Trial Outcomes & Findings for A Study of Pediatric Patients With Attention Deficit/Hyperactivity Disorder (NCT NCT00922636)

Results Overview

Assesses 18 Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision ADHD diagnosis symptoms/severity in past week. Each item: 0 (none/never, rarely) to 3 (severe/very often). Total score ranges from 0 to 54. Higher total scores indicate greater illness severity. Change scores=Week 8 score-baseline score. Least Squares (LS) Mean Change adjusted for fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline score and baseline score\*visit interaction.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

340 participants

Primary outcome timeframe

Baseline, 8 weeks

Results posted on

2014-08-18

Participant Flow

Treatment phase: Participants were randomized to: 1 of 3 fixed-dose LY2216684 treatment arms, placebo, or extended-release methylphenidate (stimulant-naive stratum) 1 of 3 fixed-dose LY2216684 treatment arms or placebo only (stimulant-prior stratum) Optional Taper phase: Participants received study drug (at reduced dose) or placebo for 2 weeks

Participant milestones

Participant milestones
Measure	Methylphenidate Participants were given 18 milligrams per day (mg/day) to 54 mg/day of extended-release methylphenidate capsules, based on weight, once daily (QD) and orally (po) for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo tablets to maintain LY2216684 blinding during the double-blind treatment phase.	Placebo Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Overall Study STARTED	36	78	76	75	75
Overall Study Entered Optional Taper Phase	4	10	15	7	12
Overall Study COMPLETED	29	62	56	58	59
Overall Study NOT COMPLETED	7	16	20	17	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Methylphenidate Participants were given 18 milligrams per day (mg/day) to 54 mg/day of extended-release methylphenidate capsules, based on weight, once daily (QD) and orally (po) for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo tablets to maintain LY2216684 blinding during the double-blind treatment phase.	Placebo Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Overall Study Adverse Event	3	3	2	3	2
Overall Study Lack of Efficacy	1	7	3	2	4
Overall Study Sponsor Decision	0	0	2	0	0
Overall Study Withdrawal by Subject	0	0	5	2	4
Overall Study Protocol Violation	0	0	2	2	0
Overall Study Entry Criteria Not Met	0	0	1	1	0
Overall Study Parent/Caregiver Decision	2	4	3	5	2
Overall Study Lost to Follow-up	1	2	2	2	4

Baseline Characteristics

A Study of Pediatric Patients With Attention Deficit/Hyperactivity Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Methylphenidate n=36 Participants Participants were given 18 milligrams per day (mg/day) to 54 mg/day of extended-release methylphenidate capsules, based on weight, once daily (QD) and orally (po) for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo tablets to maintain LY2216684 blinding during the double-blind treatment phase.	Placebo n=78 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) n=76 Participants Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) n=75 Participants Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) n=75 Participants Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	Total n=340 Participants Total of all reporting groups
Age, Continuous	9.92 years STANDARD_DEVIATION 2.94 • n=5 Participants	11.37 years STANDARD_DEVIATION 3.07 • n=7 Participants	11.90 years STANDARD_DEVIATION 3.03 • n=5 Participants	12.59 years STANDARD_DEVIATION 2.81 • n=4 Participants	11.47 years STANDARD_DEVIATION 3.10 • n=21 Participants	11.63 years STANDARD_DEVIATION 3.07 • n=10 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	25 Participants n=7 Participants	24 Participants n=5 Participants	22 Participants n=4 Participants	20 Participants n=21 Participants	100 Participants n=10 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	53 Participants n=7 Participants	52 Participants n=5 Participants	53 Participants n=4 Participants	55 Participants n=21 Participants	240 Participants n=10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants	20 Participants n=7 Participants	21 Participants n=5 Participants	20 Participants n=4 Participants	19 Participants n=21 Participants	89 Participants n=10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	27 Participants n=5 Participants	58 Participants n=7 Participants	55 Participants n=5 Participants	55 Participants n=4 Participants	56 Participants n=21 Participants	251 Participants n=10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	4 Participants n=10 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	3 Participants n=4 Participants	5 Participants n=21 Participants	17 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants	8 Participants n=7 Participants	9 Participants n=5 Participants	10 Participants n=4 Participants	12 Participants n=21 Participants	45 Participants n=10 Participants
Race (NIH/OMB) White	25 Participants n=5 Participants	60 Participants n=7 Participants	55 Participants n=5 Participants	57 Participants n=4 Participants	50 Participants n=21 Participants	247 Participants n=10 Participants
Race (NIH/OMB) More than one race	5 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	4 Participants n=4 Participants	7 Participants n=21 Participants	27 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Region of Enrollment Canada	1 participants n=5 Participants	4 participants n=7 Participants	4 participants n=5 Participants	5 participants n=4 Participants	4 participants n=21 Participants	18 participants n=10 Participants
Region of Enrollment Mexico	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants	2 participants n=10 Participants
Region of Enrollment Puerto Rico	2 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants	2 participants n=4 Participants	3 participants n=21 Participants	14 participants n=10 Participants
Region of Enrollment Taiwan	0 participants n=5 Participants	4 participants n=7 Participants	5 participants n=5 Participants	3 participants n=4 Participants	4 participants n=21 Participants	16 participants n=10 Participants
Region of Enrollment United States	33 participants n=5 Participants	67 participants n=7 Participants	62 participants n=5 Participants	65 participants n=4 Participants	63 participants n=21 Participants	290 participants n=10 Participants

PRIMARY outcome

Timeframe: Baseline, 8 weeks

Population: Per protocol (PP) population included all randomized participants with a baseline and at least 1 post-baseline result, excluding data from participants whose data might have been compromised.

Assesses 18 Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision ADHD diagnosis symptoms/severity in past week. Each item: 0 (none/never, rarely) to 3 (severe/very often). Total score ranges from 0 to 54. Higher total scores indicate greater illness severity. Change scores=Week 8 score-baseline score. Least Squares (LS) Mean Change adjusted for fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) n=58 Participants Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) n=60 Participants Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) n=59 Participants Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator-Administered and Scored (ADHD-RS-IV-PV:IR) Total Score at Week 8	-10.35 units on a scale Standard Error 1.52	-12.20 units on a scale Standard Error 1.63	-16.09 units on a scale Standard Error 1.53	-16.39 units on a scale Standard Error 1.57

PRIMARY outcome

Timeframe: Baseline, 8 weeks

Population: Stimulant naive participants randomized to methylphenidate with a baseline and at least 1 post-baseline result but excluded the participants whose data may have been compromised.

Assesses 18 Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision ADHD diagnosis symptoms/severity in past week. Each item: 0 (none/never, rarely) to 3 (severe/very often). Total score ranges from 0 to 54. Higher total scores indicate greater illness severity. Change scores=Week 8 score-baseline score. LS Mean Change adjusted for fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=26 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator-Administered and Scored (ADHD-RS-IV-PV:IR) Total Score at Week 8 in Stimulant Naive Methylphenidate Group	-19.46 units on a scale Standard Error 2.50	—	—	—

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Per protocol (PP) participant population included all randomized participants with a baseline and at least 1 post-baseline result, excluding data from participants whose data may have been compromised.

Includes Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision ADHD criteria for inattention (items 1-9) and hyperactivity/impulsivity (items 11-19) symptom subsets. Item score: 0 (not at all) to 3 (very much) rating scale. Total score is average of 18 items. Higher total scores=greater ADHD symptoms. Least Squares Mean change is adjusted for fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and the continuous, fixed effects of baseline score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) n=9 Participants Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) n=7 Participants Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) n=10 Participants Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Swanson, Nolan and Pelham Questionnaire: Attention-Deficit/Hyperactivity Disorder Subscale (SNAP-IV: ADHD) Total Score at Week 8	0.10 units on a scale Standard Error 0.25	0.35 units on a scale Standard Error 0.26	-0.21 units on a scale Standard Error 0.24	-0.46 units on a scale Standard Error 0.20

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Stimulant naive participants randomized to methylphenidate with a baseline and at least 1 post-baseline result but excluded the participants whose data may have been compromised.

