Study to Evaluate the Effect on Nitrogen Retention of Two Different Posology Schemes of PKU GOLIKE PLUS 3-16 and Free AAs in Patients With Phenylketonuria

NCT05229549 | Terminated

• 1 other identifier: GLK-2021
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, randomized, 4-way crossover, monocentric, controlled study in patients (3 ≤ years of age ≤ 20 )) with phenylketonuria (PKU). The primary comparison will be between the test product (PKU GOLIKE PLUS 3-16, a prolonged-release amino-acids (AAs) mixture) and the reference product (an immediate-release free AAs mixture with the same qualitative and quantitative composition of PKU GOLIKE PLUS 3-16). PKU GOLIKE PLUS 3-16 is a food for special medicinal purposes (FSMP) for the dietary management of PKU. The study will consist of a screening visit (T0), four test days taking place on Sunday (T1-T4), each separated by a washout period (a period of time when a participant is taken off a treatment in order to eliminate its effects) and with the study products being self-administered at home, and a final visit (T5). Following informed consent and verification of eligibility criteria, 24 patients with PKU will be randomized in a 1:1:1:1 ratio to one of the four randomization sequences ABCD, BDAC, DCBA or CADB. A, B, C and D will be: A. One day treatment with 3 self-administrations of GOLIKE PLUS 3-16 (1.2 g/kg total daily dose of AA) B. One day treatment with 2 self-administrations of GOLIKE PLUS 3-16 (1.2 g/kg total daily dose of AA) C. One day treatment with 3 self-administrations of free AAs (1.2 g/kg total daily dose of AA) D. One day treatment with 2 self-administrations of free AAs (1.2 g/kg total daily dose of AA) GOLIKE PLUS 3-16 and the free AAs mixture will be the only protein substitute allowed on each test day, and no sports activities will be allowed on the test days. 24-hour urines and five blood spots will be collected on each test day. A patient's diary will be used to collect information on patient compliance, 24-hour urines and blood spot collections, diet, daily activities, adverse events and concomitant medications. Patients completing all four test days will be asked to go to the center for a final visit (T5) taking place within 2 weeks from the last product administration.

Conditions

Phenylketonurias

Outcome Measures

Primary Outcomes (1)

• Difference of GOLIKE PLUS 3-16 versus free AAs in terms of nitrogen retention after one day of product intake

  Nitrogen excretion in the 24-hour urines of each test day is measured.

  Over 24 hours of each test day.

Secondary Outcomes (3)

• Comparison of impact of 2 self-administrations of GOLIKE PLUS 3-16 and of 3-self administrations of free AAs on nitrogen retention after one day of product intake

  Over 24 hours of each test day.

• Comparison of the impact of 2 self-administrations of GOLIKE PLUS 3-16 and of 3 self-administrations of GOLIKE PLUS 3-16 on nitrogen excretion

  Over 24 hours of each test day.

• Comparison of the the impact of GOLIKE PLUS 3-16 and of free AAs on phenylalanine (Phe) and tyrosine (Tyr) levels in blood on each test day.

  Over 24 hours of each test day.

Other Outcomes (2)

• Comparison of the impact of GOLIKE PLUS 3-16 and of free AAs on branched-chained amino acids (leucine, isoleucine, valine) levels in blood on each test day.

  Over 24 hours of each test day.

• Comparison of the impact of GOLIKE PLUS 3-16 and of free AAs on the urinary creatinine/height index after one day of product intake.

  Over 24 hours of each test day.

Study Arms (4)

A. One day treatment with 3 self-administrations of GOLIKE PLUS 3-16

ACTIVE COMPARATOR

Other: GOLIKE PLUS 3-16

B. One day treatment with 2 self-administrations of GOLIKE PLUS 3-16

ACTIVE COMPARATOR

Other: GOLIKE PLUS 3-16

C. One day treatment with 3 self-administrations of free AAs

PLACEBO COMPARATOR

Other: Free AAs

D. One day treatment with 2 self-administrations of free AAs

PLACEBO COMPARATOR

Other: Free AAs

Interventions

GOLIKE PLUS 3-16 OTHER

PKU GOLIKE PLUS 3-16 is a food for special medicinal purposes (FSMP) for the dietary management of PKU.

A. One day treatment with 3 self-administrations of GOLIKE PLUS 3-16; B. One day treatment with 2 self-administrations of GOLIKE PLUS 3-16

Free AAs OTHER

It is an immediate-release free AAs mixture with the same qualitative and quantitative composition of PKU GOLIKE PLUS 3-16.

C. One day treatment with 3 self-administrations of free AAs; D. One day treatment with 2 self-administrations of free AAs

Eligibility Criteria

• Age: 3 Years - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Signed, informed consent obtained prior to being enrolled into the study and prior to starting any data collection. Consent of a legally authorized guardian is required for legally minor patients as defined by local regulation. If the patient is legally a minor, signed written consent shall be obtained from parent(s)/legal guardian and assent obtained from the patient, if applicable.
• Male or female, aged 3-20 (limits included).
• Patients with diagnosis of PKU at newborn screening.
• Patients starting low Phe diet before 1 month of age.
• Ability and willingness to comply with all study procedures and availability for the duration of the study.

You may not qualify if:

• Known or suspected hypersensitivity to any excipients/components of the investigational products.
• Treatment with therapy for PKU other than amino-acids supplementation.
• Patients aged \>12 years old with 4 repeated average values of blood Phe \>600 µM in the previous 6 months.
• Patients aged \<12 years old with 4 repeated average values of blood Phe \>360 µM in the previous 6 months.
• Any moderate to severe medical condition, which in the opinion of the Investigator would interfere with the study procedures or study outcome (reasoning to be provided), such as history of clinically significant diseases or malfunctions including, but not limited to, gastrointestinal, renal, hepatic, pulmonary, cardiovascular or endocrine disease, hemophilia, hyperlipidemia, impaired glucose tolerance or diabetes (type 1 or 2), or anemia.
• History of poor co-operation, non-compliance with medical treatments and diet, or poor adherence to investigational procedures.
• Pregnancy or lactation.

Sponsors & Collaborators

• APR Applied Pharma Research s.a.: lead

Study Sites (1)

San Paolo Hospital

Milan, Italy

Location

MeSH Terms

Conditions

Phenylketonurias

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Giuseppe Banderali

  ASST Santi Paolo e Carlo, Presidio Ospedale San Paolo, Via Antonio di Rudinì 8 - 20142, Milano (Italy)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2022
• First Posted: February 8, 2022
• Study Start: May 6, 2022
• Primary Completion: November 29, 2022
• Study Completion: February 7, 2023
• Last Updated: July 7, 2023

Record last verified: 2022-01

Locations

IT (1)