Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of CDX 6114 in PKU Patients
- Conditions
- Phenylketonurias
- Interventions
- Drug: Cohort 2 0.75gDrug: Cohort 3 2.25 gDrug: cohort 1 0.225g
- Registration Number
- NCT04256655
- Lead Sponsor
- Société des Produits Nestlé (SPN)
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 2 0.75g Cohort 2 0.75g Randomized to treatment with either CDX-6114 0.75g or matching Placebo Cohort 3 2.25g Cohort 3 2.25 g Randomized to treatment with either CDX-6114 2.25 g or matching Placebo Cohort 1 0.225 g cohort 1 0.225g Randomized to treatment with either CDX-6114 0.225g or matching Placebo
- Primary Outcome Measures
Name Time Method Change in the serum levels of CDX-6114 will be summarized descriptively over time 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 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 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 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 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 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 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 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 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 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 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 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
- Secondary Outcome Measures
Name Time Method 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 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 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 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
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 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
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 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 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 attention during the study will be assessed by using the inattention subscale of the Attention-Deficit Hyperactivity Disorder Self-Report Scale (ASRS-v1.1).
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 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
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 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 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 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 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). Any change in mood symptoms will be assessed by using the Profile of Mood States 2nd Edition (POMS-2) questionnaire