Includes Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision ADHD criteria for inattention (items 1-9) and hyperactivity/impulsivity (items 11-19) symptom subsets. Item score: 0 (not at all) to 3 (very much) rating scale. Total score is average of 18 items. Higher total scores=greater ADHD symptoms. Least Squares Mean change is adjusted for fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and the continuous, fixed effects of baseline score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=3 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Swanson, Nolan and Pelham Questionnaire: Attention-Deficit/Hyperactivity Disorder Subscale (SNAP-IV: ADHD) Total Score at Week 8 in Stimulant Naive Methylphenidate Group	NA units on a scale Standard Error NA Sample size not able to be analyzed.	—	—	—

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Per protocol (PP) population included all randomized participants with a baseline and at least 1 post-baseline result, excluding data from participants whose data may have been compromised.

The CP-CBRS academic difficulties total/language/math subscale score is a measure of academic performance. Each subscale item score ranges from 0 (never, seldom) to 3 (very often, very frequently). Total score is expressed as T-score based on gender/age norms. Academic difficulties T-score range: 0-100. Higher T-scores denote greater academic difficulties. Change scores=Week 8 score-baseline score. Least Squares Mean Change is from a restricted maximum likelihood-based, mixed model repeated measure (MMRM) analysis adjusted for fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline total score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) n=52 Participants Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) n=58 Participants Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) n=57 Participants Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Academic Difficulties Total Score and the Language and Math Subscales at Week 8 Total Score	-6.09 T-Score Standard Error 1.43	-6.13 T-Score Standard Error 1.53	-5.93 T-Score Standard Error 1.46	-12.53 T-Score Standard Error 1.49
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Academic Difficulties Total Score and the Language and Math Subscales at Week 8 Language Subscale Score	-5.87 T-Score Standard Error 1.43	-6.75 T-Score Standard Error 1.54	-6.07 T-Score Standard Error 1.45	-12.5 T-Score Standard Error 1.49
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Academic Difficulties Total Score and the Language and Math Subscales at Week 8 Math Subscales Score	-4.63 T-Score Standard Error 1.67	-3.8 T-Score Standard Error 1.79	-2.85 T-Score Standard Error 1.7	-7.78 T-Score Standard Error 1.74

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Stimulant naive participants randomized to methylphenidate with a baseline and at least 1 post-baseline result but excluded the participants whose data may have been compromised.

The CP-CBRS academic difficulties total/language/math subscale score is a measure of academic performance. Each subscale item score ranges from 0 (never, seldom) to 3 (very often, very frequently). Total score is expressed as T-score based on gender/age norms. Academic difficulties T-score range: 0-100. Higher T-scores denote greater academic difficulties. Change scores=Week 8 score-baseline score. Least Squares Mean Change is adjusted for fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline total score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Academic Difficulties Total Score and the Language and Math Subscales at Week 8 in Stimulant Naive Methylphenidate Group Total Score	-12.14 T-Score Standard Error 2.30	—	—	—
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Academic Difficulties Total Score and the Language and Math Subscales at Week 8 in Stimulant Naive Methylphenidate Group Language Subscale Score	-12.24 T-Score Standard Error 2.32	—	—	—
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Academic Difficulties Total Score and the Language and Math Subscales at Week 8 in Stimulant Naive Methylphenidate Group Math Subscales Score	-7.11 T-Score Standard Error 2.68	—	—	—

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Per protocol (PP) population included all randomized participants with a baseline and at least 1 post-baseline result, excluding data from participants whose data may have been compromised.

Measures participant's overall ADHD symptom severity. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Higher scores represent greater illness severity. Change scores=Week 8 score-baseline score. The Least Squares (LS) Mean Change was based on the fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, as well as the continuous, fixed effects of baseline CGI-S score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=62 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) n=59 Participants Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) n=60 Participants Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) n=59 Participants Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Severity Scale (CGI-ADHD-S) Total Score at Week 8	-1.07 units on a scale Standard Error 0.15	-0.96 units on a scale Standard Error 0.16	-1.52 units on a scale Standard Error 0.15	-1.41 units on a scale Standard Error 0.16

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Stimulant naive participants randomized to methylphenidate with a baseline and at least 1 post-baseline result but excluded the participants whose data may have been compromised.

Measures participant's overall ADHD symptom severity. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Higher scores represent greater illness severity. Change scores=Week 8 score-baseline score. The Least Squares (LS) Mean Change was based on the fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, as well as the continuous, fixed effects of baseline CGI-S score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=26 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Severity Scale (CGI-ADHD-S) Total Score at Week 8 in Stimulant Naive Methylphenidate Group	-1.69 units on a scale Standard Error 0.25	—	—	—

SECONDARY outcome

Timeframe: Weeks 1 through 8

Population: Per protocol (PP) population included all randomized participants with a post-baseline result, excluding data from participants whose data may have been compromised.

Measures total improvement (or worsening) of a participant's ADHD symptoms from the beginning of treatment. Scores range from 1 (very much improved) to 7 (very much worsened). Lower scores represent greater improvement. Least Squares (LS) Mean Change for weeks 1-8 is from a restricted maximum likelihood-based, mixed model repeated measure analysis. The model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) n=59 Participants Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) n=60 Participants Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) n=59 Participants Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Improvement Scale (CGI-ADHD-I) Endpoint Score During the Treatment Phase (Weeks 1-8)	3.05 units on a scale Standard Error 0.14	3.01 units on a scale Standard Error 0.15	2.54 units on a scale Standard Error 0.14	2.53 units on a scale Standard Error 0.15

SECONDARY outcome

Timeframe: Weeks 1 through 8

Population: Stimulant naive participants randomized to methylphenidate with a baseline and at least 1 post-baseline result but excluded the participants whose data may have been compromised.

Measures total improvement (or worsening) of a participant's ADHD symptoms from the beginning of treatment. Scores range from 1 (very much improved) to 7 (very much worsened). Lower scores represent greater improvement. Least Squares (LS) Mean Change for weeks 1-8 is from a restricted maximum likelihood-based, mixed model repeated measure analysis. The model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=26 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Improvement Scale (CGI-ADHD-I) Endpoint Score During the Treatment Phase (Weeks 1-8) in Stimulant Naive Methylphenidate Group	2.31 Total Score Standard Error 0.23	—	—	—

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Per protocol (PP) population included all randomized participants with a baseline and at least 1 post-baseline result, excluding data from participants whose data may have been compromised.

Measures ADHD symptom severity. Individual items on each subscale are scored from 0 (never) to 3 (very often). Total score expressed as T-score based on gender/age norms. Subscale total T-scores (0-100); higher T-scores=greater symptom severity. Least Squares Mean Change is from restricted maximum likelihood-based, mixed model repeated measure analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline total score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) n=52 Participants Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) n=58 Participants Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) n=57 Participants Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR ADHD) Predominantly Hyperactive-Impulsive Type and Predominantly Inattentive Type Total Score and Symptom Scores at Week 8 Predominantly Hyperactive-Impulsive Type Total	-8.70 T-Score Standard Error 1.71	-6.30 T-Score Standard Error 1.84	-12.94 T-Score Standard Error 1.75	-15.69 T-Score Standard Error 1.78
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR ADHD) Predominantly Hyperactive-Impulsive Type and Predominantly Inattentive Type Total Score and Symptom Scores at Week 8 Predominantly Inattentive Type Total Scale	-10.71 T-Score Standard Error 1.62	-8.32 T-Score Standard Error 1.74	-10.99 T-Score Standard Error 1.66	-16.99 T-Score Standard Error 1.69

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Stimulant naive participants randomized to methylphenidate with a baseline and at least 1 post-baseline result but excluded the participants whose data may have been compromised.

