Sapropterin on Cognitive Abilities in Young Adults With Phenylketonuria (SIGNAL)

This study has been terminated.
(Recruitment challenges)
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01977820
First received: October 31, 2013
Last updated: January 14, 2016
Last verified: January 2016
  Purpose
This is a Phase 2a multicenter, double-blind, placebo-controlled, randomized, 2-arm pilot trial designed to assess the effect of sapropterin on cognitive abilities in young adults with Phenylketonuria (PKU) over a 26-week treatment period.

Condition Intervention Phase
Phenylketonuria
Drug: Sapropterin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Number of Subjects With Adverse Events (AEs), Serious AEs (SAEs), AEs Leading to Death and AEs Leading to Discontinuation [ Time Frame: Screening up to 24 weeks + 4-week follow-up ] [ Designated as safety issue: Yes ]
    An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.


Enrollment: 2
Study Start Date: February 2014
Study Completion Date: November 2014
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sapropterin Drug: Sapropterin
Sapropterin tablets will be administered orally once daily at a dose of 20 milligram per kilogram (mg/kg) during both the 2-Week response test period and 24-Week study period.
Other Name: Kuvan®
Placebo Comparator: Placebo Drug: Placebo
Sapropterin tablets will be administered orally once daily at a dose of 20 milligram per kilogram (mg/kg) during both the 2-Week response test period and Placebo tablets matching to sapropterin will be administered orally once daily during the 24-Week study period.

  Eligibility

Ages Eligible for Study:   18 Years to 29 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 phenylalanine levels equal or greater than 600 micromole per liter (mcmol/L)
  • For women of childbearing potential: a negative urine pregnancy test is required at screening and willingness to use a highly effective method of contraception is required during the study and follow-up periods
  • Aged greater than or equal to (>=) 18 to 29 years, inclusive
  • Mean blood phenylalanine levels 600 to 1000 mcmol/L during 12 months preceding inclusion in the study. The mean should be calculated from at least 3 blood phenylalanine values over the last 12 months. Screening blood phenylalanine 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 greater than or equal to 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

Exclusion Criteria:

  • Subjects with tetrahydrobiopterin (BH4) deficiency
  • Previous exposure to sapropterin or BH4 for greater than 30 days (or exposure to sapropterin or BH4 for less than or equal to 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 (for example, 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 (for example, methotrexate, trimethoprim), medications that are known to affect nitric oxide synthesis (for example, 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 to another clinical trial or who participated in a previous clinical trial within 30 days prior to screening
  • Legal incapacity or limited legal capacity
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01977820

Locations
Italy
Research Site
Bologna, Italy
Switzerland
Research site
Lausanne, Switzerland
Sponsors and Collaborators
Merck KGaA
Investigators
Study Director: Medical Responsible Merck KGaA
  More Information

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01977820     History of Changes
Other Study ID Numbers: EMR 700773-004  2010-024311-13 
Study First Received: October 31, 2013
Results First Received: September 21, 2015
Last Updated: January 14, 2016
Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Switzerland: Swissmedic
Switzerland: Ethikkommission

Keywords provided by Merck KGaA:
Phenylketonuria
Sapropterin
Placebo
Cognitive Abilities
Kuvan®

Additional relevant MeSH terms:
Phenylketonurias
Amino Acid Metabolism, Inborn Errors
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Genetic Diseases, Inborn
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Verapamil
Anti-Arrhythmia Agents
Calcium Channel Blockers
Cardiovascular Agents
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on May 02, 2016