Clinical trial NCT00890565: Safety Study of Electrocardiogram (ECG) Effects of Sancuso® (Granisetron TDS)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Electrocardiogram
Effect on electrocardiogram
Granisetron
Moxifloxacin
Pharmacokinetic profile
Sancuso® patch
Transdermal
Lead sponsor: Kyowa Kirin Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2009-04-30
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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

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 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.

Primary outcomes:
measure: Time-matched, placebo-corrected change from baseline in QTc based on the Fridericia correction (QTcF).
timeFrame: 0 to 120 hours post-dose
Secondary outcomes:
measure: 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
timeFrame: 0 to 120 hours post-dose
measure: Relationship of plasma concentration of granisetron versus QTcF, both graphical and mixed effects analyses of plasma concentration of granisetron versus QTcF will be performed
timeFrame: 0 to 120 hours post-dose
measure: Patch adhesion and residual granisetron after patch use.
timeFrame: 0 to 120 hours post-dose
Other outcomes:
Locations:
city: West Bend
country: United States
facility: Spaulding Clinical Research, LLC
state: Wisconsin
Study officials:
affiliation: Kyowa Kirin Co., Ltd.
name: Bridget O'Mahony, PhD
role: STUDY_DIRECTOR
References: