Investigation of the Pharmacokinetic Characteristics of Two New CG5503 Formulations as Compared to CG5503 PR Tablets and Exploration of the Effect of Food on the Bioavailability of the Two New CG5503 Formulations Following Single Oral Administration of 116 mg CG5503 in a Single Center, Open, Randomized, 5-way-crossover, Single Dose, Phase I Study in 10 Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Pharmacokinetic parameter: AUC0-inf
研究概览
简要总结
This study investigated the pharmacokinetics (how a drug is taken up and excreted from the body), safety, and tolerability of 2 new tapentadol (CG5503) tablet formulations compared to a previously characterized tapentadol prolonged-release (PR) tablet formulation.
详细描述
The study was performed to evaluate the pharmacokinetic characteristics (relative bioavailability) of 2 new tapentadol (CG5503) tablet formulations (Test Product 1 and Test Product 2) containing 116 mg tapentadol hydrochloride each, as compared to a 116-mg tapentadol hydrochloride PR tablet (Reference Product) and to explore the effect of food on the bioavailability of the 2 new tapentadol formulations. Participants received a single dose of each of the test formulations under fasting or fed conditions and of the reference formulation under fasting conditions in a randomized order. There was a wash-out period of at least 3 days between consecutive treatments. Blood samples were taken from pre-dose up to 32 hours post-dose for pharmacokinetic analyses.
Furthermore, the study compared the safety and tolerability of the test formulations with that of the reference. Adverse events and vital signs were documented at screening, pre-dose, and up to 32 hours post-dose. Clinical laboratory parameters were determined and 12-lead electrocardiograms (ECG) were recorded at screening and at discharge. A final medical examination was performed at 2-14 days after discharge following the last treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Male Caucasian participants, aged 18-55 years;
- •Body Mass Index between 18 and 30 kg/m2 inclusive;
- •Participants must be in good health as determined by medical history, physical examination, 12-lead electrocardiogram, vital signs, and clinical laboratory parameters;
- •Participants giving written informed consent to participate within this study.
排除标准
- •Resting pulse rate equal to or less than 45 or equal to or above 95 beats / min;
- •Resting blood pressure: systolic blood pressure equal to or less than 100 and equal to or above 140 mmHg, diastolic blood pressure equal to or less than 50 and equal to or above 90 mmHg;
- •Positive human immunodeficiency virus (HIV) type 1/2 antibodies, hepatitis B surface (HBs) antigen, hepatitis B core (HBc) antibodies, hepatitis C virus (HCV) antibodies;
- •History or presence of orthostatic hypotension;
- •Participation in another clinical study in the last three months before starting this study (exception: characterization of metabolizer status);
- •Positive screening of drug abuse;
- •Diseases or condition known to interfere with the absorption, distribution, metabolism or excretion of drugs;
- •Marked repolarization abnormality (e.g., suspicious or definite congenital long QT syndrome);
- •Bronchial asthma;
- •Definite or suspected history of drug allergy or hypersensitivity;
- •Participants who have received any prescribed and non-prescribed systemic or topical medication two weeks before and during the study with the exception of short term medication, e.g. headache with paracetamol;
- •Evidence of alcohol or drug abuse;
- •Not able to abstain from drinking of caffeine containing beverages (tea, coffee, chocolate or cola),
- •Consumption of any quinine containing beverages (bitter lemon, tonic water) or food within two weeks before and during the study;
- •Drinking of alcohol containing beverages within 48 hours before administration of investigational product(s);
- •Blood donation (above 100 mL) or comparable blood losses during the last 3 months;
- •History of seizures or at risk (i.e. head trauma, epilepsy in family anamnesis, unclear loss of consciousness);
- •Known or suspected of not being able to comply with the study protocol;
- •Not able to communicate meaningfully with the investigator and staff;
- •Smoking of more than 20 cigarettes/day.
研究组 & 干预措施
Tapentadol Test Product 2 (fasting)
Tapentadol new tablet formulation, given as single oral dose with 240 mL of still mineral water under fasting condition.
干预措施: Tapentadol Test Product 2 (Drug)
Tapentadol Test Product 1 (fasting)
Tapentadol new tablet formulation, given as single oral dose with 240 mL of still mineral water under fasting condition.
干预措施: Tapentadol Test Product 1 (Drug)
Tapentadol Test Product 1 (fed)
Tapentadol new tablet formulation, given as single oral dose with 240 mL of still mineral water under fed condition.
干预措施: Tapentadol Test Product 1 (Drug)
Tapentadol Test Product 2 (fed)
Tapentadol new tablet formulation, given as single oral dose with 240 mL of still mineral water under fed condition.
干预措施: Tapentadol Test Product 2 (Drug)
Tapentadol PR Reference Product
Tapentadol PR tablet formulation given as single oral dose with 240 mL of still mineral water under fasting condition.
干预措施: Tapentadol Prolonged-release Reference Product (Drug)
结局指标
主要结局
Pharmacokinetic parameter: AUC0-inf
时间窗: Pre-dose up to 32 hours post-dose
19 Blood samples were collected from pre-dose up to 32 hours post-dose. The AUC from 0 hours to infinity (AUC0-inf) was extrapolated from the AUC from administration to the last measured concentration.
Pharmacokinetic parameter: tmax
时间窗: Pre-dose up to 32 hours post-dose
19 Blood samples were collected from pre-dose up to 32 hours post-dose. The evaluation of the time to reach Cmax (tmax) was determined based on the tapentadol base concentrations measured in serum samples.
Pharmacokinetic parameter: Cmax
时间窗: Pre-dose up to 32 hours post-dose
19 Blood samples were collected from pre-dose up to 32 hours post-dose. The evaluation of the maximum observed serum concentration (Cmax) was based on the tapentadol base concentrations measured in serum samples using a validated liquid chromatography/tandem mass spectrometry (LC-MS/MS) method.
Pharmacokinetic parameter: AUC0-t
时间窗: Pre-dose up to 32 hours post-dose
19 Blood samples were collected from pre-dose up to 32 hours post-dose. The evaluation of the area under the concentration time curve (AUC) from 0 hours to time t (=32 hours) (AUC0-t) was based on the tapentadol base concentrations measured in serum samples.
次要结局
- Pharmacokinetic parameter: MRT(Pre-dose up to 32 hours post-dose)
- Pharmacokinetic parameter: CL/f(Pre-dose up to 32 hours post-dose)
- Pharmacokinetic parameter: Vz/f(Pre-dose up to 32 hours post-dose)
- Pharmacokinetic parameter: tlag(Pre-dose up to 32 hours post-dose)
- Pharmacokinetic parameter: t1/2z(Pre-dose up to 32 hours post-dose)