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)
Primary Purpose
Spasticity
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Tizanidine
Placebo
Moxifloxacin
Sponsored by
About this trial
This is an interventional treatment trial for Spasticity
Eligibility Criteria
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
Sites / Locations
- Covance- Dallas
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Placebo Comparator
Active Comparator
Arm Label
Tizanidine
Placebo
Moxifloxacin
Arm Description
Oral dose of 2 and 4 milligram (mg) tablets
Placebo followed by a single dose 400 mg moxifloxacin tablets.
Single dose of 400 mg moxifloxacin followed by placebo.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Maximum Plasma Concentration (Cmax) of Single Doses of 8 and 24 mg Tizanidine After Reaching Steady State.
Time to Reach Maximum Plasma Concentration (Tmax) of Single Doses of 8 and 24 mg Tizanidine After Reaching Steady State.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01839279
Brief Title
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
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
April 2013 (undefined)
Primary Completion Date
February 2014 (Actual)
Study Completion Date
May 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Acorda Therapeutics
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spasticity
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
136 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tizanidine
Arm Type
Experimental
Arm Description
Oral dose of 2 and 4 milligram (mg) tablets
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo followed by a single dose 400 mg moxifloxacin tablets.
Arm Title
Moxifloxacin
Arm Type
Active Comparator
Arm Description
Single dose of 400 mg moxifloxacin followed by placebo.
Intervention Type
Drug
Intervention Name(s)
Tizanidine
Other Intervention Name(s)
Zanaflex
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Type
Drug
Intervention Name(s)
Moxifloxacin
Primary Outcome Measure Information:
Title
The Primary Endpoint Will be the Baseline-adjusted, Placebo-corrected Effect on QTc (ΔΔQTc) on Day 14.
Description
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.
Time Frame
Baseline and Day 14
Secondary Outcome Measure Information:
Title
The Baseline-adjusted, Placebo-corrected (ΔΔQTc) on QTc Method Not Selected as Primary Endpoint.
Description
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 Frame
Baseline and Day 5
Title
Assessing the Relationship Between Changes in the QTc Interval and Plasma Levels of Tizanidine Using Concentration-effect Modeling
Description
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.
Time Frame
Day 5, Day 14
Title
Maximum Plasma Concentration (Cmax) of Single Doses of 8 and 24 mg Tizanidine After Reaching Steady State.
Time Frame
0.5, 1, 1.5, 2, 4, 8, 12 & 24 hours post dose on Days 5 (8 mg) and 14 (24 mg)
Title
Time to Reach Maximum Plasma Concentration (Tmax) of Single Doses of 8 and 24 mg Tizanidine After Reaching Steady State.
Time Frame
0.5, 1, 1.5, 2, 4, 8, 12 & 24 hours post dose on Days 5 (8 mg) and 14 (24 mg)
Title
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.
Time Frame
0.5, 1, 1.5, 2, 4, 8, 12 & 24 hours post dose on Days 5 (8 mg) and 14 (24 mg)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mathews Adera, MD
Organizational Affiliation
Acorda Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Covance- Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75247
Country
United States
12. IPD Sharing Statement
Learn more about this trial
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
We'll reach out to this number within 24 hrs