Clinical trial NCT01839279: 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
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Spasticity
Lead sponsor: Acorda Therapeutics
Sponsor class: INDUSTRY
First posted: 2013-04-24
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: The Primary Endpoint Will be the Baseline-adjusted, Placebo-corrected Effect on QTc (ΔΔQTc) on Day 14.
timeFrame: Baseline and Day 14
Secondary outcomes:
measure: The Baseline-adjusted, Placebo-corrected (ΔΔQTc) on QTc Method Not Selected as Primary Endpoint.
timeFrame: Baseline and Day 5
measure: Assessing the Relationship Between Changes in the QTc Interval and Plasma Levels of Tizanidine Using Concentration-effect Modeling
timeFrame: Day 5, Day 14
measure: Maximum Plasma Concentration (Cmax) of Single Doses of 8 and 24 mg Tizanidine After Reaching Steady State.
timeFrame: 0.5, 1, 1.5, 2, 4, 8, 12 & 24 hours post dose on Days 5 (8 mg) and 14 (24 mg)
measure: Time to Reach Maximum Plasma Concentration (Tmax) of Single Doses of 8 and 24 mg Tizanidine After Reaching Steady State.
timeFrame: 0.5, 1, 1.5, 2, 4, 8, 12 & 24 hours post dose on Days 5 (8 mg) and 14 (24 mg)
measure: 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.
timeFrame: 0.5, 1, 1.5, 2, 4, 8, 12 & 24 hours post dose on Days 5 (8 mg) and 14 (24 mg)
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Covance- Dallas
state: Texas
Study officials:
affiliation: Acorda Therapeutics
name: Mathews Adera, MD
role: STUDY_DIRECTOR
References: