Effects of Synergy on Nutrient Intake and Acceptability in Phenylketonuria (PKU)

An Open-label, Explorative, Post Launch, Multicenter, Multi-country Intervention Study of PKU Synergy (an Amino-acid Mixture) to Evaluate Change in Nutrient Intake in PKU Subjects With an Increased Phe-tolerance/Intake

Phenylketonuria (PKU) is a rare inherited metabolic disorder, where subjects are born with a genetic deficiency in the phenylalanine hydroxylase enzyme (PAH), which leaves them unable to convert Phenylalanine (Phe) into Tyrosine (Tyr). Patients with mild PKU or partly responsive to the drug synthetic tetrahydrobiopterin (BH4) (Kuvan®) can change to a more relaxed diet. However due to difficulty to adapt their diet, these patients are at risk of an imbalanced nutritional status and an insufficient intake of specific micronutrients, essential amino acids and DHA (Docosahexaenoic acid). The study product is designed to improve the nutritional status of the patients.

The study investigates if the nutritional status is indeed improved following 24 week use of the study product, and also the study aims to evaluate product acceptability.

Inclusion criteria:

1. PKU subjects identified by newborn screening and started low-Phe diet before 3 months of age

2. PKU subjects (with or without current AAM use) with an increased Phe-tolerance/intake due to:

   • Mild PKU phenotype
   • BH4 treatment

3. If treated with BH4, PKU subjects should be on a stable BH4 treatment for at least 26 consecutive weeks up to start test product intake

4. Age≥12 years

5. If subjects (irrespective whether BH4 users or mild PKU) use amino-acid mixture(s; AAM), then a maximum of 25 Protein Equivalents (PE) derived from the AAM per day applies and usage on a daily basis for at least 26 consecutive weeks up to Visit 1

6. If subjects (irrespective whether BH4 users or mild PKU) use AAMs they should be capable and willing to substitute their current AAM(s; maximum of 25 PE per day) with one portion of the test product per day

7. If subjects (irrespective whether BH4 users or mild PKU) use omega-3, antioxidant, and/or vitamin supplements, to stop usage of the supplements and be able and willing to substitute with the test product

8. Willing and able to comply with study procedures

9. Willing and able to provide informed consent (and assent in case of minors if required by local law/regulations)

10. For women of childbearing potential: not to have the intention to become pregnant during the study

Exclusion Criteria:

1. For women: Currently pregnant or lactating
2. Current or prior use of the test product within six weeks prior to entry into the study
3. Concurrent conditions (including renal failure and severe hepatic failure) and medication that could interfere with participation, outcome parameters or safety (as determined by Investigator)
4. Psychotropic medication (i.e. medication affecting the nervous system) and inotropic medication
5. Any condition creating high risk of poor compliance with study
6. Participation in any other studies involving investigational or marketed products concomitantly or within six weeks prior to entry into the study. Except for studies related to Kuvan® (synthetic tetrahydrobiopterin (BH4)) without diagnostic, therapeutic or experimental intervention.