Safety Study of Electrocardiogram (ECG) Effects of Sancuso® (Granisetron TDS) Compared to Placebo and Moxifloxacin in Healthy Men and Women - Full Text View

Sponsored by:	Prostrakan Pharmaceuticals
Information provided by:	Prostrakan Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00890565

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 I

Drug Information available for: Granisetron hydrochloride Granisetron Moxifloxacin Moxifloxacin hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Randomized, Single Blind (Subject), Parallel Assignment, Safety Study
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

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 ]

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

Arms	Assigned Interventions
Treatment A: Sancuso® patch: Experimental 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
Treatment B: IV Granisetron 10 mcg/kg: Experimental 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
Treatment C: Matching placebo patch: Placebo Comparator 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
Treatment D: Oral Moxifloxacin 400 mg: Active Comparator 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

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

Contacts

Contact: Albert Dietz, MD

1 262 306 3350

Locations

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

Sponsors and Collaborators

Prostrakan Pharmaceuticals

Investigators

Investigator:

Bridget O'Mahony, PhD

Prostrakan Pharmaceuticals

More Information

No publications provided

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

Keywords provided by Prostrakan Pharmaceuticals:

Electrocardiogram
Effect on electrocardiogram
Granisetron
Moxifloxacin

Pharmacokinetic profile
Sancuso® patch
Transdermal

Study placed in the following topic categories:

Neurotransmitter Agents
Moxifloxacin
Antiemetics
Peripheral Nervous System Agents

Granisetron
Healthy
Serotonin

Additional relevant MeSH terms:

Anti-Infective Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Gastrointestinal Agents
Antiemetics
Pharmacologic Actions
Serotonin Antagonists

Serotonin Agents
Moxifloxacin
Autonomic Agents
Therapeutic Uses
Granisetron
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on May 07, 2009