Sapropterin on Cognitive Abilities in Young Adults With Phenylketonuria

NCT01977820 | Terminated Phase 2 Results

• 2 other identifiers: EMR 700773-0042010-024311-13
• Study Type: interventional
• Target: 2
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Phenylketonuria

Keywords

Phenylketonuria; Sapropterin; Placebo; Cognitive Abilities; Kuvan®

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Adverse Events (AEs), Serious AEs (SAEs), AEs Leading to Death and AEs Leading to Discontinuation

  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.

  Screening up to 24 weeks + 4-week follow-up

Study Arms (2)

Sapropterin

EXPERIMENTAL

Drug: Sapropterin

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Sapropterin DRUG

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.

Also known as: Kuvan®

Sapropterin

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 29 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (2)

Research Site

Bologna, Italy

Location

Research site

Lausanne, Switzerland

Location

MeSH Terms

Conditions

Phenylketonurias

Interventions

sapropterin

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

The study was prematurely discontinued by the Sponsor due to severe enrolment difficulties as a consequence of the limited availability of treatment naïve patients with a diagnosis of phenyl ketonuria.

Results Point of Contact

• Title: Medical Information Services
• Organization: BioMarin Pharmaceutical Inc.

medinfo@bmrn.com

+1-800-983-4587

Study Officials

• Medical Responsible

  BioMarin Pharmaceutical

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2013
• First Posted: November 7, 2013
• Study Start: February 1, 2014
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: February 22, 2018
• Results First Posted: February 12, 2016

Record last verified: 2018-01

Locations

IT (1); CH (1)