Trial Outcomes & Findings for Open-Label Study of the Long Term Tolerability and Safety of Atomoxetine in Children With FASD and ADD/ADHD (NCT NCT00418262)

NCT ID: NCT00418262

Last Updated: 2017-07-02

Results Overview

Motor Tics Parent rating of none (0), mild (1) , moderate (2) or severe (3) for each manifestation

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 27 participants
• Primary outcome timeframe: 12 months or study duration
• Results posted on: 2017-07-02

Participant Flow

The study the recruited 29 (21 male/8 female) children between 10/18/2006 and 9/21/2011. The children were recruited from a prior efficacy trial. Participants for the efficacy trial were drawn from physician referral resources, self-referral, and a pool of subjects identified for a study sponsored by the Center for Disease Control and Prevention.

Two recruits declined particicpation in this open-label study. Participants continued to take atomoxetine/placeblo (depending on prior RCT assignment) until entry into this open label study.

Participant milestones

Measure	Atomoxetine HCL (Strattera) The subjects will receive atomoxetine at 0.5 mg/kg/day for the first week. The children will be seen weekly for assessment for 4 weeks, every month for two months, then every three months until the 12 month treatment period is complete. After one week of treatment response will be reassessed and the dose will be increased to 1.0 mg/kg/d unless there are excessive side effects. If there are mild side effects the dose will be held the same. If there are excessive side effects the dose will be split to 0.25 mg/kg-d BID. At visit 3 the dose will be increased to 1.0 or 1.4 mg/kg-d, depending on the previous dose, if there are not excessive side effects. This titration will occur at each visit.
Visits 1 (Baseline) Thru 5 STARTED	27
Visits 1 (Baseline) Thru 5 COMPLETED	25
Visits 1 (Baseline) Thru 5 NOT COMPLETED	2
Visits 5 Thru 8 STARTED	25
Visits 5 Thru 8 COMPLETED	16
Visits 5 Thru 8 NOT COMPLETED	9
Visits 8 Thru 10 STARTED	16
Visits 8 Thru 10 COMPLETED	11
Visits 8 Thru 10 NOT COMPLETED	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Open-Label Study of the Long Term Tolerability and Safety of Atomoxetine in Children With FASD and ADD/ADHD

Baseline characteristics by cohort

Measure	Atomoxetine HCL (Strattera) n=27 Participants The subjects will receive atomoxetine at 0.5 mg/kg/day for the first week. The children will be seen weekly for assessment for 4 weeks, every month for two months, then every three months until the 12 month treatment period is complete. After one week of treatment response will be reassessed and the dose will be increased to 1.0 mg/kg/d unless there are excessive side effects. If there are mild side effects the dose will be held the same. If there are excessive side effects the dose will be split to 0.25 mg/kg-d BID. At visit 3 the dose will be increased to 1.0 or 1.4 mg/kg-d, depending on the previous dose, if there are not excessive side effects. This "titration" will occur at each visit.
Age, Categorical <=18 years	27 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	7.4 years n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	15 Participants n=5 Participants
Race (NIH/OMB) More than one race	NA Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	9 Participants n=5 Participants
Region of Enrollment United States	27 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months or study duration

Population: Children with FAS participating in the extend safety efficacy study

Motor Tics

Parent rating of none (0), mild (1) , moderate (2) or severe (3) for each manifestation

Outcome measures

Measure	Atomoxetine HCL (Strattera) n=26 Participants Treatment of children with fetal alcohol syndrome and ADHD with Atomoxetine HCL (Strattera)
Pittsburg Side-Effects Scale: Motor Tics Visit 1	0.15 units on a scale Standard Deviation 0.54
Pittsburg Side-Effects Scale: Motor Tics Visit 5	0.20 units on a scale Standard Deviation 0.50
Pittsburg Side-Effects Scale: Motor Tics Visit 8	0.31 units on a scale Standard Deviation 0.60
Pittsburg Side-Effects Scale: Motor Tics Visit 10	0.27 units on a scale Standard Deviation 0.47

PRIMARY outcome

Timeframe: 12 months or study duration

Population: Attrition

Buccal, Lingual Movements

Parent rating of none (0), mild (1), moderate (2) or severe (3) for each manifestation.

