PK, Tolerability and Safety of the co-Administration of Sancuso® (Transdermal Granisetron) and IV Granisetron

Study Overview
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Brief Summary
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This study has been designed to investigate the pharmacokinetic and safety profile of the co-administration of intravenous (IV) and transdermal granisetron, as well as characterise the pharmacokinetics of multiple transdermal dosing.

Detailed Description
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Sancuso® is designed to provide antiemetic prophylaxis for chemotherapy of up to 5 days duration. In exceptional clinical situations in which the patch is not applied at the appropriate time (i.e. 24-48 hours pre-chemotherapy), clinicians might use a single IV dose of granisetron to provide prophylaxis while the granisetron from the patch reaches a therapeutic plasma concentration. Most chemotherapeutics are dosed in a single day, with a 2- or 3-week interval between doses; however, several regimens are administered over more than 5 days and others are given at frequencies (e.g. every 5 days). Thus, more than one patch may be required to provide continuous antiemetic prophylaxis. Characterisation of the pharmacokinetics of multiple transdermal dosing offers useful information for clinicians who treat patients with the latter types of regimens.

Official Title
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A Study to Assess the Pharmacokinetics, Tolerability and Safety of the co-Administration of Sancuso® (Transdermal Granisetron) and Intravenous Granisetron in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: granisetron


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female Caucasian subjects Aged between 18 and 70 years, inclusive, at screening BMI between 20.0 and 29.9 kg/m², inclusive. Must demonstrate understanding of the purposes and risks of the study Must agree to follow the restrictions and schedule of study procedures Exclusion Criteria: Current or previous disease, disorder, allergy or condition that could affect study conduct or laboratory assessments, or that presents undue risk from study medication or procedures. Physical examination or screening investigation result that indicates subject is unfit for the study. Scarring on upper arms. Positive virology, urine drugs of abuse or pregnancy test result (females of childbearing potential only). Recent use of prescribed or over the counter medication. Participation in any clinical study or loss of ≥ 400 mL of blood (e.g. been a blood donor) within the previous 60 days. Average weekly alcohol consumption of greater than 21 units (males) or 14 units (females), or habitually smokes ≥ 5 cigarettes or equivalent tobacco per day within the 6 months before the first study drug administration. Lactating female subjects and female subjects of childbearing potential who are not willing to use an acceptable form of contraception during and for 90 days after the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sancuso® patch/IV granisetron<br>Subjects will receive 1 Sancuso® patch worn for 7 days (168 hours). Immediately after the patch has been applied on Day 1, IV granisetron will be administered over 30 seconds. Following patch removal at 168 hours, a new patch will be immediately applied to the opposite arm and will remain in place for a further 7 days (168 to 336 hours). | Drug: granisetron<br>* Sancuso® 3.1 mg/24 hours; transdermal. One patch applied to healthy intact skin on the upper outer arm and worn for 7 days (168 hours) followed by a second patch applied to the opposite arm at 168 hours for a further 7 days (168 to 336 hours). Kytril® (granisetron hydrochloride) 1 mg/mL; IV; 0.01 mg/kg (maximum 1 mg) administered over 30 seconds immediately following patch application on Day 1 only.<br>* Other names: Granisetron Injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile of the co-administration of IV granisetron and the Sancuso® patch |  | 0 to 336 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of the coadministration of IV granisetron and the Sancuso® patch |  | Up to 28 days post-dose | 
| Patch adhesion and residual granisetron after patch |  | 0 to 336 hours post-dose | 
| Pharmacokinetic profile of repeated Sancuso® patch application |  | 0 to 336 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Co-administration of transdermal and intravenous granisetron, Granisetron, Healthy subjects, Intravenous, Pharmacokinetic profile, Sancuso® patch, Transdermal, Pharmacokinetics