Measures ADHD symptom severity. Individual items on each subscale are scored from 0 (never) to 3 (very often). Total score expressed as T-score based on gender/age norms. Subscale total T-scores (0-100); higher T-scores=greater symptom severity. Least Squares Mean Change is from restricted maximum likelihood-based, mixed model repeated measure analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline total score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the CP-CBRS DSM-IV-TR ADHD Predominantly Hyperactive-Impulsive Type and Predominantly Inattentive Type Total Score and Symptom Scores at Week 8 in Stimulant Naive Methylphenidate Group Predominantly Hyperactive-Impulsive Type Total	-12.41 T-Score Standard Error 2.64	—	—	—
Change From Baseline in the CP-CBRS DSM-IV-TR ADHD Predominantly Hyperactive-Impulsive Type and Predominantly Inattentive Type Total Score and Symptom Scores at Week 8 in Stimulant Naive Methylphenidate Group Predominantly Inattentive Type Total Scale	-18.28 T-Score Standard Error 2.63	—	—	—

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Per protocol (PP) population included all randomized participants with a baseline and at least 1 post-baseline result, excluding data from participants whose data may have been compromised.

Measures oppositional defiance disorder symptoms. Total scores range from 0 (not at all) to 3 (very much). Higher total scores represent greater ODD. Change scores=Week 8 score-baseline score. Least Squares Mean Change is from a restricted maximum likelihood-based, mixed model repeated measure (MMRM) analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline total score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) n=9 Participants Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) n=7 Participants Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) n=11 Participants Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Swanson, Nolan and Pelham (SNAP-IV) Oppositional Defiant Disorder (ODD) Total Score at Week 8	0.19 units on a scale Standard Error 0.16	0.62 units on a scale Standard Error 0.18	-0.04 units on a scale Standard Error 0.17	-0.30 units on a scale Standard Error 0.13

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Stimulant naive participants randomized to methylphenidate with a baseline and at least 1 post-baseline result but excluded the participants whose data may have been compromised.

Measures oppositional defiance disorder symptoms. Total scores range from 0 (not at all) to 3 (very much). Higher total scores represent greater ODD. Change scores=Week 8 score-baseline score. Least Squares Mean Change is from a restricted maximum likelihood-based, mixed model repeated measure (MMRM) analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline total score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=3 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Swanson, Nolan and Pelham (SNAP-IV) Oppositional Defiant Disorder (ODD) Total Score at Week 8 in Stimulant Naive Methylphenidate Group	-0.72 units on a scale Standard Error 0.38	—	—	—

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Per protocol (PP) population included all randomized participants with a baseline and at least 1 post-baseline result, excluding data from participants whose data may have been compromised.

Rates schoolwork/grades, friendships/relationships, home life functioning (0=never to 3=very often). Total score expressed as a T-score based on gender/age norms (range 0-100). Higher T-score=greater symptom severity. Change scores=Week 8 score-baseline score. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis; included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) n=52 Participants Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) n=58 Participants Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) n=57 Participants Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Impairment Items Subscales-Total Score at Week 8 Schoolwork/Grades Score	-0.49 T-Score Standard Error 0.12	-0.35 T-Score Standard Error 0.13	-0.53 T-Score Standard Error 0.12	-0.81 T-Score Standard Error 0.13
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Impairment Items Subscales-Total Score at Week 8 Friendships/Relationships Score	-0.43 T-Score Standard Error 0.12	-0.00 T-Score Standard Error 0.13	-0.22 T-Score Standard Error 0.12	-0.65 T-Score Standard Error 0.13
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Impairment Items Subscales-Total Score at Week 8 Home Life Score	-0.40 T-Score Standard Error 0.12	-0.08 T-Score Standard Error 0.13	-0.44 T-Score Standard Error 0.13	-0.73 T-Score Standard Error 0.13

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Stimulant naive participants randomized to methylphenidate with a baseline and at least 1 post-baseline result but excluded the participants whose data may have been compromised.

Rates schoolwork/grades, friendships/relationships, home life functioning (0=never to 3=very often). Total score expressed as a T-score based on gender/age norms (range 0-100). Higher T-score=greater symptom severity. Change scores=Week 8 score-baseline score. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis; included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Impairment Items Subscales-Total Score at Week 8 in Stimulant Naive Methylphenidate Group Schoolwork/Grades Score	-0.65 T-Score Standard Error 0.19	—	—	—
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Impairment Items Subscales-Total Score at Week 8 in Stimulant Naive Methylphenidate Group Friendships/Relationships Score	-0.28 T-Score Standard Error 0.20	—	—	—
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Impairment Items Subscales-Total Score at Week 8 in Stimulant Naive Methylphenidate Group Home Life Score	-0.44 T-Score Standard Error 0.21	—	—	—

SECONDARY outcome

Timeframe: 8 weeks

Population: Intent to treat (ITT). All randomized participants with a baseline and at least 1 post-baseline C-SSRS assessment.

Captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Number of participants with suicidal behaviors, ideations, and acts are provided. Suicidal behavior: a "yes" answer to any of 3 suicidal behavior questions: preparatory acts or behavior, aborted attempt, and interrupted attempt. Suicidal ideation: "yes" answer to any one of 5 suicidal ideation questions, which includes wish to be dead, and 4 different categories of active suicidal ideation. Suicidal act: a "yes" answer to actual attempt or completed suicide, nonfatal suicide attempt, and completed suicide.

Outcome measures

Outcome measures
Measure	Placebo n=78 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) n=75 Participants Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) n=73 Participants Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) n=73 Participants Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 8 Suicidal Ideation	1 Participants	1 Participants	5 Participants	2 Participants
Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 8 Suicidal Behavior	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 8 Suicidal Acts	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 8 weeks

Population: Stimulant naive participants randomized to methylphenidate with a baseline and at least 1 post-baseline result but excluded the participants whose data may have been compromised.

Captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Number of participants with suicidal behaviors, ideations, and acts are provided. Suicidal behavior: a "yes" answer to any of 3 suicidal behavior questions: preparatory acts or behavior, aborted attempt, and interrupted attempt. Suicidal ideation: "yes" answer to any one of 5 suicidal ideation questions, which includes wish to be dead, and 4 different categories of active suicidal ideation. Suicidal act: a "yes" answer to actual attempt or completed suicide, nonfatal suicide attempt, and completed suicide.

Outcome measures

Outcome measures
Measure	Placebo n=35 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 8 in Stimulant Naive Methylphenidate Group Suicidal Ideation	1 Participants	—	—	—
Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 8 in Stimulant Naive Methylphenidate Group Suicidal Behavior	0 Participants	—	—	—
Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 8 in Stimulant Naive Methylphenidate Group Suicidal Acts	0 Participants	—	—	—

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Per protocol (PP) population included all randomized participants with a baseline and at least 1 post-baseline result, excluding data from participants whose data may have been compromised.

Measures manic symptom severity. Individual subscale items range: 0 (never) to 3 (very often). Total score expressed as T-score based on gender/age norms (0-100). Higher T-scores=greater symptom severity. Change scores=Week 8 score-baseline score. Least Squares Mean Change is from a restricted maximum likelihood-based, mixed model repeated measure analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) n=52 Participants Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) n=58 Participants Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) n=56 Participants Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Symptom Subscale for Manic Episode - Total Score at Week 8	-9.35 T-Score Standard Error 1.74	-5.00 T-Score Standard Error 1.88	-12.60 T-Score Standard Error 1.79	-12.41 T-Score Standard Error 1.85

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Stimulant naive participants randomized to methylphenidate with a baseline and at least 1 post-baseline result but excluded the participants whose data may have been compromised.

Measures manic symptom severity. Individual subscale items range: 0 (never) to 3 (very often). Total score expressed as T-score based on gender/age norms (0-100). Higher T-scores=greater symptom severity. Change scores=Week 8 score-baseline score. Least Squares Mean Change is from a restricted maximum likelihood-based, mixed model repeated measure analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Symptom Subscale for Manic Episode - Total Score at 8 Weeks in Stimulant Naive Methylphenidate Group	-11.85 T-Score Standard Error 2.76	—	—	—

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Per protocol (PP) population included all randomized participants with a baseline and at least 1 post-baseline result, excluding data from participants whose data may have been compromised.

