Trial Outcomes & Findings for A Trial of Levodopa in Angelman Syndrome (NCT NCT01281475)

NCT ID: NCT01281475

Last Updated: 2020-07-15

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 67 participants
• Primary outcome timeframe: 12 months
• Results posted on: 2020-07-15

Participant Flow

Participant milestones

Measure	Levodopa Levodopa is a prodrug that "delivers" dopamine to the brain. It is usually given with carbidopa, a peripheral decarboxylase inhibitor, to increase the bioavailability of levodopa. Levodopa/carbidopa: Levodopa/Carbidopa (4:1) Dosages are based on levodopa. Subjects randomized to the levodopa arm will receive a levodopa dose of 5 mg/kg/day in the first 2 weeks of the study, a levodopa dose of 10 mg/kg/day in the second 2 weeks of the study, and a levodopa dose of 15 mg/kg/day (up to a maximum of 800 mg per day) for the remaining duration of the study. Levodopa/Carbidopa is a combined formulation that will be dispensed as capsules. It should be taken 3 times a day.	Placebo The placebo (in this study, microcellulose) is not expected to have any effect.
Overall Study STARTED	33	34
Overall Study COMPLETED	29	26
Overall Study NOT COMPLETED	4	8

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Trial of Levodopa in Angelman Syndrome

Baseline characteristics by cohort

Measure	Levodopa n=29 Participants Levodopa is a prodrug that "delivers" dopamine to the brain. It is usually given with carbidopa, a peripheral decarboxylase inhibitor, to increase the bioavailability of levodopa. Levodopa/carbidopa: Levodopa/Carbidopa (4:1) Dosages are based on levodopa. Subjects randomized to the levodopa arm will receive a levodopa dose of 5 mg/kg/day in the first 2 weeks of the study, a levodopa dose of 10 mg/kg/day in the second 2 weeks of the study, and a levodopa dose of 15 mg/kg/day (up to a maximum of 800 mg per day) for the remaining duration of the study. Levodopa/Carbidopa is a combined formulation that will be dispensed as capsules. It should be taken 3 times a day.	Placebo n=26 Participants The placebo (in this study, microcellulose) is not expected to have any effect. It is also taken 3 times a day, just like Levodopa.	Total n=55 Participants Total of all reporting groups
Age, Categorical <=18 years	29 Participants n=5 Participants	26 Participants n=7 Participants	55 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex/Gender, Customized Female	13 participants n=5 Participants	12 participants n=7 Participants	25 participants n=5 Participants
Sex/Gender, Customized Male	16 participants n=5 Participants	14 participants n=7 Participants	30 participants n=5 Participants
Developmental age - Bayley Cognitive	19 months STANDARD_DEVIATION 8 • n=5 Participants	18 months STANDARD_DEVIATION 6 • n=7 Participants	19 months STANDARD_DEVIATION 7 • n=5 Participants
Tremors	16 Participants n=5 Participants	15 Participants n=7 Participants	31 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Outcome measures

Measure	Levodopa n=29 Participants Levodopa is a prodrug that "delivers" dopamine to the brain. It is usually given with carbidopa, a peripheral decarboxylase inhibitor, to increase the bioavailability of levodopa. Levodopa/carbidopa: Levodopa/Carbidopa (4:1) Dosages are based on levodopa. Subjects randomized to the levodopa arm will receive a levodopa dose of 5 mg/kg/day in the first 2 weeks of the study, a levodopa dose of 10 mg/kg/day in the second 2 weeks of the study, and a levodopa dose of 15 mg/kg/day (up to a maximum of 800 mg per day) for the remaining duration of the study. Levodopa/Carbidopa is a combined formulation that will be dispensed as capsules. It should be taken 3 times a day.	Placebo n=26 Participants The placebo (in this study, microcellulose) is not expected to have any effect. The placebo capsules are taken 3 times a day, just like the levodopa / carbidopa capsules
Bayley Cognitive Age Equivalent at 1 Year	19 months Standard Deviation 7	19 months Standard Deviation 8

SECONDARY outcome

Timeframe: 1 year

Outcome measures

Measure	Levodopa n=29 Participants Levodopa is a prodrug that "delivers" dopamine to the brain. It is usually given with carbidopa, a peripheral decarboxylase inhibitor, to increase the bioavailability of levodopa. Levodopa/carbidopa: Levodopa/Carbidopa (4:1) Dosages are based on levodopa. Subjects randomized to the levodopa arm will receive a levodopa dose of 5 mg/kg/day in the first 2 weeks of the study, a levodopa dose of 10 mg/kg/day in the second 2 weeks of the study, and a levodopa dose of 15 mg/kg/day (up to a maximum of 800 mg per day) for the remaining duration of the study. Levodopa/Carbidopa is a combined formulation that will be dispensed as capsules. It should be taken 3 times a day.	Placebo n=26 Participants The placebo (in this study, microcellulose) is not expected to have any effect. The placebo capsules are taken 3 times a day, just like the levodopa / carbidopa capsules
Presence of Tremors	14 Participants	12 Participants

Adverse Events

Levodopa

Serious events: 3 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	Levodopa n=33 participants at risk Levodopa is a prodrug that "delivers" dopamine to the brain. It is usually given with carbidopa, a peripheral decarboxylase inhibitor, to increase the bioavailability of levodopa. Levodopa/carbidopa: Levodopa/Carbidopa (4:1) Dosages are based on levodopa. Subjects randomized to the levodopa arm will receive a levodopa dose of 5 mg/kg/day in the first 2 weeks of the study, a levodopa dose of 10 mg/kg/day in the second 2 weeks of the study, and a levodopa dose of 15 mg/kg/day (up to a maximum of 800 mg per day) for the remaining duration of the study. Levodopa/Carbidopa is a combined formulation that will be dispensed as capsules. It should be taken 3 times a day.	Placebo n=34 participants at risk The placebo (in this study, microcellulose) is not expected to have any effect.
Nervous system disorders Seizure	6.1% 2/33 • Number of events 2	0.00% 0/34
Gastrointestinal disorders Vomiting	3.0% 1/33 • Number of events 1	0.00% 0/34
General disorders Fever	0.00% 0/33	2.9% 1/34 • Number of events 1

Other adverse events

Measure	Levodopa n=33 participants at risk Levodopa is a prodrug that "delivers" dopamine to the brain. It is usually given with carbidopa, a peripheral decarboxylase inhibitor, to increase the bioavailability of levodopa. Levodopa/carbidopa: Levodopa/Carbidopa (4:1) Dosages are based on levodopa. Subjects randomized to the levodopa arm will receive a levodopa dose of 5 mg/kg/day in the first 2 weeks of the study, a levodopa dose of 10 mg/kg/day in the second 2 weeks of the study, and a levodopa dose of 15 mg/kg/day (up to a maximum of 800 mg per day) for the remaining duration of the study. Levodopa/Carbidopa is a combined formulation that will be dispensed as capsules. It should be taken 3 times a day.	Placebo n=34 participants at risk The placebo (in this study, microcellulose) is not expected to have any effect.
Nervous system disorders Seizures	33.3% 11/33	26.5% 9/34

Additional Information

Wen-Hann Tan

Boston Children's Hospital

Phone: 617-355 6394

Email: wen-hann.tan@childrens.harvard.edu

Results disclosure agreements

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