Open-label, Randomized, 2-way Crossover, Monocentric, Controlled Study to Evaluate the Effect on Daily PHE Fluctuation of PKU GOLIKE Versus SoC in Patients With PKU.

Open-label, Randomized, 2-way Crossover, Monocentric, Controlled Study to Evaluate the Effect on Daily PHE Fluctuation of PKU GOLIKE Versus Standard of Care in Patients With Phenylketonuria

This is an open-label, randomized, 2-way crossover, monocentric controlled study in patients (≥ 16 years old) with phenylketonuria (PKU).

The comparison will be between the test product (PKU GOLIKE, a prolonged-release amino-acids (AAs) mixture) and standard of care.

Study Overview

• Status: Terminated
• Conditions: Phenylketonurias
• Intervention / Treatment: Dietary supplement: PKU GOLIKE; Dietary supplement: Standard of Care

Detailed Description

The study will consist of a screening visit (V1), two treatment periods with two test days each and a final visit planned at the end of the second treatment period (V2). Test days will occur on two consecutive preferably non-working/school days (T1-T2 and T3-T4,) preferably over two consecutive weeks. Treatment days in the two periods will have to be the same days of the week. T1 should be within two weeks after V1. The study products will be self-administered at home. Following informed consent and verification of eligibility criteria, 20 patients with PKU will be randomized in a 1:1 ratio to one of the following two sequences: AB or BA where A=standard of care and B=PKU GOLIKE. In details:

• AB: patients will receive 3 daily self-administrations of their usual standard of care for 2 consecutive days in the first period followed by 3 daily self-administrations of PKU GOLIKE for 2 consecutive days in thesecond period.
• BA: patients will receive 3 daily self-administrations of PKU GOLIKE for 2 consecutive days in the first period followed by 3 daily self administrations of their usual standard of care for 2 consecutive days in the second period.

No change in the randomization sequence will be allowed.

Each patient will follow the same diet in terms of food, calories and nutrients ranges during the first days (T1 and T3) of each period and the same diet during the second days (T2 and T4) of each period, according to the age and body weight of the patient. The days before the test days each patient will follow her/his standard diet.

PKU GOLIKE /standard of care will be the only protein substitute allowed on each test day, and no sports activities will be allowed on sampling days. Five blood spots will be collected on the second test day of each period. Timing of self-administrations, meals and blood spots will be standardized for each test day. On the test days, no food will be allowed outside of the defined time windows. The first self-administration of each test day will be performed after an overnight fasting (10 -12 h) and before any food intake.

A patient's e-diary will be used to collect information on patient compliance, 24-hour blood spot collections, diet, daily activities, adverse events and event-related concomitant medications.

Adverse events will be continuously monitored during the study, starting from informed consent. Adverse events will be collected by the patients (or by a parent/guardian) in the e-diary and during the telephone calls made by the Investigator to the patients. Moreover, patients (or parents/guardians) will be instructed to promptly report adverse events occurring during the study to the Investigator.

The end of study (V2) will be performed (remotely, by phone) at the end ofthe second treatment period, within 2 weeks after the last test day. Patients prematurely discontinued from the study will be asked to attend (remotely, by phone) a discontinuation visit possibly taking place within 2 weeks from the last test day. At the final/discontinuation visit, the investigator will organize collection of blood spots test and residual PKU GOLIKE product from the patient's domicile through a dedicated courier service. The account of the e-diary will be inactivated.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20142
    • ASST Santi Paolo e Carlo, Presidio Ospedale San Paolo, Via Antonio di Rudinì 8

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed, informed consent obtained by the patient prior to beingenrolled into the study and prior to starting any data collection. For legally minor patients, signed written consent shall be obtained also by the parents/legal guardian
2. Male or female, aged ≥16 years.
3. Patients with a registered diagnosis of PKU
4. Ability and willingness to comply with all study procedures and availability for the duration of the study.
5. Patients with mean value of blood Phe >360 µM in the previous 12 months (calculated on at least 3 samples during the previous 12 months; the last sample should be preferably obtained in the 30 days preceding inclusion in the study).
6. Patient taking free-AA and/or GMP as usual amino-acidssupplementation.

Exclusion Criteria:

1. Known or suspected hypersensitivity to any excipients/components of PKU GOLIKE.
2. Treatment with any drug therapy for PKU
3. Patient taking PKU GOLIKE as usual amino-acids supplementation
4. Patient taking LNAA as usual amino-acids supplementation
5. Any moderate to severe medical condition, which in the opinion of the Investigator would interfere with the study procedures or study outcome (reason to be provided)
6. Any current participation in another clinical trial involving investigational or marketed products in the 3 months prior to the inclusion in this study.
7. Pregnancy or lactation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: AB where A=standard of care and B=PKU GOLIKE; Patients will receive 3 daily self-administrations of their usual standard of care for 2 consecutive days in the first period followed by 3 daily self-administrations of PKU GOLIKE for 2 consecutive days in the second period.	Dietary supplement: PKU GOLIKE; PKU GOLIKE is a food for special medicinal purposes (FSMP) for the dietary management of PKU.; Dietary supplement: Standard of Care; Protein substitute
Other: BA where B=PKU GOLIKE and A=standard of care; Patients will receive 3 daily self-administrations of PKU GOLIKE for 2 consecutive days in the first period followed by 3 daily self-administrations of their usual standard of care for 2 consecutive days in the second period.	Dietary supplement: PKU GOLIKE; PKU GOLIKE is a food for special medicinal purposes (FSMP) for the dietary management of PKU.; Dietary supplement: Standard of Care; Protein substitute

