A Study to Define the ECG Effects of Tizanidine Compared to Placebo and the Positive Control, Moxifloxacin, in Healthy Men and Women Using a Blinded ECG Evaluator: A Thorough ECG Trial (TQT)

A Partial-Blind, Randomized, Parallel Design Study With a Nested Crossover Comparison to Define the ECG Effects of Tizanidine Compared to Placebo and the Positive Control, Moxifloxacin, in Healthy Men and Women Using a Blinded ECG Evaluator: A Thorough ECG Trial

This is a single-center, partial-blind, randomized, placebo-controlled, parallel design study with a nested crossover comparison to define the ECG effects of tizanidine compared to placebo and the positive control, moxifloxacin, in healthy men and women. The study will be conducted in a Phase 1 unit with sufficient facilities to house subjects as required by the protocol.

Study Overview

• Status: Completed
• Conditions: Spasticity
• Intervention / Treatment: Drug: Placebo; Drug: Moxifloxacin; Drug: Tizanidine

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • Covance- Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Women of childbearing potential should have a negative urine pregnancy test prior to Screening and Day -2 of the trial
• All subjects of childbearing potential must practice a highly effective method of birth control excluding oral contraceptives for the duration of the trial and up to 3 months after the last dose of investigational product. Oral contraceptives are not allowed, based on the precaution listed in the Zanaflex package insert.
• Have a body mass index (BMI) ranging between 19 and 30 kg/m2
• Comprehend and be able to provide written informed consent
• Be willing and able to comply with all trial requirements

Exclusion Criteria:

• Female who is either pregnant, breastfeeding or planning to become pregnant
• History of hypersensitivity or allergic reaction to tizanidine or moxifloxacin or any of the tablet components
• Any condition possibly affecting drug absorption, metabolism or excretion including previous surgery for removal of parts of stomach, bowel, liver, gall bladder, or pancreas
• History of Long QT Syndrome or a first-generation relative with this condition
• Evidence or history of clinically significant allergies except for untreated, asymptomatic, seasonal allergies at time of dosing, hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, renal, psychiatric, or neurological disease. Determination of clinical significance is to be made at the Investigator's discretion
• History or presence of any malignant or benign neoplasm considered by the investigator to be clinically significant
• History of drug or alcohol abuse or dependence within the last year
• Have an active infectious disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tizanidine; Oral dose of 2 and 4 milligram (mg) tablets	Drug: Tizanidine; Other Names: Zanaflex
Placebo Comparator: Placebo; Placebo followed by a single dose 400 mg moxifloxacin tablets.	Drug: Placebo; Drug: Moxifloxacin
Active Comparator: Moxifloxacin; Single dose of 400 mg moxifloxacin followed by placebo.	Drug: Placebo; Drug: Moxifloxacin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Primary Endpoint Will be the Baseline-adjusted, Placebo-corrected Effect on QTc (ΔΔQTc) on Day 14.	Change from baseline in Cardiac Repolarization (QTc Interval) at Day 14 (Tizanidine 24 mg). Moxifloxacin was not investigational drug, it was used to assess the sensitivity of the study.	Baseline and Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Baseline-adjusted, Placebo-corrected (ΔΔQTc) on QTc Method Not Selected as Primary Endpoint.	Change from baseline in Cardiac Repolarization (QTc Interval) at Day 5 (Tizanidine 8 mg). Moxifloxacin was not investigational drug, it was used to assess the sensitivity of the study.	Baseline and Day 5
Assessing the Relationship Between Changes in the QTc Interval and Plasma Levels of Tizanidine Using Concentration-effect Modeling	The relationship will be quantified using a linear mixed effects model with an intercept. Data from Day 5 and Day 14 were fitted into regression model to obtain a slope of change. The measure type 'Number' followed by (90% Confidence Interval) shown in results is the slope from the linear fit.	Day 5, Day 14
Maximum Plasma Concentration (Cmax) of Single Doses of 8 and 24 mg Tizanidine After Reaching Steady State.		0.5, 1, 1.5, 2, 4, 8, 12 & 24 hours post dose on Days 5 (8 mg) and 14 (24 mg)
Time to Reach Maximum Plasma Concentration (Tmax) of Single Doses of 8 and 24 mg Tizanidine After Reaching Steady State.		0.5, 1, 1.5, 2, 4, 8, 12 & 24 hours post dose on Days 5 (8 mg) and 14 (24 mg)
Area Under the Plasma Concentration-time Curve During a Dosing Interval (AUCt) of Single Doses of 8 and 24 mg Tizanidine After Reaching Steady State.		0.5, 1, 1.5, 2, 4, 8, 12 & 24 hours post dose on Days 5 (8 mg) and 14 (24 mg)

Collaborators and Investigators

• Sponsor: Acorda Therapeutics
• Investigators: Study Director: Mathews Adera, MD, Acorda Therapeutics

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: April 22, 2013
• First Submitted That Met QC Criteria: April 23, 2013
• First Posted (Estimate): April 24, 2013

Study Record Updates

• Last Update Posted (Actual): March 23, 2021
• Last Update Submitted That Met QC Criteria: March 1, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Muscle Hypertonia; Muscle Spasticity; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Antineoplastic Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Anticonvulsants; Neuromuscular Agents; Muscle Relaxants, Central; Moxifloxacin; Tizanidine
• Other Study ID Numbers: ZAN-QT-1006

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No