Phase 3
Completed N=56
Kuvan® in Phenylketonuria Patients Less Than 4 Years Old
Source: ClinicalTrials.gov NCT01376908 ↗Enrolled (actual)
56
Serious AEs
7.4%
Results posted
May 2016
Primary outcomePrimary: Dietary Phenylalanine (Phe) Tolerance at Week 26 — 80.6; 50.1 mg/kg/day
◆ Published Evidence
Established
41citations · ~5 / year
Efficacy, safety and population pharmacokinetics of sapropterin in PKU patients <4 years: results from the SPARK open-label, multicentre, randomized phase IIIb trial.
Summary
This is a Phase 3b, multicenter, open-label, randomized, controlled study to evaluate efficacy, safety and population pharmacokinetics of sapropterin dihydrochloride (Kuvan®) in less than 4 year-old infants and children with phenylketonuria (PKU).
Linked Publications (2)
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Efficacy, safety and population pharmacokinetics of sapropterin in PKU patients <4 years: results from the SPARK open-label, multicentre, randomized phase IIIb trial.
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Long-term efficacy and safety of sapropterin in patients who initiated sapropterin at < 4 years of age with phenylketonuria: results of the 3-year extension of the SPARK open-label, multicentre, randomised phase IIIb trial.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Dietary Phenylalanine (Phe) Tolerance at Week 26 |
80.6; 50.1 | — |
| SECONDARY Mean Blood Phe Levels |
287.3; 352.9; 214.3; 321.3; 202.1; 308.0 | — |
| SECONDARY Change From Baseline in Dietary Phe Tolerance After 26 Weeks |
37.1; 35.8; 74.0; 49.8; 36.9; 13.1 | — |
| SECONDARY Number of Subjects With Any TEAEs, AEs Related to Kuvan, Serious AEs, AEs Leading to Death, and AEs Leading to Discontinuation |
27; 27; 8; 0; 3; 1 | — |
| SECONDARY Number of Subjects With Normal Neuromotor Developmental Milestones Assessed Using Denver Developmental Scale (DDS) |
18; 21; 21; 23; 20; 23 | — |
| SECONDARY Neurodevelopmental Status Assessed Using Bayley III Scales of Infant and Toddler Development |
106.5; 96.2; 102.4; 93.4; 100.0; 101.2 | — |
| SECONDARY Growth Parameters Standard Deviation Scores (SDS) |
0.37; 0.34; 0.33; 0.36; 0.47; 0.38 | — |
| SECONDARY Number of Subjects With Hypophenylalanemia |
10; 9 | — |
| SECONDARY Dietary Phe Tolerance During Extension Period |
— | — |
| SECONDARY Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) |
93.5; 93.1; 95.9; 101.5; 95.9; 95.7 | — |
| SECONDARY Number of Samples With Phenylalanine Hydroxylase (PAH) Gene Mutations |
73 | — |
| SECONDARY Population Pharmacokinetic (PK) Parameter: Apparent Clearance (CL/f) |
2780 | — |
| SECONDARY Population PK Parameter: Apparent Volume of Distribution (V/f) |
3870 | — |
| SECONDARY Population PK Parameter: Area Under the Plasma Concentration Curve, Time 0 to Infinity (AUC [0-infinity]) |
234.89; 215.74; 206.22 | — |
| SECONDARY Population PK Parameter: Terminal Elimination Half-life (t1/2) |
0.96 | — |
| SECONDARY Population PK Parameter: Maximum Observed Plasma Concentration (Cmax) |
— | — |
| SECONDARY Population PK Parameter: Time to Maximum Plasma Concentration (Tmax) |
— | — |
Eligibility Criteria
Inclusion Criteria
- Male or female PKU infants and young children less than ( =) 400 micromol per liter (mcmol/L) obtained on 2 separate occasions
- Previously responded, as assessed by the Investigator, to a tetrahydrobiopterin (BH4) test, if all 3 of the following criteria are satisfied:
- The BH4 dose was 20 milligram per kilogram per day (mg/kg/day)
- The duration of the test was at least for 24 hours
- A 30% decrease in blood Phe levels.
- Defined level of dietary Phe tolerance consistent with the diagnosis of PKU
- Good adherence to dietary treatment, including prescribed dietary Phe restriction and prescribed amounts of Phe-free protein supplements and low-Phe foods
- Maintenance of blood Phe levels within the therapeutic target range of 120-360 mcmol/L (defined as >=120 to )30 days
- Known hypersensitivity to Kuvan® or its excipients
- Known hypersensitivity to other approved or non-approved formulations of tetrahydrobiopterin
- Previous diagnosis of BH4 deficiency
- Current use of methotrexate, trimethoprim, or other dihydrofolate reductase inhibitors
- Current use of medications that are known to affect nitric oxide synthesis, metabolism or action
- Current use of levodopa
- Current use of experimental/other investigational or unregistered drugs that may affect the study outcomes
- Inability to comply with study procedures
- Inability to tolerate oral intake
- History of organ transplantation
- Concurrent disease or condition that would interfere with study participation or increase the risk for adverse events, including seizure disorders, corticosteroid administration, active malignancy, diabetes mellitus, severe congenital heart disease, renal or hepatic failure
- Other significant disease that in the Investigator's opinion would exclude the subject from the trial
- Any condition that, in the view of the Principal Investigator renders the subject at high risk for failure to comply with treatment or to complete the study
Data sourced from ClinicalTrials.gov (NCT01376908) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.