A Randomized, Double-Blind Comparison of Placebo and Atomoxetine Hydrochloride Given Once a Day in Adults With Attention-Deficit/Hyperactivity Disorder (ADHD)

Phase 4

Completed

Conditions: Attention Deficit Hyperactivity Disorder

Interventions: Drug: Atomoxetine Hydrochloride
Drug: Placebo

Registration Number: NCT00190775

Lead Sponsor: Eli Lilly and Company

Brief Summary: This is a parallel design, double-blind, placebo-controlled, multi-center, 38-week treatment trial of atomoxetine in adults with attention deficit hyperactivity disorder (ADHD) who are currently living in a family situation with at least one child. The primary objective of the study is to demonstrate the efficacy of atomoxetine compared to placebo in the reduction of ADHD symptoms over 12 and 24 weeks of blinded treatment.

Detailed Description: The initial study was 34 weeks long; however, the protocol was amended to extend the open-label period of the study from 8 weeks to 12 weeks (38 weeks total).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 502

Inclusion Criteria

Meet Diagnostic and Statistical Manual of Mental Disorders Fourth Edition - Text Revision (DSM-IV-TR) criteria for Adult Attention-Deficit/Hyperactivity Disorder (ADHD) as assessed by the Conners' Adult ADHD Diagnostic Interview for DSM-IV (CAADID).
Have a Clinical Global Impression for ADHD Severity Score (CGI-ADHD-S) of 4 or greater Visit 2 and 3.
Adult Men and Women age 18 years or older at time informed consent is obtained.
Must be in a reciprocal relationship with a person of the opposite sex living in same defined household (cohabitating) with their spouse/significant other for a period of at least 3 months. This spouse/significant other cannot change during the study.
Must have one or more children 6-17 years of age living the home as the primary residence.

Exclusion Criteria

Anyone meeting Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria for any history of bipolar disorder or any history of a psychotic disorder.
Anyone meeting diagnostic (DSM-IV) criteria for current major depression or current anxiety disorder.
Taking psychotropic medications on a regular basis.
Having any medical condition that would be exacerbated or not appropriate for inclusion in this trial.
Previously taken an adequate trial of atomoxetine.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Atomoxetine	Atomoxetine Hydrochloride	Atomoxetine 40 milligrams (mg) once daily (QD) for 3 days followed by 80 mg QD for 11 days OR 40 mg QD for 7 days followed by 80 mg QD for 7 days, then 60/80/100 mg as determined by the investigator up to 24 weeks, orally
Placebo	Placebo	Placebo is administered once daily (QD), orally for 24 weeks. At the end of 24 weeks, the placebo arm is titrated to atomoxetine 40 mg QD for 3 days followed by 80 mg QD for 11 days OR 40 mg QD for 7 days followed by 80 mg QD for 7 days, then 40-100 mg QD, orally.

