3-Way Crossover Study to Compare the PK (Pharmokinetics) and to Evaluate the Effect of Food on the Bioavailability
A Phase 1, Randomized, Open-Label, Single-Dose, 3-Way Crossover Study to Compare the PK of Two Oral Formulations of SMP-100 and to Evaluate the Effect of Food on the Bioavailability of SMP-100 Tablets in Normal Healthy Volunteers
研究概览
详细说明
SMP-100 is a novel serotonin receptor 3 (5-HT3) partial agonist. The compound is under development in an oral dosage form for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-d). The study drug also has the potential to treat chemotherapy induced nausea and emesis and diarrhea due to carcinoid syndrome.
A single ascending dose (SAD) and multiple ascending dose (MAD) clinical study (study number SMP-100-101) evaluating the safety, tolerability, and PK profile of orally administered SMP-100 in healthy volunteers is ongoing. Regarding safety, there have been no clinically relevant abnormal vital signs, ECGs, laboratory results or SAEs.
In each period, subjects will receive a single 4 mg dose of SMP-100 on Day 1 (Period 1), Day 4 (Period 2), and Day 7 (Period 3), under fasting or fed conditions, followed by 48 hours of PK and safety assessments.
The study will include a screening visit from Day -28 to Day -2. Eligible subjects will be admitted to the clinical site on Day -1 and will be confined until completion of the assessments on Day 9. There will be a washout period of at least 72 hours between doses.
Primary objectives:
- To compare the PK of SMP-100 dissolved in water for oral administration with SMP-100 tablets under fasting conditions, following a single dose in healthy subjects.
- To evaluate the effect of a high-fat, high-calorie meal on the bioavailability of SMP-100 tablets, following a single dose in healthy subjects.
Secondary objective:
• To evaluate the safety and tolerability of two SMP-100 oral formulations when administered to healthy subjects.
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
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Adelaide、澳大利亚、SA 5000
- CMAX Clinical Research Pty Ltd
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Male or female, non-smoker (no use of tobacco or nicotine products within 3 months prior to screening), ≥18 and ≤59 years old at time of screening.
- Body mass index (BMI) >18.5 and <30.0 kg/m2 and body weight ≥50.0 kg for males and ≥45.0 kg for females.
Healthy as defined by:
- the absence of clinically significant illness and surgery within 4 weeks prior to dosing.
- the absence of clinically significant history of neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.
- the absence of clinically significant history of constipation, diarrhea, or irregular bowel transit in the last 4 weeks.
- the absence of clinically significant history of irritable bowel syndrome (IBS) of any type.
- the absence of current or history of ischemic colitis.
- the absence of any other gastrointestinal disease which could interfere with the absorption of orally-administered medication.
Female subjects of non-childbearing potential must be:
- post-menopausal (spontaneous amenorrhea for at least 12 months prior to dosing) with confirmation by documented follicle-stimulating hormone (FSH) levels ≥40 mIU/mL at screening; or
- surgically sterile (bilateral oophorectomy, hysterectomy or tubal ligation at least 3 months prior to dosing).
- Sexually active female subjects of childbearing potential and non-sterile male subjects must be willing to use an acceptable contraceptive method throughout the study as detailed in section 11.1.
- Willing to take off dentures or mouth piercing at the time of dosing (for Treatment A).
- Able to understand the study procedures and provide signed informed consent form (ICF) to participate in the study.
Exclusion Criteria:
- Any clinically significant (in the opinion of the Investigator) abnormal finding at physical examination at screening.
- Any clinically significant (in the opinion of the Investigator) abnormal laboratory test results or positive serology test results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antigen and antibody at screening.
- Positive pregnancy test or lactating female subject.
- Positive urine drug screen, urine cotinine test, or alcohol breath test at screening or Day -1.
- Known allergic reactions to any excipient in the formulations.
- History of hypersensitivity to 5-hydroxytryptamine 3 receptor (5-HT3) receptor antagonists or agonists.
- Clinically significant ECG abnormalities (Fridericia's corrected QT interval [QTcF] >450 ms for males and >470 ms for females).
- Clinically significant vital signs abnormalities (systolic BP lower than 90 or over 160 mmHg, diastolic BP lower than 50 or over 95 mmHg, or HR less than 45 bpm) at screening.
- Clinically significant orthostatic vital signs abnormalities such as decrease in systolic BP of 20 mmHg or higher, decrease in diastolic BP of 10 mmHg or higher, or increase in HR of 30 bpm or higher within 3 minutes after passing from a supine to a standing position.
- History of significant drug abuse within 1 year prior to screening or use of drugs such as marijuana within 3 months prior to the screening visit or drugs such as cocaine, phencyclidine (PCP), crack, opioid derivatives including heroin, and amphetamine derivatives within 1 year prior to screening.
