phenylacetic acid and Adverse Drug Event

phenylacetic acid has been researched along with Adverse Drug Event in 2 studies

phenylacetic acid : A monocarboxylic acid that is toluene in which one of the hydrogens of the methyl group has been replaced by a carboxy group.

Research

Studies (2)

Authors

Clinical Trials (6)

Trial Overview

Trial Outcomes

Average Ammonia Values on NaPBA vs. HPN-100 on the Last Day of Treatment With Each Drug (Switch Over)

blood samples were collected at pre-dose, 4, 8, 12, 16, 20, and 24 hour post dose on both Day 7 (NaPBA) and Day 14 (HPN-100). (NCT00947544)
Timeframe: Day 7 (NaPBA) and Day 14 (HPN-100)

Blood Ammonia Control

To evaluate control of blood ammonia by HPN-100 compared with NaPBA in pediatric patients with UCDs. (NCT00947544)
Timeframe: Day 7 (NaPBA) and Day 14 (HPN-100)

NH3 Cmax on NaPBA vs. HPN-100 on the Last Day of Treatment With Each Drug

blood samples were collected at pre-dose, 4, 8, 12, 16, 20, and 24 hour post dose on both Day 7 (NaPBA) and Day 14 (HPN-100). (NCT00947544)
Timeframe: Day 7 (NaPBA) and Day 14 (HPN-100)

Plasma PAA (Phenylacetate) AUC0-24 Values on NaPBA vs. HPN-100 on on the Last Day of Treatment With Each Drug

blood samples were collected at pre-dose, 4, 8, 12, 16, 20, and 24 hour post dose on both Day 7 (NaPBA) and Day 14 (HPN-100). (NCT00947544)
Timeframe: Day 7 (NaPBA) and Day 14 (HPN-100)

Plasma PAGN AUC0-24 Values on NaPBA vs. HPN-100 on on the Last Day of Treatment With Each Drug

blood samples were collected at pre-dose, 4, 8, 12, 16, 20, and 24 hour post dose on both Day 7 (NaPBA) and Day 14 (HPN-100). (NCT00947544)
Timeframe: Day 7 (NaPBA) and Day 14 (HPN-100)

Plasma PBA (Phenylbutyrate) AUC0-24 Values on NaPBA vs. HPN-100 on on the Last Day of Treatment With Each Drug

blood samples were collected at pre-dose, 4, 8, 12, 16, 20, and 24 hour post dose on both Day 7 (NaPBA) and Day 14 (HPN-100). (NCT00947544)
Timeframe: Day 7 (NaPBA) and Day 14 (HPN-100)

Quality of Life Assessed by the SF-15 Questionnaire

"change from baseline to Month 12.~The SF 15 questionnaire consists of 15 questions that assess the following:~Physical functioning (5 questions)~Emotional functioning (4 questions)~Social functioning (3 questions)~School functioning (3 questions) Items were scored on a 5-point Likert scale from 0 (never) to 4 (almost always) or a 3-point scale (0 [not at all], 2 [sometimes], or 4 [a lot] for the young child self-report). Items were reverse-scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score was 0-100 scale (averaged from each functional areas). In the 0-100 scale, 0 is the worst score and 100 is best score.~Improved quality of life was shown by increased total score from baseline to Month 12." (NCT00947544)
Timeframe: 1 year

Rate (Percentage) of Ammonia Values Above Upper Limit of Normal (ULN) on NaPBA vs. HPN-100

blood samples were collected at pre-dose, 4, 8, 12, 16, 20, and 24 hour post dose on both Day 7 (NaPBA) and Day 14 (HPN-100). (NCT00947544)
Timeframe: Day 7 (NaPBA) and Day 14 (HPN-100)

Rate of Adverse Events During the Switchover Part of the Study Rate of Adverse Events (Number of Participants Showing Adverse Events)

To evaluate the safety and PK characteristics of HPN-100 compared with sodium phenylbutyrate (NaPBA) in pediatric patients with urea cycle disorders (UCDs) (NCT00947544)
Timeframe: 1 week on each treatment for a total of 2 week.

