A Study of Pediatric Patients With Attention Deficit/Hyperactivity Disorder

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00922636
First received: June 16, 2009
Last updated: July 29, 2014
Last verified: July 2014
Results First Received: September 26, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Attention Deficit Hyperactivity Disorder
Interventions: Drug: LY2216684
Drug: Methylphenidate
Drug: Placebo (tablet)
Drug: Placebo (capsule)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

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


Reporting Groups
  Description
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.

Participant Flow:   Overall Study
    Methylphenidate     Placebo     LY2216684 (0.1 mg/kg/Day)     LY2216684 (0.2 mg/kg/Day)     LY2216684 (0.3 mg/kg/Day)  
STARTED     36     78     76     75     75  
Entered Optional Taper Phase     4     10     15     7     12  
COMPLETED     29     62     56     58     59  
NOT COMPLETED     7     16     20     17     16  
Adverse Event                 3                 3                 2                 3                 2  
Lack of Efficacy                 1                 7                 3                 2                 4  
Sponsor Decision                 0                 0                 2                 0                 0  
Withdrawal by Subject                 0                 0                 5                 2                 4  
Protocol Violation                 0                 0                 2                 2                 0  
Entry Criteria Not Met                 0                 0                 1                 1                 0  
Parent/Caregiver Decision                 2                 4                 3                 5                 2  
Lost to Follow-up                 1                 2                 2                 2                 4  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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.
Total Total of all reporting groups

Baseline Measures
    Methylphenidate     Placebo     LY2216684 (0.1 mg/kg/Day)     LY2216684 (0.2 mg/kg/Day)     LY2216684 (0.3 mg/kg/Day)     Total  
Number of Participants  
[units: participants]
  36     78     76     75     75     340  
Age  
[units: years]
Mean ± Standard Deviation
  9.92  ± 2.94     11.37  ± 3.07     11.90  ± 3.03     12.59  ± 2.81     11.47  ± 3.10     11.63  ± 3.07  
Gender  
[units: participants]
           
Female     9     25     24     22     20     100  
Male     27     53     52     53     55     240  
Ethnicity (NIH/OMB)  
[units: participants]
           
Hispanic or Latino     9     20     21     20     19     89  
Not Hispanic or Latino     27     58     55     55     56     251  
Unknown or Not Reported     0     0     0     0     0     0  
Race (NIH/OMB)  
[units: participants]
           
American Indian or Alaska Native     0     0     2     1     1     4  
Asian     0     4     5     3     5     17  
Native Hawaiian or Other Pacific Islander     0     0     0     0     0     0  
Black or African American     6     8     9     10     12     45  
White     25     60     55     57     50     247  
More than one race     5     6     5     4     7     27  
Unknown or Not Reported     0     0     0     0     0     0  
Region of Enrollment  
[units: participants]
           
Canada     1     4     4     5     4     18  
Mexico     0     0     1     0     1     2  
Puerto Rico     2     3     4     2     3     14  
Taiwan     0     4     5     3     4     16  
United States     33     67     62     65     63     290  



  Outcome Measures
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1.  Primary:   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   [ Time Frame: Baseline, 8 weeks ]

2.  Primary:   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   [ Time Frame: Baseline, 8 weeks ]

3.  Secondary:   Change From Baseline in the Swanson, Nolan and Pelham Questionnaire: Attention-Deficit/Hyperactivity Disorder Subscale (SNAP-IV: ADHD) Total Score at Week 8   [ Time Frame: Baseline, 8 weeks ]

4.  Secondary:   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   [ Time Frame: Baseline, 8 weeks ]

5.  Secondary:   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   [ Time Frame: Baseline, 8 weeks ]

6.  Secondary:   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   [ Time Frame: Baseline, 8 weeks ]

7.  Secondary:   Change From Baseline in the Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Severity Scale (CGI-ADHD-S) Total Score at Week 8   [ Time Frame: Baseline, 8 weeks ]

8.  Secondary:   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   [ Time Frame: Baseline, 8 weeks ]

9.  Secondary:   Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Improvement Scale (CGI-ADHD-I) Endpoint Score During the Treatment Phase (Weeks 1-8)   [ Time Frame: Weeks 1 through 8 ]

10.  Secondary:   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   [ Time Frame: Weeks 1 through 8 ]

11.  Secondary:   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   [ Time Frame: Baseline, 8 weeks ]

12.  Secondary:   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   [ Time Frame: Baseline, 8 weeks ]

13.  Secondary:   Change From Baseline in the Swanson, Nolan and Pelham (SNAP-IV) Oppositional Defiant Disorder (ODD) Total Score at Week 8   [ Time Frame: Baseline, 8 weeks ]

14.  Secondary:   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   [ Time Frame: Baseline, 8 weeks ]

15.  Secondary:   Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Impairment Items Subscales-Total Score at Week 8   [ Time Frame: Baseline, 8 weeks ]

16.  Secondary:   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   [ Time Frame: Baseline, 8 weeks ]

17.  Secondary:   Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 8   [ Time Frame: 8 weeks ]

18.  Secondary:   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   [ Time Frame: 8 weeks ]

19.  Secondary:   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   [ Time Frame: Baseline, 8 weeks ]

20.  Secondary:   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   [ Time Frame: Baseline, 8 weeks ]

21.  Secondary:   Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Content Subscales - Total Score at Week 8   [ Time Frame: Baseline, 8 weeks ]

22.  Secondary:   Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Content Subscales - Total Score at Week 8 in Stimulant Naive Methylphenidate Group   [ Time Frame: Baseline, 8 weeks ]

