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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Kyowa Kirin Co., Ltd.
- Enrollment
- 240
- Locations
- 1
- Primary Endpoint
- Time-matched, placebo-corrected change from baseline in QTc based on the Fridericia correction (QTcF).
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Other
- Masking
- Single (Participant)
Eligibility Criteria
- Ages
- 18 Years to 50 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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.
Arms & Interventions
Treatment A: Sancuso® patch
Treatment A: Sancuso® patch (Day 1) and placebo IV (Day 3)
Intervention: granisetron (Drug)
Treatment B: IV Granisetron 10 mcg/kg
Treatment B: placebo patch (Day 1) and granisetron IV (Day 3)
Intervention: granisetron (Drug)
Treatment C: Matching placebo patch
Treatment C: placebo patch (Day 1) and placebo IV (Day 3)
Intervention: granisetron (Drug)
Treatment D: Oral Moxifloxacin 400 mg
Treatment D: placebo patch (Day 1) and oral moxifloxacin (Day 3).
Intervention: granisetron (Drug)
Outcomes
Primary Outcomes
Time-matched, placebo-corrected change from baseline in QTc based on the Fridericia correction (QTcF).
Time Frame: 0 to 120 hours post-dose
Secondary Outcomes
- 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)
- Patch adhesion and residual granisetron after patch use.(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)