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

Kyowa Kirin

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: granisetron

Study type: Interventional

Funder types: Industry

Identifiers

NCT00890565

392MD/39/C

Details and patient eligibility

About

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

Full 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.

Enrollment: 240 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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240 participants in 4 patient groups, including a placebo group

Treatment A: Sancuso® patch

Experimental group

Description:

Treatment A: Sancuso® patch (Day 1) and placebo IV (Day 3)

Treatment:

Drug: granisetron

Treatment B: IV Granisetron 10 mcg/kg

Experimental group

Description:

Treatment B: placebo patch (Day 1) and granisetron IV (Day 3)

Treatment:

Drug: granisetron

Treatment C: Matching placebo patch

Placebo Comparator group

Description:

Treatment C: placebo patch (Day 1) and placebo IV (Day 3)

Treatment:

Drug: granisetron

Treatment D: Oral Moxifloxacin 400 mg

Active Comparator group

Description:

Treatment D: placebo patch (Day 1) and oral moxifloxacin (Day 3).

Treatment:

Drug: granisetron