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Multiple Ascending Oral Dose Phase I Study With Px-102

2014年11月3日 更新者:Phenex Pharmaceuticals AG

A Double-blind, Randomised, Placebo-controlled, Dose-escalation Study of the Safety, Tolerability and Pharmacokinetics of Increasing Multiple Oral Doses of Px-102 to Healthy Subjects

The purpose of this study is to assess the safety and tolerability of the FXR agonist Px-102 in healthy subjects after 7 days multiple oral dosing.

研究概览

地位

完全的

条件

详细说明

The study is a single-centre, double-blind, randomized, placebo-controlled, parallel group phase I study with healthy male subjects receiving ascending multiple oral oral doses of Px-102 to assess the safety and tolerability, pharmacokinetics and pharmacodynamics.

研究类型

介入性

注册 (实际的)

42

阶段

  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习地点

      • Neuss、德国
        • FOCUS Clinical Drug Development GmbH

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 45年 (成人)

接受健康志愿者

是的

有资格学习的性别

男性

描述

Inclusion Criteria:

  • Healthy male subject of Caucasian origin 18 to 45 years of age (inclusive).
  • Good state of health (mentally and physically) as determined by medical history, physical examination, vital signs, ECG recording and clinical lab results.
  • BMI in between 20-29 kg/m² (inclusive); with absolute weight in between 70 to 120 kg.
  • Total cholesterol and liver enzyme levels [alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), alkaline phosphatase (AP)] strictly within the normal ranges at screening and on Day -1. Serum triglyceride not exceeding the upper limit of normal range.
  • HbA1c ≤ 6.5%
  • Subject has been informed both verbally and in writing and has given written consent to participation in the study prior to start and any study-related procedure.
  • Negative results for HIV- and Hepatitis-B and -C serology at screening.
  • Subject (including female partners of childbearing potential) has to use a highly effective method of birth control (failure rate less than 1% per year when used consistently and correctly), e.g. implants, injectables, combined oral contra-ceptives in combination with a barrier method, some intrauterine contraceptive devices or sexual abstinence.

Exclusion Criteria:

  • Female gender
  • Use of prescription or non-prescription drugs within 7 days (30 if the drug is a possible enzyme inducer) prior to administration of study medication. Use of drugs known to induce steatosis (e.g. valproate, amiodarone or prednisone) or to affect body weight and carbohydrate metabolism
  • Any acute or chronic illness or clinically relevant finding at screening and at base-line examination which may jeopardize the subject's participation in the study
  • History or presence of biliary obstruction or biliary disease, hepatic encephalopathy, advanced ascites, portal hypertension, esophageal/gastric variceal bleeding, hepatocellular carcinoma, previous liver transplantation or any other chronic liver disease
  • Renal dysfunction, e.g. glomerular filtration rate ≤ 80 ml/min/1.73 m2 (as determined by the formula of Cockroft-Gault)
  • Type I or II Diabetes
  • Any clinically relevant abnormality on screening medical assessment, laboratory examination, 12-lead ECG
  • Any clinically relevant finding in the baseline telemetry within the pre-dose evaluated observation period of at least 20 hours
  • Marked baseline prolongation of QT/QTc interval (QTc interval > 440 ms) in the 12-lead ECG using the Fridericia method for QTc analysis
  • Heart rate < 50 bpm.
  • History of pathological cardiovascular symptoms or a severe cardiovascular event
  • History of severe chronic autoimmune diseases such as severe allergy, atopic eczema, chronic dermatitis, severe psoriasis, multiple sclerosis, severe asthma, lupus or related disorders
  • Allergies (except for mild forms of hay fever) or history of hypersensitivity reactions
  • Smoking (regular or irregular) > 5 cigarettes (or equivalent) per day
  • Excessive alcohol drinking (more than approximately 20 g alcohol per day), unable to refrain from alcohol drinking from 48 hours prior to dosing until the last pharmacokinetic blood sample has been withdrawn
  • Positive test for drugs or alcohol at screening or prior to the dosing session
  • History of alcoholism or drug/chemical/substance abuse within past 2 years
  • Investigator deems the subject unable or unwilling to comply fully with the study protocol
  • Has received clinical study medication within the last 30 days prior to this study
  • Donation or loss of 400 ml or more of blood within eight (8) weeks prior to dosing
  • Allergic to any of the active or inactive ingredients in the study medication
  • Any other reason which the Investigator considers unsuitable for the subject to participate
  • Any condition or previous disease leading to pruritus or itching of the skin.

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

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:并行分配
  • 屏蔽:三倍

武器和干预

参与者组/臂
干预/治疗
有源比较器:Px-102
Px-102 drinking solution, 0.5 mg/kg, 1.0 mg/kg and 1.5 mg/kg
Px-102 drinking solution, 0.5 mg/kg, 1.0 mg/kg and 1.5 mg/kg
安慰剂比较:Placebo
Oral drinking solution
Drinking solution

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
Safety and tolerability of Px-102
大体时间:7 days
Adverse event monitoring, laboratory values, cardiovascular monitoring. Comparison active vs. placebo
7 days

次要结果测量

结果测量
措施说明
大体时间
Pharmacokinetics of Px-102 and metabolites
大体时间:Day 1: 0 min, 15 min, 30 min, 60 min, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 12 h, 22 h, 24 h; Day 5 and 6: pre-dose; Day 7: 0 min, 15 min, 30 min, 60 min, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 12 h, 22 h, 24 h, 30 h.
Plasma, urine and fecal concentrations (ng/mL) of Px-102 and metabolites measured by LC-MS/MS. AUC, Cmax and other pk parameters. Comparison of the pk data on day 7 vs. day 1
Day 1: 0 min, 15 min, 30 min, 60 min, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 12 h, 22 h, 24 h; Day 5 and 6: pre-dose; Day 7: 0 min, 15 min, 30 min, 60 min, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 12 h, 22 h, 24 h, 30 h.
Pharmacodynamics
大体时间:Pre-dose, 1, 2, 4, 8 and 10 hours after administration on Days 1 and 7; Pre-dose, 2 hours and 8 hours after administration on Days 2 to 6; at 22 hours after the last administration
Markers for FXR activation (e.G. FGF19 (pg/mL) measurement by ELISA). Comparison active vs. placebo
Pre-dose, 1, 2, 4, 8 and 10 hours after administration on Days 1 and 7; Pre-dose, 2 hours and 8 hours after administration on Days 2 to 6; at 22 hours after the last administration

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

调查人员

  • 学习椅:Claus Kremoser, Dr.、Phenex Pharmaceuticals AG

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2012年2月1日

初级完成 (实际的)

2012年10月1日

研究完成 (实际的)

2012年10月1日

研究注册日期

首次提交

2013年11月19日

首先提交符合 QC 标准的

2013年11月25日

首次发布 (估计)

2013年12月2日

研究记录更新

最后更新发布 (估计)

2014年11月4日

上次提交的符合 QC 标准的更新

2014年11月3日

最后验证

2014年11月1日

更多信息

与本研究相关的术语

其他研究编号

  • PHS-Px-102-I-02

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

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