- History of significant alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to the screening visit that exceeds 14 units of alcohol per week (1 unit = 150 mL of wine, 375 mL of mid strength beer, or 30 mL of distilled alcohol 40%).
- Use of medications within the timeframes specified in section 11.2.
- Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to dosing or of a biological product within 90 days prior to dosing.
- Previous participation in a clinical research study involving the administration of SMP-100.
- Donation of plasma within 7 days prior to dosing or donation or loss of 500 mL or more of whole blood within 8 weeks prior to dosing.
- Presence of orthodontic braces or orthodontic retention wires, or any physical findings in the mouth or tongue that would be likely to interfere with successful completion of the dosing procedure.
- Any reason which, in the opinion of the Investigator, would prevent the subject from participating in the study.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:交叉作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:Treatment A: SMP-100 dissolved in water administered under fasting conditions
12 subjects,For Treatment A, SMP-100 will be dissolved in a total of 240 mL of water and administered orally to each subjects, and a hand and mouth check will be performed to ensure consumption of the medication.
Subjects will be required not to wear dentures or mouth piercing at the time of dosing.
No food will be allowed from at least 10 hours before dosing until at least 4 hours post-dose.
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In each period, subjects will receive a single dose of SMP-100 on Day 1 (Period 1), Day 4 (Period 2), and Day 7 (Period 3), under fasting or fed conditions, followed by 48 hours of PK and safety assessments.
其他名称:
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实验性的:Treatment B: SMP-100 tablets administered under fasting conditions
12 subjects,For Treatment B, SMP-100 tablets will be administered to each subject with 240 mL of water and a hand and mouth check will be performed to ensure consumption of the medication.
The dosing procedure must be completed within 2 minutes.
In the event that subjects cannot swallow all tablets with 240 mL of water, additional water may be allowed up to a maximum total volume of 400 mL.
No food will be allowed from at least 10 hours before dosing until at least 4 hours post-dose.
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In each period, subjects will receive a single dose of SMP-100 on Day 1 (Period 1), Day 4 (Period 2), and Day 7 (Period 3), under fasting or fed conditions, followed by 48 hours of PK and safety assessments.
其他名称:
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实验性的:Treatment C: SMP-100 tablets administered under fed conditions
12 subjects,For Treatment C, SMP-100 tablets will be administered to each subject with 240 mL of water and a hand and mouth check will be performed to ensure consumption of the medication. The dosing procedure must be completed within 2 minutes. In the event that subjects cannot swallow all tablets with 240 mL of water, additional water may be allowed up to a maximum total volume of 400 mL. After a supervised fast of at least 10 hours, subjects will be served a high-fat, high-calorie meal of approximately 800 to 1000 calories (approximately 50% of total caloric content of the meal derived from fat). This test meal should derive approximately 150, 250, and 500-600 calories from protein, carbohydrate, and fat, respectively. Subjects should start the meal approximately 30 minutes prior to drug administration. Subjects will be required to completely eat the meal in 30 minutes or less. No food will be allowed until at least 4 hours post-dose. |
In each period, subjects will receive a single dose of SMP-100 on Day 1 (Period 1), Day 4 (Period 2), and Day 7 (Period 3), under fasting or fed conditions, followed by 48 hours of PK and safety assessments.
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Primary PK endpoints: AUC( 0-inf)
大体时间:pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
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Area under the concentration-time curve from time zero to infinity (extrapolated)
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pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
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Primary PK endpoint: AUC(0-t)
大体时间:pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
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Area under the concentration-time curve from time zero until the last observed concentration
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pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
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Primary PK endpoint: Cmax
大体时间:pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
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Maximal observed concentration
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pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Secondary PK endpoint: Tmax
大体时间:pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
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Time when the maximal concentration is observed
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pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
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Secondary PK endpoint: Tlag
大体时间:pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
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Time of observation prior to the first observation with a measurable (non-zero)
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pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
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Secondary PK endpoint: T½ el
大体时间:pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
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Terminal elimination half-life
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pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
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Secondary PK endpoint: Kel
大体时间:pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
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Elimination rate constant
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pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
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Secondary PK endpoint: Cl/F
大体时间:pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
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Apparent body clearance
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pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
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Secondary PK endpoint: Vz/F
大体时间:pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
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Apparent volume of distribution
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pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
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Adverse event profile
大体时间:Day -1 to Day 9
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Nature, incidence and severity of treatment-emergent adverse events
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Day -1 to Day 9
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合作者和调查者
调查人员
- 首席研究员:Thomas Polasek、CMAX Clinical Research Pty Ltd
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他研究编号
- SciMount
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