Assess aggressive behaviors, academic difficulties, social problems, violence potential. Individual subscale items range: 0=never to 3=very often. Total expressed as T-score based on gender/age norms (0-100). Change scores=Week 8 score-baseline score. Least Squares (LS) Mean Change from restricted maximum likelihood-based, mixed model repeated measure (MMRM) analysis; included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline score, baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) n=52 Participants Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) n=58 Participants Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) n=57 Participants Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Content Subscales - Total Score at Week 8 Social Problems T-score	-6.77 T-Score Standard Error 1.52	-3.33 T-Score Standard Error 1.63	-5.19 T-Score Standard Error 1.55	-12.06 T-Score Standard Error 1.58
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Content Subscales - Total Score at Week 8 Aggressive Behaviors Scale Score	-5.52 T-Score Standard Error 1.55	-3.32 T-Score Standard Error 1.68	-8.09 T-Score Standard Error 1.59	-11.01 T-Score Standard Error 1.62
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Content Subscales - Total Score at Week 8 Violence Potential T-score	-6.97 T-Score Standard Error 1.36	-4.22 T-Score Standard Error 1.46	-7.95 T-Score Standard Error 1.39	-11.88 T-Score Standard Error 1.42

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Stimulant naive participants randomized to methylphenidate with a baseline and at least 1 post-baseline result but excluded the participants whose data may have been compromised.

Assess aggressive behaviors, academic difficulties, social problems, violence potential. Individual subscale items range: 0=never to 3=very often. Total expressed as T-score based on gender/age norms (0-100). Change scores=Week 8 score-baseline score. Least Squares (LS) Mean Change from restricted maximum likelihood-based, mixed model repeated measure (MMRM) analysis; included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline score, baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Content Subscales - Total Score at Week 8 in Stimulant Naive Methylphenidate Group Aggressive Behaviors Scale Score	-10.96 T-Score Standard Error 2.43	—	—	—
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Content Subscales - Total Score at Week 8 in Stimulant Naive Methylphenidate Group Social Problems T-score	-2.12 T-Score Standard Error 2.50	—	—	—
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Content Subscales - Total Score at Week 8 in Stimulant Naive Methylphenidate Group Violence Potential T-score	-9.58 T-Score Standard Error 2.11	—	—	—

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Per protocol (PP) population included all randomized participants with a baseline and at least 1 post-baseline result, excluding data from participants whose data may have been compromised.

Assesses adolescent's health status/functioning level. Domains: Achievement, Satisfaction, Comfort, Risk Avoidance, Resilience. Items assess frequency of activities/feelings (1=never, 5=always). Standard scores (T-scores) calculated for all domains by adjusting raw scores based on established reference group mean, standard deviation (T-scores mean=50, standard deviation=10). Higher scores=better health. Least Squares (LS) Mean Change from analysis of covariance model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), and baseline score.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) n=32 Participants Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) n=32 Participants Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) n=26 Participants Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Child Health and Illness Profile-Adolescent Edition (CHIP-AE) Domain Scores at Week 8 Achievement Section (n=3,3,4,3)	-339.71 T-Score Standard Error 0.00	301.79 T-Score Standard Error 0.00	-12.42 T-Score Standard Error 0.00	64.55 T-Score Standard Error 0.00
Change From Baseline in the Child Health and Illness Profile-Adolescent Edition (CHIP-AE) Domain Scores at Week 8 Discomfort Section (n=30,31,32,26)	-1.29 T-Score Standard Error 1.03	0.99 T-Score Standard Error 1.07	1.10 T-Score Standard Error 0.98	2.39 T-Score Standard Error 1.14
Change From Baseline in the Child Health and Illness Profile-Adolescent Edition (CHIP-AE) Domain Scores at Week 8 Resilience Section (n=30,30,31,26)	1.90 T-Score Standard Error 1.38	0.21 T-Score Standard Error 1.45	1.62 T-Score Standard Error 1.33	1.28 T-Score Standard Error 1.49
Change From Baseline in the Child Health and Illness Profile-Adolescent Edition (CHIP-AE) Domain Scores at Week 8 Risks Section (n=30,30,31,26)	-0.08 T-Score Standard Error 1.20	-0.28 T-Score Standard Error 1.27	2.18 T-Score Standard Error 1.16	0.74 T-Score Standard Error 1.32
Change From Baseline in the Child Health and Illness Profile-Adolescent Edition (CHIP-AE) Domain Scores at Week 8 Satisfaction Section (n=30,32,32,26)	-0.12 T-Score Standard Error 1.43	-0.05 T-Score Standard Error 1.44	2.95 T-Score Standard Error 1.35	0.72 T-Score Standard Error 1.55

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Stimulant naive participants randomized to methylphenidate with a baseline and at least 1 post-baseline result but excluded the participants whose data may have been compromised.

Assesses adolescent's health status/functioning level. Domains: Achievement, Satisfaction, Comfort, Risk Avoidance, Resilience. Items assess frequency of activities/feelings (1=never, 5=always). Standard scores (T-scores) calculated for all domains by adjusting raw scores based on established reference group mean, standard deviation (T-scores mean=50, standard deviation=10). Higher scores=better health. Least squares (LS) mean of the change from baseline to endpoint (week 8) is from an ANCOVA model. The model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), and baseline CHIP-AE domain score.

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Child Health and Illness Profile-Adolescent Edition (CHIP-AE) Domain Scores at Week 8 in Stimulant Naive Methylphenidate Group Achievement Section (n=1)	NA T-Score Standard Error NA Sample size not able to be analyzed.	—	—	—
Change From Baseline in the Child Health and Illness Profile-Adolescent Edition (CHIP-AE) Domain Scores at Week 8 in Stimulant Naive Methylphenidate Group Discomfort Section (n=6)	-1.97 T-Score Standard Error 2.47	—	—	—
Change From Baseline in the Child Health and Illness Profile-Adolescent Edition (CHIP-AE) Domain Scores at Week 8 in Stimulant Naive Methylphenidate Group Resilience Section (n=6)	-4.06 T-Score Standard Error 3.21	—	—	—
Change From Baseline in the Child Health and Illness Profile-Adolescent Edition (CHIP-AE) Domain Scores at Week 8 in Stimulant Naive Methylphenidate Group Risks Section (n=6)	2.01 T-Score Standard Error 3.06	—	—	—
Change From Baseline in the Child Health and Illness Profile-Adolescent Edition (CHIP-AE) Domain Scores at Week 8 in Stimulant Naive Methylphenidate Group Satisfaction Section (n=6)	2.19 T-Score Standard Error 3.25	—	—	—

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Per protocol (PP) population included all randomized participants with a baseline and at least 1 post-baseline result, excluding data from participants whose data may have been compromised.

76-item parent-rated assessment of child's health status/functioning level. Most items assess frequency of activities/feelings (1=never, 5=always). Standard scores (T-scores) were calculated for all domains by adjusting raw scores based on an established reference group mean and standard deviation (T-scores mean=50, standard deviation=10). Higher scores denote improvement. Least Squares (LS) Mean Change is from an analysis of covariance model that included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), and baseline domain score.