Primary Outcome Measures

Name	Time	Method
Change From Baseline to 24 Weeks in the Conners' Adult Attention Deficit Hyperactivity Disorder Rating Scale - Investigator Rated: Screening Version (CAARS-Inv:SV) Total ADHD Symptoms Score	Baseline, 24 weeks	30-item scale containing 3 subscales: inattention (9 items), hyperactivity/ impulsivity (9 items), and ADHD Index (12 items). Each item is scored 0-3 (0=not at all/never; 1=just a little/once in a while; 2=pretty much/often; 3=very much/very frequently). Total ADHD symptoms score=sum of the inattention and hyperactivity/impulsivity subscales. Total Scores range from 0-54 (range of 0-27 for the inattention and hyperactivity subscales; 0-36 for the ADHD Index) with higher scores indicating more impaired participants. The scale was administered by a physician/PhD at the investigative site.
Change From Baseline to 12 Weeks in the Conners' Adult Attention Deficit Hyperactivity Disorder Rating Scale - Investigator Rated: Screening Version (CAARS-Inv:SV) Total ADHD Symptoms Score	Baseline, 12 weeks	30-item scale containing 3 subscales: inattention (9 items), hyperactivity/ impulsivity (9 items), and ADHD Index (12 items). Each item is scored 0-3 (0=not at all/never; 1=just a little/once in a while; 2=pretty much/often; 3=very much/very frequently). Total ADHD symptoms score=sum of the inattention and hyperactivity/impulsivity subscales. Total Scores range from 0-54 (range of 0-27 for the inattention and hyperactivity subscales; 0-36 for the ADHD Index) with higher scores indicating more impaired participants. The scale was administered by a physician/PhD at the investigative site.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline to 8 Weeks in the Family Assessment Measure Version III (FAM) Dyadic Relationship Scale (DRS) - Participant	Baseline, 8 weeks	FAM consists of 3 components: General Scale; Dyadic Relationships Scale (DRS), and Self-Rating Scale. Participants completed the DRS scale, a 42-item self-report scale providing quantitative indices of family strengths/weaknesses. Items are rated 0-3 (strongly agree, agree, disagree, strongly disagree). Raw scores=0-18 (each subscale) and are converted to a t-score (mean=50, standard deviation (SD)=10; scores range from 0-100). T-scores should be between 40-60. T-scores \>=60 indicate disturbance in family functioning.
Change From Baseline to 24 Weeks in the Family Assessment Measure Version III (FAM) Dyadic Relationship Scale (DRS) - Participant	Baseline, 24 weeks	FAM consists of 3 components: General Scale; Dyadic Relationships Scale (DRS), and Self-Rating Scale. Participants completed the DRS scale, a 42-item self-report scale providing quantitative indices of family strengths/weaknesses. Items are rated 0-3 (strongly agree, agree, disagree, strongly disagree). Raw scores=0-18 (each subscale) and are converted to a t-score (mean=50, standard deviation (SD)=10; scores range from 0-100). T-scores should be between 40-60. T-scores \>=60 indicate disturbance in family functioning.
Change From Baseline to 8 Weeks in the Family Assessment Measure Version III (FAM) Dyadic Relationship Scale (DRS) - Spouse/Significant Other	Baseline, 8 weeks	FAM consists of 3 components: General Scale; Dyadic Relationships Scale (DRS), and Self-Rating Scale. The spouse/significant other completed the DRS scale, a 42-item self-report scale providing quantitative indices of family strengths/weaknesses. Items are rated 0-3 (strongly agree, agree, disagree, strongly disagree). Raw scores=0-18 (each subscale) and are converted to a t-score (mean=50, standard deviation (SD)=10; scores range from 0-100). T-scores should be between 40-60. T-scores \>=60 indicate disturbance in family functioning.
Change From Baseline to 24 Weeks in the Family Assessment Measure Version III (FAM) Dyadic Relationship Scale (DRS) - Spouse/Significant Other	Baseline, 24 weeks	FAM consists of 3 components: General Scale; Dyadic Relationships Scale (DRS), and Self-Rating Scale. The spouse/significant other completed the DRS scale, a 42-item self-report scale providing quantitative indices of family strengths/weaknesses. Items are rated 0-3 (strongly agree, agree, disagree, strongly disagree). Raw scores=0-18 (each subscale) and are converted to a t-score (mean=50, standard deviation (SD)=10; scores range from 0-100). T-scores should be between 40-60. T-scores \>=60 indicate disturbance in family functioning.
