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

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

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.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Drug: GNS Spray 0.5mg; Drug: GNS Spray 1.0mg; Drug: GNS Spray 2.0mg; Drug: Kytril 1mg (IV injection); Drug: Kytril 1mg (Tablet)

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • Taipei City
    • Neihu District, Taipei City, Taiwan, 114
      • Tri-Service General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy males or females between the ages of 20-64 years
2. Body Mass Index (BMI) of 18.5 (inclusive) to 24 kg/m2; and a total body weight >45 kg
3. Accessible vein for blood sampling
4. No significant abnormalities in electrocardiogram (ECG) recording as per sites' local practice
5. No significant abnormalities in general physical examination as per sites' local practice
6. No significantly abnormal findings in laboratory assessments including hematology, biochemistry and urinalysis as per site's local practice
7. A signed and dated written informed consent must be obtained from the subject prior to study participation
8. Capable of understanding and willing to comply with study procedures
9. A negative serum pregnancy test before the first dose of study drug must be available for women of childbearing potential

Exclusion Criteria:

1. Females who are pregnant, breast-feeding or have positive pregnancy test
2. History of hypersensitivity to granisetron or its analogs
3. Subjects with nasal ulcer, septal perforation, or other nasal conditions that may interfere with nasal administration and determined by the investigator to be ineligible
4. 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
5. 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
6. Subjects with a history of drug and/or alcohol abuse within 12 months prior to dosing
7. Inability to read and/or sign the consent form
8. Treatment with any other investigational drug during the 4 weeks prior to the initial dosing for this study
9. Subjects who have donated or lost more than 250 ml blood within 2 months prior to the initial dosing for this study
10. 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
11. Clinical significant rhinitis or rhinorrhea at screening determined by the investigator to be ineligible
12. 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
13. For subjects who smoke or use tobacco products or are currently using nicotine products (patches, gums, etc.), 2 weeks abstinence is required
14. Conditions upon screening which might contraindicate or require that caution be used in the administration of granisetron

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GNS Spray 0.5mg; One spray of GNS 0.5mg/spray into right nostril.	Drug: GNS Spray 0.5mg; Other Names: Granisetron Nasal Spray
Experimental: GNS Spray 1.0mg; One spray of GNS 0.5mg/spray into both left and right nostril.	Drug: GNS Spray 1.0mg; Other Names: Granisetron Nasal Spray
Experimental: GNS Spray 2.0mg; One spray of GNS 1.0mg/spray into both left and right nostril.	Drug: GNS Spray 2.0mg; Other Names: Granisetron Nasal Spray
Active Comparator: Kytril 1mg (IV injection); 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); Other Names: Granisetron
Active Comparator: Kytril 1mg (Tablet); a single dose (kytril 1mg, one tablet) orally administered with 240mL of water	Drug: Kytril 1mg (Tablet); Other Names: Granisetron

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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.

Collaborators and Investigators

• Sponsor: Maxinase Life Sciences Ltd.
• Collaborators: Tri-Service General Hospital
• Investigators: Principal Investigator: Kai-Min Chu, M.D Ph.D., Tri-Service General Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: September 16, 2015
• First Submitted That Met QC Criteria: September 28, 2015
• First Posted (Estimate): September 30, 2015

Study Record Updates

• Last Update Posted (Estimate): January 8, 2016
• Last Update Submitted That Met QC Criteria: January 7, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Nausea; Vomiting; Chemotherapy; Radiation therapy
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Serotonin Agents; Serotonin Antagonists; Granisetron
• Other Study ID Numbers: GNS-CL001