Trial Outcomes & Findings for A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder (NCT NCT00576732)

NCT ID: NCT00576732

Last Updated: 2014-05-09

Results Overview

Measure of irritability symptoms of autism. Score range 0 to 45 (lower score = lesser severity).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

96 participants

Primary outcome timeframe

Baseline and 6 weeks

Results posted on

2014-05-09

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Double-blind Period. Oral solution for 6 weeks.	Risperidone Low Dose Double-blind Period. Risperidone oral solution 0.125 mg (if \<45 kg) or 0.175 mg (if \>=45 kg) for 6 weeks.	Risperidone High Dose Double-blind Period. Risperidone oral solution 1.25 mg (if \<45 kg) or 1.75 mg (if \>=45 kg) for 6 weeks.	Placebo/RIS Open-label Period. Subjects in the double-blind placebo group who continued into open-label risperidone period. Risperidone oral solution 0.125 mg (if \<45 kg) or 0.175 mg (if \>=45 kg) for 3 days, 0.25 mg tablet on Day 4, flexible dose in 0.25 mg or 0.5 mg increments every 2 weeks, as clinically indicated, to a maximum dose of 1.25 mg (if \<45 kg) or 1.75 mg (if \>=45 kg).	Ris Low Dose/RIS Open-label Period. Subjects in the double-blind risperidone low dose group who continued into open-label risperidone period. Risperidone oral solution 0.125 mg (if \<45 kg) or 0.175 mg (if \>=45 kg) for 3 days, 0.25 mg tablet on Day 4, flexible dose in 0.25 mg or 0.5 mg increments every 2 weeks, as clinically indicated, to a maximum dose of 1.25 mg (if \<45 kg) or 1.75 mg (if \>=45 kg).	Ris High Dose/RIS Open-label Period. Subjects in the double-blind risperidone high dose group who continued into open-label risperidone period. Risperidone oral solution 0.125 mg (if \<45 kg) or 0.175 mg (if \>=45 kg) for 3 days, 0.25 mg tablet on Day 4, flexible dose in 0.25 mg or 0.5 mg increments every 2 weeks, as clinically indicated, to a maximum dose of 1.25 mg (if \<45 kg) or 1.75 mg (if \>=45 kg).
DOUBLE BLIND STARTED	35	30	31	0	0	0
DOUBLE BLIND COMPLETED	27	25	25	0	0	0
DOUBLE BLIND NOT COMPLETED	8	5	6	0	0	0
OPEN LABEL STARTED	0	0	0	30	24	25
OPEN LABEL COMPLETED	0	0	0	19	20	17
OPEN LABEL NOT COMPLETED	0	0	0	11	4	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Double-blind Period. Oral solution for 6 weeks.	Risperidone Low Dose Double-blind Period. Risperidone oral solution 0.125 mg (if \<45 kg) or 0.175 mg (if \>=45 kg) for 6 weeks.	Risperidone High Dose Double-blind Period. Risperidone oral solution 1.25 mg (if \<45 kg) or 1.75 mg (if \>=45 kg) for 6 weeks.	Placebo/RIS Open-label Period. Subjects in the double-blind placebo group who continued into open-label risperidone period. Risperidone oral solution 0.125 mg (if \<45 kg) or 0.175 mg (if \>=45 kg) for 3 days, 0.25 mg tablet on Day 4, flexible dose in 0.25 mg or 0.5 mg increments every 2 weeks, as clinically indicated, to a maximum dose of 1.25 mg (if \<45 kg) or 1.75 mg (if \>=45 kg).	Ris Low Dose/RIS Open-label Period. Subjects in the double-blind risperidone low dose group who continued into open-label risperidone period. Risperidone oral solution 0.125 mg (if \<45 kg) or 0.175 mg (if \>=45 kg) for 3 days, 0.25 mg tablet on Day 4, flexible dose in 0.25 mg or 0.5 mg increments every 2 weeks, as clinically indicated, to a maximum dose of 1.25 mg (if \<45 kg) or 1.75 mg (if \>=45 kg).	Ris High Dose/RIS Open-label Period. Subjects in the double-blind risperidone high dose group who continued into open-label risperidone period. Risperidone oral solution 0.125 mg (if \<45 kg) or 0.175 mg (if \>=45 kg) for 3 days, 0.25 mg tablet on Day 4, flexible dose in 0.25 mg or 0.5 mg increments every 2 weeks, as clinically indicated, to a maximum dose of 1.25 mg (if \<45 kg) or 1.75 mg (if \>=45 kg).
DOUBLE BLIND Adverse Event	0	0	1	0	0	0
DOUBLE BLIND Lost to Follow-up	0	1	1	0	0	0
DOUBLE BLIND Withdrawal by Subject	1	1	3	0	0	0
DOUBLE BLIND OTHER	0	2	1	0	0	0
DOUBLE BLIND Lack of Efficacy	6	1	0	0	0	0
DOUBLE BLIND Protocol Violation	1	0	0	0	0	0
OPEN LABEL Adverse Event	0	0	0	4	0	1
OPEN LABEL Lost to Follow-up	0	0	0	2	1	1
OPEN LABEL Withdrawal by Subject	0	0	0	1	0	1
OPEN LABEL OTHER	0	0	0	0	0	2
OPEN LABEL Lack of Efficacy	0	0	0	2	2	3
OPEN LABEL Protocol Violation	0	0	0	2	1	0

