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

NCT01839279 | Completed Phase 2 Results DMC

• 1 other identifier: ZAN-QT-1006
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 1

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.

Conditions

Spasticity

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline and Day 14

Secondary Outcomes (5)

• The Baseline-adjusted, Placebo-corrected (ΔΔQTc) on QTc Method Not Selected as Primary Endpoint.

  Baseline and Day 5

• Assessing the Relationship Between Changes in the QTc Interval and Plasma Levels of Tizanidine Using Concentration-effect Modeling

  Day 5, Day 14

• 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)

• 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)

• 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)

Study Arms (3)

Tizanidine

EXPERIMENTAL

Oral dose of 2 and 4 milligram (mg) tablets

Drug: Tizanidine

Placebo

PLACEBO COMPARATOR

Placebo followed by a single dose 400 mg moxifloxacin tablets.

Drug: Placebo; Drug: Moxifloxacin

Moxifloxacin

ACTIVE COMPARATOR

Single dose of 400 mg moxifloxacin followed by placebo.

Drug: Placebo; Drug: Moxifloxacin

Interventions

Tizanidine DRUG

Also known as: Zanaflex

Tizanidine

Placebo DRUG

Moxifloxacin; Placebo

Moxifloxacin DRUG

Moxifloxacin; Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Acorda Therapeutics: lead

Study Sites (1)

Covance- Dallas

Dallas, Texas, 75247, United States

Location

MeSH Terms

Conditions

Muscle Spasticity

Interventions

tizanidine; Moxifloxacin

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Executive Medical Director
• Organization: Acorda Therapeutics, Inc.

paupperle@acorda.com

914-437-4300

Study Officials

• Mathews Adera, MD

  Acorda Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2013
• First Posted: April 24, 2013
• Study Start: April 1, 2013
• Primary Completion: February 1, 2014
• Study Completion: May 1, 2014
• Last Updated: March 23, 2021
• Results First Posted: June 1, 2015

Record last verified: 2021-03

Locations

US (1)