Study of Granisetron Hydrochloride Nasal Spray (GNS) in Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to examine the pharmacokinetics (PK), safety and tolerability of 3 intranasal (IN) doses (0.5, 1.0 and 2.0 mg) of Granisetron Hydrochloride Nasal Sprays (GNS) as compared to Granisetron IV Injection and Granisetron Tablet in healthy Volunteers.

Official Title
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A Phase I Pharmacokinetic Study of Granisetron Hydrochloride Nasal Spray (GNS) in Healthy Volunteers

Conditions
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Cancer

Intervention / Treatment
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* Drug: GNS Spray 0.5mg
* Drug: GNS Spray 1.0mg
* Drug: GNS Spray 2.0mg
* Drug: Kytril 1mg (IV injection)
* Drug: Kytril 1mg (Tablet)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males or females between the ages of 20-64 years Body Mass Index (BMI) of 18.5 (inclusive) to 24 kg/m2; and a total body weight >45 kg Accessible vein for blood sampling No significant abnormalities in electrocardiogram (ECG) recording as per sites' local practice No significant abnormalities in general physical examination as per sites' local practice No significantly abnormal findings in laboratory assessments including hematology, biochemistry and urinalysis as per site's local practice A signed and dated written informed consent must be obtained from the subject prior to study participation Capable of understanding and willing to comply with study procedures A negative serum pregnancy test before the first dose of study drug must be available for women of childbearing potential Exclusion Criteria: Females who are pregnant, breast-feeding or have positive pregnancy test History of hypersensitivity to granisetron or its analogs Subjects with nasal ulcer, septal perforation, or other nasal conditions that may interfere with nasal administration and determined by the investigator to be ineligible Subjects with a QT interval greater than 500 ms or with acute ischemic changes or cardiac abnormality predisposing to arrhythmia on screening electrocardiogram (ECG) or by history Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or other significant disease or clinical findings at screening and determined by the investigator to be ineligible Subjects with a history of drug and/or alcohol abuse within 12 months prior to dosing Inability to read and/or sign the consent form Treatment with any other investigational drug during the 4 weeks prior to the initial dosing for this study Subjects who have donated or lost more than 250 ml blood within 2 months prior to the initial dosing for this study Male and female subjects with reproductive potential who are not willing to use effective method of contraception. Use of hormonal contraceptive is not allowed during the study period Clinical significant rhinitis or rhinorrhea at screening determined by the investigator to be ineligible Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to dosing of study medication For subjects who smoke or use tobacco products or are currently using nicotine products (patches, gums, etc.), 2 weeks abstinence is required Conditions upon screening which might contraindicate or require that caution be used in the administration of granisetron

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 64 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

