Trial Outcomes & Findings for Kuvan Therapy in Phenylketonuria (PKU): The Effect of Blood Phenylalanine Concentration on Kuvan Response (NCT NCT00841100)

Last Updated: 2019-12-03

Results Overview

Percent change in phenylalanine in (uM) on Kuvan Response evaluated via fasting morning blood serum. A decrease of 30% or greater indicates positive response on Kuvan.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

21 participants

Primary outcome timeframe

Baseline to Day 1 of the Acute Phase, Baseline to Day 28 of Phase 1, Baseline to Day 28 of Phase 3

Results posted on

2019-12-03

Participant Flow

All participants enrolled in the acute phase were eligible to continue onto the Phase 1 component of the trial. Only the participants who were non-responsive on the Phase 1 component of the study continued on to Phase 2. Only Phase 2 participants who achieved a fasting blood phenylalanine of less than 600 umol/l can continue to Phase 3.

Participant milestones

Participant milestones
Measure	All Participants All participants were enrolled into the four arms of the study. The 24-hour component consisted of participants received one dose of Kuvan 20 mg/kg on Day 1 and assessed for Acute 24 hour Kuvan response. The Phase 1 arm consisted of participants who after completion of the acute 24-hour component, enrolled and received Kuvan 20 mg/kg by mouth once daily for 28 consecutive days. The Phase 2 arm consisted of participants in Phase 1 that were not responsive and continued on to Phase 2 of the study. Positive response is defined as a decrease of blood phenylalanine of 30% or greater from baseline taken from morning blood serum. The Phase 2 component of the study will be a 2 week period of dietary restriction. The Phase 3 arm of the study consisted of participants in Phase 2 that achieved a fasting blood phenylalanine of less than 600 umol/l after 2-week dietary restriction will be retreated with Kuvan 20 mg/kg by mouth once daily for a period of 28 consecutive days.
Acute Component (24 Hours) STARTED	21
Acute Component (24 Hours) COMPLETED	21
Acute Component (24 Hours) NOT COMPLETED	0
Phase 1 (28 Days) STARTED	18
Phase 1 (28 Days) COMPLETED	15
Phase 1 (28 Days) NOT COMPLETED	3
Phase 2 (2 Weeks) STARTED	5
Phase 2 (2 Weeks) COMPLETED	5
Phase 2 (2 Weeks) NOT COMPLETED	0
Phase 3 (28 Days) STARTED	4
Phase 3 (28 Days) COMPLETED	4
Phase 3 (28 Days) NOT COMPLETED	0

Reasons for withdrawal

Reasons for withdrawal
Measure	All Participants All participants were enrolled into the four arms of the study. The 24-hour component consisted of participants received one dose of Kuvan 20 mg/kg on Day 1 and assessed for Acute 24 hour Kuvan response. The Phase 1 arm consisted of participants who after completion of the acute 24-hour component, enrolled and received Kuvan 20 mg/kg by mouth once daily for 28 consecutive days. The Phase 2 arm consisted of participants in Phase 1 that were not responsive and continued on to Phase 2 of the study. Positive response is defined as a decrease of blood phenylalanine of 30% or greater from baseline taken from morning blood serum. The Phase 2 component of the study will be a 2 week period of dietary restriction. The Phase 3 arm of the study consisted of participants in Phase 2 that achieved a fasting blood phenylalanine of less than 600 umol/l after 2-week dietary restriction will be retreated with Kuvan 20 mg/kg by mouth once daily for a period of 28 consecutive days.
Phase 1 (28 Days) Adverse Event	1
Phase 1 (28 Days) Participant non-compliance	2

Baseline Characteristics

Kuvan Therapy in Phenylketonuria (PKU): The Effect of Blood Phenylalanine Concentration on Kuvan Response

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=21 Participants All participants that was enrolled in the study
Age, Categorical <=18 years	13 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Day 1 of the Acute Phase, Baseline to Day 28 of Phase 1, Baseline to Day 28 of Phase 3

Population: 3 participants from the acute phase elected not to continue to the Phase 1 component of the study. Participants who were non-responsive on the Phase 1 component of the study continued on to Phase 2. Participants who achieved a fasting blood phenylalanine of \<600 umol/l can in Phase 2, continued to Phase 3.

Percent change in phenylalanine in (uM) on Kuvan Response evaluated via fasting morning blood serum. A decrease of 30% or greater indicates positive response on Kuvan.

Outcome measures

Outcome measures
Measure	Ove.Erall Participants n=21 Participants All participants enrolled in the study.
Percent Change in Blood Phenylalanine Baseline to Day 1 of the Acute phase	-13.71 Percent change in blood phenylalanine Standard Deviation 21.62
Percent Change in Blood Phenylalanine Baseline to Day 28 of Phase 1	-8.13 Percent change in blood phenylalanine Standard Deviation 31.84
Percent Change in Blood Phenylalanine Baseline to Day 28 of Phase 3	48.75 Percent change in blood phenylalanine Standard Deviation 61.87

Adverse Events

All Participants

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	All Participants n=21 participants at risk All participants that was enrolled in the study
Psychiatric disorders Anxiety	4.8% 1/21 • Number of events 1 • 3 months

Additional Information

Judy Schaechter

University of Miami

Phone: 305-243-3993

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place