Trial Outcomes & Findings for Comparative Efficacy of Phenylbutyrate (PBA) vs. Benzoate in Urea Cycle Disorders (NCT NCT02111200)
NCT ID: NCT02111200
Last Updated: 2018-01-09
Results Overview
The objective of this protocol is to directly compare the efficacy of benzoate, phenylbutyrate and a combination of the two, to conjugate nitrogenous compounds in healthy volunteers. The nitrogenous compound of interest in each arm would be based on the medication used. This would be hippuric acid in the benzoate arm, phenylacetylglutamine in the phenylbutyrate arm, and hippuric acid AND phenylacetylglutamine in the MIX arm. The mean hippuric acid levels in the phenylbutyrate arm would thus be 0.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
7 participants
Primary outcome timeframe
4 days per arm
Results posted on
2018-01-09
Participant Flow
There was no washout period prior to enrollment. Individuals who were enrolled in the trial were not on any medications.
Participant milestones
| Measure |
Sodium Phenylbutyrate->MIX->Sodium Benzoate (4 Days)
1. Sodium phenylbutyrate arm: Participants received ONLY sodium phenylbutyrate at a dose of 7.15 g/m2/day divided into three equal doses per day (maximum dose of 20 g/day) for 3 days. Subjects took the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
Followed by a Washout period of at least 7 days
2. MIX arm: Participants received a combination of Sodium Phenylbutyrate 3.575 g/m2/day and Sodium Benzoate 2.75 g/m2/day were given in three equal doses per day for 3 days. Subjects took the study medications with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
Followed by a Washout period of at least 7 days
3. Sodium benzoate: Participants received ONLY Sodium Benzoate at a dose of 5.5 g/m2/day divided into three equal doses per day (maximum dose 12 g/day) for 3 days. Subjects took the study medications with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
|
Sodium Benzoate->MIX-> Sodium Phenylbutyrate (4 Days)
1. Sodium benzoate: Participants received ONLY Sodium Benzoate at a dose of 5.5 g/m2/day divided into three equal doses per day (maximum dose 12 g/day) for 3 days. Subjects took the study medications with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
Followed by a Washout period of at least 7 days
2. MIX arm: Participants received a combination of Sodium Phenylbutyrate 3.575 g/m2/day and Sodium Benzoate 2.75 g/m2/day were given in three equal doses per day for 3 days. Subjects took the study medications with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
Followed by a Washout period of at least 7 days
3. Sodium phenylbutyrate arm: Participants received ONLY sodium phenylbutyrate at a dose of 7.15 g/m2/day divided into three equal doses per day (maximum dose of 20 g/day) for 3 days. Subjects took the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
|
MIX->Sodium Benzoate-> Sodium Phenylbutyrate (4 Days)
1. MIX arm: Participants received a combination of Sodium Phenylbutyrate 3.575 g/m2/day and Sodium Benzoate 2.75 g/m2/day were given in three equal doses per day for 3 days. Subjects took the study medications with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
Followed by a Washout period of at least 7 days
2. Sodium benzoate: Participants received ONLY Sodium Benzoate at a dose of 5.5 g/m2/day divided into three equal doses per day (maximum dose 12 g/day) for 3 days. Subjects took the study medications with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
Followed by a Washout period of at least 7 days
3. Sodium phenylbutyrate arm: Participants received ONLY sodium phenylbutyrate at a dose of 7.15 g/m2/day divided into three equal doses per day (maximum dose of 20 g/day) for 3 days. Subjects took the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
|
MIX-> Sodium Phenylbutyrate-> Sodium Benzoate (4 Days)
1. MIX arm: Participants received a combination of Sodium Phenylbutyrate 3.575 g/m2/day and Sodium Benzoate 2.75 g/m2/day were given in three equal doses per day for 3 days. Subjects took the study medications with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
Followed by a Washout period of at least 7 days
2. Sodium phenylbutyrate arm: Participants received ONLY sodium phenylbutyrate at a dose of 7.15 g/m2/day divided into three equal doses per day (maximum dose of 20 g/day) for 3 days. Subjects took the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
Followed by a Washout period of at least 7 days
3. Sodium benzoate: Participants received ONLY Sodium Benzoate at a dose of 5.5 g/m2/day divided into three equal doses per day (maximum dose 12 g/day) for 3 days. Subjects took the study medications with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
2
|
1
|
1
|
|
Overall Study
COMPLETED
|
3
|
2
|
1
|
1
