concentration)
Change From Baseline in Electrocardiogram Results (QT) Interval at Tmax on Day 6	QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval).	Baseline and Tmax (time of subject-specific maximum plasma concentration)

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum Plasma Concentration (Cmax) of Guanfacine and Moxifloxacin on Day 1	pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose
Maximum Plasma Concentration (Cmax) of Guanfacine and Moxifloxacin on Day 6	pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose
Time of Maximum Plasma Concentration (Tmax) of Guanfacine and Moxifloxacin on Day 1	pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose
Time of Maximum Plasma Concentration (Tmax) of Guanfacine and Moxifloxacin on Day 6	pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose
Area Under the Steady-state Plasma Concentration-time Curve (AUC) for Guanfacine and Moxifloxacin on Day 1	pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose
Area Under the Steady-state Plasma Concentration-time Curve (AUC) for Guanfacine and Moxifloxacin on Day 6	pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• Martin P, Satin L, Kahn RS, Robinson A, Corcoran M, Purkayastha J, Youcha S, Ermer JC. A thorough QT study of guanfacine. Int J Clin Pharmacol Ther. 2015 Apr;53(4):301-16. doi: 10.5414/CP202065.

Helpful Links

• FDA Recall Information
• FDA-approved Label

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2008
• Primary Completion (Actual): August 7, 2008
• Study Completion (Actual): August 7, 2008

Study Registration Dates

• First Submitted: May 2, 2008
• First Submitted That Met QC Criteria: May 5, 2008
• First Posted (Estimate): May 6, 2008

Study Record Updates

• Last Update Posted (Actual): June 14, 2021
• Last Update Submitted That Met QC Criteria: June 10, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: QT/QTc
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin; Guanfacine
• Other Study ID Numbers: SPD503-112