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)
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.
Drug: Placebo crossover to moxifloxacin
Drug: Moxifloxacin crossover to placebo
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|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|
- A single supratherapeutic oral dose of tizanidine 24 mg given with food and its effects on cardiac repolarization (QTc interval) in healthy volunteers [ Time Frame: on Day 14 ] [ Designated as safety issue: No ]The primary endpoint will be the baseline-adjusted, placebo-corrected effect on QTc (ΔΔQTc) on Day 14.
- Safety of a single therapeutic dose of tizanidine 8 mg given with food and its effects on cardiac repolarization (QTc) interval in healthy volunteers [ Time Frame: Day 5 ] [ Designated as safety issue: No ]The baseline-adjusted, placebo-corrected (ΔΔQTc) on QTc method not selected as primary endpoint
- Assessing the relationship between changes in the QTc interval and plasma levels of tizanidine using concentration-effect modeling [ Time Frame: Days -1, 1, 5, 14, 15 ] [ Designated as safety issue: No ]1) Model 1 will be a linear model with an intercept; 2) Model 2 will be a linear model with mean intercept fixed to 0 (with variability); and 3) Model 3 will be a linear model with no intercept.
- Pharmacokinetic (PK) profile of single doses of 8 and 24 mg tizanidine after reaching steady state [ Time Frame: Days 5 and 14 ] [ Designated as safety issue: No ]Area under the plasma concentration-time curve during a dosing interval (AUCt), maximum plasma concentration (Cmax), the lowest plasma concentration (Ctrough), and time to reach maximum plasma concentration (tmax).
|Study Start Date:||April 2013|
|Study Completion Date:||May 2014|
|Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
Oral dose of 2 and 4 milligram (mg) tablets
Other Name: Zanaflex
Placebo Comparator: Placebo crossover to moxifloxacin
Placebo followed by a single dose 400 mg moxifloxacin tablets.
|Drug: Placebo crossover to moxifloxacin|
Active Comparator: Moxifloxacin crossover to placebo
single dose of 400 mg moxifloxacin followed by placebo
|Drug: Moxifloxacin crossover to placebo|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01839279
|United States, Texas|
|Dallas, Texas, United States, 75247|
|Study Director:||Mathews Adera, MD||Acorda Therapeutics|