Trial Outcomes & Findings for Arginine and Buphenyl in Patients With Argininosuccinic Aciduria (ASA), a Urea Cycle Disorder (NCT NCT00345605)
NCT ID: NCT00345605
Last Updated: 2018-01-31
Results Overview
Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
12 participants
Primary outcome timeframe
Measured after each 1-week treatment period
Results posted on
2018-01-31
Participant Flow
12 subjects with argininosuccinic aciduria were recruited at Baylor College of Medicine from May 2008 to December 2010.
patients were randomly assigned to one of the two arms HDA or LDA after treatment and an interval the same patients returned and received the crossover treatment LD or HDA depending.
Participant milestones
| Measure |
High Dose First
High dose arm 3 day wash-out followed by 7 days of: Arg 500 mg/kg/d or 10 g/m2 BSA Placebo instead of NaPBA interval then: Arg 100 mg/kg/d or 2 g/m2 BSA NaPBA 500 mg/kg/d or 10 g/m2 BSA
|
Low Dose First
low dose arm 3 day wash-out followed by 7 days of: Arg 100 mg/kg/d or 2 g/m2 BSA NaPBA 500 mg/kg/d or 10 g/m2 BSA interval then: Arg 500 mg/kg/d or 10 g/m2 BSA Placebo instead of NaPBA
|
|---|---|---|
|
Initial Washout
STARTED
|
6
|
6
|
|
Initial Washout
COMPLETED
|
6
|
6
|
|
Initial Washout
NOT COMPLETED
|
0
|
0
|
|
Arm 1
STARTED
|
6
|
6
|
|
Arm 1
COMPLETED
|
6
|
5
|
|
Arm 1
NOT COMPLETED
|
0
|
1
|
|
Interval
STARTED
|
6
|
6
|
|
Interval
COMPLETED
|
6
|
6
|
|
Interval
NOT COMPLETED
|
0
|
0
|
|
Crossover Wash-out
STARTED
|
6
|
6
|
|
Crossover Wash-out
COMPLETED
|
6
|
6
|
|
Crossover Wash-out
NOT COMPLETED
|
0
|
0
|
|
Arm 2, Opposite Treatment
STARTED
|
6
|
6
|
|
Arm 2, Opposite Treatment
COMPLETED
|
5
|
6
|
|
Arm 2, Opposite Treatment
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
High Dose First
High dose arm 3 day wash-out followed by 7 days of: Arg 500 mg/kg/d or 10 g/m2 BSA Placebo instead of NaPBA interval then: Arg 100 mg/kg/d or 2 g/m2 BSA NaPBA 500 mg/kg/d or 10 g/m2 BSA
|
Low Dose First
low dose arm 3 day wash-out followed by 7 days of: Arg 100 mg/kg/d or 2 g/m2 BSA NaPBA 500 mg/kg/d or 10 g/m2 BSA interval then: Arg 500 mg/kg/d or 10 g/m2 BSA Placebo instead of NaPBA
|
|---|---|---|
|
Arm 1
Adverse Event
|
0
|
1
|
|
Arm 2, Opposite Treatment
Adverse Event
|
1
|
0
|
Baseline Characteristics
Arginine and Buphenyl in Patients With Argininosuccinic Aciduria (ASA), a Urea Cycle Disorder
Baseline characteristics by cohort
| Measure |
High-dose Arginine vs Low-dose Arginine Plus Buphenyl
n=12 Participants
|
|---|---|
|
Age, Categorical
<=18 years
|
8 Participants
n=93 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
|
Age, Continuous
|
15.4 years
STANDARD_DEVIATION 7.2 • n=93 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=93 Participants
|
|
Region of Enrollment
United States
|
12 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Measured after each 1-week treatment periodPlasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured.