23.  Secondary:   Change From Baseline in the Child Health and Illness Profile-Adolescent Edition (CHIP-AE) Domain Scores at Week 8   [ Time Frame: Baseline, 8 weeks ]

24.  Secondary:   Change From Baseline in the Child Health and Illness Profile-Adolescent Edition (CHIP-AE) Domain Scores at Week 8 in Stimulant Naive Methylphenidate Group   [ Time Frame: Baseline, 8 weeks ]

25.  Secondary:   Change From Baseline in the Child Health and Illness Profile - Child Edition (CHIP-CE) at Week 8   [ Time Frame: Baseline, 8 weeks ]

26.  Secondary:   Change From Baseline in the Child Health and Illness Profile - Child Edition (CHIP-CE) at Week 8 in Stimulant Naive Methylphenidate Group   [ Time Frame: Baseline, 8 weeks ]

27.  Secondary:   Change From Baseline in the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) Letter-Number Sequencing Score at Week 8   [ Time Frame: Baseline, 8 weeks ]

28.  Secondary:   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   [ Time Frame: Baseline, 8 weeks ]

29.  Secondary:   Change From Baseline in the Rapid Automatized Naming/Rapid Alternating Stimulus Test (RAN/RAS) Subtotal Scores at Week 8   [ Time Frame: Baseline, 8 weeks ]

30.  Secondary:   Change From Baseline in the Rapid Automatized Naming/Rapid Alternating Stimulus Test (RAN/RAS) Subtotal Scores at Week 8 in Stimulant Naive Methylphenidate Group   [ Time Frame: Baseline, 8 weeks ]

31.  Secondary:   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   [ Time Frame: Baseline, 8 weeks ]

32.  Secondary:   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   [ Time Frame: Baseline, 8 weeks ]

33.  Secondary:   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   [ Time Frame: Baseline, 8 weeks ]

34.  Secondary:   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   [ Time Frame: Baseline, 8 weeks ]

35.  Secondary:   Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Conduct Disorder Symptom Subscale Score at Week 8   [ Time Frame: Baseline, 8 weeks ]

36.  Secondary:   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   [ Time Frame: Baseline, 8 weeks ]

37.  Secondary:   Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Major Depressive Episode Score at Week 8   [ Time Frame: Baseline, 8 weeks ]

38.  Secondary:   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   [ Time Frame: Baseline, 8 weeks ]

39.  Secondary:   Change From Baseline in the Weekly Parent Ratings of Evening and Morning Behavior-Revised (WPREMB-R) Total Score at Week 8   [ Time Frame: Baseline, 8 weeks ]

40.  Secondary:   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   [ Time Frame: Baseline, 8 weeks ]

41.  Secondary:   Change From Baseline in the Weekly Parent Ratings of Evening and Morning Behavior-Revised (WPREMB-R) Morning Summary Score at Week 8   [ Time Frame: Baseline, 8 weeks ]

42.  Secondary:   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   [ Time Frame: Baseline, 8 weeks ]

43.  Secondary:   Change From Baseline in the Weekly Parent Ratings of Evening and Morning Behavior-Revised (WPREMB-R ) Evening Summary Score at Week 8   [ Time Frame: Baseline, 8 weeks ]

44.  Secondary:   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   [ Time Frame: Baseline, 8 weeks ]

45.  Secondary:   Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Mixed Episode Score at Week 8   [ Time Frame: Baseline, 8 weeks ]

46.  Secondary:   Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Mixed Episode Score at Week 8 in Stimulant Naive Methylphenidate Group   [ Time Frame: Baseline, 8 weeks ]

47.  Secondary:   Change From Baseline in the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Hyperactivity-Impulsivity and Inattention Subtotal Scores at Week 8   [ Time Frame: Baseline, 8 weeks ]

48.  Secondary:   Change From Baseline in the ADHDRS-IV-Parent:Inv Hyperactivity-Impulsivity and Inattention Subtotal Scores at Week 8 in Stimulant Naive Methylphenidate Group   [ Time Frame: Baseline, 8 weeks ]

49.  Secondary:   Change From Baseline in the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) Digit Span Total Score at Week 8   [ Time Frame: Baseline, 8 weeks ]

50.  Secondary:   Change From Baseline in the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) Digit Span Total Score at Week 8 in Stimulant Naive Methylphenidate Group   [ Time Frame: Baseline, 8 weeks ]

51.  Secondary:   Change From Baseline in the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) Digit Span Subtotal Scores at Week 8   [ Time Frame: Baseline, 8 weeks ]

52.  Secondary:   Change From Baseline in the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) Digit Span Subtotal Scores at Week 8 in Stimulant Naive Methylphenidate Group   [ Time Frame: Baseline, 8 weeks ]

53.  Secondary:   Number of Participants With a Response (Response Rate) up to Week 8   [ Time Frame: Baseline, up to 8 weeks ]

54.  Secondary:   Number of Participants With a Response (Response Rate) up to Week 8 in Stimulant Naive Methylphenidate Group   [ Time Frame: Baseline, up to 8 weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Some sites may have received data with identifying information from the central lab; data from 69 participants were excluded from efficacy analyses. Data were excluded from efficacy analyses for a participant randomized before study site approval.


  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 800-545-5979


No publications provided by Eli Lilly and Company

Publications automatically indexed to this study:

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00922636     History of Changes
Other Study ID Numbers: 10925, H9P-MC-LNBF
Study First Received: June 16, 2009
Results First Received: September 26, 2013
Last Updated: July 29, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Mexico: Ethics Committee
Mexico: Ministry of Health
Taiwan: Department of Health
Taiwan: Institutional Review Board