Urinary PAGN 24-hour Excretion Values on NaPBA vs. HPN-100 (Switch Over)

Urinary PAGN (phenylacetylglutamine) 24-hour excretion. Urine was collect during 0-12 hrs and 12-24 hrs. (NCT00947544)
Timeframe: Day 7 (NaPBA) and Day 14 (HPN-100)

Number and Causes of Hyperammonemic Events (Safety Extension)

"Number of Subjects with at Least One Hyperammonemic Crisis.~Hyperammonemic crisis is defined as follows:~• Clinical symptoms associated with ammonia of ≥ 100 µmol/L" (NCT00947544)
Timeframe: 1 year

Part B: Proportion of Subjects Who Exhibit an HE Episode, Defined as Either of the Following During the Treatment Phase: WH ≥2; WH Grade and Asterixis Grade Increase of 1 Each, if Baseline WH = 0

"An HE event was defined as occurrences of either a West Haven (WH) Grade ≥2 or a WH Grade 1 and asterixis grade increase of 1 (if baseline WH = 0).~The WH criteria are widely used for rating the severity of HE and are summarized below:~Grade 1: trivial lack of awareness, euphoria or anxiety, shortened attention span, impaired performance of addition Grade 2: lethargy or apathy, minimal disorientation for time or place, subtle personality change, inappropriate behavior, impaired performance of subtraction Grade 3: somnolence to semi-stupor but responsive to verbal stimuli, confusion, gross disorientation Grade 4: coma (unresponsive to verbal or noxious stimuli)~Asterixis was assessed after arm and forearm extension along with wrist dorsiflexion for 30 seconds and assigned a grade according to the following criteria:~Grade 1: rare flaps Grade 2: occasional irregular flaps Grade 3: frequent flaps Grade 4: continuous flaps" (NCT00999167)
Timeframe: Part B: 112 Days

Time to Meeting the Primary Endpoint

Secondary efficacy endpoint. The time to the first HE episode during the treatment period was calculated using the Kaplan-Meier method. Subjects who did not experience an HE episode were censored at the time of their last asterixis assessment. Subjects who had no post-randomization data for the primary endpoint were considered to have an HE episode at Day 1. (NCT00999167)
Timeframe: 112 Days

Total Number of HE Events

Secondary efficacy endpoint. The total number of HE events during the treatment phase for subjects in the placebo and active arms. (NCT00999167)
Timeframe: 112 Days

Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score

Changes from Baseline to Day 56 and the Final Visit were compared between treatment groups using an ANCOVA model for the total index RBANS score ). The index score is a sum of the scores for each of the 5 individual domains (immediate memory, visuospatial/constructional, language, attention). The minimum and maximum total index scores are 40 and 160, respectively; a higher score is better. (NCT00999167)
Timeframe: Day 56, Final Visit (D112)

Part A: The Rate of AEs and Tolerability of HPN-100

Part A: The rate of AEs and tolerability of 6 mL and 9 mL doses of HPN-100 were considered the primary safety endpoints for Part A. Safety assessments included adverse events, laboratory tests (including ammonia, hematology, coagulation, liver function and serum chemistry parameters), vital signs, physical and neurological examinations, and electrocardiograms. (NCT00999167)
Timeframe: Part A: 28 days

Cmax for PAA of NaPBA and HPN-100 in Plasma

Blood samples were collected at pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28. (NCT00992459)
Timeframe: pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28

Cmax for PBA of NaPBA and HPN-100 in Plasma

Blood samples were collected at pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28. (NCT00992459)
Timeframe: pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28

Cmax PAGN of NaPBA and HPN-100 in Plasma

Blood samples were collected at pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28. (NCT00992459)
Timeframe: pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28

Correlation Between Urinary Phenylacetylglutamine (PAGN) Excretion Over 24 Hours (U-PAGN24-hour Excr) and Venous Ammonia - Area Under the Concentration-time Curve From Time 0 (Predose) to 24 Hours (AUC0-24)

The correlation between 24-hour urinary phenylacetylglutamine (PAGN) excretion (U-PAGN24-hour Excr) and venous ammonia AUC0-24 was summarized and the correlation was tested using the Spearman rank-order correlation. (NCT00992459)
Timeframe: 28 Days

Maximum Ammonia Values Observed on NaPBA Versus HPN-100

Blood samples were collected at pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28. (NCT00992459)
Timeframe: pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28

Number and Severity of Symptomatic Hyperammonemic Crises

Severity of symptomatic hyperammonemic crises was measured by peak ammonia level (µmol/L) when it is >= 100 µmol/L. (NCT00992459)
Timeframe: 29 Days

Rate (Percentage) of Ammonia Values Above Upper Limit of Normal (ULN) on NaPBA Versus HPN-100

NaPBA treated arm: total 345 blood samples were collected. HPN-100 treated arm: 343 blood samples were collected. (NCT00992459)
Timeframe: on Day 14 and Day 28

Rate of Adverse Events in Each Treatment Group

(NCT00992459)
Timeframe: 29 Days

The Primary Endpoint Was the 24-hour Area Under the Curve for Blood Ammonia (NH324-hour AUC) on Days 14 and 28.