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Comparative Efficacy of Phenylbutyrate (PBA) vs. Benzoate in Urea Cycle Disorders
Baseline characteristics by cohort
| Measure |
Sodium Phenylbutyrate->MIX->Sodium Benzoate
n=3 Participants
1. Sodium phenylbutyrate arm: Participants received ONLY sodium phenylbutyrate at a dose of 7.15 g/m2/day divided into three equal doses per day (maximum dose of 20 g/day) for 3 days. Subjects took the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
Followed by a Washout period of at least 7 days
2. MIX arm: Participants received a combination of Sodium Phenylbutyrate 3.575 g/m2/day and Sodium Benzoate 2.75 g/m2/day were given in three equal doses per day for 3 days. Subjects took the study medications with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
Followed by a Washout period of at least 7 days
3. Sodium benzoate: Participants received ONLY Sodium Benzoate at a dose of 5.5 g/m2/day divided into three equal doses per day (maximum dose 12 g/day) for 3 days. Subjects took the study medications with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
|
Sodium Benzoate->MIX-> Sodium Phenylbutyrate
n=2 Participants
1. Sodium benzoate: Participants received ONLY Sodium Benzoate at a dose of 5.5 g/m2/day divided into three equal doses per day (maximum dose 12 g/day) for 3 days. Subjects took the study medications with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
Followed by a Washout period of at least 7 days
2. MIX arm: Participants received a combination of Sodium Phenylbutyrate 3.575 g/m2/day and Sodium Benzoate 2.75 g/m2/day were given in three equal doses per day for 3 days. Subjects took the study medications with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
Followed by a Washout period of at least 7 days
3. Sodium phenylbutyrate arm: Participants received ONLY sodium phenylbutyrate at a dose of 7.15 g/m2/day divided into three equal doses per day (maximum dose of 20 g/day) for 3 days. Subjects took the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
|
MIX->Sodium Benzoate-> Sodium Phenylbutyrate
n=1 Participants
1. MIX arm: Participants received a combination of Sodium Phenylbutyrate 3.575 g/m2/day and Sodium Benzoate 2.75 g/m2/day were given in three equal doses per day for 3 days. Subjects took the study medications with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
Followed by a Washout period of at least 7 days
2. Sodium benzoate: Participants received ONLY Sodium Benzoate at a dose of 5.5 g/m2/day divided into three equal doses per day (maximum dose 12 g/day) for 3 days. Subjects took the study medications with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
Followed by a Washout period of at least 7 days
3. Sodium phenylbutyrate arm: Participants received ONLY sodium phenylbutyrate at a dose of 7.15 g/m2/day divided into three equal doses per day (maximum dose of 20 g/day) for 3 days. Subjects took the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
|
MIX-> Sodium Phenylbutyrate-> Sodium Benzoate
n=1 Participants
1. MIX arm: Participants received a combination of Sodium Phenylbutyrate 3.575 g/m2/day and Sodium Benzoate 2.75 g/m2/day were given in three equal doses per day for 3 days. Subjects took the study medications with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
Followed by a Washout period of at least 7 days
2. Sodium phenylbutyrate arm: Participants received ONLY sodium phenylbutyrate at a dose of 7.15 g/m2/day divided into three equal doses per day (maximum dose of 20 g/day) for 3 days. Subjects took the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
Followed by a Washout period of at least 7 days
3. Sodium benzoate: Participants received ONLY Sodium Benzoate at a dose of 5.5 g/m2/day divided into three equal doses per day (maximum dose 12 g/day) for 3 days. Subjects took the study medications with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
|
Total
n=7 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
26 years
n=5 Participants
|
42.5 years
n=7 Participants
|
28 years
n=5 Participants
|
33 years
n=4 Participants
|
28 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=5 Participants
|
2 participants
n=7 Participants
|
1 participants
n=5 Participants
|
1 participants
n=4 Participants
|
7 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 4 days per armThe objective of this protocol is to directly compare the efficacy of benzoate, phenylbutyrate and a combination of the two, to conjugate nitrogenous compounds in healthy volunteers. The nitrogenous compound of interest in each arm would be based on the medication used. This would be hippuric acid in the benzoate arm, phenylacetylglutamine in the phenylbutyrate arm, and hippuric acid AND phenylacetylglutamine in the MIX arm. The mean hippuric acid levels in the phenylbutyrate arm would thus be 0.