Change From Baseline to 8 Weeks in the Dyadic Adjustment Scale (DAS) - Participant	Baseline, 8 weeks	32-item self-report scale to assess quality of the relationship perceived by participants. Response anchors vary and include a 5-, 6- or 7-point Likert scale (always agree/disagree; all the time/never); and 2 yes/no items. Assesses 4 relationship aspects (# items): dyadic satisfaction (10), cohesion (5), consensus (13), affectional expression (4). Raw score total=0-151 and is converted to a t-score (0-100; mean=50, standard deviation (SD)=10). T-scores of 45-55 indicate a typical score (no concern). Scores \<30 indicate significant impairment. Lower scores indicate poorer dyadic adjustment.
Change From Baseline to 24 Weeks in the Dyadic Adjustment Scale (DAS) - Participant	Baseline, 24 weeks	32-item self-report scale to assess quality of the relationship perceived by participants. Response anchors vary and include a 5-, 6- or 7-point Likert scale (always agree/disagree; all the time/never); and 2 yes/no items. Assesses 4 relationship aspects (# items): dyadic satisfaction (10), cohesion (5), and consensus (13), and affectional expression (4). Raw score total=0-151 and is converted to a t-score (0-100; mean=50, SD=10). T-scores of 45-55 indicate a typical score (no concern). Scores \<30 indicate significant impairment. Lower scores indicate poorer dyadic adjustment.
Change From Baseline to 8 Weeks in the Dyadic Adjustment Scale (DAS) - Spouse/Significant Other	Baseline, 8 weeks	32-item self-report scale to assess quality of the relationship perceived by the spouse/significant other. Response anchors vary and include a 5-, 6- or 7-point Likert scale (always agree/disagree; all the time/never); and 2 yes/no items. Assesses 4 relationship aspects (# items): dyadic satisfaction (10), cohesion (5), and consensus (13), and affectional expression (4). Raw score total=0-151 and is converted to a t-score (0-100; mean=50, SD=10). T-scores of 45-55 indicate a typical score (no concern). Scores \<30 indicate significant impairment. Lower scores indicate poorer dyadic adjustment.
Change From Baseline to 24 Weeks in the Dyadic Adjustment Scale (DAS) - Spouse/Significant Other	Baseline, 24 weeks	32-item self-report scale to assess quality of the relationship perceived by the spouse/significant other. Response anchors vary and include a 5-, 6- or 7-point Likert scale (always agree/disagree; all the time/never); and 2 yes/no items. Assesses 4 relationship aspects (# items): dyadic satisfaction (10), cohesion (5), and consensus (13), and affectional expression (4). Raw score total=0-151 and is converted to a t-score (0-100; mean=50, SD=10). T-scores of 45-55 indicate a typical score (no concern). Scores \<30 indicate significant impairment. Lower scores indicate poorer dyadic adjustment.
Change From Baseline to 8 Weeks in the Parenting Stress Index (PSI) Score - Total Stress and Life Stress	Baseline, 8 weeks	The PSI 19-item Stress Life Events scale has yes/no responses and measures situational circumstances beyond control (death of family member, divorce, etc.) in the past 12 months. Maximum score (all answers=yes) is 79; a Life Stress raw score \>=17 indicates high stress. Each question is weighted based upon the event. Total Score measures relative magnitude of stress in parent-child system. High scores (\>=85th percentile) indicate higher stress. Total Stress \>=258 is indicative of impairment. Participants with a child aged 6-12 or 13-17 years living at home completed the scale.
Change From Baseline to 8 Weeks in the Parenting Stress Index (PSI) Score - Parent Domains	Baseline, 8 weeks	120-item scale includes 101 items rated on 5-point Likert scale (strongly agree/strongly disagree) or 4-5 point multiple choices. Adult Domain characteristics' subscales and score ranges include: Competence (13-65), Isolation (6-30), Attachment (7-35), Health (5-25), Role Restriction (7-35), Depression (9-45), Spouse (7-35). Total Score measures relative magnitude of stress in parent-child system. Parent Domain score \>=148 (\>=85th percentile) is indicative of impairment. Participants with a child aged 6-12 or 13-17 years living at home completed the scale.
Change From Baseline to 8 Weeks in the Parenting Stress Index (PSI) Score - Child Domains	Baseline, 8 weeks	120-item scale includes 101 items rated on 5-point Likert scale (strongly agree/strongly disagree) or 4-5 point multiple choices. Child Domain characteristics' subscales and score ranges include: Distractibility/Hyperactivity (9-45), Adaptability (11-55), Reinforces Parent (6-30), Demandingness (9-45), Mood (5-25), Acceptability (7-35). Total Score measures relative magnitude of stress in parent-child system. A Child Domain score \>=116 (\>=85th percentile) is indicative of impairment. Participants with a child aged 6-12 or 13-17 years living at home completed the scale.
Change From Baseline to 24 Weeks in the Parenting Stress Index (PSI) Score - Total Stress and Life Stress	Baseline, 24 weeks	The PSI 19-item Stress Life Events scale has yes/no responses and measures situational circumstances beyond control (death of family member, divorce, etc.) in the past 12 months. Maximum score (all answers=yes) is 79; a Life Stress raw score \>=17 indicates high stress. Each question is weighted based upon the event. Total Score measures relative magnitude of stress in parent-child system. High scores (\>=85th percentile) indicate higher stress. Total Stress \>=258 is indicative of impairment. Participants with a child aged 6-12 or 13-17 years living at home completed the scale.
Change From Baseline to 24 Weeks in the Parenting Stress Index (PSI) Score - Parent Domains	Baseline, 24 weeks	120-item scale includes 101 items rated on 5-point Likert scale (strongly agree/strongly disagree) or 4-5 point multiple choices. Adult Domain characteristics' subscales and score ranges include: Competence (13-65), Isolation (6-30), Attachment (7-35), Health (5-25), Role Restriction (7-35), Depression (9-45), Spouse (7-35). Total Score measures relative magnitude of stress in parent-child system. Parent Domain score \>=148 (\>=85th percentile) is indicative of impairment. Participants with a child aged 6-12 or 13-17 years living at home completed the scale.
Change From Baseline to 24 Weeks in the Parenting Stress Index (PSI) Score - Child Domains	Baseline, 24 weeks	120-item scale includes 101 items rated on 5-point Likert scale (strongly agree/strongly disagree) or 4-5 point multiple choices. Child Domain characteristics' subscales and score ranges include: Distractibility/Hyperactivity (9-45), Adaptability (11-55), Reinforces Parent (6-30), Demandingness (9-45), Mood (5-25), Acceptability (7-35). Total Score measures relative magnitude of stress in parent-child system. A Child Domain score \>=116 (\>=85th percentile) is indicative of impairment. Participants with a child aged 6-12 or 13-17 years living at home completed the scale.
Change From Baseline to 12 Weeks in the Alabama Parenting Questionnaire (APQ) Parent Form	Baseline, 12 weeks	42-item scale, 3 subscales (z-scores \[-2 to 2\]): Dysfunctional/Negative/Positive Parenting. Each construct rated 1=never/5=always (# items): involvement (10), supervision (10), positive parenting (6), inconsistent discipline (6), other discipline (7), harsh discipline (3). Higher scores indicate impairment: dysfunctional/negative parenting composite; supervision, inconsistent discipline, harsh punishment, other discipline. Lower scores indicate impairment: positive parenting composite; positive parenting, involvement. Completed by participants with a child 6-12 or 13-17 years living at home.
Change From Baseline to 24 Weeks in the Alabama Parenting Questionnaire (APQ) Parent Form	Baseline, 24 weeks	42-item scale, 3 subscales (z-scores \[-2 to 2\]): Dysfunctional/Negative/Positive Parenting. Each construct rated 1=never/5=always (# items): involvement (10), supervision (10), positive parenting (6), inconsistent discipline (6), other discipline (7), harsh discipline (3). Higher scores indicate impairment: dysfunctional/negative parenting composite; supervision, inconsistent discipline, harsh punishment, other discipline. Lower scores indicate impairment: positive parenting composite; positive parenting, involvement. Completed by participants with a child 6-12 or 13-17 years living at home.