Outcome measures
| Measure |
Low-dose Arginine Plus Buphenyl
n=11 Participants
Participants will undergo treatments in the following order: a 3-day washout period; a 1-week treatment period of sodium phenylbutyrate (Buphenyl-TM) plus arginine; a 3-day washout period; a 1-week treatment period of arginine alone.
|
High Dose Arginine Alone
n=11 Participants
Participants will undergo treatments in the following order: a 3-day washout period; a 1-week treatment period of arginine alone; a 3-day washout period; a 1-week treatment period of sodium phenylbutyrate (Buphenyl-TM) plus arginine
|
|---|---|---|
|
Measures of Liver Function: AST and ALT
Plasma AST
|
36.2 IU/L
Standard Error 10.9
|
52 IU/L
Standard Error 15.7
|
|
Measures of Liver Function: AST and ALT
ALT
|
31.7 IU/L
Standard Error 9.55
|
57.86 IU/L
Standard Error 17.44
|
PRIMARY outcome
Timeframe: Measured after each 1-week treatment periodProthrombin time (PT) and partial thromboplastin time (PTT) were measured PT measures factors I (fibrinogen), II (prothrombin), V, VII, and X, while PTT is a performance indicator of the efficacy of the common coagulation pathways.
Outcome measures
| Measure |
Low-dose Arginine Plus Buphenyl
n=11 Participants
Participants will undergo treatments in the following order: a 3-day washout period; a 1-week treatment period of sodium phenylbutyrate (Buphenyl-TM) plus arginine; a 3-day washout period; a 1-week treatment period of arginine alone.
|
High Dose Arginine Alone
n=11 Participants
Participants will undergo treatments in the following order: a 3-day washout period; a 1-week treatment period of arginine alone; a 3-day washout period; a 1-week treatment period of sodium phenylbutyrate (Buphenyl-TM) plus arginine
|
|---|---|---|
|
Measures of Liver Function: PT and PTT
PTT
|
30.91 seconds
Interval 29.55 to 32.54
|
30.98 seconds
Interval 29.16 to 31.74
|
|
Measures of Liver Function: PT and PTT
PT
|
14.25 seconds
Interval 13.7 to 14.6
|
13.8 seconds
Interval 13.6 to 14.37
|
PRIMARY outcome
Timeframe: Measured after each 1-week treatment periodPlasma levels of coagulation factors I and IX were used as measures of hepatic synthetic function since the treatment duration was short.
Outcome measures
| Measure |
Low-dose Arginine Plus Buphenyl
n=11 Participants
Participants will undergo treatments in the following order: a 3-day washout period; a 1-week treatment period of sodium phenylbutyrate (Buphenyl-TM) plus arginine; a 3-day washout period; a 1-week treatment period of arginine alone.
|
High Dose Arginine Alone
n=11 Participants
Participants will undergo treatments in the following order: a 3-day washout period; a 1-week treatment period of arginine alone; a 3-day washout period; a 1-week treatment period of sodium phenylbutyrate (Buphenyl-TM) plus arginine
|
|---|---|---|
|
Measures of Liver Function: Coagulation Factors
I
|
222.22 mg/dL
Standard Deviation 47.26
|
229.77 mg/dL
Standard Deviation 62.96
|
|
Measures of Liver Function: Coagulation Factors
IX
|
105.33 mg/dL
Standard Deviation 33.2
|
98.36 mg/dL
Standard Deviation 21.03
|
PRIMARY outcome
Timeframe: Measured after each 1-week treatment periodThe result (in seconds) for a prothrombin time performed on a normal individual will vary according to the type of analytical system employed. This is due to the variations between different batches of manufacturer's tissue factor used in the reagent to perform the test. The INR was devised to standardize the results. Each manufacturer assigns an ISI value (International Sensitivity Index) for any tissue factor they manufacture. The ISI value indicates how a particular batch of tissue factor compares to an international reference tissue factor. The ISI is usually between 1.0 and 2.0. The INR is the ratio of a patient's prothrombin time to a normal (control) sample, raised to the power of the ISI value for the analytical system being used.
