A Phase I Pharmacokinetic Study of Granisetron Hydrochloride Nasal Spray (GNS) in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
GNS Spray 0.5mg
One spray of GNS 0.5mg/spray into right nostril.
干预措施: GNS Spray 0.5mg (Drug)
GNS Spray 1.0mg
One spray of GNS 0.5mg/spray into both left and right nostril.
干预措施: GNS Spray 1.0mg (Drug)
GNS Spray 2.0mg
One spray of GNS 1.0mg/spray into both left and right nostril.
干预措施: GNS Spray 2.0mg (Drug)
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)
干预措施: Kytril 1mg (IV injection) (Drug)
Kytril 1mg (Tablet)
a single dose (kytril 1mg, one tablet) orally administered with 240mL of water
干预措施: Kytril 1mg (Tablet) (Drug)
结局指标
主要结局
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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
次要结局
- 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: 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: 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 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.)
- 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.)