Clinical trial NCT02563951: Study of Granisetron Hydrochloride Nasal Spray (GNS) in Healthy Volunteers
Official title: A Phase I Pharmacokinetic Study of Granisetron Hydrochloride Nasal Spray (GNS) in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: Nausea
Vomiting
Chemotherapy
Radiation therapy
Lead sponsor: Maxinase Life Sciences Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Tri-Service General Hospital
First posted: 2015-09-30
Enrollment: 50
Sex: ALL
Minimum age (years): 20
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 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.
measure: 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
timeFrame: 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.
measure: 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
timeFrame: 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.
measure: PK Parameter: Area under the plasma concentration-time curve from zero (0) hours to infinity (∞) (AUC(0-∞)) for Granisetron Tablet
timeFrame: 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
measure: PK Parameter: Area under the plasma concentration-time curve from zero (0) hours to last quantifiable concentration (t) (AUC(0-t)) for Granisetron Tablet
timeFrame: 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
measure: PK Parameter: Peak Plasma Concentration (Cmax) for Granisetron Tablet
timeFrame: 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:
measure: 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
timeFrame: 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.
measure: PK Parameter: Time to maximum plasma concentration (Tmax) for Granisetron Tablet
timeFrame: 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
measure: 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
timeFrame: 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.
measure: PK Parameter: elimination constant rate (Kel) for Granisetron Tablet
timeFrame: 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
measure: 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
timeFrame: 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.
measure: PK Parameter: half-life (t1/2) for Granisetron Tablet
timeFrame: 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
measure: 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
timeFrame: 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.
measure: PK Parameter: absolute bioavailability (F) for Granisetron Tablet
timeFrame: 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
measure: Report adverse events and measure vital signs over trial period.
timeFrame: 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
measure: 12-Lead ECG assessment
timeFrame: This will be measured at screening, and 24, 36 hours post-dose.
Other outcomes:
Locations:
city: Neihu District
country: Taiwan
facility: Tri-Service General Hospital
state: Taipei City
Study officials:
affiliation: Tri-Service General Hospital
name: Kai-Min Chu, M.D Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: