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Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of CDX 6114 in PKU Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04256655
Recruitment Status : Withdrawn (study product composition to move from liquid to solid)
First Posted : February 5, 2020
Last Update Posted : September 16, 2020
Sponsor:
Information provided by (Responsible Party):
Nestlé

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.

Condition or disease Intervention/treatment Phase
Phenylketonurias Drug: cohort 1 0.225g Drug: Cohort 2 0.75g Drug: Cohort 3 2.25 g Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: double blind study
Primary Purpose: Treatment
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).
Estimated Study Start Date : December 1, 2020
Estimated Primary Completion Date : December 30, 2021
Estimated Study Completion Date : December 30, 2021


Arm Intervention/treatment
Experimental: Cohort 1 0.225 g
Randomized to treatment with either CDX-6114 0.225g or matching Placebo
Drug: cohort 1 0.225g
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.
Other Name: placebo

Experimental: Cohort 2 0.75g
Randomized to treatment with either CDX-6114 0.75g or matching Placebo
Drug: Cohort 2 0.75g
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.
Other Name: placebo

Experimental: Cohort 3 2.25g
Randomized to treatment with either CDX-6114 2.25 g or matching Placebo
Drug: Cohort 3 2.25 g
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 Measures :
  1. Change in the incidence of Treatment-Emergent Adverse Events (AEs) will be measured [ 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 ]
    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

  2. Change in the serum levels of CDX-6114 will be summarized descriptively over time [ 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 ]
    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

  3. Change in Absolute values and changes from baseline in blood pressure measurements will be summarized over time for each treatment [ 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 ]
    The safety and tolerability of CDX-6114 following single dose oral administration assesed by blood pressure monitoring

  4. Change in absolute values and changes from baseline in Respiratory rate measurements will be summarized over time for each treatment [ 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 ]
    The safety and tolerability of CDX-6114 following single dose oral administration assesed by respiratory rate monitoring

  5. Change in absolute values and changes from baseline in Heart rate measurements will be summarized over time for each treatment [ 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 ]
    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

  6. Change in absolute values and changes from baseline in body temperature (in Fahrenheit or Celsius) measurements will be summarized over time for each treatment [ 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 ]
    The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by body temperature monitoring

  7. Change in absolute values and changes from baseline in 12 lead Electrocardiogram (ECG) measurements will be summarized over time for each treatment [ 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 ]
    The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by 12 lead ECG including P Wave, QRS Complex, QT Interval

  8. 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 [ 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 ]
    The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by weight monitoring

  9. Change in absolute blood composition values from baseline to the last post-dose time-point will be summarized for each treatment [ 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 ]
    The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by laboratory assessments as Haematology ( routine blood work)

  10. Change in absolute blood composition values from baseline to the last post-dose time-point will be summarized for each treatment [ 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 ]
    The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by laboratory assessments as Coagulation ( routine blood test)

  11. Change in absolute urine composition values and changes from baseline to the last post-dose time-point will be summarized for each treatment [ 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 ]
    The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by by routine urinalysis

  12. Any change in the incidence of treatment-Emergent Antibodies will be assesed [ 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 ]
    The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by assessment for development of anti-CDX-6114 antibodies

  13. Change in absolute values of height measurements will be summarized over time for each treatment using length measurement scale in centimeters or inches [ 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 ]
    The safety and tolerability of CDX-6114 following repeat dose oral administration assesed by height examination using Lenght scale


Secondary Outcome Measures :
  1. Change in concentration of post parandial plasma level of Phe will be summarized over time for each treatment [ 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 ]
    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

  2. Change in concentration of post parandial plasma level of CA will be summarized over time for each treatment [ 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 ]
    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

  3. Change in the peak Phe concentration in Plasma will be summarized by treatment [ 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 ]
    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

  4. Change in the peak CA concentration in Plasma will be summarized by treatment [ 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 ]
    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

  5. Phe Area under the plasma concentration versus time curve (AUC) , over a 24 hour period, following dosing and the standardized meal [ 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 ]
    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

  6. CA Area under the plasma concentration versus time curve (AUC) , over a 24 hour period, following dosing and the standardized meal [ 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 ]
    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

  7. Serum concentrations of CDX-6114 over a 24 hour period, following dosing and thestandardized meal [ 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 ]
    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

  8. Change in attention [ Time Frame: 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).

  9. Change in mood [ 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). ]
    Any change in mood symptoms will be assessed by using the Profile of Mood States 2nd Edition (POMS-2) questionnaire



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Male and female patients between the ages of 18 and 65 years, with a diagnosis of classical PKU
  2. Patients with a blood phenylalanine concentration > 600mol/L at screening as an indicator of sub-optimal dietary management
  3. Body mass index (BMI) between 18 and 35 kg/m2 at screening.
  4. 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
  5. Female patients of childbearing potential and their spouse/partner
  6. Female patients of non-childbearing potential:
  7. 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.
  8. 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.
  9. 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.
  10. Patients must agree not to participate in another interventional study while participating in the present clinical study.

Exclusion Criteria

  1. 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).
  2. 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.
  3. Active treatment with any platelet aggregation inhibitor and/or active treatment (or within the last 4 weeks) with anticoagulant medication.
  4. Presence or history of specific food intolerance. Examples include coeliac disease, severe lactose or dairy food intolerance.
  5. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04256655


Sponsors and Collaborators
Nestlé
Investigators
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Study Director: Tiago Nunes, MD PhD Global Development Lead - GI care
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Responsible Party: Nestlé
ClinicalTrials.gov Identifier: NCT04256655    
Other Study ID Numbers: 19.05.CLI
First Posted: February 5, 2020    Key Record Dates
Last Update Posted: September 16, 2020
Last Verified: September 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Phenylketonurias
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases