中文(简体)
Albanian
Arabic
Armenian
Azerbaijani
Belarusian
Bengali
Bosnian
Catalan
Czech
Danish
Deutsch
Dutch
English
Estonian
Finnish
Français
Greek
Haitian Creole
Hebrew
Hindi
Hungarian
Icelandic
Indonesian
Irish
Italian
Japanese
Korean
Latvian
Lithuanian
Macedonian
Mongolian
Norwegian
Persian
Polish
Portuguese
Romanian
Russian
Serbian
Slovak
Slovenian
Spanish
Swahili
Swedish
Turkish
Ukrainian
Vietnamese
Български
中文(简体)
中文(繁體)

Pazopanib Tolerability When Given With Food

只有注册用户可以翻译文章
登陆注册
链接已保存到剪贴板
状态已完成
赞助商
Radboud University

关键词

抽象

Pazopanib (Votrient) is registered for the treatment of patients with advanced renal cell carcinoma and patients with soft tissue sarcoma who have received prior chemotherapy. It is administered at a fixed oral dose of 800 mg once daily (OD) regardless of size, age and clinical condition. It is absorbed from the gastrointestinal tract with an oral bioavailability of ~21%. Pazopanib is practically insoluble and highly permeable. When ingested with high fat food the pazopanib exposure (area under the concentration time curve (AUC)) is doubled. Common adverse effects are diarrhea and nausea. This might be caused by the non-absorbed proportion of pazopanib. A reduced dose taken with food could be a possible approach to reduce these side effects. Therefore the investigators initially want to determine the equivalent reduced dose of pazopanib when taken with a continental breakfast. Thereafter the investigators want to investigate whether the intake with food reduces the frequently reported side effects nausea and diarrhea.

描述

Pazopanib (Votrient) is a multi targeted tyrosine kinase inhibitor of vascular endothelial growth factor receptor, (VEGFR-1, -2 en -3), platelet-derived growth factor receptor (PDGFR-α and -β), and stem cell factor receptor (c-KIT). Pazopanib is registered for the treatment of patients with advanced renal cell carcinoma and patients with soft tissue sarcoma who have received prior chemotherapy. It is administered at a fixed oral dose of 800 mg OD regardless of size, age and clinical condition. It is absorbed from the gastrointestinal tract with an oral bioavailability of ~21%. Pazopanib is practically insoluble and highly permeable. When ingested with high fat food the pazopanib exposure (area under the concentration time curve (AUC)) is doubled. Common adverse effects are diarrhea and nausea. This might be caused by the non-absorbed proportion of pazopanib. A dose reduction when ingested with food could be a logical approach to reduce these side effects; however this is not tested in patients yet. Therefore we want to perform a bioequivalent study to investigate what dose with a continental breakfast equals the dose of 800 mg in fasted conditions (study part A). In part B of the study we want to investigate whether the intake with food reduces the frequently reported side effects.

日期

最后验证: 12/31/2018
首次提交: 04/28/2014
提交的预估入学人数: 05/11/2014
首次发布: 05/13/2014
上次提交的更新: 01/20/2019
最近更新发布: 01/22/2019
实际学习开始日期: 05/31/2014
预计主要完成日期: 10/31/2018
预计完成日期: 10/31/2018

状况或疾病

Cancer

干预/治疗

Drug: pazopanib

Other: Continental breakfast

相 1

手臂组

干预/治疗
Active Comparator: fasted
Intake of pazopanib in agreement with drug label - fasted state
Experimental: Continental breakfast
Intake of a reduced equivalent pazopanib dose with a continental breakfast
Other: Continental breakfast
pazopanib 600mg OD with food

资格标准

有资格学习的年龄 18 Years 至 18 Years
有资格学习的性别All
接受健康志愿者
标准

Inclusion Criteria:

1. Subjects must provide written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow-up.

Note: informed consent may be obtained prior to start of the specified screening window.

Note: procedures conducted as part of the subject's routine clinical management (e.g. blood count) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol.

2. ≥ 18 year old men and women who use pazopanib

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

4. Adequate organ system function

Exclusion Criteria:

1. Poorly controlled hypertension; systolic blood pressure (SBP) ≥ 40 mm Hg or diastolic blood pressure (DBP) ≥ 90 mm Hg.

Note: initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Following antihypertensive medication initiation or adjustment, blood pressure (BP) must be re-assessed three times at approximately 2-minute intervals. At least 24 hours must have elapsed between anti-hypertensive medication initiation or adjustment and BP measurement. These three values should be averaged to obtain the mean diastolic blood pressure and the mean systolic blood pressure. The mean SBP / DBP ratio must be <140/90 mmHg (OR 150/90 mm Hg, if this criterion is approved by Safety Review Team) in order for a subject to be eligible for the study.

2. Corrected QT interval (QTc) > 480msecs.

3. History of any one or more of the following cardiovascular conditions within the past 6 months:

- Cardiac angioplasty or stenting

- Myocardial infarction

- Unstable angina

- Coronary artery bypass graft surgery

- Symptomatic peripheral vascular disease

- Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)

4. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:

- Active peptic ulcer disease

- Known intraluminal metastatic lesion/s with risk of bleeding

- Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation.

- History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.

5. Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:

- Malabsorption syndrome.

- Major resection of the stomach or small bowel.

6. History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.

Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible.

7. Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery).

8. Evidence of active bleeding or bleeding diathesis.

9. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage.

Note: Lesions infiltrating major pulmonary vessels (contiguous tumor and vessels) are excluded; however, the presence of a tumor that is touching, but not infiltrating (abutting) the vessel is acceptable (CT with contrast is strongly recommended to evaluate such lesions).

10. Recent hemoptysis (½ teaspoon of red blood within 8 weeks before first dose of study drug).

11. Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.

12. Unable or unwilling to discontinue use of prohibited medications for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of day 1 and for the duration of the study.

13. Concurrent use of other substances known or likely to interfere with the pharmacokinetics of pazopanib.

Patients, who are adjusted to proton pump inhibitors and had no dose modifications for over two weeks, are allowed to participate

14. Women of childbearing potential without adequate contraception, pregnant or breastfeeding women.

结果

主要结果指标

1. Area under the plasma concentration versus time curve (AUC) of pazopanib [4 weeks]

Determination of AUC of pazopanib when taken with a continental breakfast compared to 800 mg in fasted state (geometric mean ratio will be determined)

次要成果指标

1. number of side effects [2 months]

Number of side effects will be compared for the two treatments (with and food.

2. questionnaire [2 months]

Preference of patients (by questionnaire): intake of pazopanib with or without

加入我们的脸书专页

科学支持的最完整的草药数据库

  • 支持55种语言
  • 科学支持的草药疗法
  • 通过图像识别草药
  • 交互式GPS地图-在位置标记草药(即将推出)
  • 阅读与您的搜索相关的科学出版物
  • 通过药效搜索药草
  • 组织您的兴趣并及时了解新闻研究,临床试验和专利

输入症状或疾病,并阅读可能有用的草药,输入草药并查看所使用的疾病和症状。
*所有信息均基于已发表的科学研究

Google Play badgeApp Store badge