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phe Blood Concentration With Dried Blood Spots (Umol/L) on the Second Test Day With Standard of Care Right Before Product Self-administration and Before Any Food Intake	Measurement of blood phenylalanine (Phe) levels	at 8:00 am(±15 min) on the second test day (T2; T4) with SoC
Phe Blood Concentration With Dried Blood Spots (Umol/L) on the Second Test Day With GOLIKE PLUS Right Before Product Self-administration and Before Any Food Intake		at 8:00 am(±15 min) on the second test day (T2; T4) with Golike Plus
Phe Blood Concentration With Dried Blood Spots (Umol/L) on the Second Test Day With Standard of Care Right Before Product Self-administration and Before Food Intake		at 12:00 am (±15 min) on the second test day (T2; T4)with SoC
Phe Blood Concentration With Dried Blood Spots (Umol/L) on the Second Test Day With GOLIKE PLUS Right Before Product Self-administration and Before Food Intake		at 12:00 am (±15 min) on the second test day (T2; T4) with Golike Plus
Phe Blood Concentration With Dried Blood Spots (Umol/L) on the Second Test Day With Standard of Care Before Food Intake		At 4:00 pm (±15 min) on the second test (T2;T4) day with SoC
Phe Blood Concentration With Dried Blood Spots (Umol/L) on the Second Test Day With GOLIKE PLUS Before Food Intake		At 4:00 pm (±15 min) on the second test day (T2; T4) with Golike Plus
Phe Blood Concentration With Dried Blood Spots (Umol/L) on the Second Test Day With Standard of Care Right Before Product Self-administration and Before Any Food Intake		at 8:00 pm (±15 min) on the second test day (T2; T4) with SoC
Phe Blood Concentration With Dried Blood Spots (Umol/L) on the Second Test Day With GOLIKE PLUS Right Before Product Self-administration and Before Any Food Intake		at 8:00 pm (±15 min) on the second test day (T2; T4) with Golike Plus
Phe Blood Concentration With Dried Blood Spots (Umol/L) on the Day Following the Second Test Day With Standard of Care on the Following Morning, Before Any Food Intake.		at 8:00 am (±15 min) on the day following the second test day (T2; T4) with SoC
Phe Blood Concentration With Dried Blood Spots (Umol/L) on the Day Following the Second Test Day With GOLIKE PLUS on the Following Morning, Before Any Food Intake.		at 8:00 am (±15 min) on the day following the second test day (T2; T4) with Golike Plus

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tyr Blood Concentration With Dried Blood Spots (Umol/L) on the Second Test Day With Standard of Care Right Before Product Self-administration and Before Any Food Intake	Measurement of blood Tyrosine (Tyr) levels	at 8:00 am(±15 min) on the second test day (T2; T4) with SoC
Tyr Blood Concentration With Dried Blood Spots (Umol/L)on the Second Test Day With GOLIKE PLUS Right Before Product Self-administration and Before Any Food Intake		at 8:00 am(±15 min)on the second test day (T2; T4) with Golike Plus
Tyr Blood Concentration With Dried Blood Spots (Umol/L)on the Second Test Day With Standard of Care Right Before Product Self-administration and Before Any Food Intake		at 12:00 am(±15 min) on the second test day (T2; T4) with SoC
Tyr Blood Concentration With Dried Blood Spots (Umol/L) on the Second Test Day With GOLIKE PLUS Right Before Product Self-administration and Before Any Food Intake		at 12:00 am(±15 min) on the second test day (T2; T4) with Golike Plus
Tyr Blood Concentration With Dried Blood Spots (Umol/L)on the Second Test Day With Standard of Care Before Food Intake		at 4:00 pm(±15 min)on the second test day (T2; T4) with SoC
Tyr Blood Concentration With Dried Blood Spots (Umol/L) on the Second Test Day With GOLIKE PLUS Before Food Intake		at 4:00 pm(±15 min)on the second test day (T2; T4) with Golike Plus
Tyr Blood Concentration With Dried Blood Spots (Umol/L)on the Second Test Day With Standard of Care Right Before Product Self-administration and Before Any Food Intake		at 8:00 pm(±15 min) on the second test day (T2; T4) with SoC
Tyr Blood Concentration With Dried Blood Spots (Umol/L)on the Second Test Day With GOLIKE PLUS Right Before Product Self-administration and Before Any Food Intake		at 8:00 pm(±15 min) on the second test day (T2; T4) with Golike Plus
Tyr Blood Concentration With Dried Blood Spots (Umol/L)on the Day Following the Second Test Day With Standard of Care on the Following Morning, Before Any Food Intake.		at 8:00 am(±15 min) on the day following the second test day (T2; T4) with SoC
Tyr Blood Concentration With Dried Blood Spots (Umol/L) on the Day Following the Second Test Day With GOLIKE PLUS on the Following Morning, Before Any Food Intake.		at 8:00 am(±15 min) on the day following the second test day (T2; T4) with Golike Plus

Collaborators and Investigators

• Sponsor: APR Applied Pharma Research s.a.
• Investigators: Principal Investigator: Valentina Rovelli, MD, ASST Santi Paolo e Carlo, Presidio Ospedale San Paolo, Via Antonio di Rudinì 8 - 20142, Milano (Italy)

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2023
• Primary Completion (Actual): November 27, 2024
• Study Completion (Actual): November 27, 2024

Study Registration Dates

• First Submitted: March 24, 2023
• First Submitted That Met QC Criteria: April 12, 2023
• First Posted (Actual): April 25, 2023

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Amino Acid Metabolism, Inborn Errors; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Phenylketonurias; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: GLK-IT-2023

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No