Outcome measures

Outcome measures
Measure	Placebo n=28 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) n=16 Participants Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) n=19 Participants Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) n=29 Participants Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Child Health and Illness Profile - Child Edition (CHIP-CE) at Week 8 Resilience Standardized Score (n=28,16,19,29)	4.07 T-Score Standard Error 1.96	0.60 T-Score Standard Error 2.82	0.19 T-Score Standard Error 2.53	4.75 T-Score Standard Error 1.98
Change From Baseline in the Child Health and Illness Profile - Child Edition (CHIP-CE) at Week 8 Satisfaction Standardized Score(n=28,16,19,29)	1.19 T-Score Standard Error 1.72	-2.07 T-Score Standard Error 2.50	-1.24 T-Score Standard Error 2.27	3.63 T-Score Standard Error 1.72
Change From Baseline in the Child Health and Illness Profile - Child Edition (CHIP-CE) at Week 8 Achievement Standardized Score (n=27,14,19,26)	3.82 T-Score Standard Error 1.65	3.45 T-Score Standard Error 2.48	2.96 T-Score Standard Error 2.08	3.81 T-Score Standard Error 1.70
Change From Baseline in the Child Health and Illness Profile - Child Edition (CHIP-CE) at Week 8 Comfort Standardized Score (n=28,16,19,29)	8.24 T-Score Standard Error 1.69	2.96 T-Score Standard Error 2.45	3.50 T-Score Standard Error 2.17	7.82 T-Score Standard Error 1.72
Change From Baseline in the Child Health and Illness Profile - Child Edition (CHIP-CE) at Week 8 Risk Avoidance Standardized Score (n=28,16,19,29)	6.06 T-Score Standard Error 1.73	1.81 T-Score Standard Error 2.57	5.77 T-Score Standard Error 2.20	4.75 T-Score Standard Error 1.74

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Stimulant naive participants randomized to methylphenidate with a baseline and at least 1 post-baseline result but excluded the participants whose data may have been compromised.

76-item parent-rated assessment of child's health status/functioning level. Most items assess frequency of activities/feelings (1=never, 5=always). Standard scores (T-scores) were calculated for all domains by adjusting raw scores based on an established reference group mean and standard deviation (T-scores mean=50, standard deviation=10). Higher scores denote improvement. Least Squares (LS) Mean Change is from an analysis of ANCOVA model that included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), and baseline domain score.

Outcome measures

Outcome measures
Measure	Placebo n=18 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Child Health and Illness Profile - Child Edition (CHIP-CE) at Week 8 in Stimulant Naive Methylphenidate Group Risk Avoidance Standardized Score (n=18)	6.97 T-Score Standard Error 2.11	—	—	—
Change From Baseline in the Child Health and Illness Profile - Child Edition (CHIP-CE) at Week 8 in Stimulant Naive Methylphenidate Group Resilience Standardized Score (n=18)	5.10 T-Score Standard Error 2.62	—	—	—
Change From Baseline in the Child Health and Illness Profile - Child Edition (CHIP-CE) at Week 8 in Stimulant Naive Methylphenidate Group Achievement Standardized Score (n=17)	5.21 T-Score Standard Error 2.02	—	—	—
Change From Baseline in the Child Health and Illness Profile - Child Edition (CHIP-CE) at Week 8 in Stimulant Naive Methylphenidate Group Comfort Standardized Score (n=18)	4.06 T-Score Standard Error 1.93	—	—	—
Change From Baseline in the Child Health and Illness Profile - Child Edition (CHIP-CE) at Week 8 in Stimulant Naive Methylphenidate Group Satisfaction Standardized Score(n=18)	1.90 T-Score Standard Error 2.40	—	—	—

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Per protocol (PP) population included all randomized participants with a baseline and at least 1 post-baseline result, excluding data from participants whose data may have been compromised.

Working memory subtest. Task involves sequencing, mental manipulation, attention, short-term memory, visual spatial imaging, and processing speed; consists of 10 items, 3 trials each. Scaled scores range: 1 to 19. Higher scores denote better performance. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis that included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=56 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) n=50 Participants Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) n=55 Participants Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) n=51 Participants Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) Letter-Number Sequencing Score at Week 8	1.30 units on a scale Standard Error 0.31	1.36 units on a scale Standard Error 0.33	1.48 units on a scale Standard Error 0.32	1.84 units on a scale Standard Error 0.33

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Stimulant naive participants randomized to methylphenidate with a baseline and at least 1 post-baseline result but excluded the participants whose data may have been compromised.

Working memory subtest. Task involves sequencing, mental manipulation, attention, short-term memory, visual spatial imaging, and processing speed; consists of 10 items, 3 trials each. Scaled scores range: 1 to 19. Higher scores denote better performance. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis that included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=23 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) Letter-Number Sequencing Score at Week 8 in Stimulant Naive Methylphenidate Group	1.58 units on a scale Standard Error 0.50	—	—	—

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Per protocol (PP) population included all randomized participants with a baseline and at least 1 post-baseline result, excluding data from participants whose data may have been compromised.

Assesses ability to accurately and rapidly recognize and name visual symbols. The tests consist of rapid automatized naming tests (that is, Letters, Numbers, Objects, Colors) and 2 rapid alternating stimulus tests (that is, 2-Set Letters and Numbers; 3-Set Letters, Numbers, and Colors). Scores are based on the amount of time required to name all the stimulus items in each test section. Raw scores were converted to standard scores based on participant's age and conversion tables from manual (mean=100, standard deviation=15). Higher scores=better ability. Least Squares (LS) Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=28 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) n=26 Participants Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) n=30 Participants Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) n=23 Participants Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Rapid Automatized Naming/Rapid Alternating Stimulus Test (RAN/RAS) Subtotal Scores at Week 8 Objects (n=21,18,18,11)	-0.56 units on a scale Standard Error 2.35	6.45 units on a scale Standard Error 2.42	11.70 units on a scale Standard Error 2.59	5.64 units on a scale Standard Error 3.61
Change From Baseline in the Rapid Automatized Naming/Rapid Alternating Stimulus Test (RAN/RAS) Subtotal Scores at Week 8 Colors (n=25, 21, 26, 16)	2.85 units on a scale Standard Error 1.76	4.86 units on a scale Standard Error 1.99	3.30 units on a scale Standard Error 1.82	2.98 units on a scale Standard Error 2.25
Change From Baseline in the Rapid Automatized Naming/Rapid Alternating Stimulus Test (RAN/RAS) Subtotal Scores at Week 8 Numbers (n=28, 26, 30, 23)	3.44 units on a scale Standard Error 1.14	2.85 units on a scale Standard Error 1.25	2.99 units on a scale Standard Error 1.09	2.38 units on a scale Standard Error 1.26
Change From Baseline in the Rapid Automatized Naming/Rapid Alternating Stimulus Test (RAN/RAS) Subtotal Scores at Week 8 Letters (n=27,24,27,22)	1.16 units on a scale Standard Error 1.37	2.84 units on a scale Standard Error 1.57	3.62 units on a scale Standard Error 1.57	2.22 units on a scale Standard Error 1.80
Change From Baseline in the Rapid Automatized Naming/Rapid Alternating Stimulus Test (RAN/RAS) Subtotal Scores at Week 8 2-set Letters and Numbers (n=27, 23, 28, 19)	5.23 units on a scale Standard Error 1.58	3.21 units on a scale Standard Error 1.60	6.38 units on a scale Standard Error 1.61	4.69 units on a scale Standard Error 1.91
Change From Baseline in the Rapid Automatized Naming/Rapid Alternating Stimulus Test (RAN/RAS) Subtotal Scores at Week 8 3-set Letters, Numbers, and Colors (n=26,24,28,21)	7.89 units on a scale Standard Error 1.90	3.86 units on a scale Standard Error 1.92	6.47 units on a scale Standard Error 1.82	1.56 units on a scale Standard Error 2.18

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Stimulant naive participants randomized to methylphenidate with a baseline and at least 1 post-baseline result but excluded the participants whose data may have been compromised.