Outcome measures
| Measure |
Sodium Benzoate Arm
n=7 Participants
Sodium benzoate 5.5 g/m2/day divided into three equal doses per day (maximum dose 12 g/day) for 3 days
Sodium Benzoate: Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
|
Sodium Phenylbutyrate Arm
n=7 Participants
Sodium phenylbutyrate 7.15 g/m2/day divided into three equal doses per day (maximum dose of 20 g/day) for 3 days
Sodium Phenylbutyrate: Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
|
Mix Arm
n=7 Participants
Sodium Phenylbutyrate 3.575 g/m2/day and Sodium Benzoate 2.75 g/m2/day will be given in three equal doses per day for 3 days
Sodium Benzoate: Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
Sodium Phenylbutyrate: Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
|
|---|---|---|---|
|
Urinary Hippuric Acid
|
16.4 mmol/24 hours
Standard Deviation 3.1
|
0 mmol/24 hours
Standard Deviation 0
|
10.5 mmol/24 hours
Standard Deviation 1.7
|
PRIMARY outcome
Timeframe: 4 days per armThe objective of this protocol is to directly compare the efficacy of benzoate, phenylbutyrate and a combination of the two, to conjugate nitrogenous compounds in healthy volunteers. The nitrogenous compound of interest in each arm would be based on the medication used. This would be hippuric acid in the benzoate arm, phenylacetylglutamine in the phenylbutyrate arm, and hippuric acid AND phenylacetylglutamine in the MIX arm. The mean phenylacetylglutamine levels in the benzoate arm would thus be 0.
Outcome measures
| Measure |
Sodium Benzoate Arm
n=7 Participants
Sodium benzoate 5.5 g/m2/day divided into three equal doses per day (maximum dose 12 g/day) for 3 days
Sodium Benzoate: Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
|
Sodium Phenylbutyrate Arm
n=7 Participants
Sodium phenylbutyrate 7.15 g/m2/day divided into three equal doses per day (maximum dose of 20 g/day) for 3 days
Sodium Phenylbutyrate: Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
|
Mix Arm
n=7 Participants
Sodium Phenylbutyrate 3.575 g/m2/day and Sodium Benzoate 2.75 g/m2/day will be given in three equal doses per day for 3 days
Sodium Benzoate: Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
Sodium Phenylbutyrate: Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
|
|---|---|---|---|
|
Urinary PAGN Excretion
|
0 mmol/24 hours
Standard Deviation 0
|
15.3 mmol/24 hours
Standard Deviation 2.3
|
9.3 mmol/24 hours
Standard Deviation 0.8
|
PRIMARY outcome
Timeframe: 4 days per armThe objective of this protocol is to directly compare the efficacy of benzoate, phenylbutyrate and a combination of the two, to conjugate nitrogenous compounds in healthy volunteers. The nitrogenous compound of interest in each arm would be based on the medication used. This would be hippuric acid in the benzoate arm, phenylacetylglutamine in the phenylbutyrate arm, and hippuric acid AND phenylacetylglutamine in the MIX arm.
