A Single-site, Single-dose and Multiple-dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Rotigotine Transdermal Patch in Healthy Chinese Subjects.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- UCB Pharma
- 入组人数
- 24
- 主要终点
- Plasma concentrations of unconjugated Rotigotine for single-dose application (Period 1)
研究概览
简要总结
This study is to characterize the Pharmacokinetics (PK) of unconjugated and total Rotigotine after single and multiple doses of Rotigotine transdermal patch, and also to investigate the safety and tolerability of Rotigotine transdermal patch in healthy Chinese subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Chinese subjects
- •Healthy volunteers with normal body weight, female subject is willing to use a double contraceptive barrier method or an oral hormonal contraceptive during the entire study
排除标准
- •Previously participated in any Rotigotine study or participated in another clinical study for an investigational drug
- •History of drug or alcohol abuse within the last 2 years
- •Suicide attempt or suicidal ideation in the past 6 months
- •Transient ischemic attack or stroke within the last 12 months
- •Current condition of epilepsy and / or seizures
- •History of significant skin hypersensitivity to adhesives or other transdermal products or recently unsolved contact dermatitis
- •History or present condition of an atopic or eczematous dermatitis, psoriasis and / or an active skin disease
- •Female subject is pregnant or lactating
- •Subject has any medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the subject's wellbeing or ability to participate in this study
- •Subject has a QTcB (QT interval corrected for heart rate according to Bazett's formula) interval of ≥ 450 ms for female or ≥ 430 ms for male
- •Subject has a relevant hepatic dysfunction (total bilirubin > 2 mg / dL or alanine aminotransferase [ALT] or aspartate aminotransferase [AST] greater than 2 times the upper limit of the normal reference range)
- •Subject has tested positive for human immunodeficiency virus antibodies (HIV)-1 / 2Ab, hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody (HCV-Ab)
- •Subject has a positive urine drug screen and / or alcohol breath test on Day 1
- •Subject has made a blood donation or had a comparable blood loss (> 400 mL)
- •Subject smokes or has done so within 6 months prior to Eligibility Assessment (EA)
- •Subject has a clinically relevant allergy
- •Subject is currently taking any medication
- •Female subject is currently taking an oral hormonal contraceptive
- •Subject has symptomatic orthostatic hypotension
- •Subject has a pulse rate at rest less than 45 beats per minute (bpm) or more than 100 bpm
- •Subject has a systolic blood pressure (SBP) lower than 100 mmHg or higher than 140 mmHg or diastolic blood pressure (DBP) higher than 90 mmHg
- •Subject has a current or a history of clinically relevant motor disturbance, impairment of memory, sleep disturbance or neurodegenerative disease
- •Subject has consumed more than 3 cups (more than 450 ml) of caffeinated beverages per day
- •Subject's abdomen is thickly covered with hair resulting in difficulties in finding appropriate patch application sites
研究组 & 干预措施
Rotigotine, Period 1
In Period 1 (Day 1 to Day 3) all 24 subjects will receive only 1 dose 2 mg / 24 hours.
干预措施: Rotigotine, Period 1 (Drug)
Rotigotine, Period 2
In Period 2 (Day 7 to Day 14) all 24 subjects will receive 2 mg / 24 hours for 3 days then 4 mg / 24 hours for 3 days.
