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

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02563951
• Other study ID #: GNS-CL001
• Status: Completed
• Phase: Phase 1
• First received: September 16, 2015
• Last updated: January 7, 2016
• Start date: September 2015
• Est. completion date: December 2015

Study information

• Verified date: January 2016
• Source: Maxinase Life Sciences Ltd.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan : Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 20 Years to 64 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• GNS Spray 0.5mg

• GNS Spray 1.0mg

• GNS Spray 2.0mg

• Kytril 1mg (IV injection)

• Kytril 1mg (Tablet)

Locations

Country	Name	City	State
Taiwan	Tri-Service General Hospital	Neihu District	Taipei City

Sponsors (2)

Lead Sponsor	Collaborator
Maxinase Life Sciences Ltd.	Tri-Service General Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PK Parameter: Area under the plasma concentration-time curve from zero (0) hours to infinity (8) (AUC(0-8)) 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.	No
Primary	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.	No
Primary	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.	No
Primary	PK Parameter: Area under the plasma concentration-time curve from zero (0) hours to infinity (8) (AUC(0-8)) 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	No
Primary	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	No
Primary	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	No
Secondary	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.	No
Secondary	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	No
Secondary	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.	No
Secondary	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	No
Secondary	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.	No
Secondary	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	No
Secondary	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.	No
Secondary	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	No
Secondary	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	Yes
Secondary	12-Lead ECG assessment		This will be measured at screening, and 24, 36 hours post-dose.	Yes