Trial Outcomes & Findings for Effects of Kuvan on Melatonin Secretion (NCT NCT01617070)

NCT ID: NCT01617070

Last Updated: 2016-11-18

Results Overview

Evaluated for each subject under 4 conditions (washout, LNAA only, Kuvan only and LNAA+Kuvan)

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 10 participants
• Primary outcome timeframe: measured every 4 weeks up to 16 weeks
• Results posted on: 2016-11-18

Participant Flow

Participant milestones

Measure	All Study Participants LNAA, washout, Kuvan, and LNAA+Kuvan One group of 10 subjects, each under 4 conditions (each phase is 4 weeks) Kuvan: Dosed at 20 mg/kg; PO; Phase 3, Phase 4 Large Neutral Amino Acid Therapy: Dosed by weight: weight x .5 = total tablets per day; PO; Phase 1, Phase 4; taken with food
LNAA (4 Weeks) STARTED	10
LNAA (4 Weeks) COMPLETED	10
LNAA (4 Weeks) NOT COMPLETED	0
Washout (4 Weeks) STARTED	10
Washout (4 Weeks) COMPLETED	10
Washout (4 Weeks) NOT COMPLETED	0
BH4 Therapy (4 Weeks) STARTED	10
BH4 Therapy (4 Weeks) COMPLETED	10
BH4 Therapy (4 Weeks) NOT COMPLETED	0
BH4 and LNAA (4 Weeks) STARTED	10
BH4 and LNAA (4 Weeks) COMPLETED	9
BH4 and LNAA (4 Weeks) NOT COMPLETED	1

Reasons for withdrawal

Measure	All Study Participants LNAA, washout, Kuvan, and LNAA+Kuvan One group of 10 subjects, each under 4 conditions (each phase is 4 weeks) Kuvan: Dosed at 20 mg/kg; PO; Phase 3, Phase 4 Large Neutral Amino Acid Therapy: Dosed by weight: weight x .5 = total tablets per day; PO; Phase 1, Phase 4; taken with food
BH4 and LNAA (4 Weeks) started medication interfere with study	1

Baseline Characteristics

Effects of Kuvan on Melatonin Secretion

Baseline characteristics by cohort

Measure	All Study Participants n=10 Participants LNAA, washout, Kuvan, and LNAA+Kuvan One group of 10 subjects, each under 4 conditions (each phase is 4 weeks) Kuvan: Dosed at 20 mg/kg; PO; Phase 3, Phase 4 Large Neutral Amino Acid Therapy: Dosed by weight: weight x .5 = total tablets per day; PO; Phase 1, Phase 4; taken with food
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=93 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants
Gender Female	3 Participants n=93 Participants
Gender Male	7 Participants n=93 Participants
Region of Enrollment United States	10 Participants n=93 Participants

PRIMARY outcome

Timeframe: measured every 4 weeks up to 16 weeks

Population: Participates who completed all phases were measured.

Evaluated for each subject under 4 conditions (washout, LNAA only, Kuvan only and LNAA+Kuvan)

Outcome measures

Measure	LNAA n=9 Participants LNAA Large Neutral Amino Acid Therapy: Dosed by weight: weight x .5 = total tablets per day; PO; Phase 1, Phase 4; taken with food	Washout n=9 Participants no Kuvan or LNAA or any medical food products. Limited protein intake diet.	BH4 (Kuvan) n=9 Participants Kuvan (BH4): Dosed at 20 mg/kg; PO; Phase 3, Phase 4	BH4 and LNAA n=9 Participants Kuvan: Dosed at 20 mg/kg; PO; Phase 3, Phase 4 Large Neutral Amino Acid Therapy: Dosed by weight: weight x .5 = total tablets per day; PO; Phase 1, Phase 4; taken with food
Serum Melatonin at the End of 4 Weeks	266.9 pg/ml Standard Deviation 165.7	205.7 pg/ml Standard Deviation 133.1	220.4 pg/ml Standard Deviation 138.5	301.2 pg/ml Standard Deviation 179.4

PRIMARY outcome

Timeframe: measured every 4 weeks up to 16 weeks

Population: Participates who completed all phases were measured.

Evaluated for each subject under 4 conditions (washout, LNAA only, Kuvan only and LNAA+Kuvan)

Outcome measures

Measure	LNAA n=9 Participants LNAA Large Neutral Amino Acid Therapy: Dosed by weight: weight x .5 = total tablets per day; PO; Phase 1, Phase 4; taken with food	Washout n=9 Participants no Kuvan or LNAA or any medical food products. Limited protein intake diet.	BH4 (Kuvan) n=9 Participants Kuvan (BH4): Dosed at 20 mg/kg; PO; Phase 3, Phase 4	BH4 and LNAA n=9 Participants Kuvan: Dosed at 20 mg/kg; PO; Phase 3, Phase 4 Large Neutral Amino Acid Therapy: Dosed by weight: weight x .5 = total tablets per day; PO; Phase 1, Phase 4; taken with food
Urine 6-sulfatoxymelatonin at the End of 4 Weeks	14.5 ng/mg Creatinine Standard Deviation 9.0	8.2 ng/mg Creatinine Standard Deviation 4.8	8.6 ng/mg Creatinine Standard Deviation 5.7	13.2 ng/mg Creatinine Standard Deviation 9.3

PRIMARY outcome

Timeframe: measured every 4 weeks up to 16 weeks

Population: Participates who completed all phases were measured.

Evaluated for each subject under 4 conditions (washout, LNAA only, Kuvan only and LNAA+Kuvan)

Outcome measures

Measure	LNAA n=9 Participants LNAA Large Neutral Amino Acid Therapy: Dosed by weight: weight x .5 = total tablets per day; PO; Phase 1, Phase 4; taken with food	Washout n=9 Participants no Kuvan or LNAA or any medical food products. Limited protein intake diet.	BH4 (Kuvan) n=9 Participants Kuvan (BH4): Dosed at 20 mg/kg; PO; Phase 3, Phase 4	BH4 and LNAA n=9 Participants Kuvan: Dosed at 20 mg/kg; PO; Phase 3, Phase 4 Large Neutral Amino Acid Therapy: Dosed by weight: weight x .5 = total tablets per day; PO; Phase 1, Phase 4; taken with food
Urine Dopamine at the End of 4 Weeks	63.7 ug/gCreatinine Standard Deviation 26.7	42.6 ug/gCreatinine Standard Deviation 19.3	46.0 ug/gCreatinine Standard Deviation 16.8	67.6 ug/gCreatinine Standard Deviation 28.4

Adverse Events

LNAA

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Washout

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

BH4 (Kuvan)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

BH4 and LNAA

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Shoji Yano

USC/Keck School of Medicine

Phone: 323-226-3816

Email: syano@usc.edu

Results disclosure agreements

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