Open-label Evaluation of the Pharmacokinetic Profile, Safety, and Efficacy of Tapentadol Oral Solution for the Treatment of Post-surgical Pain in Children and Adolescents Aged From 2 Years to Less Than 18 Years.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 86
- 试验地点
- 1
- 主要终点
- Non-Compartmental Pharmacokinetic (PK) Parameter: Time to Maximum Concentration (Tmax) of Tapentadol-O-glucuronide After a Single Dose of Tapentadol in Adolescents (Age 12 to Less Than 18).
研究概览
简要总结
To find out if a drug called tapentadol administered by mouth safely relieves pain in children. Look at the amount of tapentadol in the blood after a single oral dose.
Tapentadol oral solution for children is still being tested and is not yet registered. Tapentadol tablets are effective in treating both acute and chronic pain in adults. This trial will help to understand how tapentadol oral solution works in children.
详细描述
The lower age limit for the clinical trial was initially set to 3 years of age in the protocol. The trial planned for the inclusion of participants in three age categories. Age 3 to less than 6 years (young children), age 6 to less than 12 years (older children) and age 12 to less than 18 years of age (adolescents). There was a request by the Paediatric Committee (PDCO) at the European Medicines Agency to include participants 2 years of age (very young children). The protocol amendment thus planned to combine the two youngest age groups into a single reporting group. The protocol amendment only planned that the very young children group would have separate analysis for the Faces Pain Scale Revised (FPS-R) Scale and for the presentation of the serum concentrations, because the pharmacokinetic sampling scheme used in the 2 year old participants was different from the young children group (aged 3 to less than 6 years).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A maximum body weight of 85.0 kg.
- •A minimum body weight of 10 kg for participants aged 2 years to less than 3 years old.
- •If female and post-menarchal, or 12 years or older, the subject has a negative urine pregnancy test within 24 hours before surgery.
- •Having completed either dental surgery or tonsillectomy with or without adenoidectomy surgery (age group: 6 to less than 18 years of age).
- •Having completed ear, nose, or throat surgery (including but not limited to tonsillectomy (age group: 2 to less than 3 years of age).
- •Participant aged 6 to less than 18 years has a post-operative pain intensity score greater than or equal to 4 on the Color Analog Scale (CAS) as a result of the surgical procedure or the participant has a pain level that the usual standard of care following the surgical procedure (which reliably produces moderate to severe pain) requires opioid treatment.
- •Participant aged 2 years to less than 6 years has a pain level following a surgical procedure that reliably produces moderate to severe pain, for which the usual standard of care requires opioid treatment.
- •Participant is alert, orientated, and able to follow commands and complete the post-operative required procedures.
排除标准
- •History of brain injury.
- •Clinically relevant abnormal ECG.
- •Clinically unstable vital signs and/or a saturation of oxygen saturation (SpO2) less than 93%. During surgery SpO2 may decrease <93%.
- •Clinically relevant abnormal values for clinical chemistry, hematology, or urinalysis at enrollment.
- •Body temperature above 38.5°C within 48 hours prior to dosing.
- •Positive drugs of abuse test result.
研究组 & 干预措施
Tapentadol
干预措施: Tapentadol (Drug)
结局指标
主要结局
Non-Compartmental Pharmacokinetic (PK) Parameter: Time to Maximum Concentration (Tmax) of Tapentadol-O-glucuronide After a Single Dose of Tapentadol in Adolescents (Age 12 to Less Than 18).
时间窗: up to 15 hours
Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as "breakdown products". The body alters the administered medication to a metabolite so that it can be more easily or quickly removed from the body. Serum samples for pharmacokinetic analysis were obtained using frequent sampling techniques in participants 12 years to less than 18 years of age. The time to maximum concentration is derived from the area under the curve from dose to 15 hours (AUC 0-15). The Tmax is the time after dosing at which the maximum concentration of the tapentadol-O-glucuronide (metabolite) occurs. Serum samples (frequent sampling) were drawn at 0.25, 0.5, 1, 2, 4, 6, 11, and 15 hours.
Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years).
时间窗: up to 15 hours
Mean and Standard Deviation of Serum Concentrations of Tapentadol. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 0.2 ng/mL.
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years).
时间窗: up to 15 hours
Mean and Standard Deviation of Serum Concentrations of Tapentadol-O-glucuronide. Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as "breakdown products". The body alters the administered medication to a metabolite so that it can be more easily or quickly removed from the body. Tapentadol-O-glucuronide concentrations were measured in participants. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 10 ng/mL.
Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Older Children (Age 6 to Less Than 12 Years).
时间窗: up to 15 hours
Mean and Standard Deviation of Serum Concentrations of Tapentadol. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 0.2 ng/mL.
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Older Children (Age 6 to Less Than 12 Years).
时间窗: up to 15 hours
Mean and Standard Deviation of Serum Concentrations of Tapentadol-O-glucuronide. Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as "breakdown products". The body alters the administered medication to a metabolite so that it can be more easily or quickly removed from the body. Tapentadol-O-glucuronide concentrations were measured in participants. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 10 ng/mL.
Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Younger Children (Age 3 to Less Than 6 Years).
时间窗: up to 15 hours
Mean and Standard Deviation of Serum Concentrations of Tapentadol. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 0.2 ng/mL.
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Younger Children (Age 3 to Less Than 6 Years).
时间窗: up to 15 hours
Mean and Standard Deviation of Serum Concentrations of Tapentadol-O-glucuronide. Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as "breakdown products". The body alters the administered medication to a metabolite so that it can be more easily or quickly removed from the body. Tapentadol-O-glucuronide concentrations were measured in participants. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 10 ng/mL.
Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Very Young Children (Age 2 to Less Than 3 Years).
时间窗: up to 15 hours
Mean and Standard Deviation of Serum Concentrations of Tapentadol. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 0.2 ng/mL.
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Very Young Children (Age 2 to Less Than 3 Years).
时间窗: up to 15 hours
Mean and Standard Deviation of Serum Concentrations of Tapentadol-O-glucuronide. Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as "breakdown products". The body alters the administered medication to a metabolite so that it can be more easily or quickly removed from the body. Tapentadol-O-glucuronide concentrations were measured in participants. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 10 ng/mL.
Non-Compartmental Pharmacokinetic (PK) Parameter of Tapentadol Area Under the Concentration-Time Curve (AUC 0-15) After a Single Dose of Tapentadol in Adolescent Participants (Age 12 to Less Than 18 Years).
时间窗: up to 15 hours
Serum samples for pharmacokinetic analysis were obtained using frequent sampling techniques in participants 12 years to less than 18 years of age. Serum samples (frequent sampling) were drawn at 0.25, 0.5, 1, 2, 4, 6, 11, and 15 hours. The Area Under the Curve (AUC) from dose to 15 hours (AUC 0-15) is a summary measure of data from each pharmacokinetic blood sample taken over the 15 hour time period. The area is that below the line fitted to the data points.
Non-Compartmental Pharmacokinetic (PK) Parameter: Cmax (Maximum Concentration) of Tapentadol After a Single Dose of Tapentadol in Adolescents (Age 12 to Less Than 18 Years).
时间窗: up to 15 hours
Serum samples for pharmacokinetic analysis were obtained using frequent sampling techniques in participants 12 years to less than 18 years of age. Serum samples (frequent sampling) were drawn at 0.25, 0.5, 1, 2, 4, 6, 11, and 15 hours. The concentration of tapentadol (active drug) is assessed during absorption and distribution. The maximum concentration is derived from the Area Under the Curve, from dose to 15 hours (AUC 0-15). It is the highest amount of active drug observed in the blood sample
Non-Compartmental Pharmacokinetic (PK) Parameter: Time to Maximum Concentration (Tmax) of Tapentadol After a Single Dose of Tapentadol in Adolescents (Age 12 to Less Than 18 Years).