Assesses ability to accurately and rapidly recognize and name visual symbols. The tests consist of rapid automatized naming tests (that is, Letters, Numbers, Objects, Colors) and 2 rapid alternating stimulus tests (that is, 2-Set Letters and Numbers; 3-Set Letters, Numbers, and Colors). Scores are based on the amount of time required to name all the stimulus items in each test section. Raw scores were converted to standard scores based on participant's age and conversion tables from manual (mean=100, standard deviation=15). Higher scores=better ability. Least Squares (LS) Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=14 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Rapid Automatized Naming/Rapid Alternating Stimulus Test (RAN/RAS) Subtotal Scores at Week 8 in Stimulant Naive Methylphenidate Group 2-set Letters and Numbers (n=12)	6.65 units on a scale Standard Error 2.57	—	—	—
Change From Baseline in the Rapid Automatized Naming/Rapid Alternating Stimulus Test (RAN/RAS) Subtotal Scores at Week 8 in Stimulant Naive Methylphenidate Group Objects (n=9)	0.65 units on a scale Standard Error 4.88	—	—	—
Change From Baseline in the Rapid Automatized Naming/Rapid Alternating Stimulus Test (RAN/RAS) Subtotal Scores at Week 8 in Stimulant Naive Methylphenidate Group Colors (n=11)	3.37 units on a scale Standard Error 2.94	—	—	—
Change From Baseline in the Rapid Automatized Naming/Rapid Alternating Stimulus Test (RAN/RAS) Subtotal Scores at Week 8 in Stimulant Naive Methylphenidate Group Numbers (n=14)	6.60 units on a scale Standard Error 2.16	—	—	—
Change From Baseline in the Rapid Automatized Naming/Rapid Alternating Stimulus Test (RAN/RAS) Subtotal Scores at Week 8 in Stimulant Naive Methylphenidate Group Letters (n=11)	7.81 units on a scale Standard Error 2.70	—	—	—
Change From Baseline in the Rapid Automatized Naming/Rapid Alternating Stimulus Test (RAN/RAS) Subtotal Scores at Week 8 in Stimulant Naive Methylphenidate Group 3-set Letters, Numbers, and Colors (n=12)	4.82 units on a scale Standard Error 2.91	—	—	—

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Per protocol (PP) population included all randomized participants with a baseline at least 1 post-baseline result, excluding data from participants whose data may have been compromised.

Assess ODD symptom severity. Individual subscale items range from 0 (never) to 3 (very often/frequently). Total is expressed as a T-score based on gender/age norms (range 0-100). Higher T-score=greater ODD. Change scores=Week 8 score-baseline score. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) n=52 Participants Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) n=58 Participants Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) n=57 Participants Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Symptom Subscale for Oppositional Defiant Disorder (ODD) Total Score at Week 8	-7.17 T-Score Standard Error 1.52	-4.00 T-Score Standard Error 1.64	-10.18 T-Score Standard Error 1.57	-12.29 T-Score Standard Error 1.59

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Stimulant naive participants randomized to methylphenidate with a baseline and at least 1 post-baseline result but excluded the participants whose data may have been compromised.

Assess ODD symptom severity. Individual subscale items range from 0 (never) to 3 (very often/frequently). Total is expressed as a T-score based on gender/age norms (range 0-100). Higher T-score=greater ODD. Change scores=Week 8 score-baseline score. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Symptom Subscale for Oppositional Defiant Disorder (ODD) Total Score at Week 8 in Stimulant Naive Methylphenidate Group	-13.83 T-Score Standard Error 2.54	—	—	—

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Per protocol (PP) population included all randomized participants with a baseline and at least 1 post-baseline result, excluding data from participants whose data may have been compromised.

Assess anxiety symptom severity. Individual subscale items: 0 (never, seldom) - 3 (very often/frequently). Total score expressed as T-score based on gender/age norms (0-100). Higher T-scores=greater anxiety. Change scores=Week 8 score-baseline score. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) n=52 Participants Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) n=58 Participants Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) n=57 Participants Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Generalized Anxiety Disorder (GAD) and Separation Anxiety Disorder Symptom Subscales at Week 8 CBRS Generalized Anxiety Disorder T-score	-9.09 T-Score Standard Error 1.46	-5.34 T-Score Standard Error 1.57	-11.07 T-Score Standard Error 1.50	-15.39 T-Score Standard Error 1.53
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Generalized Anxiety Disorder (GAD) and Separation Anxiety Disorder Symptom Subscales at Week 8 CBRS Separation Anxiety Disorder Scale T-score	-6.71 T-Score Standard Error 1.48	-1.13 T-Score Standard Error 1.59	-5.88 T-Score Standard Error 1.52	-8.60 T-Score Standard Error 1.54

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Stimulant naive participants randomized to methylphenidate with a baseline and at least 1 post-baseline result but excluded the participants whose data may have been compromised.

Assess anxiety symptom severity. Individual subscale items: 0 (never, seldom) - 3 (very often/frequently). Total score expressed as T-score based on gender/age norms (0-100). Higher T-scores=greater anxiety. Change scores=Week 8 score-baseline score. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Generalized Anxiety Disorder (GAD) and Separation Anxiety Disorder Symptom Subscales at Week 8 in Stimulant Naive Methylphenidate Group CBRS Generalized Anxiety Disorder T-score	-8.78 T-Score Standard Error 2.40	—	—	—
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Generalized Anxiety Disorder (GAD) and Separation Anxiety Disorder Symptom Subscales at Week 8 in Stimulant Naive Methylphenidate Group CBRS Separation Anxiety Disorder Scale T-score	-2.91 T-Score Standard Error 2.66	—	—	—

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Per protocol (PP) population included all randomized participants with a baseline and at least 1 post-baseline result, excluding data from participants whose data may have been compromised.

Assess conduct disorder symptom severity. Individual subscale items: 0 (never/seldom) - 3 (very often/frequently). Total expressed as T-score based on gender/age norms (0-100). Higher T-score=greater conduct disorder. Change scores=Week 8 score-baseline score. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis; included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) n=52 Participants Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) n=58 Participants Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) n=57 Participants Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Conduct Disorder Symptom Subscale Score at Week 8	-4.64 T-Score Standard Error 1.43	-2.24 T-Score Standard Error 1.55	-6.26 T-Score Standard Error 1.48	-7.62 T-Score Standard Error 1.50

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Stimulant naive participants randomized to methylphenidate with a baseline and at least 1 post-baseline result but excluded the participants whose data may have been compromised.

Assess conduct disorder symptom severity. Individual subscale items: 0 (never/seldom) - 3 (very often/frequently). Total expressed as T-score based on gender/age norms (0-100). Higher T-score=greater conduct disorder. Change scores=Week 8 score-baseline score. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis; included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Conduct Disorder Symptom Subscale Score at Week 8 in Stimulant Naive Methylphenidate Group	-7.10 T-Score Standard Error 2.27	—	—	—

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Per protocol (PP) population included all randomized participants with a baseline and at least 1 post-baseline result, excluding data from participants whose data may have been compromised.

Assess depressive symptom severity. Individual subscale items range: 0 (never, seldom) to 3 (very often/frequently). Total expressed as T-score based on gender/age norms (0-100). Higher T-scores=greater depression. Change scores=Week 8 score-baseline score. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis and included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) n=52 Participants Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) n=58 Participants Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) n=57 Participants Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Major Depressive Episode Score at Week 8	-10.27 T-Score Standard Error 1.56	-5.41 T-Score Standard Error 1.68	-9.58 T-Score Standard Error 1.59	-13.67 T-Score Standard Error 1.62

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Stimulant naive participants randomized to methylphenidate with a baseline and at least 1 post-baseline result but excluded the participants whose data may have been compromised.

Assess depressive symptom severity. Individual subscale items range: 0 (never, seldom) to 3 (very often/frequently). Total expressed as T-score based on gender/age norms (0-100). Higher T-scores=greater depression. Change scores=Week 8 score-baseline score. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis and included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Major Depressive Episode Score at Week 8 in Stimulant Naive Methylphenidate Group	-1.09 T-Score Standard Error 2.38	—	—	—

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Per protocol (PP) population included all randomized participants with a baseline and at least 1 post-baseline result, excluding data from participants whose data may have been compromised.

Parent-completed 11-item questionnaire (3 morning items, 8 evening items) on a scale of 0 (no difficulty) to 3 (a lot of difficulty). Total score ranges from 0 to 33; higher score=greater difficulty in evening and morning behavior. Least Squares (LS) Mean Change is from a restricted maximum likelihood-based, mixed model repeated measure (MMRM) analysis and includes fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) n=58 Participants Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) n=59 Participants Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) n=57 Participants Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Weekly Parent Ratings of Evening and Morning Behavior-Revised (WPREMB-R) Total Score at Week 8	-4.95 units on a scale Standard Error 0.83	-4.72 units on a scale Standard Error 0.89	-7.08 units on a scale Standard Error 0.84	-8.24 units on a scale Standard Error 0.87

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Stimulant naive participants randomized to methylphenidate with a baseline and at least 1 post-baseline result but excluded the participants whose data may have been compromised.

