Back to resultsSafety, Tolerability, Pharmacodynamics and Pharmacokinetics of CDX 6114 in PKU Patients
Primary Purpose
Phenylketonurias
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
cohort 1 0.225g
Cohort 2 0.75g
Cohort 3 2.25 g
Sponsored by
About this trial
This is an interventional treatment trial for Phenylketonurias
Eligibility Criteria
Inclusion Criteria
- Male and female patients between the ages of 18 and 65 years, with a diagnosis of classical PKU
- Patients with a blood phenylalanine concentration > 600mol/L at screening as an indicator of sub-optimal dietary management
- Body mass index (BMI) between 18 and 35 kg/m2 at screening.
- Male patients must agree not to donate sperm starting at screening and continuing throughout the clinical study period up to 90 days after last study drug administration
- Female patients of childbearing potential and their spouse/partner
- Female patients of non-childbearing potential:
- Female patients must agree not to breastfeed. This includes the period starting at screening and continuing throughout the clinical study period up to 90 days after last study drug administration.
- Female patients must agree not to donate ova. This includes the period starting at screening and continuing throughout the clinical study period up to 90 days after last study drug administration.
- Patients must be deemed competent to understand the nature of the study and capable of giving written informed consent. Patients must also be willing to attend scheduled study visits in person and to reliably communicate to study personnel on adverse events and concomitant medication use.
- Patients must agree not to participate in another interventional study while participating in the present clinical study.
Exclusion Criteria
- Presence or history of clinically significant hematological, renal, endocrine, pulmonary, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease/condition (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies and childhood asthma).
- Presence or history of gastrointestinal illness or conditions interfering with normal gastrointestinal anatomy. Examples include gastrointestinal bypass surgery, cholecystectomy, partial or total gastrectomy, gastric band surgery, small bowel resection, vagotomy, malabsorption, Crohn's disease, ulcerative colitis, or coeliac disease.
- Active treatment with any platelet aggregation inhibitor and/or active treatment (or within the last 4 weeks) with anticoagulant medication.
- Presence or history of specific food intolerance. Examples include coeliac disease, severe lactose or dairy food intolerance.
- Positive result for serum hepatitis B surface antigen (HBsAg), hepatitis A virus antibodies (HAV), hepatitis C virus antibodies (HCV), or antibodies to human immunodeficiency virus type 1 (HIV-1) and/or type 2 (HIV-2) at Screening.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Cohort 1 0.225 g
Cohort 2 0.75g
Cohort 3 2.25g
Arm Description
Randomized to treatment with either CDX-6114 0.225g or matching Placebo
Randomized to treatment with either CDX-6114 0.75g or matching Placebo
Randomized to treatment with either CDX-6114 2.25 g or matching Placebo
Outcomes
Primary Outcome Measures
Change in the incidence of Treatment-Emergent Adverse Events (AEs) will be measured
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 the serum levels of CDX-6114 will be summarized descriptively over time
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 blood pressure measurements will be summarized over time for each treatment
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 Respiratory rate measurements will be summarized over time for each treatment
The safety and tolerability of CDX-6114 following single dose oral administration assesed by respiratory rate monitoring
Change in absolute values and changes from baseline in Heart rate measurements will be summarized over time for each treatment
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 body temperature (in Fahrenheit or Celsius) measurements will be summarized over time for each treatment
The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by body temperature monitoring
Change in absolute values and changes from baseline in 12 lead Electrocardiogram (ECG) measurements will be summarized over time for each treatment
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 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
The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by weight monitoring
Change in absolute blood composition values from baseline to the last post-dose time-point will be summarized for each treatment
The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by laboratory assessments as Haematology ( routine blood work)
Change in absolute blood composition values from baseline to the last post-dose time-point will be summarized for each treatment
The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by laboratory assessments as Coagulation ( routine blood test)
Change in absolute urine composition values and changes from baseline to the last post-dose time-point will be summarized for each treatment
The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by by routine urinalysis
Any change in the incidence of treatment-Emergent Antibodies will be assesed
The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by assessment for development of anti-CDX-6114 antibodies
Change in absolute values of height measurements will be summarized over time for each treatment using length measurement scale in centimeters or inches
The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by height examination using Lenght scale
Secondary Outcome Measures
Change in concentration of post parandial plasma level of Phe will be summarized over time for each treatment
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
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
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 CA concentration in Plasma will be summarized by treatment
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
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
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
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
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 mood
Any change in mood symptoms will be assessed by using the Profile of Mood States 2nd Edition (POMS-2) questionnaire
Full Information
NCT ID
NCT04256655
First Posted
January 28, 2020
Last Updated
September 11, 2020
Sponsor
Société des Produits Nestlé (SPN)
1. Study Identification
Unique Protocol Identification Number
NCT04256655
Brief Title
Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of CDX 6114 in PKU Patients
Official Title
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).
