Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tizanidine | Experimental | Oral dose of 2 and 4 milligram (mg) tablets |
|
| Placebo | Placebo Comparator | Placebo followed by a single dose 400 mg moxifloxacin tablets. |
|
| Moxifloxacin | Active Comparator | Single dose of 400 mg moxifloxacin followed by placebo. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tizanidine | Drug |
|
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline and Day 5 |
| Assessing the Relationship Between Changes in the QTc Interval and Plasma Levels of Tizanidine Using Concentration-effect Modeling |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Mathews Adera, MD | Acorda Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Covance- Dallas | Dallas | Texas | 75247 | United States |
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Tizanidine | |
| FG001 | Initial Placebo and Crossover to Moxifloxacin | Dosing of moxifloxacin will only be analyzed for cause (if the effect of moxifloxacin is not as expected). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Drug |
|
| Moxifloxacin | Drug |
|
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. |
| 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) |
| FG002 |
| Initial Moxifloxacin and Crossover to Placebo |
Dosing of moxifloxacin will only be analyzed for cause (if the effect of moxifloxacin is not as expected). |
| QT/QTc Analysis Set |
|
| PK Analysis Set |
|
| Moxifloxacin/Placebo Analysis Set |
|
| PK/QTc Analysis Set |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
Safety Population
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Tizanidine | |
| BG001 | Initial Placebo and Crossover to Moxifloxacin | Dosing of moxifloxacin will only be analyzed for cause (if the effect of moxifloxacin is not as expected). |
| BG002 | Initial Moxifloxacin and Crossover to Placebo | Dosing of moxifloxacin will only be analyzed for cause (if the effect of moxifloxacin is not as expected). |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | QT/QTc Analysis set: Received at least 1 dose of study drug (including placebo), had measurements at baseline and on-treatment with at least 1 time point post-dose with at minimum triplicate measures giving rise to a QTc value for primary correction method. Effect of moxifloxacin was as expected. Therefore, no analysis required per Medical Monitor. | Posted | Least Squares Mean | 90% Confidence Interval | milliseconds (msec) | Baseline and Day 14 |
|
|
| ||||||||||||||||||||||||||||||||
| Secondary | 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. | QT/QTc Analysis set: Received at least 1 dose of study drug (including placebo), had measurements at baseline and on-treatment with at least 1 time point post-dose with at minimum triplicate measures giving rise to a QTc value for primary correction method. Effect of moxifloxacin was as expected. Therefore, no analysis required per Medical Monitor. | Posted | Least Squares Mean | 90% Confidence Interval | msec | Baseline and Day 5 |
| ||||||||||||||||||||||||||||||||||
| Secondary | 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. | Pk/QTc Analysis set will include all subjects in the QT/QTc analysis set with at least one valid PK assessment. Effect of moxifloxacin was as expected. Therefore, no analysis required per Medical Monitor. | Posted | Number | 90% Confidence Interval | msec per ng/mL | Day 5, Day 14 |
|
| |||||||||||||||||||||||||||||||||
| Secondary | Maximum Plasma Concentration (Cmax) of Single Doses of 8 and 24 mg Tizanidine After Reaching Steady State. | PK Analysis set: all subjects from Group 1 who received at least one study drug and have at least one valid PK assessment | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 0.5, 1, 1.5, 2, 4, 8, 12 & 24 hours post dose on Days 5 (8 mg) and 14 (24 mg) |
|
| ||||||||||||||||||||||||||||||||||
| Secondary | Time to Reach Maximum Plasma Concentration (Tmax) of Single Doses of 8 and 24 mg Tizanidine After Reaching Steady State. | PK Analysis set: all subjects from Group 1 who received at least one study drug and have at least one valid PK assessment | Posted | Median | Full Range | hour | 0.5, 1, 1.5, 2, 4, 8, 12 & 24 hours post dose on Days 5 (8 mg) and 14 (24 mg) |
|
| ||||||||||||||||||||||||||||||||||
| Secondary | 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. | PK Analysis set: all subjects from Group 1 who received at least one study drug and have at least one valid PK assessment | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 0.5, 1, 1.5, 2, 4, 8, 12 & 24 hours post dose on Days 5 (8 mg) and 14 (24 mg) |
|
|
Up to 23 days
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tizanidine | Tizanidine Arm | 0 | 72 | 44 | 72 | ||
| EG001 | Initial Placebo and Crossover to Moxifloxacin | Placebo/Moxifloxacin Arm | 0 | 32 | 16 | 32 | ||
| EG002 | Initial Moxifloxacin and Crossover to Placebo | Moxifloxacin/Placebo Arm | 1 | 32 | 23 | 32 | ||
| EG003 | Placebo and Moxifloxacin Groups Combined | Combined Moxifloxacin Arm | 1 | 64 | 39 | 64 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ectopic Pregnancy | Pregnancy, puerperium and perinatal conditions | MedDRA (15.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| NERVOUS SYSTEM DISORDERS | Nervous system disorders | MedDRA (15.1) | Systematic Assessment |
| |
| SOMNOLENCE | Nervous system disorders | MedDRA (15.1) | Systematic Assessment |
| |
| DIZZINESS | Nervous system disorders | MedDRA (15.1) | Systematic Assessment |
| |
| HEADACHE | Nervous system disorders | MedDRA (15.1) | Systematic Assessment |
| |
| PARAESTHESIA | Nervous system disorders | MedDRA (15.1) | Systematic Assessment |
| |
| DIZZINESS POSTURAL | Nervous system disorders | MedDRA (15.1) | Systematic Assessment |
| |
| GASTROINTESTINAL DISORDERS | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| NAUSEA | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| DRY MOUTH | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | General disorders | MedDRA (15.1) | Systematic Assessment |
| |
| FATIGUE | General disorders | MedDRA (15.1) | Systematic Assessment |
| |
| APPLICATION SITE PRURITUS | General disorders | MedDRA (15.1) | Systematic Assessment |
| |
| APPLICATION SITE IRRITATION | General disorders | MedDRA (15.1) | Systematic Assessment |
| |
| MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Systematic Assessment |
| |
| BACK PAIN | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Systematic Assessment |
| |
| MUSCULOSKELETAL CHEST PAIN | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Systematic Assessment |
| |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Systematic Assessment |
| |
| RASH | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Systematic Assessment |
|
Sponsor (Acorda) has right to review and comment on proposed publications within a specified time frame, up to 60 days; multi-center trials require joint publication unless specifically permitted otherwise.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Executive Medical Director | Acorda Therapeutics, Inc. | 914-437-4300 | 5263 | paupperle@acorda.com |
| ID | Term |
|---|---|
| D009128 | Muscle Spasticity |
| ID | Term |
|---|---|
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D009122 | Muscle Hypertonia |
| D020879 | Neuromuscular Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C023754 | tizanidine |
| D000077266 | Moxifloxacin |
| ID | Term |
|---|---|
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
|
| 1 |
|
| 1.5 |
|
| 2 |
|
| 4 |
|
| 8 |
|
| 12 |
|
| 24 |
|
| Units | Counts |
|---|
| Participants |
|
|
|
|
|
|