Outcome measures

Measure	Atomoxetine HCL (Strattera) n=26 Participants Treatment of children with fetal alcohol syndrome and ADHD with Atomoxetine HCL (Strattera)
Pittsburg Side-Effects Scale-Buccal, Lingual Movements Visit 1	.12 units on a scale Standard Deviation .33
Pittsburg Side-Effects Scale-Buccal, Lingual Movements Visit 5	0.2 units on a scale Standard Deviation 0.50
Pittsburg Side-Effects Scale-Buccal, Lingual Movements Visit 8	0.44 units on a scale Standard Deviation 0.73
Pittsburg Side-Effects Scale-Buccal, Lingual Movements Visit 10	0.27 units on a scale Standard Deviation 0.47

PRIMARY outcome

Timeframe: 12 months or study duration

Population: 27 IN PCT and one subject did not enroll in the safety efficacy study

Movements, Picking/Chewing Skin or Fingers

Parent rating of none (0), mild (1) , moderate (2) or severe (3) for each manifestation

Outcome measures

Measure	Atomoxetine HCL (Strattera) n=26 Participants Treatment of children with fetal alcohol syndrome and ADHD with Atomoxetine HCL (Strattera)
Pittsburg Side-Effects Scale: Movements, Picking/Chewing Skin or Fingers Visit 1	0.42 units on a scale Standard Deviation 0.70
Pittsburg Side-Effects Scale: Movements, Picking/Chewing Skin or Fingers Visit 5	0.40 units on a scale Standard Deviation 0.58
Pittsburg Side-Effects Scale: Movements, Picking/Chewing Skin or Fingers Visit 8	0.62 units on a scale Standard Deviation 0.89
Pittsburg Side-Effects Scale: Movements, Picking/Chewing Skin or Fingers Visit 10	0.64 units on a scale Standard Deviation 1.03

PRIMARY outcome

Timeframe: 12 months or study duration

Population: One subject from RCT did not enroll in the open label study

Worried/Anxious

Parent rating of none (0), mild (1) , moderate (2) or severe (3) for each manifestation

Outcome measures

Measure	Atomoxetine HCL (Strattera) n=26 Participants Treatment of children with fetal alcohol syndrome and ADHD with Atomoxetine HCL (Strattera)
Pittsburg Side-Effects Scale: Worried/Anxious Visit 1	0.27 units on a scale Standard Deviation 0.45
Pittsburg Side-Effects Scale: Worried/Anxious Visit 5	0.24 units on a scale Standard Deviation 0.60
Pittsburg Side-Effects Scale: Worried/Anxious Visit 8	0.56 units on a scale Standard Deviation 0.63
Pittsburg Side-Effects Scale: Worried/Anxious Visit 10	0.45 units on a scale Standard Deviation 0.69

PRIMARY outcome

Timeframe: 12 months or study duration

Population: One subject from the RCT did not enter the open label study

Dull/Tired/Listless

Parent rating of none (0), mild (1) , moderate (2) or severe (3) for each manifestation

Outcome measures

Measure	Atomoxetine HCL (Strattera) n=26 Participants Treatment of children with fetal alcohol syndrome and ADHD with Atomoxetine HCL (Strattera)
Pittsburg Side-Effects Scale: Dull/Tired/Listless Visit 1	0.31 units on a scale Standard Deviation 0.62
Pittsburg Side-Effects Scale: Dull/Tired/Listless Visit 5	0.36 units on a scale Standard Deviation 0.57
Pittsburg Side-Effects Scale: Dull/Tired/Listless Visit 8	0.38 units on a scale Standard Deviation 0.62
Pittsburg Side-Effects Scale: Dull/Tired/Listless Visit 10	0.36 units on a scale Standard Deviation 0.50

PRIMARY outcome

Timeframe: 12 months or study duration

Population: One subject from the RCT did not enter the open label study

Headaches

Parent rating of none (0), mild (1) , moderate (2) or severe (3) for each manifestation