Baseline Characteristics

A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=35 Participants Double-blind Period. Oral solution for 6 weeks.	Risperidone Low Dose n=30 Participants Double-blind Period. Risperidone oral solution 0.125 mg (if \<45 kg) or 0.175 mg (if \>=45 kg) for 6 weeks.	Risperidone High Dose n=31 Participants Double-blind Period. Risperidone oral solution 1.25 mg (if \<45 kg) or 1.75 mg (if \>=45 kg) for 6 weeks.	Total n=96 Participants Total of all reporting groups
Age, Categorical <=18 years	35 Participants n=5 Participants	30 Participants n=7 Participants	31 Participants n=5 Participants	96 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	8.6 years STANDARD_DEVIATION 2.57 • n=5 Participants	10.2 years STANDARD_DEVIATION 3.42 • n=7 Participants	9.3 years STANDARD_DEVIATION 3.11 • n=5 Participants	9.3 years STANDARD_DEVIATION 3.07 • n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	12 Participants n=4 Participants
Sex: Female, Male Male	31 Participants n=5 Participants	25 Participants n=7 Participants	28 Participants n=5 Participants	84 Participants n=4 Participants
Region of Enrollment United States of America	35 participants n=5 Participants	30 participants n=7 Participants	31 participants n=5 Participants	96 participants n=4 Participants
Age Categorical <12 years	30 participants n=5 Participants	20 participants n=7 Participants	24 participants n=5 Participants	74 participants n=4 Participants
Age Categorical >=12 years	5 participants n=5 Participants	10 participants n=7 Participants	7 participants n=5 Participants	22 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and 6 weeks

Population: All randomized subjects with at least one dose of study medication and both baseline and at least one postbaseline value. For subjects who discontinued, Week 6 data is imputed using the subject's last nonmissing, postbaseline value in the double-blind period (Last Observation Carried Forward \[LOCF\]).

Measure of irritability symptoms of autism. Score range 0 to 45 (lower score = lesser severity).

Outcome measures

Outcome measures
Measure	Placebo n=34 Participants Double-blind Period. Oral solution for 6 weeks.	Risperidone Low Dose n=29 Participants Double-blind Period. Risperidone oral solution 0.125 mg (if \<45 kg) or 0.175 mg (if \>=45 kg) for 6 weeks.	Risperidone High Dose n=29 Participants Double-blind Period. Risperidone oral solution 1.25 mg (if \<45 kg) or 1.75 mg (if \>=45 kg) for 6 weeks.
Change in Aberrant Behavior Checklist Irritability (ABC-I) Subscale	-3.5 units on a scale Standard Deviation 10.67	-7.4 units on a scale Standard Deviation 8.12	-12.4 units on a scale Standard Deviation 6.52

SECONDARY outcome

Timeframe: 6 weeks

ABC-I is a measure of irritability symptoms of autism with score range 0 to 45 (lower score = lesser severity).