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Withdrawn
Why Stopped
study product composition to move from liquid to solid
Study Start Date
December 1, 2020 (Anticipated)
Primary Completion Date
December 30, 2021 (Anticipated)
Study Completion Date
December 30, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Société des Produits Nestlé (SPN)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Phenylketonurias
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Masking Description
double blind study
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1 0.225 g
Arm Type
Experimental
Arm Description
Randomized to treatment with either CDX-6114 0.225g or matching Placebo
Arm Title
Cohort 2 0.75g
Arm Type
Experimental
Arm Description
Randomized to treatment with either CDX-6114 0.75g or matching Placebo
Arm Title
Cohort 3 2.25g
Arm Type
Experimental
Arm Description
Randomized to treatment with either CDX-6114 2.25 g or matching Placebo
Intervention Type
Drug
Intervention Name(s)
cohort 1 0.225g
Other Intervention Name(s)
placebo
Intervention Description
Drug: CDX 6114 CDX-6114 for oral administration is formulated in phosphate buffer, which also includes mannitol and poloxamer.The vehicle solution provided is identical to the CDX-6114 oral solution except for the active drug. Matching Placebo The placebo oral dosing solution will also be supplied as an oral solution and will be made up of the phosphate buffer diluent and the caramel flavoring.
Intervention Type
Drug
Intervention Name(s)
Cohort 2 0.75g
Other Intervention Name(s)
placebo
Intervention Description
Drug: CDX 6114 CDX-6114 for oral administration is formulated in phosphate buffer, which also includes mannitol and poloxamer.The vehicle solution provided is identical to the CDX-6114 oral solution except for the active drug. Matching Placebo The placebo oral dosing solution will also be supplied as an oral solution and will be made up of the phosphate buffer diluent and the caramel flavoring.
Intervention Type
Drug
Intervention Name(s)
Cohort 3 2.25 g
Intervention Description
Drug: CDX 6114 CDX-6114 for oral administration is formulated in phosphate buffer, which also includes mannitol and poloxamer.The vehicle solution provided is identical to the CDX-6114 oral solution except for the active drug. Matching Placebo The placebo oral dosing solution will also be supplied as an oral solution and will be made up of the phosphate buffer diluent and the caramel flavoring.
Primary Outcome Measure Information:
Title
Change in the incidence of Treatment-Emergent Adverse Events (AEs) will be measured
Description
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
Time Frame
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
Title
Change in the serum levels of CDX-6114 will be summarized descriptively over time
Description
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
Time Frame
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
Title
Change in Absolute values and changes from baseline in blood pressure measurements will be summarized over time for each treatment
Description
The safety and tolerability of CDX-6114 following single dose oral administration assesed by blood pressure monitoring
Time Frame
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
Title
Change in absolute values and changes from baseline in Respiratory rate measurements will be summarized over time for each treatment
Description
The safety and tolerability of CDX-6114 following single dose oral administration assesed by respiratory rate monitoring
Time Frame
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
Title
Change in absolute values and changes from baseline in Heart rate measurements will be summarized over time for each treatment
Description
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
Time Frame
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
Title
Change in absolute values and changes from baseline in body temperature (in Fahrenheit or Celsius) measurements will be summarized over time for each treatment
Description
The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by body temperature monitoring
Time Frame
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
Title
Change in absolute values and changes from baseline in 12 lead Electrocardiogram (ECG) measurements will be summarized over time for each treatment
Description
The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by 12 lead ECG including P Wave, QRS Complex, QT Interval
Time Frame
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
Title
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
Description
The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by weight monitoring
Time Frame
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
Title
Change in absolute blood composition values from baseline to the last post-dose time-point will be summarized for each treatment
Description
The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by laboratory assessments as Haematology ( routine blood work)
Time Frame
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
Title
Change in absolute blood composition values from baseline to the last post-dose time-point will be summarized for each treatment
Description
The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by laboratory assessments as Coagulation ( routine blood test)
Time Frame
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
Title
Change in absolute urine composition values and changes from baseline to the last post-dose time-point will be summarized for each treatment
Description
The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by by routine urinalysis