Parent-completed 11-item questionnaire (3 morning items, 8 evening items) on a scale of 0 (no difficulty) to 3 (a lot of difficulty). Total score ranges from 0 to 33; higher score=greater difficulty in evening and morning behavior. Least Squares (LS) Mean Change is from a restricted maximum likelihood-based, mixed model repeated measure (MMRM) analysis and includes fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=25 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Weekly Parent Ratings of Evening and Morning Behavior-Revised (WPREMB-R) Total Score at Week 8 in Stimulant Naive Methylphenidate Group	-6.88 units on a scale Standard Error 1.45	—	—	—

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Per protocol (PP) population included all randomized participants with a baseline and at least 1 post-baseline result, excluding data from participants whose data may have been compromised.

Measures difficulty level of 3 common morning behaviors (for example, get out of bed) from 0 (no difficulty) to 3 (a lot of difficulty). Total score range is from 0 to 9; a higher score indicates greater difficulty in morning behavior. Least Squares (LS) Mean Change from restricted maximum likelihood-based, mixed model repeated measure (MMRM) analysis and includes fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline morning score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) n=58 Participants Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) n=59 Participants Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) n=58 Participants Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Weekly Parent Ratings of Evening and Morning Behavior-Revised (WPREMB-R) Morning Summary Score at Week 8	-1.07 units on a scale Standard Error 0.28	-0.91 units on a scale Standard Error 0.30	-1.53 units on a scale Standard Error 0.29	-2.20 units on a scale Standard Error 0.29

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Stimulant naive participants randomized to methylphenidate with a baseline and at least 1 post-baseline result but excluded the participants whose data may have been compromised.

Measures difficulty level of 3 common morning behaviors (for example, get out of bed) from 0 (no difficulty) to 3 (a lot of difficulty). Total score range is from 0 to 9; a higher score indicates greater difficulty in morning behavior. Least Squares (LS) Mean Change from restricted maximum likelihood-based, mixed model repeated measure (MMRM) analysis and includes fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline morning score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=26 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Weekly Parent Ratings of Evening and Morning Behavior-Revised (WPREMB-R) Morning Summary Score at Week 8 in Stimulant Naive Methylphenidate Group	-0.80 units on a scale Standard Error 0.44	—	—	—

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Per protocol (PP) population included all randomized participants with a baseline and at least 1 post-baseline result, excluding data from participants whose data may have been compromised.

Measures difficulty level of 8 common evening behaviors (for example, sit through dinner) from 0 (no difficulty) to 3 (a lot of difficulty). Total score ranges: 0 to 24; higher scores indicate greater difficulty in evening behavior. Least Squares (LS) Mean Change is from restricted maximum likelihood-based, mixed model repeated measure analysis (MMRM) and included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline evening score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) n=58 Participants Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) n=60 Participants Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) n=58 Participants Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Weekly Parent Ratings of Evening and Morning Behavior-Revised (WPREMB-R ) Evening Summary Score at Week 8	-3.34 units on a scale Standard Error 0.58	-3.37 units on a scale Standard Error 0.61	-4.77 units on a scale Standard Error 0.58	-5.24 units on a scale Standard Error 0.60

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Stimulant naive participants randomized to methylphenidate with a baseline and at least 1 post-baseline result but excluded the participants whose data may have been compromised.

Measures difficulty level of 8 common evening behaviors (for example, sit through dinner) from 0 (no difficulty) to 3 (a lot of difficulty). Total score ranges: 0 to 24; higher scores indicate greater difficulty in evening behavior. Least Squares (LS) Mean Change is from restricted maximum likelihood-based, mixed model repeated measure analysis (MMRM) and included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment\*visit interaction, and continuous, fixed effects of baseline evening score and baseline score\*visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=25 Participants Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase.	LY2216684 (0.1 mg/kg/Day) Participants were given 0.1 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the optional taper phase. Participants were also given placebo capsules to maintain methylphenidate blinding.
Change From Baseline in the Weekly Parent Ratings of Evening and Morning Behavior-Revised (WPREMB-R ) Evening Summary Score at Week 8 in Stimulant Naive Methylphenidate Group	-6.17 units on a scale Standard Error 1.04	—	—	—