Outcome measures

Measure	Atomoxetine HCL (Strattera) n=26 Participants Treatment of children with fetal alcohol syndrome and ADHD with Atomoxetine HCL (Strattera)
Pittsburg Side-Effects Scale: Headaches Visit 1	0.23 units on a scale Standard Deviation 0.51
Pittsburg Side-Effects Scale: Headaches Visit 5	0.40 units on a scale Standard Deviation 0.82
Pittsburg Side-Effects Scale: Headaches Visit 8	0.31 units on a scale Standard Deviation 0.60
Pittsburg Side-Effects Scale: Headaches Visit 10	0.18 units on a scale Standard Deviation 0.40

PRIMARY outcome

Timeframe: 12 months or study duration

Population: One subject in the RCT did not enroll in the Open Label Study

Stomachaches

Parent rating of none (0), mild (1) , moderate (2) or severe (3) for each manifestation

Outcome measures

Measure	Atomoxetine HCL (Strattera) n=26 Participants Treatment of children with fetal alcohol syndrome and ADHD with Atomoxetine HCL (Strattera)
Pittsburg Side-Effects Scale: Stomachaches Visit 1	0.23 units on a scale Standard Deviation 0.51
Pittsburg Side-Effects Scale: Stomachaches Visit 5	0.36 units on a scale Standard Deviation 0.49
Pittsburg Side-Effects Scale: Stomachaches Visit 8	0.25 units on a scale Standard Deviation 0.58
Pittsburg Side-Effects Scale: Stomachaches Visit 10	0.45 units on a scale Standard Deviation 0.82

PRIMARY outcome

Timeframe: 12 months or study duration

Population: One Subject in the RCT did not enroll in the open label study

Crabby/Irritable

Parent rating of none (0), mild (1) , moderate (2) or severe (3) for each manifestation

Outcome measures

Measure	Atomoxetine HCL (Strattera) n=26 Participants Treatment of children with fetal alcohol syndrome and ADHD with Atomoxetine HCL (Strattera)
Pittsburg Side-Effects Scale: Crabby/Irritable Visit 1	0.85 units on a scale Standard Deviation 0.88
Pittsburg Side-Effects Scale: Crabby/Irritable Visit 5	0.68 units on a scale Standard Deviation 0.85
Pittsburg Side-Effects Scale: Crabby/Irritable Visit 8	1.06 units on a scale Standard Deviation 0.85
Pittsburg Side-Effects Scale: Crabby/Irritable Visit 10	0.73 units on a scale Standard Deviation 0.65

PRIMARY outcome

Timeframe: 12 months or study duration

Population: One subject in RCT did not participate in the open label study

Tearful/Sad/Depressed

Parent rating of none (0), mild (1) , moderate (2) or severe (3) for each manifestation

Outcome measures

Measure	Atomoxetine HCL (Strattera) n=26 Participants Treatment of children with fetal alcohol syndrome and ADHD with Atomoxetine HCL (Strattera)
Pittsburg Side-Effects Scale: Tearful/Sad/Depressed Visit 1	0.19 units on a scale Standard Deviation 0.40
Pittsburg Side-Effects Scale: Tearful/Sad/Depressed Visit 5	0.24 units on a scale Standard Deviation 0.52
Pittsburg Side-Effects Scale: Tearful/Sad/Depressed Visit 8	0.50 units on a scale Standard Deviation 0.63
Pittsburg Side-Effects Scale: Tearful/Sad/Depressed Visit 10	0.27 units on a scale Standard Deviation 0.47

PRIMARY outcome

Timeframe: 12 months or study duration

Population: One subject in the RCT did not enroll in the open label study

Socially Withdrawn

Parent rating of none (0), mild (1) , moderate (2) or severe (3) for each manifestation

Outcome measures

Measure	Atomoxetine HCL (Strattera) n=26 Participants Treatment of children with fetal alcohol syndrome and ADHD with Atomoxetine HCL (Strattera)
Pittsburg Side-Effects Scale: Socially Withdrawn Visit 1	0.12 units on a scale Standard Deviation 0.43
Pittsburg Side-Effects Scale: Socially Withdrawn Visit 5	0.16 units on a scale Standard Deviation 0.47
Pittsburg Side-Effects Scale: Socially Withdrawn Visit 8	0.25 units on a scale Standard Deviation 0.58
Pittsburg Side-Effects Scale: Socially Withdrawn Visit 10	0.09 units on a scale Standard Deviation 0.30

