Trial Outcomes & Findings for Effectiveness of Vyvanse Compared to Concerta in Adolescents With Attention-deficit/Hyperactivity Disorder (NCT NCT01552902)

Last Updated: 2021-06-10

Results Overview

The ADHD-RS-IV was developed to measure the behaviors of children with ADHD and is commonly used in clinical studies of ADHD. The ADHD-RS-IV consisted of 18 items designed to reflect current symptomatology of ADHD based on Diagnostic and Statistical Manual of Mental Disorders, 4th Edition-Text Revision (DSM-IV-TR) criteria. Each item was scored on a 4-point scale ranging from 0 (reflecting no symptoms) to 3 (reflecting severe symptoms) with total scores ranging from 0-54, Higher score = more severe symptoms.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

549 participants

Primary outcome timeframe

Baseline, Week 6

Results posted on

2021-06-10

Participant Flow

The study was conducted at 77 sites in the United States, Canada, and Europe.

Of the 778 screened participants, 229 were screen failures and 549 were randomized to treatment. A total of 547 participants were treated and the reasons for 2 'randomized but not treated' participants included withdrawal by 1 participant in the Methylphenidate group and 1 participant with a protocol violation in the Lisdexamfetamine group.

Participant milestones

Participant milestones
Measure	Placebo 2 placebo over encapsulated capsules once daily orally for 6 weeks.	Lisdexamfetamine Dimesylate Lisdexamfetamine dimesylate (LDX, Vyvanse®, SPD489) 30 to 70 milligram (mg) over encapsulated capsule once daily orally along with placebo over encapsulated capsule for 4 weeks (forced dose titration), followed by LDX 70 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule for 2 weeks (dose maintenance).	Methylphenidate Methylphenidate (Concerta, Osmotic controlled oral release delivery system-methylphenidate \[OROS-MPH\]) 18 to 72 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule (no placebo administered when methylphenidate 72 mg \[2\36 mg capsules\] was administered) for 4 weeks (forced dose titration), followed by methylphenidate 72 mg (2\36 mg capsules) over encapsulated capsule once daily orally for 2 weeks (dose maintenance).
Overall Study STARTED	110	218	219
Overall Study COMPLETED	97	181	186
Overall Study NOT COMPLETED	13	37	33

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo 2 placebo over encapsulated capsules once daily orally for 6 weeks.	Lisdexamfetamine Dimesylate Lisdexamfetamine dimesylate (LDX, Vyvanse®, SPD489) 30 to 70 milligram (mg) over encapsulated capsule once daily orally along with placebo over encapsulated capsule for 4 weeks (forced dose titration), followed by LDX 70 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule for 2 weeks (dose maintenance).	Methylphenidate Methylphenidate (Concerta, Osmotic controlled oral release delivery system-methylphenidate \[OROS-MPH\]) 18 to 72 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule (no placebo administered when methylphenidate 72 mg \[2\36 mg capsules\] was administered) for 4 weeks (forced dose titration), followed by methylphenidate 72 mg (2\36 mg capsules) over encapsulated capsule once daily orally for 2 weeks (dose maintenance).
Overall Study Adverse Event	1	15	14
Overall Study Protocol Violation	3	3	3
Overall Study Lack of Efficacy	4	3	1
Overall Study Withdrawal by Subject	1	9	6
Overall Study Lost to Follow-up	1	3	6
Overall Study Other	3	4	3