Blood samples were collected at pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28. Arm A day 14 and Arm B day 28 data were combined as a NaPBA treatment Arm. Arm B day 14 and Arm A day 28 data were combined as a HPN-100 treatment Arm. (NCT00992459)
Timeframe: pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28

U-PAGN24-hour Excr of NaPBA and HPN-100

(NCT00992459)
Timeframe: 24 hours on Day 14 of each treatments

Number and Causes of Hyperammonemic Events

Number of hyperammonemic crises per patient (NCT00947297)
Timeframe: 1 year

Patient Satisfaction With HPN-100

Drug preference will be noted at week 3 (NCT00947297)
Timeframe: Month 1 post dose

Rate of Adverse Events (Number of Participants Who Experienced Any AE Considered Related to Study Drug)

(NCT00947297)
Timeframe: 1 year

Blood Ammonia Levels

Venous Ammonia levels over time (NCT00947297)
Timeframe: 1 Year

Adverse Events

Rate of adverse events during the Safety Extension portion of the protocol ( please note: HPN-100 treatment only during Safety Extension ) (NCT01347073)
Timeframe: 12 months

Adverse Events

Rate of adverse events during the Switch-Over portion of the Protocol (NCT01347073)
Timeframe: 2 weeks

Blood Ammonia

24-hour ammonia AUC of blood ammonia levels on Days 1 (NaPBA) and 10 (HPN-100) were compared. Ammonia was assessed at Hour 0 (pre-first dose, fasted), Hour 8 (~2-4 hours after lunch or the second main meal and dose of NaPBA), Hour 12 (~4 hours after the last main meal) and 24 hours post-first dose (pre-first dose on following day, fasted). (NCT01347073)
Timeframe: 2 weeks

Frequency of Ammonia Levels Greater Than the Upper Limit of Normal (ULN) on HPN-100 Compared With NaPBA

Ammonia values were converted to SI units (umol/L) and normalized to a standard ULN of 35 umol/L prior to analysis (NCT01347073)
Timeframe: 2 weeks

Hyperammonemic Crisis

Rate of HAC during pre-enrollment on NaPBA compared to HAC during HPN-100 treatment (NCT01347073)
Timeframe: 1 year

Number of Subjects Experienced Adverse Events

(NCT00551200)
Timeframe: during the period on 100% Buphenyl (up to 4 weeks) or HPN-100 (up to 10 weeks)

Number of Subjects Experienced Serious Adverse Events

(NCT00551200)
Timeframe: during the period subjects on 100% Buphenyl (up to 4 weeks) or HPN-100 (up to 10 weeks)

Drug Preference for HPN-100 or Buphenyl® (as Assessed by Global Preference Question)

(NCT00551200)
Timeframe: End of Study

Pharmacokinetics (Plasma and Urine PK Parameters of Study Drugs and Their Metabolites)

measured AUC0-24 (Area under the curve from time 0 (pre-dose) to 24 hours) for each metabolite in plasma. Data were collected at 30 minutes and 1, 2, 4, 5, 6, 8, 10, 12, and 24 hours post-first dose. (NCT00551200)
Timeframe: At steady state (1 week) on each medication (Buphenyl® alone, HPN-100 alone)

Venous Ammonia Levels at the Peak and Mean TNUAC Time-normalized Area Under the Curve)

Data were collected at pre-first dose and at 30 minutes and 1, 2, 4, 5, 6, 8, 10, 12, and 24 hours post first dose. (NCT00551200)
Timeframe: At steady state (1 week) on each medication (Buphenyl® alone, HPN-100 alone), and at steady state (1 week) after each dose escalation

Other Studies

2 other studies available for phenylacetic acid and Adverse Drug Event