时间窗: up to 15 hours
Serum samples for pharmacokinetic analysis were obtained using frequent sampling techniques in participants 12 years to less than 18 years of age. The time to maximum concentration is derived from the area under the curve from dose to 15 hours (AUC 0-15). The Tmax is the time after dosing at which the maximum concentration of the tapentadol (active drug) occurs. Serum samples (frequent sampling) were drawn at 0.25, 0.5, 1, 2, 4, 6, 11, and 15 hours.
Non-Compartmental Pharmacokinetic (PK) Parameter of Tapentadol-O-glucuronide Area Under the Concentration-Time Curve (AUC 0-15) After a Single Dose of Tapentadol in Adolescents (Age 12 to Less Than 18 Years).
时间窗: up to 15 hours
Serum samples for pharmacokinetic analysis were obtained using frequent sampling techniques in participants 12 years to less than 18 years of age. Serum samples (frequent sampling) were drawn at 0.25, 0.5, 1, 2, 4, 6, 11, and 15 hours. The concentration of tapentadol (active drug) is assessed during absorption and distribution. The maximum concentration is derived from the Area Under the Curve, from dose to 15 hours (AUC 0-15). It is the highest amount of active drug observed in the blood sample.
Non-Compartmental Pharmacokinetic (PK) Parameter: Cmax (Maximum Concentration) of Tapentadol-O-glucuronide After a Single Dose of Tapentadol in Adolescents (Age 12 to Less Than 18 Years).
时间窗: up to 15 hours
Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as "breakdown products". The body alters the administered medication to a metabolite so that it can be more easily or quickly removed from the body. Serum samples (frequent sampling) were drawn at 0.25, 0.5, 1, 2, 4, 6, 11, and 15 hours. The concentration of tapentadol-O-glucuronide (metabolite) is assessed to study absorption and distribution. The maximum concentration is derived from the Area Under the Curve, from dose to 15 hours (AUC 0-15). It is the highest amount of metabolite observed in the blood sample.
次要结局
- Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years).(Baseline; 15 hours post-dose)
- Change From Enrollment in 12-lead Electrocardiogram Parameters(Enrollment (pre-surgery); Discharge Visit)
- Intake of Additional Analgesic Medication During the Trial(Baseline; 15 hours post dosing)
- Biochemistry Safety Laboratory Parameters: Blood Chloride Concentration(Enrollment Visit; Visit 2 and Discharge Visit)
- Biochemistry Safety Laboratory Parameters: Aspartate Aminotransferase (AST) Enzyme Activity(Enrollment Visit; Visit 2 and Discharge Visit)
- Biochemistry Safety Laboratory Parameters: Liver Function Test - Gamma-Glutamyl Transferase (GGT) Enzyme Activity(Enrollment Visit, Visit 2 and Discharge Visit)
- Pain Intensity Assessments Using the Visual Analog Scale (VAS) in Adolescents (Age 12 to Less Than 18 Years).(Baseline; 15 hours)
- Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years.(Baseline; 15 hours post-dose)
- Pain Intensity Assessment Using the Face, Legs, Activity, Cry, Consolability Scale in Young and Very Young Children (Age 2 to Less Than 6 Years).(Baseline; 15 hours post-dose)
- Sum of Pain Intensity Differences Over the 4 Hours After Dosing Derived From the Different Pain Scales and for All Age Groups(Baseline; 4 hours post-dose)
- Respiratory Rate Assessments(Enrollment Visit; 15 hours post-dose)
- Oxygen Saturation Assessments(Enrollment Visit; 15 hours post-dose)