Baseline Characteristics

Effectiveness of Vyvanse Compared to Concerta in Adolescents With Attention-deficit/Hyperactivity Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=110 Participants 2 placebo over encapsulated capsules once daily orally for 6 weeks.	Lisdexamfetamine Dimesylate n=218 Participants Lisdexamfetamine dimesylate (LDX, Vyvanse®, SPD489) 30 to 70 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule for 4 weeks (forced dose titration), followed by LDX 70 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule for 2 weeks (dose maintenance).	Methylphenidate n=219 Participants Methylphenidate (Concerta, OROS-MPH) 18 to 72 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule (no placebo administered when methylphenidate 72 mg \[2\36 mg capsules\] was administered) for 4 weeks (forced dose titration), followed by methylphenidate 72 mg (2\36 mg capsules) over encapsulated capsule once daily orally for 2 weeks (dose maintenance).	Total n=547 Participants Total of all reporting groups
Age, Categorical <=18 years	110 Participants n=93 Participants	218 Participants n=4 Participants	219 Participants n=27 Participants	547 Participants n=483 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Continuous	14.7 years STANDARD_DEVIATION 1.37 • n=93 Participants	14.6 years STANDARD_DEVIATION 1.38 • n=4 Participants	14.7 years STANDARD_DEVIATION 1.42 • n=27 Participants	14.7 years STANDARD_DEVIATION 1.40 • n=483 Participants
Sex: Female, Male Female	34 Participants n=93 Participants	83 Participants n=4 Participants	69 Participants n=27 Participants	186 Participants n=483 Participants
Sex: Female, Male Male	76 Participants n=93 Participants	135 Participants n=4 Participants	150 Participants n=27 Participants	361 Participants n=483 Participants
Attention-deficit/Hyperactivity Disorder (ADHD) Subtype Predominantly Inattentive	40 Participants n=93 Participants	70 Participants n=4 Participants	71 Participants n=27 Participants	181 Participants n=483 Participants
Attention-deficit/Hyperactivity Disorder (ADHD) Subtype Predominantly Hyperactive/Impulsive	2 Participants n=93 Participants	2 Participants n=4 Participants	4 Participants n=27 Participants	8 Participants n=483 Participants
Attention-deficit/Hyperactivity Disorder (ADHD) Subtype Combined Subtype	68 Participants n=93 Participants	146 Participants n=4 Participants	144 Participants n=27 Participants	358 Participants n=483 Participants
Clinical Global Impressions - Severity of Illness (CGI-S) Borderline mentally ill	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants
Clinical Global Impressions - Severity of Illness (CGI-S) Mildly ill	2 Participants n=93 Participants	4 Participants n=4 Participants	1 Participants n=27 Participants	7 Participants n=483 Participants
Clinical Global Impressions - Severity of Illness (CGI-S) Moderately ill	60 Participants n=93 Participants	93 Participants n=4 Participants	115 Participants n=27 Participants	268 Participants n=483 Participants
Clinical Global Impressions - Severity of Illness (CGI-S) Markedly ill	41 Participants n=93 Participants	106 Participants n=4 Participants	90 Participants n=27 Participants	237 Participants n=483 Participants
Clinical Global Impressions - Severity of Illness (CGI-S) Severely ill	6 Participants n=93 Participants	15 Participants n=4 Participants	13 Participants n=27 Participants	34 Participants n=483 Participants
Attention-deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) Total Score	36.1 units on a scale STANDARD_DEVIATION 5.91 • n=93 Participants	37.2 units on a scale STANDARD_DEVIATION 6.46 • n=4 Participants	36.9 units on a scale STANDARD_DEVIATION 6.42 • n=27 Participants	36.9 units on a scale STANDARD_DEVIATION 6.34 • n=483 Participants

PRIMARY outcome

Timeframe: Baseline, Week 6

Population: Full Analysis Set (FAS) was defined as all participants in the Safety set who had at least 1 post-baseline measurement of the ADHD-RS-IV. Not all FAS participants were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants 2 placebo over encapsulated capsules once daily orally for 6 weeks.	Lisdexamfetamine Dimesylate n=175 Participants Lisdexamfetamine dimesylate (LDX, Vyvanse®, SPD489) 30 to 70 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule for 4 weeks (forced dose titration), followed by LDX 70 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule for 2 weeks (dose maintenance).	Methylphenidate n=181 Participants Methylphenidate (Concerta, OROS-MPH) 18 to 72 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule (no placebo administered when methylphenidate 72 mg \[2\36 mg capsules\] was administered) for 4 weeks (forced dose titration), followed by methylphenidate 72 mg (2\36 mg capsules) over encapsulated capsule once daily orally for 2 weeks (dose maintenance).
Change From Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale, Fourth Edition (ADHD-RS-IV) Total Score at Week 6	-17 units on a scale Standard Error 1.03	-25.4 units on a scale Standard Error 0.74	-22.1 units on a scale Standard Error 0.73

SECONDARY outcome

Timeframe: Week 6

Population: FAS.

The Clinical Global Impressions Scale permits a global evaluation of the participant's severity of illness and improvement over time. The scale included a severity of illness item and a global improvement item. The investigator performed the CGI-I to rate the improvement of a participant's ADHD symptoms based on a 7-point scale (1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; or 7=very much worse.). Percentage of participants with an improved measurement (response of very much improved and much improved) is reported.