Change From Baseline to 12 Weeks in the Alabama Parenting Questionnaire (APQ) Child Form	Baseline, 12 Weeks	42-item scale, 3 subscales (z-scores \[-2 to 2\]): Dysfunctional/Negative/Positive Parenting. Each construct rated 1=never/5=always (# items): involvement (10), supervision (10), positive parenting (6), inconsistent discipline (6), other discipline (7), harsh discipline (3). Higher scores indicate impairment: dysfunctional/negative parenting composite; supervision, inconsistent discipline, harsh punishment, other discipline. Lower scores indicate impairment: positive parenting composite; positive parenting, involvement. Completed by child 6-12 or 13-17 years living at home.
Change From Baseline to 24 Weeks in the Alabama Parenting Questionnaire (APQ) Child Form	Baseline, 24 Weeks	42-item scale, 3 subscales (z-scores \[-2 to 2\]): Dysfunctional/Negative/Positive Parenting. Each construct rated 1=never/5=always (# items): involvement (10), supervision (10), positive parenting (6), inconsistent discipline (6), other discipline (7), harsh discipline (3). Higher scores indicate impairment: dysfunctional/negative parenting composite; supervision, inconsistent discipline, harsh punishment, other discipline. Lower scores indicate impairment: positive parenting composite; positive parenting, involvement. Completed by child 6-12 or 13-17 years living at home.
Mean Change From Baseline to 24 Weeks in the Child Disruptive Behavior Rating Scale (CDBRS) Parent Form	Baseline, 24 weeks	Contains the symptoms of ADHD (9 items for Inattention/9 items for Hyperactive-Impulsive). Total maximum severity score is 54 (0-27 for each subscale). Higher scores indicate greater impairment. Participants with a child 6-12 years old living in the home completed the scale.
Mean Change From Baseline to 24 Weeks in the Child Disruptive Behavior Rating Scale (CDBRS) Parent Form Oppositional Defiant Disorder (ODD) and Conduct Disorder Flags	Baseline, 24 weeks	Items 19-26 of the CDBRS assess the presence of Oppositional Defiant Disorder (ODD) (yes if participant answers \>=4 items as 2 \[often\] or 3 \[very often\]). Items 1-26 are rated on a 0-3 scale (0=never/rarely, 1=sometimes, 2=often, 3=very often). 15 yes/no items assess the presence of Conduct Disorder (yes if \>3 items answered yes). Participants with a child 6-12 years old living in the home completed the scale.
Change From Baseline to 8 Weeks in the Parenting Sense of Competence (PSOC) Scale	Baseline, 8 weeks	16-item scale to assess parenting self-esteem: the Satisfaction Subscale has 9 questions (2,3,4,5,8,9,12,14,16)=54; the Efficacy Subscale has 7 questions (1,6,7,10,11,13,15)=43. Each response on the satisfaction subscale is answered on a 6-point scale (strongly agree/strongly disagree). Higher scores indicate greater satisfaction and greater self-efficacy. Lower scores mean more impairment. Participants with a child aged 6-12 or 13-17 years living at home completed the scale.
Change From Baseline to 24 Weeks in the Parenting Sense of Competence (PSOC) Scale	Baseline, 24 weeks	16-item scale to assess parenting self-esteem: the Satisfaction Subscale has 9 questions (2,3,4,5,8,9,12,14,16)=54; the Efficacy Subscale has 7 questions (1,6,7,10,11,13,15)=43. Each response on the satisfaction subscale is answered on a 6-point scale (strongly agree/strongly disagree). Higher scores indicate greater satisfaction and greater self-efficacy. Lower scores mean more impairment. Participants with a child aged 6-12 or 13-17 years living at home completed the scale.
Change From Baseline to 12 and 24 Weeks in the Adult Attention Deficit Hyperactivity Disorder Investigator Symptom Rating Scale Total and Subscale Scores	Baseline, 12 weeks, 24 weeks	18-item scale that captures the 18-item DSM-IV symptoms of ADHD. 9 inattentive items alternate with 9 hyperactive/impulsive items. Each item is scored 0 (none), 1 (mild), 2 (moderate), or 3 (severe). The total score range is 0-54 (0-27 for each subscale). Higher scores indicate more impaired participants. The scale was administered by a physician or PhD at the investigative site.