干预措施: Rotigotine, Period 2 (Drug)
结局指标
主要结局
Plasma concentrations of unconjugated Rotigotine for single-dose application (Period 1)
时间窗: Period 1; Day 1 to Day 3 of study
Period 1; Pharmacokinetic (PK) samples will be taken predose and 1, 2, 3, 4, 8, 12, 16, 24, 25, 26, 28, 30, 32, 36, 40, 48, 60 and 72 hours after patch application on Day 1
Plasma concentrations of unconjugated Rotigotine for multiple-dose application (Period 2)
时间窗: Period 2; Day 7 to Day 14 of study
Period 2; Pharmacokinetic (PK) samples will be taken prior to patch application on Day 7, 8, 9, 11 and 12 and 1, 2, 3, 4, 8, 12, 16 and 24 hours after patch application on Day 9 and 12 and 25, 26, 28, 30, 32, 36, 40, 48, 60 and 72 hours after patch application on Day 12
Plasma concentrations of total Rotigotine for single-dose application (Period 1)
时间窗: Period 1; Day 1 to Day 3 of study
Period 1; Pharmacokinetic (PK) samples will be taken predose and 1, 2, 3, 4, 8, 12, 16, 24, 25, 26, 28, 30, 32, 36, 40, 48, 60 and 72 hours after patch application on Day 1
Plasma concentrations of total Rotigotine for multiple-dose application (Period 2)
时间窗: Period 2; Day 7 to Day 14 of study
Period 2; Pharmacokinetic (PK) samples will be taken prior to patch application on Day 7, 8, 9, 11 and 12 and 1, 2, 3, 4, 8, 12, 16 and 24 hours after patch application on Day 9 and 12 and 25, 26, 28, 30, 32, 36, 40, 48, 60 and 72 hours after patch application on Day 12
Area under the plasma concentration-time curve from zero up to the last analytically quantifiable concentration (AUC 0-tz) for single-dose application (Period 1)
时间窗: Period 1; Day 1 to Day 3 of study
Period 1; Pharmacokinetic (PK) samples will be taken predose and 1, 2, 3, 4, 8, 12, 16, 24, 25, 26, 28, 30, 32, 36, 40, 48, 60 and 72 hours after patch application on Day 1
Maximum plasma concentration (Cmax) for single-dose application (Period 1)
时间窗: Period 1; Day 1 to Day 3 of study
Period 1; Pharmacokinetic (PK) samples will be taken predose and 1, 2, 3, 4, 8, 12, 16, 24, 25, 26, 28, 30, 32, 36, 40, 48, 60 and 72 hours after patch application on Day 1
Area under the plasma concentration-time curve from zero to 24 hours at steady state (AUC(0-24h),ss) for multiple-dose application (Period 2)
时间窗: Period 2; Day 9 to Day 12 of study for this Primary Outcome Measure
Period 2; Pharmacokinetic (PK) samples will be taken prior to patch application and 1, 2, 3, 4, 8, 12, 16 and 24 hours after patch application on Day 9 and Day 12
Maximum plasma concentration at steady state (Cmax,ss) for multiple-dose application (Period 2)
时间窗: Period 2; Day 9 to Day 12 of study for this Primary Outcome Measure
Period 2; Pharmacokinetic (PK) samples will be taken prior to patch application and 1, 2, 3, 4, 8, 12, 16 and 24 hours after patch application on Day 9 and Day 12
次要结局
- Terminal half-life (t½) for single-dose application (Period 1)(Period 1; Day 1 to Day 3 of study)
- Time to reach a maximum plasma concentration (tmax) for single-dose application (Period 1)(Period 1; Day1 to Day 3 of study)
- Lag time until first concentration ≥ limit of quantitation (LOQ) (tlag) for single-dose application (Period 1)(Period 1; Day 1 to Day 3 of study)
- Maximum plasma concentration normalized by Body Weight (kg) (Cmax, norm (BW)) for single-dose application (Period 1)(Period 1; Day 1 to Day 3 of study)
- Maximum plasma concentration normalized by apparent dose (mg)(Cmax, norm (apparent dose)) for single-dose application (Period 1)(Period 1; Day 1 to Day 3 of study)
- Maximum plasma concentration normalized by drug content of patch (mg) (Cmax, norm (mgdc)) for single-dose application (Period 1)(Period 1; Day 1 to Day 3 of study)
- Area under the plasma concentration-time curve from zero up to the last analytically quantifiable concentration normalized by body weight (kg) (AUC(0-tz), norm (BW)) for single-dose application (Period 1)(Perion 1; Day 1 to Day 3 of study)
- Area under the plasma concentration-time curve from zero up to the last analytically quantifiable concentration normalized by apparent dose (mg) (AUC(0-tz), norm (apparent dose)) for single-dose application (Period 1)(Period 1; Day 1 to Day 3 of study)
- Area under the plasma concentration-time curve from zero up to the last analytically quantifiable concentration normalized by drug content of patch (mg) (AUC(0-tz), norm (mgdc)) for single-dose application (Period 1)(Period 1; Day 1 to Day 3 of study)