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo - Treatment Phase n=78 participants at risk Participants were given the placebo in both tablet (LY2216684 placebo) and capsule (methylphenidate placebo) forms QD po for the 8-week double-blind treatment phase.	LY2216684 (0.1 mg/kg/Day) - Treatment Phase n=76 participants at risk Participants were given 0.1 milligrams per kilogram per day (mg/kg/day) of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.2 mg/kg/Day) - Treatment Phase n=75 participants at risk Participants were given 0.2 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	LY2216684 (0.3 mg/kg/Day) - Treatment Phase n=75 participants at risk Participants were given 0.3 mg/kg/day of LY2216684 in tablet form QD po for the 8-week double-blind treatment phase. Participants were also given placebo capsules to maintain methylphenidate blinding.	Methylphenidate - Treatment Phase n=36 participants at risk Participants were given 18 mg/day to 54 mg/day of extended-release methylphenidate capsules, based on weight QD po for the 8-week double-blind treatment phase. Participants were also given placebo tablets to maintain LY2216684 blinding.	Placebo - Taper Phase n=10 participants at risk Methylphenidate blind: Participants were given the placebo in capsule form QD po for the 2-week taper phase.	LY2216684 (0.1 mg/kg/Day) - Taper Phase n=15 participants at risk Participants were given the reduced dose of LY2216684 in tablet form QD po for 2 weeks of tapering in the taper phase.	LY2216684 (0.2 mg/kg/Day) - Taper Phase n=7 participants at risk Participants were given the reduced dose of LY2216684 in tablet form QD po for 2 weeks of tapering in taper phase.	LY2216684 (0.3 mg/kg/Day) - Taper Phase n=12 participants at risk Participants were given the reduced dose of LY2216684 in tablet form QD po for 2 weeks of tapering in the taper phase.	Methylphenidate - Taper Phase n=4 participants at risk Participants were given the placebo in capsule form QD po for the 2-week taper phase.
Gastrointestinal disorders Abdominal pain upper	9.0% 7/78 • Number of events 8	18.4% 14/76 • Number of events 16	4.0% 3/75 • Number of events 3	14.7% 11/75 • Number of events 16	22.2% 8/36 • Number of events 9	0.00% 0/10	0.00% 0/15	0.00% 0/7	0.00% 0/12	0.00% 0/4
Gastrointestinal disorders Diarrhoea	2.6% 2/78 • Number of events 2	6.6% 5/76 • Number of events 5	4.0% 3/75 • Number of events 3	1.3% 1/75 • Number of events 1	0.00% 0/36	0.00% 0/10	0.00% 0/15	0.00% 0/7	0.00% 0/12	0.00% 0/4
Gastrointestinal disorders Nausea	5.1% 4/78 • Number of events 4	6.6% 5/76 • Number of events 6	17.3% 13/75 • Number of events 18	13.3% 10/75 • Number of events 10	8.3% 3/36 • Number of events 3	0.00% 0/10	0.00% 0/15	0.00% 0/7	0.00% 0/12	0.00% 0/4
Gastrointestinal disorders Vomiting	3.8% 3/78 • Number of events 3	9.2% 7/76 • Number of events 8	12.0% 9/75 • Number of events 10	13.3% 10/75 • Number of events 11	2.8% 1/36 • Number of events 1	0.00% 0/10	0.00% 0/15	0.00% 0/7	0.00% 0/12	0.00% 0/4
General disorders Fatigue	3.8% 3/78 • Number of events 3	3.9% 3/76 • Number of events 3	4.0% 3/75 • Number of events 3	4.0% 3/75 • Number of events 3	11.1% 4/36 • Number of events 4	0.00% 0/10	0.00% 0/15	0.00% 0/7	0.00% 0/12	0.00% 0/4
General disorders Irritability	5.1% 4/78 • Number of events 4	13.2% 10/76 • Number of events 10	9.3% 7/75 • Number of events 7	6.7% 5/75 • Number of events 5	16.7% 6/36 • Number of events 6	0.00% 0/10	0.00% 0/15	0.00% 0/7	0.00% 0/12	0.00% 0/4
Infections and infestations Gastroenteritis	0.00% 0/78	0.00% 0/76	0.00% 0/75	0.00% 0/75	5.6% 2/36 • Number of events 2	0.00% 0/10	0.00% 0/15	0.00% 0/7	0.00% 0/12	0.00% 0/4
Infections and infestations Nasopharyngitis	3.8% 3/78 • Number of events 3	1.3% 1/76 • Number of events 1	5.3% 4/75 • Number of events 4	1.3% 1/75 • Number of events 1	2.8% 1/36 • Number of events 1	0.00% 0/10	0.00% 0/15	0.00% 0/7	0.00% 0/12	0.00% 0/4
Infections and infestations Upper respiratory tract infection	6.4% 5/78 • Number of events 5	9.2% 7/76 • Number of events 8	5.3% 4/75 • Number of events 4	4.0% 3/75 • Number of events 3	5.6% 2/36 • Number of events 2	0.00% 0/10	6.7% 1/15 • Number of events 1	0.00% 0/7	0.00% 0/12	0.00% 0/4
Investigations Blood creatine phosphokinase increased	0.00% 0/78	0.00% 0/76	1.3% 1/75 • Number of events 1	1.3% 1/75 • Number of events 1	0.00% 0/36	0.00% 0/10	6.7% 1/15 • Number of events 1	0.00% 0/7	0.00% 0/12	0.00% 0/4
Investigations Heart rate increased	0.00% 0/78	2.6% 2/76 • Number of events 2	0.00% 0/75	5.3% 4/75 • Number of events 4	2.8% 1/36 • Number of events 1	0.00% 0/10	0.00% 0/15	0.00% 0/7	0.00% 0/12	0.00% 0/4
Investigations Urine leukocyte esterase positive	0.00% 0/78	0.00% 0/76	0.00% 0/75	0.00% 0/75	0.00% 0/36	0.00% 0/10	6.7% 1/15 • Number of events 1	0.00% 0/7	0.00% 0/12	0.00% 0/4
Investigations Weight decreased	0.00% 0/78	0.00% 0/76	1.3% 1/75 • Number of events 1	0.00% 0/75	11.1% 4/36 • Number of events 4	0.00% 0/10	0.00% 0/15	0.00% 0/7	0.00% 0/12	0.00% 0/4
Metabolism and nutrition disorders Decreased appetite	3.8% 3/78 • Number of events 3	7.9% 6/76 • Number of events 6	13.3% 10/75 • Number of events 10	10.7% 8/75 • Number of events 9	47.2% 17/36 • Number of events 17	0.00% 0/10	0.00% 0/15	0.00% 0/7	0.00% 0/12	0.00% 0/4
Nervous system disorders Dizziness	9.0% 7/78 • Number of events 7	5.3% 4/76 • Number of events 6	8.0% 6/75 • Number of events 7	6.7% 5/75 • Number of events 5	8.3% 3/36 • Number of events 3	0.00% 0/10	0.00% 0/15	0.00% 0/7	0.00% 0/12	0.00% 0/4
Nervous system disorders Headache	15.4% 12/78 • Number of events 16	14.5% 11/76 • Number of events 13	18.7% 14/75 • Number of events 16	12.0% 9/75 • Number of events 16	19.4% 7/36 • Number of events 7	0.00% 0/10	0.00% 0/15	0.00% 0/7	0.00% 0/12	0.00% 0/4
Nervous system disorders Sedation	1.3% 1/78 • Number of events 1	5.3% 4/76 • Number of events 4	9.3% 7/75 • Number of events 7	5.3% 4/75 • Number of events 4	8.3% 3/36 • Number of events 3	0.00% 0/10	0.00% 0/15	0.00% 0/7	0.00% 0/12	0.00% 0/4
Nervous system disorders Somnolence	6.4% 5/78 • Number of events 5	5.3% 4/76 • Number of events 6	18.7% 14/75 • Number of events 15	5.3% 4/75 • Number of events 4	0.00% 0/36	0.00% 0/10	0.00% 0/15	0.00% 0/7	0.00% 0/12	0.00% 0/4
Psychiatric disorders Affect lability	0.00% 0/78	0.00% 0/76	0.00% 0/75	1.3% 1/75 • Number of events 1	5.6% 2/36 • Number of events 3	0.00% 0/10	0.00% 0/15	0.00% 0/7	0.00% 0/12	0.00% 0/4
Psychiatric disorders Aggression	1.3% 1/78 • Number of events 1	1.3% 1/76 • Number of events 1	2.7% 2/75 • Number of events 2	2.7% 2/75 • Number of events 2	5.6% 2/36 • Number of events 2	0.00% 0/10	0.00% 0/15	0.00% 0/7	0.00% 0/12	0.00% 0/4
Psychiatric disorders Depressed mood	0.00% 0/78	0.00% 0/76	0.00% 0/75	0.00% 0/75	5.6% 2/36 • Number of events 2	0.00% 0/10	0.00% 0/15	0.00% 0/7	0.00% 0/12	0.00% 0/4
Psychiatric disorders Initial insomnia	2.6% 2/78 • Number of events 3	2.6% 2/76 • Number of events 3	1.3% 1/75 • Number of events 1	1.3% 1/75 • Number of events 1	5.6% 2/36 • Number of events 2	0.00% 0/10	0.00% 0/15	0.00% 0/7	0.00% 0/12	0.00% 0/4
Psychiatric disorders Insomnia	6.4% 5/78 • Number of events 5	6.6% 5/76 • Number of events 5	5.3% 4/75 • Number of events 4	2.7% 2/75 • Number of events 2	19.4% 7/36 • Number of events 8	10.0% 1/10 • Number of events 1	0.00% 0/15	0.00% 0/7	0.00% 0/12	0.00% 0/4
Psychiatric disorders Mood altered	1.3% 1/78 • Number of events 1	1.3% 1/76 • Number of events 1	4.0% 3/75 • Number of events 3	2.7% 2/75 • Number of events 2	5.6% 2/36 • Number of events 2	0.00% 0/10	0.00% 0/15	0.00% 0/7	0.00% 0/12	0.00% 0/4
Psychiatric disorders Sleep disorder	0.00% 0/78	0.00% 0/76	1.3% 1/75 • Number of events 1	0.00% 0/75	11.1% 4/36 • Number of events 5	0.00% 0/10	0.00% 0/15	0.00% 0/7	0.00% 0/12	0.00% 0/4
Respiratory, thoracic and mediastinal disorders Cough	5.1% 4/78 • Number of events 5	3.9% 3/76 • Number of events 3	1.3% 1/75 • Number of events 1	2.7% 2/75 • Number of events 2	11.1% 4/36 • Number of events 4	0.00% 0/10	0.00% 0/15	0.00% 0/7	0.00% 0/12	0.00% 0/4
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/78	0.00% 0/76	0.00% 0/75	0.00% 0/75	0.00% 0/36	0.00% 0/10	6.7% 1/15 • Number of events 1	0.00% 0/7	0.00% 0/12	0.00% 0/4
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.6% 2/78 • Number of events 2	2.6% 2/76 • Number of events 2	4.0% 3/75 • Number of events 3	0.00% 0/75	5.6% 2/36 • Number of events 2	0.00% 0/10	0.00% 0/15	0.00% 0/7	0.00% 0/12	0.00% 0/4

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60