- Systolic and Diastolic Blood Pressure Assessments(Enrollment Visit; 15 hours post-dose)
- Hematology Safety Laboratory Assessments: Leukocyte Concentration(Enrollment Visit; Visit 2 and Discharge Visit)
- Biochemistry Safety Laboratory Parameters: Blood Calcium Concentration(Enrollment Visit; Visit 2 and Discharge Visit)
- Biochemistry Safety Laboratory Parameters: Blood Phosphate Concentration(Enrollment Visit; Visit 2 and Discharge Visit)
- Biochemistry Safety Laboratory Parameters: Creatinine Concentration(Enrollment Visit; Visit 2 and Discharge Visit)
- Biochemistry Safety Laboratory Parameters: Liver Function Test - Alanine Aminotransferase (ALT) Enzyme Activity(Enrollment Visit, Visit 2 and Discharge Visit)
- Change From Enrollment in 12-lead Electrocardiogram Heart Rate Parameter(Enrollment; Discharge Visit)
- Treatment Emergent Adverse Events by Intensity(Baseline; 48 hours post dosing)
- Hematology Safety Laboratory Assessments: Hemoglobin Concentration(Enrollment Visit; Visit 2 and Discharge Visit)
- Hematology Safety Laboratory Assessments: Hematocrit(Enrollment Visit; Visit 2 and Discharge Visit)
- Hematology Safety Laboratory Assessments: Platelet Count(Enrollment Visit; Visit 2 and Discharge Visit)
- Hematology Safety Laboratory Assessments: Erythrocyte Mean Corpuscular Volume (Mean Corpuscular Volume)(Enrollment Visit; Visit 2 and Discharge Visit)
- Biochemistry Safety Laboratory Parameters: Calculated Glomerular Filtration Rate(Enrollment Visit; Visit 2 and Discharge Visit)
- Biochemistry Safety Laboratory Parameters: Urine Specific Gravity(Enrollment Visit and Discharge Visit)
- Biochemistry Safety Laboratory Parameters: Urine pH (Acid, Alkalinity) Test(Enrollment Visit and Discharge Visit)
- Biochemistry Safety Laboratory Parameters: Blood Glucose Concentration(Enrollment Visit; Visit 2 and Discharge Visit)
- Biochemistry Safety Laboratory Parameters: Blood Sodium Concentration(Enrollment Visit; Visit 2 and Discharge Visit)
- Biochemistry Safety Laboratory Parameters: Blood Urea Nitrogen (BUN) Concentration(Enrollment Visit; Visit 2 and Discharge Visit)
- Biochemistry Safety Laboratory Parameters: Creatine Kinase (CK) Enzyme Activity(Enrollment Visit, Visit 2 and Discharge Visit)
- Biochemistry Safety Laboratory Parameters: Alkaline Phosphatase (ALP) Enzyme Activity(Enrollment Visit, Visit 2 and Discharge Visit)
- Biochemistry Safety Laboratory Parameters: Triacylglycerol Lipase (TL) Enzyme Activity(Enrollment Visit, Visit 2 and Discharge Visit)
- Biochemistry Safety Laboratory Parameters: Blood Potassium Concentration(Enrollment Visit; Visit 2 and Discharge Visit)
- Biochemistry Safety Laboratory Parameters: Triglycerides Concentration(Enrollment Visit; Visit 2 and Discharge Visit)
- Biochemistry Safety Laboratory Parameters: Serum Albumin Concentration(Enrollment Visit; Visit 2 and Discharge Visit)
- Biochemistry Safety Laboratory Parameters: Urate in the Blood(Enrollment Visit; Visit 2 and Discharge Visit)
- Biochemistry Safety Laboratory Parameters: Liver Function Test - Lactate Dehydrogenase (LDH) Enzyme Activity(Enrollment Visit, Visit 2 and Discharge Visit)
- Biochemistry Safety Laboratory Parameters: Liver Function Test - Bilirubin Concentration(Enrollment Visit, Visit 2 and Discharge Visit)
- Biochemistry Safety Laboratory Parameters: Blood Protein Concentration(Enrollment Visit, Visit 2 and Discharge Visit)