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GNS Spray 0.5mg<br>One spray of GNS 0.5mg/spray into right nostril. | Drug: GNS Spray 0.5mg<br> <br> * Other names: Granisetron Nasal Spray;|
| Experimental: GNS Spray 1.0mg<br>One spray of GNS 0.5mg/spray into both left and right nostril. | Drug: GNS Spray 1.0mg<br> <br> * Other names: Granisetron Nasal Spray;|
| Experimental: GNS Spray 2.0mg<br>One spray of GNS 1.0mg/spray into both left and right nostril. | Drug: GNS Spray 2.0mg<br> <br> * Other names: Granisetron Nasal Spray;|
| Active Comparator: Kytril 1mg (IV injection)<br>A dose of 1mg of Granisetron IV injection (kytril 1mL, 3mg/mL/vial) will be administered as a slow IV injection (over 30 seconds) | Drug: Kytril 1mg (IV injection)<br> <br> * Other names: Granisetron;|
| Active Comparator: Kytril 1mg (Tablet)<br>a single dose (kytril 1mg, one tablet) orally administered with 240mL of water | Drug: Kytril 1mg (Tablet)<br> <br> * Other names: Granisetron;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK Parameter: Area under the plasma concentration-time curve from zero (0) hours to infinity (∞) (AUC(0-∞)) for 3 intranasal (IN) doses (0.5, 1.0 and 2.0 mg) of GNS and Granisetron IV Injection |  | within 1 hour prior to drug administration; 5, 10, 15, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose. | 
| PK Parameter: Area under the plasma concentration-time curve from zero (0) hours to last quantifiable concentration(t) (AUC(0-t)) for 3 intranasal (IN) doses (0.5, 1.0 and 2.0 mg) of GNS and Granisetron IV Injection |  | within 1 hour prior to drug administration; 5, 10, 15, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose. | 
| PK Parameter: Peak Plasma Concentration (Cmax) for 3 intranasal (IN) doses (0.5, 1.0 and 2.0 mg) of GNS and Granisetron IV Injection |  | within 1 hour prior to drug administration; 5, 10, 15, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose. | 
| PK Parameter: Area under the plasma concentration-time curve from zero (0) hours to infinity (∞) (AUC(0-∞)) for Granisetron Tablet |  | within 1 hour prior to drug administration; 15, 30, 45 minutes, and 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 36 hours post-dose | 
| PK Parameter: Area under the plasma concentration-time curve from zero (0) hours to last quantifiable concentration (t) (AUC(0-t)) for Granisetron Tablet |  | within 1 hour prior to drug administration; 15, 30, 45 minutes, and 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 36 hours post-dose | 
| PK Parameter: Peak Plasma Concentration (Cmax) for Granisetron Tablet |  | within 1 hour prior to drug administration; 15, 30, 45 minutes, and 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 36 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK Parameter: Time to maximum plasma concentration (Tmax) for 3 intranasal (IN) doses (0.5, 1.0 and 2.0 mg) of Granisetron Hydrochloride Nasal Sprays (GNS) and Granisetron IV Injection |  | within 1 hour prior to drug administration; 5, 10, 15, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose. | 
| PK Parameter: Time to maximum plasma concentration (Tmax) for Granisetron Tablet |  | within 1 hour prior to drug administration; 15, 30, 45 minutes, and 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 36 hours post-dose | 
| PK Parameter: elimination constant rate (Kel) for 3 intranasal (IN) doses (0.5, 1.0 and 2.0 mg) of Granisetron Hydrochloride Nasal Sprays (GNS) and Granisetron IV Injection |  | within 1 hour prior to drug administration; 5, 10, 15, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose. | 
| PK Parameter: elimination constant rate (Kel) for Granisetron Tablet |  | within 1 hour prior to drug administration; 15, 30, 45 minutes, and 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 36 hours post-dose | 
| PK Parameter: half-life (t1/2) for 3 intranasal (IN) doses (0.5, 1.0 and 2.0 mg) of Granisetron Hydrochloride Nasal Sprays (GNS) and Granisetron IV Injection |  | within 1 hour prior to drug administration; 5, 10, 15, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose. | 
| PK Parameter: half-life (t1/2) for Granisetron Tablet |  | within 1 hour prior to drug administration; 15, 30, 45 minutes, and 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 36 hours post-dose | 
| PK Parameter: absolute bioavailability (F) for 3 intranasal (IN) doses (0.5, 1.0 and 2.0 mg) of Granisetron Hydrochloride Nasal Sprays (GNS) and Granisetron IV Injection |  | within 1 hour prior to drug administration; 5, 10, 15, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose. | 
| PK Parameter: absolute bioavailability (F) for Granisetron Tablet |  | within 1 hour prior to drug administration; 15, 30, 45 minutes, and 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 36 hours post-dose | 
| Report adverse events and measure vital signs over trial period. |  | These will be measured from 30 mins pre-dose to every 3 hours until 12 hours post-dose, then at 24 and 36 hours post-dose | 
| 12-Lead ECG assessment |  | This will be measured at screening, and 24, 36 hours post-dose. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nausea, Vomiting, Chemotherapy, Radiation therapy