Trial Outcomes & Findings for Comparison of Lisdexamfetamine Dimesylate With Atomoxetine HCl in Attention-Deficit/Hyperactivity Disorder (ADHD) Subjects With an Inadequate Response to Methylphenidate (NCT NCT01106430)

Last Updated: 2021-06-11

Results Overview

Time to first response was defined as a Clinical Global Impression-Improvement (CGI-I) value of 1 (very much improved) or 2 (much improved) first recorded following first dose of investigational product. CGI-I consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

267 participants

Primary outcome timeframe

9 weeks

Results posted on

2021-06-11

Participant Flow

Participant milestones

Participant milestones
Measure	Lisdexamfetamine Dimesylate Lisdexamfetamine Dimesylate (LDX, Vyvanse, SPD489) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at doses of either 30, 50, or 70 mg.	Atomoxetine Hydrochloride Atomoxetine Hydrochloride (Strattera) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at weight adjusted doses of 10 mg to 100 mg.
Overall Study STARTED	133	134
Overall Study COMPLETED	100	101
Overall Study NOT COMPLETED	33	33

Reasons for withdrawal

Reasons for withdrawal
Measure	Lisdexamfetamine Dimesylate Lisdexamfetamine Dimesylate (LDX, Vyvanse, SPD489) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at doses of either 30, 50, or 70 mg.	Atomoxetine Hydrochloride Atomoxetine Hydrochloride (Strattera) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at weight adjusted doses of 10 mg to 100 mg.
Overall Study Adverse Event	8	10
Overall Study Lack of Efficacy	2	13
Overall Study Lost to Follow-up	5	1
Overall Study Early Termination Requested By Sponsor	1	0
Overall Study Moved Out Of State	0	1
Overall Study Refused To Take Medication	0	1
Overall Study Noncompliance	0	1
Overall Study Hard Time Swallowing The Pills	1	0
Overall Study Previous Use Of Marijuana	1	0
Overall Study Protocol Violation	7	2
Overall Study Withdrawal by Subject	8	4

Baseline Characteristics

Comparison of Lisdexamfetamine Dimesylate With Atomoxetine HCl in Attention-Deficit/Hyperactivity Disorder (ADHD) Subjects With an Inadequate Response to Methylphenidate

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lisdexamfetamine Dimesylate n=128 Participants Lisdexamfetamine Dimesylate (LDX, Vyvanse, SPD489) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at doses of either 30, 50, or 70 mg.	Atomoxetine Hydrochloride n=134 Participants Atomoxetine Hydrochloride (Strattera) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at weight adjusted doses of 10 mg to 100 mg.	Total n=262 Participants Total of all reporting groups
Age, Customized 6 - 12 years	94 Participants n=5 Participants	100 Participants n=7 Participants	194 Participants n=5 Participants
Sex: Female, Male Female	34 Participants n=5 Participants	31 Participants n=7 Participants	65 Participants n=5 Participants
Sex: Female, Male Male	94 Participants n=5 Participants	103 Participants n=7 Participants	197 Participants n=5 Participants
Region of Enrollment BELGIUM	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Age, Continuous	10.9 Years STANDARD_DEVIATION 3.01 • n=5 Participants	10.4 Years STANDARD_DEVIATION 2.84 • n=7 Participants	10.6 Years STANDARD_DEVIATION 2.93 • n=5 Participants
Age, Customized 13 - 17 years	34 Participants n=5 Participants	34 Participants n=7 Participants	68 Participants n=5 Participants
Region of Enrollment CANADA	17 Participants n=5 Participants	18 Participants n=7 Participants	35 Participants n=5 Participants
Region of Enrollment GERMANY	20 Participants n=5 Participants	22 Participants n=7 Participants	42 Participants n=5 Participants
Region of Enrollment HUNGARY	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Region of Enrollment ITALY	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment POLAND	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment SPAIN	12 Participants n=5 Participants	10 Participants n=7 Participants	22 Participants n=5 Participants
Region of Enrollment SWEDEN	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment UNITED STATES	70 Participants n=5 Participants	68 Participants n=7 Participants	138 Participants n=5 Participants

PRIMARY outcome

Timeframe: 9 weeks

Population: Full Analysis Set defined as all subjects who were randomized and who had taken at least 1 dose of investigational product. One subject was randomized to receive Strattera, but actually received Lisdexamfetamine Dimesylate. For all efficacy analyses this subject is included in the Strattera arm per the intention to treat principle.

Outcome measures

Outcome measures
Measure	Lisdexamfetamine Dimesylate n=127 Participants Lisdexamfetamine Dimesylate (LDX, Vyvanse, SPD489) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at doses of either 30, 50, or 70 mg.	Atomoxetine Hydrochloride n=135 Participants Atomoxetine Hydrochloride (Strattera) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at weight adjusted doses of 10 mg to 100 mg.
Time to First Response	12.0 Days Interval 8.0 to 16.0	21.0 Days Interval 15.0 to 23.0

SECONDARY outcome

Timeframe: 9 weeks

Population: Full Analysis Set defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.

Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale.

Outcome measures

Outcome measures
Measure	Lisdexamfetamine Dimesylate n=126 Participants Lisdexamfetamine Dimesylate (LDX, Vyvanse, SPD489) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at doses of either 30, 50, or 70 mg.	Atomoxetine Hydrochloride n=132 Participants Atomoxetine Hydrochloride (Strattera) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at weight adjusted doses of 10 mg to 100 mg.
Percent of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores - Last Observation Carried Forward (LOCF)	81.7 percentage of participants	63.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline and 9 weeks

Population: Full Analysis Set defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.

ADHD-RS-IV consists of 18 items scored on a 4-point scale from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54. A decrease in score indicates an improvement in ADHD symptomology.

Outcome measures

Outcome measures
Measure	Lisdexamfetamine Dimesylate n=126 Participants Lisdexamfetamine Dimesylate (LDX, Vyvanse, SPD489) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at doses of either 30, 50, or 70 mg.	Atomoxetine Hydrochloride n=133 Participants Atomoxetine Hydrochloride (Strattera) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at weight adjusted doses of 10 mg to 100 mg.
Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-Fourth Edition (ADHD-RS-IV) Total Score at 9 Weeks - LOCF	-26.1 units on a scale Standard Error 1.16	-19.7 units on a scale Standard Error 1.13

SECONDARY outcome

Timeframe: Baseline and up to 9 weeks

Population: Full Analysis Set defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.

The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.

Outcome measures

Outcome measures
Measure	Lisdexamfetamine Dimesylate n=107 Participants Lisdexamfetamine Dimesylate (LDX, Vyvanse, SPD489) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at doses of either 30, 50, or 70 mg.	Atomoxetine Hydrochloride n=113 Participants Atomoxetine Hydrochloride (Strattera) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at weight adjusted doses of 10 mg to 100 mg.
Change From Baseline in the Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Up to 9 Weeks	-0.35 units on a scale Standard Error 0.034	-0.27 units on a scale Standard Error 0.032

SECONDARY outcome

Timeframe: up to 9 weeks

Population: Full Analysis Set defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.

HUI is used to describe health status and to obtain utility scores by collecting data using one or more questionnaires in formats selected to match the specific study design criteria. Scoring ranges from 0.00 (dead) to 1.00 (perfect health). Higher scores represent better health status.

Outcome measures

Outcome measures
Measure	Lisdexamfetamine Dimesylate n=116 Participants Lisdexamfetamine Dimesylate (LDX, Vyvanse, SPD489) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at doses of either 30, 50, or 70 mg.	Atomoxetine Hydrochloride n=123 Participants Atomoxetine Hydrochloride (Strattera) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at weight adjusted doses of 10 mg to 100 mg.
Health Utilities Index-2 (HUI-2) Scores at Up to 9 Weeks	0.920 units on a scale Standard Deviation 0.0961	0.922 units on a scale Standard Deviation 0.0937

SECONDARY outcome

Timeframe: Baseline and up to 9 weeks

Population: Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.

The BPRS-C characterizes psychopathology. A total of 21 items are rated on a scale from 0 (not present) to 6 (extremely severe) with a total score ranging from 0 to 126. A decrease in score indicates a reduction in psychopathology.

Outcome measures

Outcome measures
Measure	Lisdexamfetamine Dimesylate n=117 Participants Lisdexamfetamine Dimesylate (LDX, Vyvanse, SPD489) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at doses of either 30, 50, or 70 mg.	Atomoxetine Hydrochloride n=123 Participants Atomoxetine Hydrochloride (Strattera) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at weight adjusted doses of 10 mg to 100 mg.
Change From Baseline in Brief Psychiatric Rating Scale for Children (BPRS-C) Total Score at Up to 9 Weeks	-10.7 units on a scale Standard Deviation 9.27	-7.9 units on a scale Standard Deviation 9.07

SECONDARY outcome

Timeframe: 9 weeks

Population: Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.

C-SSRS is a semi-structured interview that captures the occurence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behaviour occurred. The assessment is done by the nature of the responses, not by a numbered scale.

Outcome measures

Outcome measures
Measure	Lisdexamfetamine Dimesylate n=127 Participants Lisdexamfetamine Dimesylate (LDX, Vyvanse, SPD489) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at doses of either 30, 50, or 70 mg.	Atomoxetine Hydrochloride n=132 Participants Atomoxetine Hydrochloride (Strattera) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at weight adjusted doses of 10 mg to 100 mg.
Columbia-Suicide Severity Rating Scale (C-SSRS) Suicidal ideation	0 participants	0 participants
Columbia-Suicide Severity Rating Scale (C-SSRS) Suicidal behavior	0 participants	0 participants

SECONDARY outcome

Timeframe: 9 weeks

Population: Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.

UKU-SERS-Clin is composed of 48 items each of which asks about a single side effect. Each side effect is rated based on a 4-point scale ranging from 0 (no or doubtful presence) to 3 (the least favorable rating). The rating is independent of whether the symptom is regarded as related to the investigational product.

