Response to Kuvan® in Subjects With Phenylketonuria (PKU) in a 4 Weeks Testing Period

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT01082328
• Date of registration: 05/03/2010
• Prospective Registration: Yes
• Primary sponsor: Merck KGaA
• Public title: Response to Kuvan® in Subjects With Phenylketonuria (PKU) in a 4 Weeks Testing Period ENDURE
• Scientific title: ENDURE: A Phase IV, Prospective, Open-label, Uncontrolled, Multi-centre Cohort Trial to Assess the Responsiveness of Subjects With Phenylketonuria (PKU) to Treatment With Kuvan® 20 mg/kg/Day for 28 Days
• Date of first enrolment: May 2010
• Target sample size: 59
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01082328
• Study type: Interventional
• Phase: Phase 4

Countries of recruitment

Norway

Contacts

• Name: Medical Responsible
• Affiliation: Merck Serono S.A., an affiliate of Merck KGaA, Darmstadt, Germany

Key inclusion & exclusion criteria

Inclusion Criteria:

- Subjects aged 4 years or older at the time the informed consent is obtained

- Subjects diagnosed with PKU (subgroups defined as: classic PKU [blood Phe greater than
{>}1200 micromole per liter {mcmol/L}], mild PKU [blood Phe 600 to1200 mcmol/L] or
mild hyperphenylalaninemia (HPA) [blood Phe 300 to 600 mcmol/L]

- Subjects who have received no previous treatment with sapropterin dihydrochloride
(either Kuvan® or any other formulations of tetrahydrobiopterin [BH4])

- Subjects adherent to their normal diet and willing to adhere to the given diet for the
4 weeks study period

- Subjects who provide a signed (by parent if below 18 years) written informed consent

- Subjects with documented genotyping for both phenylalanine hydroxylase (PAH) mutations
(PKU genotype)

- Phenylketonuria (PKU) diagnosis should be documented with at least two historical
blood Phe levels above 400 mcmol/L

- Female subjects of childbearing potential (and, if appropriate, male subjects with
female partners of childbearing potential) must be willing to avoid pregnancy by using
an adequate method of contraception (defined as two barrier methods or one barrier
method with spermicide, or intrauterine device or use of the oral female
contraceptive) for 4 weeks prior to, during and 12 weeks after the last dose of trial
medication

- Women of childbearing potential (for the purpose of this trial, women of childbearing
potential are defined as "All female subjects after puberty unless they are
post-menopausal for at least 2 years, are surgically sterile or are sexually
inactive") must have a negative urine pregnancy test at the Baseline visit

Exclusion Criteria:

- Subjects who have documented BH4 deficiency

- Subjects who have any contraindications to receive Kuvan® as outlined in the summary
of product characteristics (SmPC) not willing or able to comply with the study
procedures

- Subjects who are pregnant, planning for pregnancy or breastfeeding

- Subjects who have been exposed to any investigational medicinal drugs or treatments
within 30 days or 5 half-lives, whichever is longer, prior to the Screening visit

- Subjects using concomitant treatment with folate synthesis inhibiting drugs

- Subjects with concurrent use of Levodopa

- Subjects with concurrent use of inhibitors of dihydrofolate reductase (for example,
methotrexate, trimethoprim)

- Subjects with concurrent use of agents that cause vasodilation, including those
administered topically, by affecting nitric oxide (NO) metabolism or action including
classical NO donors (for example, glyceryl trinitrate (GTN), isosorbide dinitrate
(ISDN), sodium nitroprusside (SNP), molsidomin), phosphodiesterase type 5 (PDE-5)
inhibitors and minoxidil

- Subjects who have a concurrent disease potentially interfering safety (for example,
seizure disorder, oral steroid dependent asthma, other conditions requiring systemic
corticosteroids, or insulin-dependent diabetes mellitus)

- Subjects who have inadequate liver function, defined by alanine aminotransferase (ALT)
>= 2 times upper limit of normal (ULN)

- Subjects who have clinically significant renal dysfunction, defined by serum
creatinine > 250 mcmol/L

- Have any medical condition that, in the judgment of the investigator, would jeopardize
the subject's safety following exposure to study drug or would significantly interfere
with the subject's ability to comply with the provisions of the protocol



Age minimum: 4 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Phenylketonuria

Intervention(s)

Drug: Kuvan®

Primary Outcome(s)

Percentage of Participants With at Least 30 Percent Reduction From Baseline in Blood Phenylalanine (Phe) Level [Time Frame: Baseline up to Day 28 +/- 1]

Secondary Outcome(s)

Percentage of Early-, Late-, Partial-Responders and Non-responders to Treatment With Kuvan® [Time Frame: Baseline up to Day 28 +/- 1]

Percentage of Participants With Greater Than or Equal to (>=) 30 Percent, 20 to 30 Percent, 10 to 20 Percent and Less Than (<) 10 Percent Reduction in Blood Phe Levels According to Phenylketonuria (PKU) Phenotypes [Time Frame: Baseline up to Day 28 +/- 1]

Number of Participants With Adverse Events (AEs), Treatment Emergent Adverse Events, Treatment Related Adverse Events and AEs Leading to Withdrawal [Time Frame: Baseline up to Day 42 +/- 3]

Mean Change From Baseline in Blood Phenylalanine-to-tyrosine Ratio [Time Frame: Baseline, Day 28]

Percentage of Early-, Late- and Partial-Responders According to Phenotype [Time Frame: Baseline up to Day 28 +/- 1]

Secondary ID(s)

EMR 700773-503

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Merck Serono Norway

Smerud Medical Research International AS

Results

• Results available: Yes
• Date Posted: 01/08/2013
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01082328