Safety, Tolerability, Pharmacodynamics and Pharmacokineti... | NCT04256655

NCT04256655

Protocol Section

Identification Module

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Cohort 1 0.225 g	Experimental	Randomized to treatment with either CDX-6114 0.225g or matching Placebo	Drug: cohort 1 0.225g
Cohort 2 0.75g	Experimental	Randomized to treatment with either CDX-6114 0.75g or matching Placebo	Drug: Cohort 2 0.75g
Cohort 3 2.25g	Experimental	Randomized to treatment with either CDX-6114 2.25 g or matching Placebo	Drug: Cohort 3 2.25 g

Interventions

Name	Type	Description	Arm Group Labels	Other Names
cohort 1 0.225g	Drug	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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	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 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	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 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	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 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	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 Outcomes

Measure	Description	Time Frame
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	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

Eligibility Module

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.

ID	Term
D020739	Brain Diseases, Metabolic, Inborn
D001928	Brain Diseases, Metabolic
D001927	Brain Diseases
D002493	Central Nervous System Diseases