Safety Study of Electrocardiogram (ECG) Effects of Sancuso® (Granisetron TDS)

Study Overview
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Brief Summary
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This study aims to evaluate the electrocardiogram (ECG) effects of Sancuso® compared to placebo and moxifloxacin in healthy subjects.

Detailed Description
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Granisetron is a well tested and established 5-HT3 receptor antagonist used in both oral and intravenous (IV) forms. A transdermal form of granisetron (Sancuso®) was approved by the United States (US) Food and Drug Administration (FDA) in September 2008. Many of the 5-HT3 antagonists were developed and approved before the adoption of the International Conference on Harmonisation (ICH) E14 standard on QTc and cardiac testing. The association of non-cardiac medicinal products with the potential to prolong the QT interval and induce torsades des pointes (TdP) has significant implications for the future development of medicinal products.

Official Title
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A Single-Blind, Randomized, Parallel Trial to Define the ECG Effects of Sancuso® (Granisetron Transdermal System) Compared to Placebo and Moxifloxacin in Healthy Men and Women

Conditions
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Healthy

Intervention / Treatment
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* Drug: granisetron


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female subjects Aged between 18 and 50 years, inclusive, at screening BMI between 18.0 and 32.0 kg/m², inclusive Exclusion Criteria: History of drug abuse Known hypersensitivity to granisetron, moxifloxacin, or related compounds, such as ciprofloxacin and levofloxacin Sustained supine systolic blood pressure >140 mmHg or <100 mmHg or a diastolic blood pressure >95 mmHg at Screening or baseline Pulse rate at rest of < 45 bpm or > 100 bpm Abnormal Screening ECG indicating a second- or third degree AV block, or one or more of the following: QRS >120 milliseconds (ms); QTcF > 430 (males) or 450 (females) ms; PR interval >240 ms; any rhythm, other than sinus rhythm, interpreted to be clinically significant by the Investigator Known history of long-QT syndrome, angina, myocardial ischemia or infarction, congestive heart failure, myocarditis, chest pain or dyspnea on exertion Electrolyte disturbances (such as uncorrected hypokalemia/hyperkalemia, hypomagnesemia, hypocalcemia, or hypophosphatemia), idiopathic cardiomyopathy, unexplained syncope, hypertrophic cardiomyopathy, or sudden unexplained death at a young age (< 40 years) in a first-degree relative. Has used any medications or consumed any foods contraindicated in the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A: Sancuso® patch<br>Treatment A: Sancuso® patch (Day 1) and placebo IV (Day 3) | Drug: granisetron<br>* Treatment A: Sancuso® patch (3.1mg/24 hours) on Day 1 and IV placebo (0.9% saline) on Day 3 Treatment B: Granisetron IV 10 mcg/kg over 30 seconds on Day 1 and placebo patch on Day 3 Treatment C: Placebo patch on Day 1 and IV placebo on Day 3 Treatment D: 400 mg oral moxifloxacin on Day 1 and placebo patch on Day 3<br>* Other names: Avelox® Oral;|
| Experimental: Treatment B: IV Granisetron 10 mcg/kg<br>Treatment B: placebo patch (Day 1) and granisetron IV (Day 3) | Drug: granisetron<br>* Treatment A: Sancuso® patch (3.1mg/24 hours) on Day 1 and IV placebo (0.9% saline) on Day 3 Treatment B: Granisetron IV 10 mcg/kg over 30 seconds on Day 1 and placebo patch on Day 3 Treatment C: Placebo patch on Day 1 and IV placebo on Day 3 Treatment D: 400 mg oral moxifloxacin on Day 1 and placebo patch on Day 3<br>* Other names: Avelox® Oral;|
| Placebo Comparator: Treatment C: Matching placebo patch<br>Treatment C: placebo patch (Day 1) and placebo IV (Day 3) | Drug: granisetron<br>* Treatment A: Sancuso® patch (3.1mg/24 hours) on Day 1 and IV placebo (0.9% saline) on Day 3 Treatment B: Granisetron IV 10 mcg/kg over 30 seconds on Day 1 and placebo patch on Day 3 Treatment C: Placebo patch on Day 1 and IV placebo on Day 3 Treatment D: 400 mg oral moxifloxacin on Day 1 and placebo patch on Day 3<br>* Other names: Avelox® Oral;|
| Active Comparator: Treatment D: Oral Moxifloxacin 400 mg<br>Treatment D: placebo patch (Day 1) and oral moxifloxacin (Day 3). | Drug: granisetron<br>* Treatment A: Sancuso® patch (3.1mg/24 hours) on Day 1 and IV placebo (0.9% saline) on Day 3 Treatment B: Granisetron IV 10 mcg/kg over 30 seconds on Day 1 and placebo patch on Day 3 Treatment C: Placebo patch on Day 1 and IV placebo on Day 3 Treatment D: 400 mg oral moxifloxacin on Day 1 and placebo patch on Day 3<br>* Other names: Avelox® Oral;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-matched, placebo-corrected change from baseline in QTc based on the Fridericia correction (QTcF). |  | 0 to 120 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| QTc with Bazett correction (QTcB), heart rate, PR interval, QRS interval, uncorrected QT interval, change in ECG morphological patterns and correlation between the QTcF change from baseline and plasma granisetron concentrations |  | 0 to 120 hours post-dose | 
| Relationship of plasma concentration of granisetron versus QTcF, both graphical and mixed effects analyses of plasma concentration of granisetron versus QTcF will be performed |  | 0 to 120 hours post-dose | 
| Patch adhesion and residual granisetron after patch use. |  | 0 to 120 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Electrocardiogram, Effect on electrocardiogram, Granisetron, Moxifloxacin, Pharmacokinetic profile, Sancuso® patch, Transdermal