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

Spasticity Clinical Trial

— TQT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01839279
• Other study ID #: ZAN-QT-1006
• Status: Completed
• Phase: Phase 2
• Start date: April 2013
• Est. completion date: May 2014

Study information

• Verified date: March 2021
• Source: Acorda Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 136
• Est. completion date: May 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Muscle Spasticity
• Spasticity

Intervention

Drug:
• Tizanidine

• Placebo

• Moxifloxacin

Locations

Country	Name	City	State
United States	Covance- Dallas	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Acorda Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Primary Endpoint Will be the Baseline-adjusted, Placebo-corrected Effect on QTc (??QTc) 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	The Baseline-adjusted, Placebo-corrected (??QTc) 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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)