Outcome measures

Outcome measures
Measure	Placebo n=106 Participants 2 placebo over encapsulated capsules once daily orally for 6 weeks.	Lisdexamfetamine Dimesylate n=210 Participants Lisdexamfetamine dimesylate (LDX, Vyvanse®, SPD489) 30 to 70 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule for 4 weeks (forced dose titration), followed by LDX 70 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule for 2 weeks (dose maintenance).	Methylphenidate n=216 Participants Methylphenidate (Concerta, OROS-MPH) 18 to 72 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule (no placebo administered when methylphenidate 72 mg \[2\36 mg capsules\] was administered) for 4 weeks (forced dose titration), followed by methylphenidate 72 mg (2\36 mg capsules) over encapsulated capsule once daily orally for 2 weeks (dose maintenance).
Percentage of Participants With an Improvement on Clinical Global Impression - Global Improvement (CGI-I) at Week 6	50 percentage of participants	81.4 percentage of participants	71.3 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 3 days after last dose (last dose at Week 6)

Population: Safety set.

An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered as a pharmaceutical product that did not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were events between first dose of double-blind investigational product and up to 3 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

Outcome measures

Outcome measures
Measure	Placebo n=110 Participants 2 placebo over encapsulated capsules once daily orally for 6 weeks.	Lisdexamfetamine Dimesylate n=218 Participants Lisdexamfetamine dimesylate (LDX, Vyvanse®, SPD489) 30 to 70 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule for 4 weeks (forced dose titration), followed by LDX 70 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule for 2 weeks (dose maintenance).	Methylphenidate n=219 Participants Methylphenidate (Concerta, OROS-MPH) 18 to 72 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule (no placebo administered when methylphenidate 72 mg \[2\36 mg capsules\] was administered) for 4 weeks (forced dose titration), followed by methylphenidate 72 mg (2\36 mg capsules) over encapsulated capsule once daily orally for 2 weeks (dose maintenance).
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Participants with TEAEs	49 participants	145 participants	129 participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Participants with serious TEAEs	1 participants	1 participants	1 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 6

Population: Safety set. Not all Safety set participants were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants 2 placebo over encapsulated capsules once daily orally for 6 weeks.	Lisdexamfetamine Dimesylate n=175 Participants Lisdexamfetamine dimesylate (LDX, Vyvanse®, SPD489) 30 to 70 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule for 4 weeks (forced dose titration), followed by LDX 70 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule for 2 weeks (dose maintenance).	Methylphenidate n=181 Participants Methylphenidate (Concerta, OROS-MPH) 18 to 72 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule (no placebo administered when methylphenidate 72 mg \[2\36 mg capsules\] was administered) for 4 weeks (forced dose titration), followed by methylphenidate 72 mg (2\36 mg capsules) over encapsulated capsule once daily orally for 2 weeks (dose maintenance).
Change From Baseline in Blood Pressure at Week 6 Systolic blood pressure	-1 millimeter of mercury (mmHg) Standard Deviation 9.88	1.5 millimeter of mercury (mmHg) Standard Deviation 9.56	2.4 millimeter of mercury (mmHg) Standard Deviation 9.97
Change From Baseline in Blood Pressure at Week 6 Diastolic blood pressure	-0.1 millimeter of mercury (mmHg) Standard Deviation 8.1	3.4 millimeter of mercury (mmHg) Standard Deviation 8.15	3.5 millimeter of mercury (mmHg) Standard Deviation 8.59

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 6

Population: Safety set. Not all Safety set participants were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants 2 placebo over encapsulated capsules once daily orally for 6 weeks.	Lisdexamfetamine Dimesylate n=175 Participants Lisdexamfetamine dimesylate (LDX, Vyvanse®, SPD489) 30 to 70 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule for 4 weeks (forced dose titration), followed by LDX 70 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule for 2 weeks (dose maintenance).	Methylphenidate n=181 Participants Methylphenidate (Concerta, OROS-MPH) 18 to 72 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule (no placebo administered when methylphenidate 72 mg \[2\36 mg capsules\] was administered) for 4 weeks (forced dose titration), followed by methylphenidate 72 mg (2\36 mg capsules) over encapsulated capsule once daily orally for 2 weeks (dose maintenance).
Change From Baseline in Pulse Rate at Week 6	2.4 Beats per minute Standard Deviation 10.81	6.7 Beats per minute Standard Deviation 12.46	8.2 Beats per minute Standard Deviation 12.7

