A Phase 1, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of CDX 6114 After Multiple Ascending Oral Dose Administration to Patients With Phenylketonuria (PKU).
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 主要终点
- Change in the serum levels of CDX-6114 will be summarized descriptively over time
研究概览
简要总结
The primary objective is of this Phase 1 study is to evaluate the safety and tolerability of daily, multiple, oral doses of CDX-6114 when administered to patients with PKU for 14 days. The aim is to check if administration of daily, multiple, oral doses of CDX-6114 to patients with PKU for 14 days shows a clinically acceptable safety and tolerability profile.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
double blind study
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Cohort 1 0.225 g
Randomized to treatment with either CDX-6114 0.225g or matching Placebo
干预措施: cohort 1 0.225g (Drug)
Cohort 2 0.75g
Randomized to treatment with either CDX-6114 0.75g or matching Placebo
干预措施: Cohort 2 0.75g (Drug)
Cohort 3 2.25g
Randomized to treatment with either CDX-6114 2.25 g or matching Placebo
干预措施: Cohort 3 2.25 g (Drug)
结局指标
主要结局
Change in the serum levels of CDX-6114 will be summarized descriptively over time
时间窗: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
Blood will be collected for pharmacokinetic analysis of CDX-6114 at the following time points following a repeat dose of CDX-6114 , oral administration for 14 days
Change in absolute values and changes from baseline in Respiratory rate measurements will be summarized over time for each treatment
时间窗: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
The safety and tolerability of CDX-6114 following single dose oral administration assesed by respiratory rate monitoring
Change in absolute blood composition values from baseline to the last post-dose time-point will be summarized for each treatment
时间窗: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by laboratory assessments as Coagulation ( routine blood test)
Change in absolute values and changes from baseline in 12 lead Electrocardiogram (ECG) measurements will be summarized over time for each treatment
时间窗: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by 12 lead ECG including P Wave, QRS Complex, QT Interval
Change in absolute urine composition values and changes from baseline to the last post-dose time-point will be summarized for each treatment
时间窗: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by by routine urinalysis
Change in the incidence of Treatment-Emergent Adverse Events (AEs) will be measured
时间窗: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
The safety and tolerability of CDX-6114 following repeat oral administration of CDX-6114 for 14 days assesed by Adverse events monitoring following following repeat-dose, oral administration for 14 days
Change in absolute values and changes from baseline in body temperature (in Fahrenheit or Celsius) measurements will be summarized over time for each treatment
时间窗: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by body temperature monitoring
Change in absolute values of height measurements will be summarized over time for each treatment using length measurement scale in centimeters or inches
时间窗: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by height examination using Lenght scale
Change in Absolute values and changes from baseline in blood pressure measurements will be summarized over time for each treatment
时间窗: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
The safety and tolerability of CDX-6114 following single dose oral administration assesed by blood pressure monitoring
Change in absolute values and changes from baseline in Heart rate measurements will be summarized over time for each treatment
时间窗: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
Blood will be collected for pharmacokinetic analysis of CDX-6114 at the following time points following a repeat dose of CDX-6114 , oral administration for 14 days
Change in absolute values of Weight measurements will be summarized over time for each treatment using a weighing scale in Kg or pounds over time for each treatment
时间窗: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by weight monitoring
Any change in the incidence of treatment-Emergent Antibodies will be assesed
时间窗: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by assessment for development of anti-CDX-6114 antibodies
次要结局
- Change in concentration of post parandial plasma level of Phe will be summarized over time for each treatment(Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14)
- Change in concentration of post parandial plasma level of CA will be summarized over time for each treatment(Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14)
- Serum concentrations of CDX-6114 over a 24 hour period, following dosing and thestandardized meal(Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14)
- CA Area under the plasma concentration versus time curve (AUC) , over a 24 hour period, following dosing and the standardized meal(Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14)
- Change in attention(The questionnaire will be completed at home by the patient on Day -1 and on Day 13 before each in-house period)
- Change in the peak CA concentration in Plasma will be summarized by treatment(Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14)
- Phe Area under the plasma concentration versus time curve (AUC) , over a 24 hour period, following dosing and the standardized meal(Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14)
- Change in the peak Phe concentration in Plasma will be summarized by treatment(Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14)
- Change in mood(The questionnaire will be completed at home by the patient on Day -1 and Day 13 before each in-house period. The POMS-2 questionnaire used is the full-length adult (18+ years) version (POMS 2-A).)