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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: granisetron

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • West Bend, Wisconsin, United States, 53095
      • Spaulding Clinical Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A: Sancuso® patch; Treatment A: Sancuso® patch (Day 1) and placebo IV (Day 3)	Drug: granisetron; 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; Other Names: Granisetron Transdermal System; Sancuso® patch; Kytril®; Granisetron Injection; IV Placebo (0.9% saline); Placebo patches; Avelox® Oral
Experimental: Treatment B: IV Granisetron 10 mcg/kg; Treatment B: placebo patch (Day 1) and granisetron IV (Day 3)	Drug: granisetron; 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; Other Names: Granisetron Transdermal System; Sancuso® patch; Kytril®; Granisetron Injection; IV Placebo (0.9% saline); Placebo patches; Avelox® Oral
Placebo Comparator: Treatment C: Matching placebo patch; Treatment C: placebo patch (Day 1) and placebo IV (Day 3)	Drug: granisetron; 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; Other Names: Granisetron Transdermal System; Sancuso® patch; Kytril®; Granisetron Injection; IV Placebo (0.9% saline); Placebo patches; Avelox® Oral
Active Comparator: Treatment D: Oral Moxifloxacin 400 mg; Treatment D: placebo patch (Day 1) and oral moxifloxacin (Day 3).	Drug: granisetron; 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; Other Names: Granisetron Transdermal System; Sancuso® patch; Kytril®; Granisetron Injection; IV Placebo (0.9% saline); Placebo patches; Avelox® Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Prostrakan Pharmaceuticals
• Investigators: Study Director: Bridget O'Mahony, PhD, Prostrakan Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: April 29, 2009
• First Submitted That Met QC Criteria: April 29, 2009
• First Posted (Estimate): April 30, 2009

Study Record Updates

• Last Update Posted (Estimate): September 27, 2010
• Last Update Submitted That Met QC Criteria: September 24, 2010
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Keywords: Transdermal; Granisetron; Electrocardiogram; Moxifloxacin; Pharmacokinetic profile; Sancuso® patch; Effect on electrocardiogram
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Serotonin Agents; Serotonin Antagonists; Granisetron
• Other Study ID Numbers: 392MD/39/C