Outcome measures
| Measure |
Low-dose Arginine Plus Buphenyl
n=11 Participants
Participants will undergo treatments in the following order: a 3-day washout period; a 1-week treatment period of sodium phenylbutyrate (Buphenyl-TM) plus arginine; a 3-day washout period; a 1-week treatment period of arginine alone.
|
High Dose Arginine Alone
n=11 Participants
Participants will undergo treatments in the following order: a 3-day washout period; a 1-week treatment period of arginine alone; a 3-day washout period; a 1-week treatment period of sodium phenylbutyrate (Buphenyl-TM) plus arginine
|
|---|---|---|
|
Measures of Liver Function: INR
|
14.2 seconds
Interval 13.7 to 14.6
|
13.8 seconds
Interval 13.6 to 14.3
|
SECONDARY outcome
Timeframe: Measured after each 1-week treatment periodOutcome measures
| Measure |
Low-dose Arginine Plus Buphenyl
n=11 Participants
Participants will undergo treatments in the following order: a 3-day washout period; a 1-week treatment period of sodium phenylbutyrate (Buphenyl-TM) plus arginine; a 3-day washout period; a 1-week treatment period of arginine alone.
|
High Dose Arginine Alone
n=11 Participants
Participants will undergo treatments in the following order: a 3-day washout period; a 1-week treatment period of arginine alone; a 3-day washout period; a 1-week treatment period of sodium phenylbutyrate (Buphenyl-TM) plus arginine
|
|---|---|---|
|
Argininosuccinic Acid Levels
|
69 micromole/l
Interval 44.0 to 165.0
|
53 micromole/l
Interval 29.0 to 118.0
|
SECONDARY outcome
Timeframe: Measured after each 1-week treatment periodOutcome measures
| Measure |
Low-dose Arginine Plus Buphenyl
n=11 Participants
Participants will undergo treatments in the following order: a 3-day washout period; a 1-week treatment period of sodium phenylbutyrate (Buphenyl-TM) plus arginine; a 3-day washout period; a 1-week treatment period of arginine alone.
|
High Dose Arginine Alone
n=11 Participants
Participants will undergo treatments in the following order: a 3-day washout period; a 1-week treatment period of arginine alone; a 3-day washout period; a 1-week treatment period of sodium phenylbutyrate (Buphenyl-TM) plus arginine
|
|---|---|---|
|
Arginine Levels
|
129 micromoles/L
Interval 83.0 to 197.0
|
53 micromoles/L
Interval 41.0 to 61.0
|
SECONDARY outcome
Timeframe: Measured after each 1-week treatment periodOutcome measures
| Measure |
Low-dose Arginine Plus Buphenyl
n=11 Participants
Participants will undergo treatments in the following order: a 3-day washout period; a 1-week treatment period of sodium phenylbutyrate (Buphenyl-TM) plus arginine; a 3-day washout period; a 1-week treatment period of arginine alone.
|
High Dose Arginine Alone
n=11 Participants
Participants will undergo treatments in the following order: a 3-day washout period; a 1-week treatment period of arginine alone; a 3-day washout period; a 1-week treatment period of sodium phenylbutyrate (Buphenyl-TM) plus arginine
|
|---|---|---|
|
Urea Production Rate
|
215 micromoles/kg/hr
Standard Deviation 56
|
97 micromoles/kg/hr
Standard Deviation 35
|
Adverse Events
High-dose Arginine Alone
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Low-dose Arginine Plus Buphenyl
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
High-dose Arginine Alone
n=12 participants at risk
|
Low-dose Arginine Plus Buphenyl
n=12 participants at risk
|
|---|---|---|
|
Gastrointestinal disorders
Vomiting
|
8.3%
1/12 • Number of events 1 • during both of the 7 day treatment phases
|
8.3%
1/12 • Number of events 1 • during both of the 7 day treatment phases
|
|
Metabolism and nutrition disorders
Hyperammonemia
|
8.3%
1/12 • Number of events 1 • during both of the 7 day treatment phases
|
8.3%
1/12 • Number of events 1 • during both of the 7 day treatment phases
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place