Outcome measures

Outcome measures
Measure	Lisdexamfetamine Dimesylate n=127 Participants Lisdexamfetamine Dimesylate (LDX, Vyvanse, SPD489) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at doses of either 30, 50, or 70 mg.	Atomoxetine Hydrochloride n=132 Participants Atomoxetine Hydrochloride (Strattera) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at weight adjusted doses of 10 mg to 100 mg.
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Weight Loss	46 participants	19 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Reduced Duration of Sleep	29 participants	16 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Asthenia/Lassitude/Increased Fatigability	25 participants	29 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Tension/Inner Unrest	20 participants	22 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Nausea/Vomiting	19 participants	26 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Sleepiness/Sedation	16 participants	35 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Reduced Salivation	16 participants	6 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Headache-Tension Headache	15 participants	17 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Concentration Difficulties	75 participants	92 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Failing Memory	10 participants	21 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Depression	6 participants	10 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Increased Duration of Sleep	12 participants	12 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Increased Dream Activity	3 participants	8 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Emotional Indifference	12 participants	10 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Dystonia	0 participants	1 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Rigidity	0 participants	1 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Hypokinesia/Akinesia	1 participants	0 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Hyperkinesia Logic	2 participants	3 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Tremor	3 participants	1 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Akathisia	0 participants	2 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Paraesthesias	1 participants	0 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Accomodation Disturbances	0 participants	2 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Increased Salivation	1 participants	2 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Diarrhea	6 participants	9 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Constipation	9 participants	5 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Micturition Disturbances	0 participants	1 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Polyuria/Polydipsia	3 participants	2 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Orthostatic Dizziness	10 participants	9 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Palpitations/Tachycardia	1 participants	5 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Increased Tendency to Sweating	3 participants	5 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Rash-Morbiliform	0 participants	1 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Rash-Petechial	1 participants	0 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Rash-Urticarial	1 participants	1 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Rash-Cannot be Classified	1 participants	2 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Pruritus	4 participants	7 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Weight Gain	1 participants	0 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Headache-Migraine	2 participants	2 participants
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 Headache-Other Forms	11 participants	10 participants

Adverse Events

Lisdexamfetamine Dimesylate

Serious events: 0 serious events

Other events: 92 other events

Deaths: 0 deaths

Atomoxetine Hydrochloride

Serious events: 0 serious events

Other events: 95 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

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

Measure	Lisdexamfetamine Dimesylate n=128 participants at risk Lisdexamfetamine Dimesylate (LDX, Vyvanse, SPD489) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at doses of either 30, 50, or 70 mg.	Atomoxetine Hydrochloride n=134 participants at risk Atomoxetine Hydrochloride (Strattera) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at weight adjusted doses of 10 mg to 100 mg.
Gastrointestinal disorders ABDOMINAL PAIN	2.3% 3/128 • Number of events 3 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.	6.0% 8/134 • Number of events 10 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.
Gastrointestinal disorders ABDOMINAL PAIN UPPER	2.3% 3/128 • Number of events 3 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.	7.5% 10/134 • Number of events 12 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.
Gastrointestinal disorders CONSTIPATION	6.2% 8/128 • Number of events 9 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.	1.5% 2/134 • Number of events 2 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.
Gastrointestinal disorders DIARRHOEA	1.6% 2/128 • Number of events 3 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.	6.7% 9/134 • Number of events 11 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.
Gastrointestinal disorders DRY MOUTH	6.2% 8/128 • Number of events 8 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.	3.0% 4/134 • Number of events 4 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.
Gastrointestinal disorders NAUSEA	12.5% 16/128 • Number of events 16 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.	15.7% 21/134 • Number of events 27 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.
Gastrointestinal disorders VOMITING	4.7% 6/128 • Number of events 6 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.	9.7% 13/134 • Number of events 17 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.
General disorders FATIGUE	9.4% 12/128 • Number of events 14 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.	10.4% 14/134 • Number of events 16 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.
General disorders IRRITABILITY	6.2% 8/128 • Number of events 8 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.	2.2% 3/134 • Number of events 3 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.
Infections and infestations NASOPHARYNGITIS	6.2% 8/128 • Number of events 9 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.	6.0% 8/134 • Number of events 9 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	2.3% 3/128 • Number of events 3 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.	6.0% 8/134 • Number of events 8 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.
Investigations WEIGHT DECREASED	21.9% 28/128 • Number of events 30 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.	6.7% 9/134 • Number of events 9 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.
Metabolism and nutrition disorders DECREASED APPETITE	25.8% 33/128 • Number of events 36 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.	10.4% 14/134 • Number of events 14 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.
Nervous system disorders HEADACHE	13.3% 17/128 • Number of events 25 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.	16.4% 22/134 • Number of events 29 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.
Nervous system disorders SEDATION	3.9% 5/128 • Number of events 5 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.	6.0% 8/134 • Number of events 9 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.
Nervous system disorders SOMNOLENCE	3.1% 4/128 • Number of events 4 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.	11.9% 16/134 • Number of events 23 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.
Psychiatric disorders INSOMNIA	11.7% 15/128 • Number of events 16 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.	6.0% 8/134 • Number of events 8 Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.