Safety Study of Electrocardiogram (ECG) Effects of Sancuso® (Granisetron TDS) - Full Text View

Purpose

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

Condition	Intervention	Phase
Healthy	Drug: granisetron	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Single Blind (Subject)
Official Title:	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

Resource links provided by NLM:

Drug Information available for: Granisetron hydrochloride Granisetron Moxifloxacin Moxifloxacin hydrochloride

U.S. FDA Resources

Further study details as provided by Prostrakan Pharmaceuticals:

Primary Outcome Measures:

Time-matched, placebo-corrected change from baseline in QTc based on the Fridericia correction (QTcF). [ Time Frame: 0 to 120 hours post-dose ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 [ Time Frame: 0 to 120 hours post-dose ] [ Designated as safety issue: Yes ]
Relationship of plasma concentration of granisetron versus QTcF, both graphical and mixed effects analyses of plasma concentration of granisetron versus QTcF will be performed [ Time Frame: 0 to 120 hours post-dose ] [ Designated as safety issue: Yes ]
Patch adhesion and residual granisetron after patch use. [ Time Frame: 0 to 120 hours post-dose ] [ Designated as safety issue: No ]

Enrollment:	240
Study Start Date:	May 2009
Study Completion Date:	September 2009
Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00890565

Locations

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

Sponsors and Collaborators

Prostrakan Pharmaceuticals

Investigators

Study Director:

Bridget O'Mahony, PhD

Prostrakan Pharmaceuticals

More Information

No publications provided

Responsible Party:	Dr Bridget O'Mahony/Clinical Research Manager, Strakan Pharmaceuticals Ltd
ClinicalTrials.gov Identifier:	NCT00890565 History of Changes
Other Study ID Numbers:	392MD/39/C
Study First Received:	April 29, 2009
Last Updated:	September 24, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Prostrakan Pharmaceuticals:

Electrocardiogram
Effect on electrocardiogram
Granisetron
Moxifloxacin

Pharmacokinetic profile
Sancuso® patch
Transdermal

Additional relevant MeSH terms:

Granisetron
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents

Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents

ClinicalTrials.gov processed this record on May 16, 2013