Outcome measures

Outcome measures
Measure	Placebo n=34 Participants Double-blind Period. Oral solution for 6 weeks.	Risperidone Low Dose n=29 Participants Double-blind Period. Risperidone oral solution 0.125 mg (if \<45 kg) or 0.175 mg (if \>=45 kg) for 6 weeks.	Risperidone High Dose n=29 Participants Double-blind Period. Risperidone oral solution 1.25 mg (if \<45 kg) or 1.75 mg (if \>=45 kg) for 6 weeks.
Number of Participants Who Had at Least 25% Improvement in ABC-I	14 participants	15 participants	24 participants

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Investigator evaluation of severity of illness and functional impairment on a 7-point scale (1="not ill", 2="very mild", 3="mild", 4="moderate", 5="marked", 6="severe", 7="extremely severe").

Outcome measures

Outcome measures
Measure	Placebo n=34 Participants Double-blind Period. Oral solution for 6 weeks.	Risperidone Low Dose n=29 Participants Double-blind Period. Risperidone oral solution 0.125 mg (if \<45 kg) or 0.175 mg (if \>=45 kg) for 6 weeks.	Risperidone High Dose n=29 Participants Double-blind Period. Risperidone oral solution 1.25 mg (if \<45 kg) or 1.75 mg (if \>=45 kg) for 6 weeks.
Change in Clinical Global Impression Severity (CGI-S)	-0.3 units on a scale Standard Deviation 0.79	-0.4 units on a scale Standard Deviation 0.73	-1.0 units on a scale Standard Deviation 0.78

SECONDARY outcome

Timeframe: 6 weeks

Population: All randomized subjects with at least one dose of study medication and at least one postbaseline value. For subjects who discontinued, Week 6 data is imputed using the subject's last nonmissing, postbaseline value in the double-blind period (Last Observation Carried Forward \[LOCF\]).

Investigator impression of change over time from double-blind baseline on a 7-point scale (1="very much improved", 2="much improved", 3="minimally improved", 4="no change", 5="minimally worse", 6="much worse", 7="very much worse").

Outcome measures

Outcome measures
Measure	Placebo n=34 Participants Double-blind Period. Oral solution for 6 weeks.	Risperidone Low Dose n=30 Participants Double-blind Period. Risperidone oral solution 0.125 mg (if \<45 kg) or 0.175 mg (if \>=45 kg) for 6 weeks.	Risperidone High Dose n=30 Participants Double-blind Period. Risperidone oral solution 1.25 mg (if \<45 kg) or 1.75 mg (if \>=45 kg) for 6 weeks.
Number of Participants Who Had Clinical Global Impression Change Ratings of Much or Very Much Improved.	5 participants	5 participants	19 participants

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: All randomized subjects with at least one dose of study medication and both baseline and at least one postbaseline fasting laboratory samples. For subjects who discontinued, Week 6 data is imputed using the subject's last nonmissing, postbaseline value in the double-blind period (Last Observation Carried Forward \[LOCF\]).

Outcome measures

Outcome measures
Measure	Placebo n=22 Participants Double-blind Period. Oral solution for 6 weeks.	Risperidone Low Dose n=23 Participants Double-blind Period. Risperidone oral solution 0.125 mg (if \<45 kg) or 0.175 mg (if \>=45 kg) for 6 weeks.	Risperidone High Dose n=23 Participants Double-blind Period. Risperidone oral solution 1.25 mg (if \<45 kg) or 1.75 mg (if \>=45 kg) for 6 weeks.
Change in Fasting Glucose (mg/dL) at 6 Weeks	-0.4 mg/dL Standard Deviation 8.20	-0.1 mg/dL Standard Deviation 8.81	-0.3 mg/dL Standard Deviation 9.74

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: All randomized subjects with \>=1 dose of study medication and fasting glucose and insulin at baseline and at \>=1 postbaseline time point. For subjects who discontinued, Week 6 data is imputed using the subject's last nonmissing, postbaseline value in the double-blind period. Means are adjusted for baseline weight (\<45 kg, \>=45 kg) and baseline IR.

Insulin resistance calculated using the homeostatic model assessment 1 (HOMA1)formula: fasting glucose (mmol/L) times fasting insulin (uU/L) divided by 22.5. HOMA-IR is a widely used clinical tool for estimating insulin resistance based upon the balance between glucose output and insulin secretion. Normal values should be close to 1, while an increase indicates a decrease in insulin sensitivity (or increase in insulin resistance), a potential predictor for the development of Type 2 Diabetes Mellitus.