- Area under the plasma concentration-time curve from zero up to infinity (AUC(0-∞)) for single-dose application (Period 1)(Period 1; Day 1 to Day 3 of study)
- Area under the plasma concentration-time curve from zero up to infinity normalized by apparent dose (mg) (AUC(0-∞), norm (apparent dose)) for single-dose application (Period 1)(Period 1; Day 1 to Day 3 of study)
- Area under the plasma concentration-time curve from zero up to infinity normalized by body weight (kg) (AUC(0-∞), norm (BW)) for single-dose application (Period 1)(Period 1; Day 1 to Day 3 of study)
- Area under the plasma concentration-time curve from zero up to infinity normalized by drug content of patch (mg) (AUC(0-∞), norm (mgdc)) for single-dose application (Period 1)(Period 1; Day 1 to Day 3 of study)
- Apparent total body clearance (CL/F) for single-dose application (Period 1)(Period 1; Day 1 to Day 3 of study)
- Apparent total body clearance normalized by body weight (kg) (CL/F norm (BW)) for single-dose application (Period 1)(Period 1; Day 1 to Day 3 of study)
- Apparent volume of distribution (Vz/f) for single-dose application (Period 1)(Period 1; Day 1 to Day 3 of study)
- Apparent volume of distribution normalized by body weight (kg) (Vz/f norm (BW)) for single-dose application (Period 1)(Period 1; Day 1 to Day 3 of study)
- Mean residence time (MRT) for single-dose application (Period 1)(Period 1; Day 1 to Day 3 of study)
- Rate constant of elimination (ke) for single-dose application (Period 1)(Period 1; Day 1 to Day 3 of study)
- Terminal half-life (t½) for multiple-dose application(Period 2; Day 7 to Day 14 of study)
- Time to reach a maximum plasma concentration at steady state (tmax,ss) for multiple-dose application (Period 2)(Period 2; Day 9 to Day 12 of study for this Outcome Measure.)
- Maximum plasma concentration at steady state normalized by body weight (kg) (Cmax,ss,norm(BW)) for multiple-dose application (Period 2)(Period 2; Day 9 to Day 12 of study for this Outcome Measure.)
- Maximum plasma concentration at steady state normalized by apparent dose (mg) (Cmax, ss, norm (apparent dose)) for multiple-dose application (Period 2)(Period 2; Day 9 to Day 12 of study for this Outcome Measure.)
- Maximum plasma concentration at steady state normalized by drug content of patch (mg) (Cmax, ss, norm (mgdc)) for multiple-dose application (Period 2)(Period 2; Day 9 to Day 12 of study for this Outcome Measure)
- Minimum plasma concentration at steady state (Cmin, ss) for multiple-dose application (Period 2)(Period 2; Day 9 to Day 12 of study for this Outcome Measure)
- Area under the plasma concentration-time curve from zero to 24 hours at steady state normalized by body weight (kg) (AUC(0-24h), ss, norm (BW)) for multiple-dose application (Period 2)(Period 2; Day 9 to Day 12 of study for this Outcome Measure)
- Area under the plasma concentration-time curve from zero to 24 hours at steady state normalized by apparent dose (mg) (AUC(0-24), ss, norm (apparent dose)) for multiple-dose application (Period 2)(Period 2; Day 9 to Day 12 of study for this Outcome Measure)
- Area under the plasma concentration-time curve from zero to 24 hours at steady state normalized by drug content of patch (mg) (AUC(0-24), ss, norm (mgdc)) for multiple-dose application (Period 2)(Period 2; Day 9 to Day 12 of study for this Outcome Measure)
- Apparent total body clearance (CL/F) for multiple-dose application (Period 2)(Period 2; Day 7 to Day 14 of study)
- Apparent total body clearance normalized by body weight (kg) (CL/F norm (BW)) for multiple-dose application (Period 2)(Period 2; Day 7 to Day 14 of study)
- Apparent volume of distribution (Vz/f) for multiple-dose application (Period 2)(Period 2; Day 7 to Day 14 of study)
- Apparent volume of distribution normalized by body weight (kg) (Vz/f norm (BW)) for multiple-dose application (Period 2)(Period 2; Day 7 to Day 14 of study)
- Mean residence time (MRT) for multiple-dose application (Period 2)(Period 2; Day 7 to Day 14 of study)
- Rate constant of elimination (ke) for multiple-dose application (Period 2)(Period 2; Day 7 to Day 14 of study)
- Peak to trough fluctuation (PTF) for multiple-dose application (Period 2)(Period 2; Day 9 to Day 12 of study for this Outcome Measure)