Change From Baseline to 8 and 24 Weeks in the Clinical Global Improvement Attention Deficit Hyperactivity Disorder Severity (CGI-ADHD-S)	Baseline, 8 weeks, 24 weeks	The CGI-ADHD-S is a single-item rating of the clinician's assessment of the severity of ADHD symptoms in relation to the clinician's total experience with ADHD subjects. Severity is rated on a 7-point scale (1=normal, not at all ill; 7=among the most extremely ill subjects). The scale was administered by a physician or PhD at the investigative site.
Change From Baseline to 12 and 24 Weeks in the Montgomery-Asberg Depression Rating Scale Total Score (MADRS)	Baseline 12 weeks, 24 weeks	The MADRS is an investigator administered rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
Change From Baseline to 12 and 24 Weeks in the State-Trait Anxiety Inventories (STAI)	Baseline, 12 weeks, 24 weeks	Self-report scale completed by the participant. Separate scales measure state (20 items) and trait (20 items) anxiety. The participant reports how they feel "right now at this moment" for state anxiety and how they "generally" feel for trait anxiety. The "state" items are scored as: 1 (not at all), 2 (somewhat true), 3 (moderately true), 4 (very true). The "trait" items are scored as: 1 (almost never), 2 (sometimes), 3 (often), 4 (almost always). Scores range from 4-80 for each scale. Higher scores indicate more impaired participants.
Change From Baseline to 1 Week of Titration in the CAARS-Inv:SV Total Attention Deficit Hyperactivity Disorder (ADHD) Symptoms and Subscale Scores	Baseline, 1 week	30-item scale containing 3 subscales: inattention (9 items), hyperactivity/ impulsivity (9 items), and ADHD Index (12 items). Each item is scored 0-3 (0=not at all/never; 1=just a little/once in a while; 2=pretty much/often; 3=very much/very frequently). Total ADHD symptoms score=sum of the inattention and hyperactivity/impulsivity subscales. Total Scores range from 0-54 (range of 0-27 for the inattention and hyperactivity subscales; 0-36 for the ADHD Index) with higher scores indicating more impaired participants. The scale was administered by a physician/PhD at the investigative site.
Change From Baseline to 2 Weeks of Titration in the CAARS-Inv:SV Total Attention Deficit Hyperactivity Disorder (ADHD) Symptoms and Subscale Scores	Baseline, 2 weeks	30-item scale containing 3 subscales: inattention (9 items), hyperactivity/ impulsivity (9 items), and ADHD Index (12 items). Each item is scored 0-3 (0=not at all/never; 1=just a little/once in a while; 2=pretty much/often; 3=very much/very frequently). Total ADHD symptoms score=sum of the inattention and hyperactivity/impulsivity subscales. Total Scores range from 0-54 (range of 0-27 for the inattention and hyperactivity subscales; 0-36 for the ADHD Index) with higher scores indicating more impaired participants. The scale was administered by a physician/PhD at the investigative site.
Change From Baseline to After a 2-Week Titration Period Beginning at Week 24 and Ending at Week 26 in the CAARS-Inv:SV Total Attention Deficit Hyperactivity Disorder (ADHD) Symptoms and Subscale Scores: Dosing Titration Strategy After Placebo	Baseline, after 2-week titration period beginning at Week 24	30-item scale containing 3 subscales: inattention (9 items), hyperactivity/ impulsivity (9 items), and ADHD Index (12 items). Each item is scored 0-3 (0=not at all/never; 1=just a little/once in a while; 2=pretty much/often; 3=very much/very frequently). Total ADHD symptoms score=sum of the inattention and hyperactivity/impulsivity subscales. Total Scores range from 0-54 (range of 0-27 for the inattention and hyperactivity subscales; 0-36 for the ADHD Index) with higher scores indicating more impaired participants. The scale was administered by a physician/PhD at the investigative site.

Trial Locations

Locations (1): For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
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Santurce, Puerto Rico