Time Frame
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
Title
Any change in the incidence of treatment-Emergent Antibodies will be assesed
Description
The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by assessment for development of anti-CDX-6114 antibodies
Time Frame
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
Title
Change in absolute values of height measurements will be summarized over time for each treatment using length measurement scale in centimeters or inches
Description
The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by height examination using Lenght scale
Time Frame
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
Secondary Outcome Measure Information:
Title
Change in concentration of post parandial plasma level of Phe will be summarized over time for each treatment
Description
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
Time Frame
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
Title
Change in concentration of post parandial plasma level of CA will be summarized over time for each treatment
Description
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
Time Frame
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
Title
Change in the peak Phe concentration in Plasma will be summarized by treatment
Description
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
Time Frame
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
Title
Change in the peak CA concentration in Plasma will be summarized by treatment
Description
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
Time Frame
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
Title
Phe Area under the plasma concentration versus time curve (AUC) , over a 24 hour period, following dosing and the standardized meal
Description
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
Time Frame
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
Title
CA Area under the plasma concentration versus time curve (AUC) , over a 24 hour period, following dosing and the standardized meal
Description
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
Time Frame
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
Title
Serum concentrations of CDX-6114 over a 24 hour period, following dosing and thestandardized meal
Description
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
Time Frame
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
Title
Change in attention
Description
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).
Time Frame
The questionnaire will be completed at home by the patient on Day -1 and on Day 13 before each in-house period
Title
Change in mood
Description
Any change in mood symptoms will be assessed by using the Profile of Mood States 2nd Edition (POMS-2) questionnaire
Time Frame
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).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Male and female patients between the ages of 18 and 65 years, with a diagnosis of classical PKU
Patients with a blood phenylalanine concentration > 600mol/L at screening as an indicator of sub-optimal dietary management
Body mass index (BMI) between 18 and 35 kg/m2 at screening.
Male patients must agree not to donate sperm starting at screening and continuing throughout the clinical study period up to 90 days after last study drug administration
Female patients of childbearing potential and their spouse/partner
Female patients of non-childbearing potential:
Female patients must agree not to breastfeed. This includes the period starting at screening and continuing throughout the clinical study period up to 90 days after last study drug administration.
Female patients must agree not to donate ova. This includes the period starting at screening and continuing throughout the clinical study period up to 90 days after last study drug administration.
Patients must be deemed competent to understand the nature of the study and capable of giving written informed consent. Patients must also be willing to attend scheduled study visits in person and to reliably communicate to study personnel on adverse events and concomitant medication use.
Patients must agree not to participate in another interventional study while participating in the present clinical study.
Exclusion Criteria
Presence or history of clinically significant hematological, renal, endocrine, pulmonary, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease/condition (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies and childhood asthma).
Presence or history of gastrointestinal illness or conditions interfering with normal gastrointestinal anatomy. Examples include gastrointestinal bypass surgery, cholecystectomy, partial or total gastrectomy, gastric band surgery, small bowel resection, vagotomy, malabsorption, Crohn's disease, ulcerative colitis, or coeliac disease.
Active treatment with any platelet aggregation inhibitor and/or active treatment (or within the last 4 weeks) with anticoagulant medication.
Presence or history of specific food intolerance. Examples include coeliac disease, severe lactose or dairy food intolerance.
Positive result for serum hepatitis B surface antigen (HBsAg), hepatitis A virus antibodies (HAV), hepatitis C virus antibodies (HCV), or antibodies to human immunodeficiency virus type 1 (HIV-1) and/or type 2 (HIV-2) at Screening.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tiago Nunes, MD PhD
Organizational Affiliation
Global Development Lead - GI care
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of CDX 6114 in PKU Patients
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