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 32 other events

Deaths: 0 deaths

Lisdexamfetamine Dimesylate

Serious events: 1 serious events

Other events: 113 other events

Deaths: 0 deaths

Methylphenidate

Serious events: 1 serious events

Other events: 99 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=110 participants at risk 2 placebo over encapsulated capsules once daily orally for 6 weeks.	Lisdexamfetamine Dimesylate n=218 participants at risk Lisdexamfetamine dimesylate (LDX, Vyvanse®, SPD489) 30 to 70 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule for 4 weeks (forced dose titration), followed by LDX 70 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule for 2 weeks (dose maintenance).	Methylphenidate n=219 participants at risk Methylphenidate (Concerta, OROS-MPH) 18 to 72 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule (no placebo administered when methylphenidate 72 mg \[2\36 mg capsules\] was administered) for 4 weeks (forced dose titration), followed by methylphenidate 72 mg (2\36 mg capsules) over encapsulated capsule once daily orally for 2 weeks (dose maintenance).
Psychiatric disorders Suicidal ideation	0.00% 0/110 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.	0.46% 1/218 • Number of events 1 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.	0.00% 0/219 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.
Psychiatric disorders Psychotic episode	0.91% 1/110 • Number of events 1 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.	0.00% 0/218 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.	0.00% 0/219 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.
Infections and infestations Appendicitis	0.00% 0/110 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.	0.00% 0/218 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.	0.46% 1/219 • Number of events 1 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.

Other adverse events

Other adverse events
Measure	Placebo n=110 participants at risk 2 placebo over encapsulated capsules once daily orally for 6 weeks.	Lisdexamfetamine Dimesylate n=218 participants at risk Lisdexamfetamine dimesylate (LDX, Vyvanse®, SPD489) 30 to 70 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule for 4 weeks (forced dose titration), followed by LDX 70 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule for 2 weeks (dose maintenance).	Methylphenidate n=219 participants at risk Methylphenidate (Concerta, OROS-MPH) 18 to 72 mg over encapsulated capsule once daily orally along with placebo over encapsulated capsule (no placebo administered when methylphenidate 72 mg \[2\36 mg capsules\] was administered) for 4 weeks (forced dose titration), followed by methylphenidate 72 mg (2\36 mg capsules) over encapsulated capsule once daily orally for 2 weeks (dose maintenance).
Investigations Weight decreased	0.00% 0/110 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.	10.6% 23/218 • Number of events 23 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.	5.0% 11/219 • Number of events 11 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.
Nervous system disorders Headache	8.2% 9/110 • Number of events 13 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.	15.1% 33/218 • Number of events 45 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.	16.0% 35/219 • Number of events 40 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.
Nervous system disorders Dizziness	0.00% 0/110 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.	5.5% 12/218 • Number of events 12 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.	5.0% 11/219 • Number of events 11 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.
General disorders Irritability	6.4% 7/110 • Number of events 7 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.	5.0% 11/218 • Number of events 11 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.	6.8% 15/219 • Number of events 16 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.
Gastrointestinal disorders Dry mouth	0.91% 1/110 • Number of events 1 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.	7.3% 16/218 • Number of events 18 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.	3.2% 7/219 • Number of events 7 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.
Gastrointestinal disorders Nausea	2.7% 3/110 • Number of events 3 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.	5.0% 11/218 • Number of events 12 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.	5.0% 11/219 • Number of events 11 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.
Gastrointestinal disorders Abdominal pain upper	1.8% 2/110 • Number of events 2 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.	5.0% 11/218 • Number of events 11 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.	3.7% 8/219 • Number of events 8 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.
Psychiatric disorders Insomnia	2.7% 3/110 • Number of events 3 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.	7.8% 17/218 • Number of events 17 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.	7.8% 17/219 • Number of events 20 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.
Metabolism and nutrition disorders Decreased appetite	10.0% 11/110 • Number of events 11 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.	31.7% 69/218 • Number of events 74 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.	23.3% 51/219 • Number of events 52 • Baseline up to 3 days after last dose (last dose at Week 6) AEs occurred during the double-blind evaluation phase were considered as TEAEs if AEs had a start date on or after the first dose of double-blind study drug or a start date before the date of the first dose of double-blind study drug, but increased in severity on or after the date of the first dose of double-blind study drug. Safety Set.

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Publication restrictions are in place

Restriction type: OTHER