Outcome measures
| Measure |
Sodium Benzoate Arm
n=7 Participants
Sodium benzoate 5.5 g/m2/day divided into three equal doses per day (maximum dose 12 g/day) for 3 days
Sodium Benzoate: Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
|
Sodium Phenylbutyrate Arm
n=7 Participants
Sodium phenylbutyrate 7.15 g/m2/day divided into three equal doses per day (maximum dose of 20 g/day) for 3 days
Sodium Phenylbutyrate: Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
|
Mix Arm
n=7 Participants
Sodium Phenylbutyrate 3.575 g/m2/day and Sodium Benzoate 2.75 g/m2/day will be given in three equal doses per day for 3 days
Sodium Benzoate: Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
Sodium Phenylbutyrate: Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
|
|---|---|---|---|
|
Total Nitrogen as a Conjugate of the Drug
|
16.4 mmol/24 hours
Standard Deviation 3.1
|
29 mmol/24 hours
Standard Deviation 3.3
|
30.7 mmol/24 hours
Standard Deviation 4.5
|
Adverse Events
Sodium Benzoate Treatment
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Sodium Phenylbutyrate Treatment
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
MIX Treatment
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Sodium Benzoate Treatment
n=7 participants at risk
Sodium benzoate 5.5 g/m2/day divided into three equal doses per day (maximum dose 12 g/day) for 3 days
Sodium Benzoate: Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
|
Sodium Phenylbutyrate Treatment
n=7 participants at risk
Sodium phenylbutyrate 7.15 g/m2/day divided into three equal doses per day (maximum dose of 20 g/day) for 3 days
Sodium Phenylbutyrate: Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
|
MIX Treatment
n=7 participants at risk
Sodium Phenylbutyrate 3.575 g/m2/day and Sodium Benzoate 2.75 g/m2/day will be given in three equal doses per day for 3 days
Sodium Benzoate: Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
Sodium Phenylbutyrate: Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal discomfort
|
14.3%
1/7 • Number of events 1 • The adverse events were collected through 4 days of each study arm.
|
28.6%
2/7 • Number of events 2 • The adverse events were collected through 4 days of each study arm.
|
14.3%
1/7 • Number of events 1 • The adverse events were collected through 4 days of each study arm.
|
|
Investigations
Lab anormalities
|
14.3%
1/7 • Number of events 1 • The adverse events were collected through 4 days of each study arm.
|
57.1%
4/7 • Number of events 8 • The adverse events were collected through 4 days of each study arm.
|
28.6%
2/7 • Number of events 5 • The adverse events were collected through 4 days of each study arm.
|
|
Skin and subcutaneous tissue disorders
Itch
|
14.3%
1/7 • Number of events 1 • The adverse events were collected through 4 days of each study arm.
|
14.3%
1/7 • Number of events 1 • The adverse events were collected through 4 days of each study arm.
|
0.00%
0/7 • The adverse events were collected through 4 days of each study arm.
|
|
Gastrointestinal disorders
Vomiting
|
14.3%
1/7 • Number of events 1 • The adverse events were collected through 4 days of each study arm.
|
0.00%
0/7 • The adverse events were collected through 4 days of each study arm.
|
0.00%
0/7 • The adverse events were collected through 4 days of each study arm.
|
|
General disorders
Headache
|
0.00%
0/7 • The adverse events were collected through 4 days of each study arm.
|
14.3%
1/7 • Number of events 1 • The adverse events were collected through 4 days of each study arm.
|
0.00%
0/7 • The adverse events were collected through 4 days of each study arm.
|
|
General disorders
Toe injury
|
14.3%
1/7 • Number of events 1 • The adverse events were collected through 4 days of each study arm.
|
0.00%
0/7 • The adverse events were collected through 4 days of each study arm.
|
14.3%
1/7 • Number of events 1 • The adverse events were collected through 4 days of each study arm.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place