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

Phase 2

Completed

Brief 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 & 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

Arm && Interventions

Group	Intervention	Description
Moxifloxacin	Placebo	Single dose of 400 mg moxifloxacin followed by placebo.
Placebo	Placebo	Placebo followed by a single dose 400 mg moxifloxacin tablets.
Tizanidine	Tizanidine	Oral dose of 2 and 4 milligram (mg) tablets
Placebo	Moxifloxacin	Placebo followed by a single dose 400 mg moxifloxacin tablets.
Moxifloxacin	Moxifloxacin	Single dose of 400 mg moxifloxacin followed by placebo.

Primary Outcome Measures

Name	Time	Method
The Primary Endpoint Will be the Baseline-adjusted, Placebo-corrected Effect on QTc (ΔΔQTc) on Day 14.	Baseline and 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.

Secondary Outcome Measures

Name	Time	Method
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)
Assessing the Relationship Between Changes in the QTc Interval and Plasma Levels of Tizanidine Using Concentration-effect Modeling	Day 5, Day 14	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.
The Baseline-adjusted, Placebo-corrected (ΔΔQTc) on QTc Method Not Selected as Primary Endpoint.	Baseline and Day 5	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.
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)
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)