Outcome measures

Outcome measures
Measure	Placebo n=22 Participants Double-blind Period. Oral solution for 6 weeks.	Risperidone Low Dose n=21 Participants Double-blind Period. Risperidone oral solution 0.125 mg (if \<45 kg) or 0.175 mg (if \>=45 kg) for 6 weeks.	Risperidone High Dose n=22 Participants Double-blind Period. Risperidone oral solution 1.25 mg (if \<45 kg) or 1.75 mg (if \>=45 kg) for 6 weeks.
Change in Insulin Resistance (IR) at 6 Weeks	0.36 units on a scale Interval -0.34 to 1.07	-0.10 units on a scale Interval -0.76 to 0.55	0.45 units on a scale Interval -0.18 to 1.08

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: All subjects with at least one dose of study medication in the open label phase and both double-blind baseline and at least one open-label period fasting laboratory samples. For subjects who discontinued, Month 6 data is imputed using the subject's last nonmissing, postbaseline value in the open-label period.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Double-blind Period. Oral solution for 6 weeks.	Risperidone Low Dose n=16 Participants Double-blind Period. Risperidone oral solution 0.125 mg (if \<45 kg) or 0.175 mg (if \>=45 kg) for 6 weeks.	Risperidone High Dose n=16 Participants Double-blind Period. Risperidone oral solution 1.25 mg (if \<45 kg) or 1.75 mg (if \>=45 kg) for 6 weeks.
Change in Fasting Glucose (mg/dL) at 6 Months	4.0 mg/dL Standard Deviation 12.27	3.5 mg/dL Standard Deviation 12.26	2.3 mg/dL Standard Deviation 8.70

SECONDARY outcome

Timeframe: Baseline and 6 months

Insulin resistance calculated using the homeostatic model assessment 1 (HOMA1) formula: fasting glucose (mmol/L) times fasting insulin (uU/L) divided by 22.5. HOMA-IR is a widely used clinical tool for estimating insulin resistance based upon the balance between glucose output and insulin secretion. Normal values should be close to 1, while an increase indicates a decrease in insulin sensitivity (or increase in insulin resistance), a potential predictor for the development of Type 2 Diabetes Mellitus.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Double-blind Period. Oral solution for 6 weeks.	Risperidone Low Dose n=16 Participants Double-blind Period. Risperidone oral solution 0.125 mg (if \<45 kg) or 0.175 mg (if \>=45 kg) for 6 weeks.	Risperidone High Dose n=16 Participants Double-blind Period. Risperidone oral solution 1.25 mg (if \<45 kg) or 1.75 mg (if \>=45 kg) for 6 weeks.
Change in Insulin Resistance (IR) at 6 Months	0.09 units on a scale Standard Deviation 2.67	0.36 units on a scale Standard Deviation 0.89	0.75 units on a scale Standard Deviation 0.91

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Risperidone Low Dose

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Risperidone High Dose

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

Open-label Risperidone

Serious events: 1 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=35 participants at risk Double-blind Period. Oral solution for 6 weeks.	Risperidone Low Dose n=30 participants at risk Double-blind Period. Risperidone oral solution 0.125 mg (if \<45 kg) or 0.175 mg (if \>=45 kg) for 6 weeks.	Risperidone High Dose n=31 participants at risk Double-blind Period. Risperidone oral solution 1.25 mg (if \<45 kg) or 1.75 mg (if \>=45 kg) for 6 weeks.	Open-label Risperidone n=79 participants at risk Subjects who continued into open-label risperidone period. Risperidone oral solution 0.125 mg (if \<45 kg) or 0.175 mg (if \>=45 kg) for 3 days, 0.25 mg tablet on Day 4, flexible dose in 0.25 mg or 0.5 mg increments every 2 weeks, as clinically indicated, to a maximum dose of 1.25 mg (if \<45 kg) or 1.75 mg (if \>=45 kg).
Psychiatric disorders Aggression	2.9% 1/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Congenital, familial and genetic disorders Hydrocele	0.00% 0/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	1.3% 1/79 • Double-blind period: 6 weeks. Open-label period: 6 months.

