Trial · NCT01376908
Registered outcomes17
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
1 to 17 of 17
Download this page as JSON| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Dietary Phenylalanine (Phe) Tolerance at Week 26 | Week 26 | Phe tolerance was defined as the amount of dietary Phe prescribed (milligram per kilogram per day \[mg/kg/day\]) while maintaining blood Phe levels within the selected therapeutic target range (defined as greater than or equal to \[\>=\] 120 to less than \[\<\] 360 micromoles per liter \[mcmol/L\]). |
| Secondary | Mean Blood Phe Levels | Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, and 26 | Mean blood phe levels were defined as the mean of blood phe levels assessed over each 2-week intervals |
| Secondary | Change From Baseline in Dietary Phe Tolerance After 26 Weeks | Baseline and at Week 26 (last observation carried-forward [LOCF]) | Phe tolerance was defined as the amount of dietary Phe ingested (mg/kg/day) while maintaining blood Phe levels within the selected therapeutic target range (defined as \>=120 to \<360 mcmol/L). |
| Secondary | Number of Subjects With Any TEAEs, AEs Related to Kuvan, Serious AEs, AEs Leading to Death, and AEs Leading to Discontinuation | From the first dose of study drug administration up to 31 days after the last dose of study drug administration | An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A serious adverse event (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. Treatment-emergent are events between first dose of study treatment and up to 31 days after last dose that were absent before treatment or that worsened relative to pretreatment state. |
| Secondary | Number of Subjects With Normal Neuromotor Developmental Milestones Assessed Using Denver Developmental Scale (DDS) | Baseline, Weeks 12, 26 | Subjects with normal neuromotor development were assessed by standardized developmental milestones using a parent/guardian report form in the following areas: fine motor, gross motor, language, and personal-social using DDS Test. DDS Test is a widely used to examine the developmental progress of 0-6 years of children. The scale reflects what percentage of a certain age group is able to perform a certain task. Tasks are grouped into 4 categories (social contact, fine motor skill, language, and gross motor skill) and include items such as smiles spontaneously (performed by 90% of three-month-olds), knocks 2 building blocks against each other (90% of 13-month-olds), speaks 3 words other than "mom" and "dad" (90% of 21-month-olds), or hops on 1 leg (90% of 5-year-olds). The more items a child fails to perform (passed by 90% of his/her peers), the more likely the child manifests a significant developmental problems. |
| Secondary | Neurodevelopmental Status Assessed Using Bayley III Scales of Infant and Toddler Development | Baseline and Week 26 | Neurodevelopmental assessments was done using the following age-dependent scales: Bayley III for subjects less than (\<) 3.5 years of age and WPPSI III for subjects greater than or equal to (\>=) 3.5 to \<4 years of age, based on following scores: adaptive behavior composite (ABC) score, cognitive composite (CC) score, language composite (LC) score, motor composite (MC) score., and social-emotional composite (SEC) score. Composite scores ranged from 40 (very poor) to 160 (excellent) and are classified as following: \>=115: accelerated performance; 85-114: development within normal limits; 70-84: mildly delayed development; less than or equal to (\<=) 69: significant delayed development. |
| Secondary | Growth Parameters Standard Deviation Scores (SDS) | Baseline, Weeks 4, 8, 12, 16, 20, and 26 | Growth assessment was performed by monitoring body mass index, height (or length), weight, and maximal occipital-frontal head circumference (MOFHC). Supine length was measured up to 2 years of age thereafter standing height was measured unless subject was unable to stand upright, in which case supine length was measured. Respective parameter SDS was calculated as the value of parameter minus reference mean value of parameter divided by standard deviation of the reference population. |
| Secondary | Number of Subjects With Hypophenylalanemia | Week 26 | Hypophenylalanemia is defined as the condition of blood Phe levels \<120 mcmol/L. |
| Secondary | Dietary Phe Tolerance During Extension Period | Every 6 months during 3 year extension period or until product is commercially approved | Phe tolerance was defined as the amount of dietary Phe ingested (mg/kg/day) while maintaining blood Phe levels within the selected therapeutic target range (defined as \>=120 to \<360 mcmol/L). |
| Secondary | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Baseline, Weeks 4, 8, 12, 16, 20, and 26 | |
