Trial Outcomes & Findings for Phenylbutyrate Therapy for Maple Syrup Urine Disease (NCT NCT01529060)

NCT ID: NCT01529060

Last Updated: 2019-03-19

Results Overview

Total Leucine exposure over 24 hours was calculated by serial blood draws at times 0, 2, 4, 8, 12, 16, 20, and 24 hours

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 20 participants
• Primary outcome timeframe: 24 Hours
• Results posted on: 2019-03-19

Participant Flow

Participant milestones

Measure	Phenylbutyrate First and Placebo Second Group Individuals randomized to this group received phenylbutyrate powder (500 mg/kg/day in patients weighing less than 20kg and 10 g/m2/day in larger patients in 3 divided doses per day) for 14 days (week 1 and week 2) and then crossed over to receive placebo powder in identical doses for the next 14 days (Week 3 and week 4)	Placebo First and Phenylbutyrate Second Group Individuals randomized to this group received first received placebo powder for 14 days (week 1 and week 2) and then were crossed over to receive phenylbutyrate (500 mg/kg/day in patients weighing less than 20kg and 10 g/m2/day in larger patients in 3 divided doses per day) for 14 days (week 3 and week 4) week 4).
Overall Study STARTED	10	10
Overall Study COMPLETED	10	10
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phenylbutyrate Therapy for Maple Syrup Urine Disease

Baseline characteristics by cohort

Measure	Phenylbutyrate First and Placebo Second n=10 Participants Individuals randomized to this group received phenylbutyrate (500 mg/kg/day in patients weighing less than 20kg and 10 g/m2/day in larger patients in divided doses per day) for 14 days (week 1 and week 2) and then crossed over to receive placebo powder in identical doses for the next 14 days (Week 3 and week 4)	Placebo First and Phenylbutyrate Second n=10 Participants Individuals randomized to this group received first received placebo powder for 14 days (week 1 and week 2) and then were crossed over to receive phenylbutyrate (500 mg/kg/day in patients weighing less than 20kg and 10 g/m2/day in larger patients in 3 divided doses per day) for 14 days (week 3 and week 4) week 4).	Total n=20 Participants Total of all reporting groups
Age, Continuous	23 years n=5 Participants	23 years n=7 Participants	23 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Ethnic Categories · Not Hispanic or Latino	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Race/Ethnicity, Customized Ethnic Categories · Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment United States	9 participants n=5 Participants	10 participants n=7 Participants	19 participants n=5 Participants
Region of Enrollment Canada	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants

PRIMARY outcome

Timeframe: 24 Hours

Total Leucine exposure over 24 hours was calculated by serial blood draws at times 0, 2, 4, 8, 12, 16, 20, and 24 hours

Outcome measures

Measure	Phenylbutyrate n=20 Participants Cumulative results when individuals were treated with phenylbutyrate	Placebo First and Phenylbutyrate Second Group n=20 Participants Cumulative results from when individuals were treated with placebo
0-24 Hour AUC Leucine (Samples Collected at 0, 2, 4, 8, 12, 16, 20, and 24 Hours)	6217 micromoles*hour/L Standard Deviation 5168	4616 micromoles*hour/L Standard Deviation 4106

PRIMARY outcome

Timeframe: 24 hours

Maximal leucine concentration in 0-24 hours

Outcome measures

Measure	Phenylbutyrate n=20 Participants Cumulative results when individuals were treated with phenylbutyrate	Placebo First and Phenylbutyrate Second Group n=20 Participants Cumulative results from when individuals were treated with placebo
Leucine CMax 0-24 Hours	361 Micromoles/L Standard Deviation 244	295 Micromoles/L Standard Deviation 211

Adverse Events

Phenylbutyrate

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Inactive Powder

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Phenylbutyrate n=20 participants at risk Study Drug Phenylbutyrate: Dosage of phenylbutyrate powder will be 500 mg/kg/day in patients weighing less than 20kg and 10 g/m2/day in larger patients in four divided doses per day, the standard UCD dose studied in our preliminary studies, for 14 days.	Inactive Powder n=20 participants at risk Placebo powder Placebo powder: Dosage of inactive placebo powder will be 500 mg/kg/day in patients weighing less than 20kg and 10 g/m2/day in larger patients in four divided doses per day for 14 days. Subjects will receive the same amount of powder for each arm of the study.
Respiratory, thoracic and mediastinal disorders Oral or Nasal Complaints	75.0% 15/20 • Number of events 15 • Adverse events were collected over the 14 days of Treatment period 1 and 14 days of treatment period 2	20.0% 4/20 • Number of events 4 • Adverse events were collected over the 14 days of Treatment period 1 and 14 days of treatment period 2
Blood and lymphatic system disorders Labs	95.0% 19/20 • Number of events 19 • Adverse events were collected over the 14 days of Treatment period 1 and 14 days of treatment period 2	80.0% 16/20 • Number of events 16 • Adverse events were collected over the 14 days of Treatment period 1 and 14 days of treatment period 2
Gastrointestinal disorders Gastrointestinal Symptoms	80.0% 16/20 • Number of events 16 • Adverse events were collected over the 14 days of Treatment period 1 and 14 days of treatment period 2	35.0% 7/20 • Number of events 7 • Adverse events were collected over the 14 days of Treatment period 1 and 14 days of treatment period 2
Nervous system disorders Neurological Complaints	35.0% 7/20 • Number of events 7 • Adverse events were collected over the 14 days of Treatment period 1 and 14 days of treatment period 2	35.0% 7/20 • Number of events 7 • Adverse events were collected over the 14 days of Treatment period 1 and 14 days of treatment period 2
Musculoskeletal and connective tissue disorders Muscular Pain	20.0% 4/20 • Number of events 4 • Adverse events were collected over the 14 days of Treatment period 1 and 14 days of treatment period 2	10.0% 2/20 • Number of events 2 • Adverse events were collected over the 14 days of Treatment period 1 and 14 days of treatment period 2
Skin and subcutaneous tissue disorders Minor Skin Complaints	30.0% 6/20 • Number of events 6 • Adverse events were collected over the 14 days of Treatment period 1 and 14 days of treatment period 2	10.0% 2/20 • Number of events 2 • Adverse events were collected over the 14 days of Treatment period 1 and 14 days of treatment period 2
Renal and urinary disorders Urine Odor	5.0% 1/20 • Number of events 1 • Adverse events were collected over the 14 days of Treatment period 1 and 14 days of treatment period 2	5.0% 1/20 • Number of events 1 • Adverse events were collected over the 14 days of Treatment period 1 and 14 days of treatment period 2
Reproductive system and breast disorders Menstral Cramps	10.0% 2/20 • Number of events 2 • Adverse events were collected over the 14 days of Treatment period 1 and 14 days of treatment period 2	0.00% 0/20 • Adverse events were collected over the 14 days of Treatment period 1 and 14 days of treatment period 2

Additional Information

Alyssa Tran, BS

Baylor

Phone: 832-822-4264

Email: alyssat@bcm.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place