Other adverse events

Additional Information

Clinical Leader

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Phone: 609 730 2317

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor can embargo results from a PI's center until the combined results from the completed study have been published in full or the sponsor confirms there will be no multicenter study publication. Results communications must be provided to the sponsor for review at least 60 days before submission for publication. By written request, the sponsor can extend the embargo up to an additional 60 days. The sponsor cannot require changes to scientific content and cannot further extend the embargo.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=35 participants at risk Double-blind Period. Oral solution for 6 weeks.	Risperidone Low Dose n=30 participants at risk Double-blind Period. Risperidone oral solution 0.125 mg (if \<45 kg) or 0.175 mg (if \>=45 kg) for 6 weeks.	Risperidone High Dose n=31 participants at risk Double-blind Period. Risperidone oral solution 1.25 mg (if \<45 kg) or 1.75 mg (if \>=45 kg) for 6 weeks.	Open-label Risperidone n=79 participants at risk Subjects who continued into open-label risperidone period. Risperidone oral solution 0.125 mg (if \<45 kg) or 0.175 mg (if \>=45 kg) for 3 days, 0.25 mg tablet on Day 4, flexible dose in 0.25 mg or 0.5 mg increments every 2 weeks, as clinically indicated, to a maximum dose of 1.25 mg (if \<45 kg) or 1.75 mg (if \>=45 kg).
Gastrointestinal disorders Abdominal discomfort	8.6% 3/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	2.5% 2/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	3.3% 1/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	6.5% 2/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	1.3% 1/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Psychiatric disorders Aggression	5.7% 2/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	2.5% 2/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Psychiatric disorders Agitation	5.7% 2/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	3.2% 1/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	3.8% 3/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Nervous system disorders Akathisia	2.9% 1/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	6.5% 2/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Gastrointestinal disorders Constipation	2.9% 1/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	6.5% 2/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	3.8% 3/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Psychiatric disorders Depression	0.00% 0/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	6.5% 2/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Infections and infestations Ear infection	0.00% 0/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	6.5% 2/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	1.3% 1/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Renal and urinary disorders Enuresis	0.00% 0/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	6.7% 2/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	6.5% 2/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	5.1% 4/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	6.5% 2/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Nervous system disorders Headache	11.4% 4/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	6.7% 2/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	6.5% 2/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	5.1% 4/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Nervous system disorders Hypersomnia	2.9% 1/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	6.5% 2/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Metabolism and nutrition disorders Increased appetite	5.7% 2/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	16.7% 5/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	35.5% 11/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	11.4% 9/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Psychiatric disorders Insomnia	5.7% 2/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	3.8% 3/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Infections and infestations Nasopharyngitis	5.7% 2/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	6.7% 2/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	12.9% 4/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	6.3% 5/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Gastrointestinal disorders Nausea	2.9% 1/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	3.3% 1/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	6.5% 2/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Nervous system disorders Psychomotor hyperactivity	5.7% 2/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	3.3% 1/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	3.2% 1/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	1.3% 1/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
General disorders Pyrexia	0.00% 0/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	6.5% 2/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	7.6% 6/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Skin and subcutaneous tissue disorders Rash	0.00% 0/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	6.7% 2/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	3.8% 3/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Nervous system disorders Sedation	0.00% 0/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	3.3% 1/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	25.8% 8/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	7.6% 6/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Nervous system disorders Somnolence	2.9% 1/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	22.6% 7/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	5.1% 4/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
General disorders Thirst	0.00% 0/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	6.5% 2/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Infections and infestations Upper respiratory tract infection	2.9% 1/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	3.3% 1/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	9.7% 3/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	7.6% 6/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Gastrointestinal disorders Vomiting	5.7% 2/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	6.7% 2/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	6.5% 2/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	8.9% 7/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Investigations Weight increased	5.7% 2/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	10.0% 3/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	12.9% 4/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	8.9% 7/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	5.1% 4/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
Gastrointestinal disorders Diarrhea	2.9% 1/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	3.3% 1/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	5.1% 4/79 • Double-blind period: 6 weeks. Open-label period: 6 months.
General disorders Fatigue	0.00% 0/35 • Double-blind period: 6 weeks. Open-label period: 6 months.	0.00% 0/30 • Double-blind period: 6 weeks. Open-label period: 6 months.	3.2% 1/31 • Double-blind period: 6 weeks. Open-label period: 6 months.	5.1% 4/79 • Double-blind period: 6 weeks. Open-label period: 6 months.