| Secondary | Number of Samples With Phenylalanine Hydroxylase (PAH) Gene Mutations | Screening (within 42 days prior to Day 1 of the 26-week study period) | The DNA samples received were quantified by using a nanophotometer, and were aliquoted to a concentration of 20 nanogram/microliter DNA and aliquots from each sample were distributed to one 96-well plate. All samples were Sanger sequenced regarding exons 1 to 13 of the PAH gene in forward direction using the DNAs in the 96-well plate. All samples showing variants were Sanger sequenced regarding the concerned exon in reverse direction using DNA from the original tube. All samples showing a homozygous mutation were analyzed by MLPA. All samples showing only 1 mutation were analyzed by MLPA. All samples showing only 1 or no mutation were resequenced completely (exons 1 to 13) in both directions. |
| Secondary | Population Pharmacokinetic (PK) Parameter: Apparent Clearance (CL/f) | Weeks 5 to 12 | CL/f is the rate at which a drug is removed from the body via renal, hepatic and other clearance pathways.The reason for pooling subjects receiving Kuvan and subjects with Phe-restricted Diet was to facilitate the estimation of baseline endogenous value of BH4 which can only be observed in subjects not receiving the treatment. Ignoring this baseline endogenous value would have led to biased stimated of the Kuvan PK parameters. This pooling assumes that the addition of Kuvan does not confound the BH4 measurements in these analyses as a consequence the population PK parameters describing the PK of BH4 are the same for the 2 arms and so cannot be presented in terms of per arm/per treatment group based as per the planned analysis. |
| Secondary | Population PK Parameter: Apparent Volume of Distribution (V/f) | Weeks 5 to 12 | V/f is defined as the distribution of a medication between the plasma and the rest of the body after the dose. It is the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of the drug. The reason for pooling subjects receiving Kuvan and subjects with Phe-restricted Diet was to facilitate the estimation of baseline endogenous value of BH4 which can only be observed in subjects not receiving the treatment. Ignoring this baseline endogenous value would have led to biased stimated of the Kuvan PK parameters. This pooling assumes that the addition of Kuvan does not confound the BH4 measurements in these analyses as a consequence the population PK parameters describing the PK of BH4 are the same for the 2 arms and so cannot be presented in terms of per arm/per treatment group based as per the planned analysis. |
| Secondary | Population PK Parameter: Area Under the Plasma Concentration Curve, Time 0 to Infinity (AUC [0-infinity]) | Weeks 5 to 12 | AUC \[0-infinity\] was estimated by determining total area under the curve of the concentration versus time curve extrapolated to infinity. Since AUC could not be obtained from non-compartmental analysis because of sparse data, AUC = Dose/(CL/F); CL/F was population apparent clearance estimated from the population PK model, \& Dose the actual total dose received by the patient on one dosing interval. The reason for pooling subjects receiving Kuvan \&subjects with Phe-restricted Diet was to facilitate estimation of baseline endogenous value of BH4 which can only be observed in subjects not receiving treatment. Ignoring this baseline endogenous value would have led to biased estimated of Kuvan PK parameters. This pooling assumes that the the addition of Kuvan does not confound the BH4 measurements in these analyses as a consequence the population PK parameters describing the PK of BH4 were same for the 2 arms and cannot be presented per arm/per treatment group as per planned analysis. |
| Secondary | Population PK Parameter: Terminal Elimination Half-life (t1/2) | Weeks 5 to 12 | The t1/2 was defined as the time required for plasma concentration of drug to decrease 50 percent (%) in the final stage of elimination. Since t1/2 could not be obtained from non-compartmental analysis because of sparse data, t1/2 was estimated as Log(2)\*(V/F)/(CL/F), where V/F \& CL/F were the population apparent central Volume \& clearance, estimated from population PK model. The reason for pooling subjects receiving Kuvan \& subjects with Phe-restricted Diet was to facilitate the estimation of baseline endogenous value of BH4 which can only observed in subjects not receiving treatment. Ignoring this baseline endogenous value would have led biased stimated of the Kuvan PK parameters. This pooling assumes that the addition of Kuvan does not confound the BH4 measurements in these analyses as a consequence the population PK parameters describing the PK of BH4 are the same for the 2 arms and so cannot be presented in terms of per arm/per treatment group based as per the planned analysis. |
| Secondary | Population PK Parameter: Maximum Observed Plasma Concentration (Cmax) | Up to Week 26 | |
| Secondary | Population PK Parameter: Time to Maximum Plasma Concentration (Tmax) | Up to Week 26 |
Source ClinicalTrials.govtrials-2026-11-12-0.5.0
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
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