A clinical study, carried out in different centers and using a placebo, to assess the effect of a medicinal product, containing sapropterin as the active substance, on mental abilities in young adults suffering from phenylketonuria, a genetic disease in which an enzyme defect leads to accumulation of a waste product (phenylketone) which can be detected in urine.

• Register: EUCTR
• Last refreshed on: 17 August 2015
• Main ID: EUCTR2010-024311-13-BE
• Date of registration: 25/09/2013
• Prospective Registration: Yes
• Primary sponsor: Merck KGaA
• Public title: A clinical study, carried out in different centers and using a placebo, to assess the effect of a medicinal product, containing sapropterin as the active substance, on mental abilities in young adults suffering from phenylketonuria, a genetic disease in which an enzyme defect leads to accumulation of a waste product (phenylketone) which can be detected in urine.
• Scientific title: A Multicenter, Double-Blind, Placebo Controlled, Randomized, 2-Arm Phase IIa Pilot Trial Assessing the Effect of Sapropterin on Cognitive Abilities in Young Adults with Phenylketonuria - SIGNAL (SapropterIn on coGnitive abilities in youNg Adults with phenyLketonuria)
• Date of first enrolment: 23/12/2013
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-024311-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Belgium, France, Germany, Italy, Netherlands, Spain, Switzerland

Contacts

• Name: Communication Center Merck KGaA
• Affiliation: Merck KGaA

• Name: Communication Center Merck KGaA
• Affiliation: Merck KGaA

Key inclusion & exclusion criteria

Inclusion criteria:
• Written informed consent given before any trial-related activities are carried out.
• Women or men with documented PKU diagnosed by at least two Phe levels = 400 µmol/L.
• Willingness to use a highly effective method of
contraception is required during the study and follow-up
periods. For women of childbearing potential: a negative urine pregnancy test is required at the end of screening.
• Aged = 18 to 29 years, inclusive.
• Mean blood Phe levels 600 to 1000 µmol/L during 12 months preceding inclusion in the study. The mean should be calculated from at least 3 blood Phe values over the last 12 months. Screening blood Phe level can be one of these values. There should be at least one value dated between Month -12 and -6 before screening and at least one value dated between Month -6 and screening.
• An intelligence quotient (IQ) score = 85, assessed a maximum of 2 years before screening with an age appropriate Wechsler scale. If no IQ test result is available, IQ testing must be performed as part of screening using an age-appropriate Wechsler scale before the subject can be included.
• Subjects willing to comply with all study procedures, including willingness to continue current dietary recommendations during the whole trial duration.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Subjects with tetrahydrobiopterin (BH4) deficiency.
• Previous exposure to sapropterin or BH4 for > 30 days (or exposure to sapropterin or BH4 for = 30 days but within the previous 6 months prior to screening visit).
• Subjects who, according to the Investigator, will not be able to comply with study procedures and computerized neuropsychological testing.
• Any significant illness which, according to the Investigator, might preclude participation in the study (including neurological disease, cardio-vascular disease, history of seizure, predisposition to convulsions, renal or hepatic insufficiency, and active malignancy).
• Any significant illness, medication or substance abuse which, according to the Investigator, might affect cognitive function and cognitive testing (e.g., significant visual or motor impairment, history of major head trauma, history of stroke, alcoholism, drug dependency, psychological disorder requiring chronic use of psychotropic medications such as anxiolytics, antidepressants, antipsychotic medication, mood stabilizers, and hypnotics).
• Concomitant forbidden medication as described in the Kuvan® Summary of Product Characteristics, namely, inhibitors of dihydrofolate reductase (e.g., methotrexate, trimethoprim), medications that are known to affect nitric oxide synthesis (e.g., glyceryl trinitrate, isosorbide dinitrate, sodium nitroprusside, molsidomin, phosphodiesterase type 5 inhibitors, and minoxidil), and levodopa, as it may cause increased excitability and irritability.
• Known hypersensitivity to sapropterin or any ingredients in the product’s formulation, or to other approved or non-approved formulations of BH4.
• Subjects who have undergone cognitive neuropsychological testing similar to that to be performed as part of this trial with the following time limits: tasks with limited practice effect performed in the last 6 months, and tasks with important practice effect (such as tasks involving development of strategies) performed in the year preceding inclusion in the trial. Whether a task falls into one or the other category is left to Investigator judgment.
• Female subjects who are pregnant or in the lactation period.
• Subjects currently participating in another clinical trial or who participated in a previous clinical trial within 30 days prior to screening.
• Legal incapacity or limited legal capacity.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Phenylketonuria
MedDRA version: 16.0 Level: LLT Classification code 10034873 Term: Phenylketonuria (PKU) System Organ Class: 100000004850

Intervention(s)

Trade Name: Kuvan®
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Sapropterin
CAS Number: 62989-33-7
Other descriptive name: SAPROPTERIN DIHYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): As this trial is exploratory in nature, no statistical endpoints were defined as primary or secondary.

Secondary Objective: Not applicable.

Main Objective: The purpose of this pilot trial is to assess the effect of sapropterin on the cognitive abilities of young adults with phenylketonuria (PKU).

Timepoint(s) of evaluation of this end point: Not applicable.

Secondary Outcome(s)

Secondary end point(s): As this trial is exploratory in nature, no statistical endpoints were defined as primary or secondary.

Timepoint(s) of evaluation of this end point: Not applicable.

Secondary ID(s)

2010-024311-13-DE

EMR700773-004

Source(s) of Monetary Support

Merck KGaA