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

NCT02563951 | Completed Phase 1 DMC

• 1 other identifier: GNS-CL001
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cancer

Keywords

Nausea; Vomiting; Chemotherapy; Radiation therapy

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (10)

• 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.

Study Arms (5)

GNS Spray 0.5mg

EXPERIMENTAL

One spray of GNS 0.5mg/spray into right nostril.

Drug: GNS Spray 0.5mg

GNS Spray 1.0mg

EXPERIMENTAL

One spray of GNS 0.5mg/spray into both left and right nostril.

Drug: GNS Spray 1.0mg

GNS Spray 2.0mg

EXPERIMENTAL

One spray of GNS 1.0mg/spray into both left and right nostril.

Drug: GNS Spray 2.0mg

Kytril 1mg (IV injection)

ACTIVE COMPARATOR

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)

Kytril 1mg (Tablet)

ACTIVE COMPARATOR

a single dose (kytril 1mg, one tablet) orally administered with 240mL of water

Drug: Kytril 1mg (Tablet)

Interventions

GNS Spray 0.5mg DRUG

Also known as: Granisetron Nasal Spray

GNS Spray 0.5mg

GNS Spray 1.0mg DRUG

Also known as: Granisetron Nasal Spray

GNS Spray 1.0mg

GNS Spray 2.0mg DRUG

Also known as: Granisetron Nasal Spray

GNS Spray 2.0mg

Kytril 1mg (IV injection) DRUG

Also known as: Granisetron

Kytril 1mg (IV injection)

Kytril 1mg (Tablet) DRUG

Also known as: Granisetron

Kytril 1mg (Tablet)

Eligibility Criteria

• Age: 20 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Maxinase Life Sciences Ltd.: lead
• Tri-Service General Hospital: collaborator

Study Sites (1)

Tri-Service General Hospital

Neihu District, Taipei City, 114, Taiwan

Location

MeSH Terms

Conditions

Neoplasms; Nausea; Vomiting

Interventions

Granisetron; Injections, Intravenous; Tablets

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Administration, Intravenous; Drug Administration Routes; Drug Therapy; Therapeutics; Injections; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Kai-Min Chu, M.D Ph.D.

  Tri-Service General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2015
• First Posted: September 30, 2015
• Study Start: September 1, 2015
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: January 8, 2016

Record last verified: 2016-01

Locations

TW (1)