PRIMARY outcome

Timeframe: 12 months or study duration

Population: One subject in the RCT did not enroll in the open label study

Hallucinations

Parent rating of none (0), mild (1) , moderate (2) or severe (3) for each manifestation

Outcome measures

Measure	Atomoxetine HCL (Strattera) n=26 Participants Treatment of children with fetal alcohol syndrome and ADHD with Atomoxetine HCL (Strattera)
Pittsburg Side-Effects Scale: Hallucinations Visit 1	0.04 units on a scale Standard Deviation 0.20
Pittsburg Side-Effects Scale: Hallucinations Visit 5	0.00 units on a scale Standard Deviation 0.00
Pittsburg Side-Effects Scale: Hallucinations Visit 8	0.12 units on a scale Standard Deviation 0.50
Pittsburg Side-Effects Scale: Hallucinations Visit 10	0.00 units on a scale Standard Deviation 0.00

PRIMARY outcome

Timeframe: 12 months or study duration

Population: One subject in the RCT did not enroll in the open label study

Loss of Appetite

Parent rating of none (0), mild (1) , moderate (2) or severe (3) for each manifestation

Outcome measures

Measure	Atomoxetine HCL (Strattera) n=26 Participants Treatment of children with fetal alcohol syndrome and ADHD with Atomoxetine HCL (Strattera)
Pittsburg Side-Effects Scale: Loss of Appetite Visit 1	0.46 units on a scale Standard Deviation .65
Pittsburg Side-Effects Scale: Loss of Appetite Visit 5	0.56 units on a scale Standard Deviation 0.65
Pittsburg Side-Effects Scale: Loss of Appetite Visit 8	0.38 units on a scale Standard Deviation 0.50
Pittsburg Side-Effects Scale: Loss of Appetite Visit 10	0.45 units on a scale Standard Deviation 0.52

PRIMARY outcome

Timeframe: 12 months or study duration

Population: One subject participating in the RCT did not participate in the open label

Trouble Sleeping Parent rating of none (0), mild (1) , moderate (2) or severe (3) for each manifestation.

Outcome measures

Measure	Atomoxetine HCL (Strattera) n=26 Participants Treatment of children with fetal alcohol syndrome and ADHD with Atomoxetine HCL (Strattera)
Pittsburg Side-Effects Scale: Trouble Sleeping Visit 1	0.35 units on a scale Standard Deviation 0.57
Pittsburg Side-Effects Scale: Trouble Sleeping Visit 5	0.64 units on a scale Standard Deviation 0.70
Pittsburg Side-Effects Scale: Trouble Sleeping Visit 8	0.53 units on a scale Standard Deviation 0.74
Pittsburg Side-Effects Scale: Trouble Sleeping Visit 10	0.40 units on a scale Standard Deviation 0.52

SECONDARY outcome

Timeframe: 12 months or study duration

Population: ADHD Parent Rating Scale

Parent rate the frequency of 18 of their child's behaviors from not at all (0), just a little (1) , pretty much (2) to very much (3) for each behavior. The Item scores were summed to arrive at a total score which ranged from 0 to 54. The higher the score, the worse the behavior.

Outcome measures

Measure	Atomoxetine HCL (Strattera) n=26 Participants Treatment of children with fetal alcohol syndrome and ADHD with Atomoxetine HCL (Strattera)
Determine if Changes in Behavior Seen With Short-term (Eight Weeks) Treatment of Children Are Maintained Over a Twelve Month Period. Visit 1	37.35 units on a scale Interval 32.64 to 42.35
Determine if Changes in Behavior Seen With Short-term (Eight Weeks) Treatment of Children Are Maintained Over a Twelve Month Period. Visit 8	27.87 units on a scale Interval 23.52 to 32.26
Determine if Changes in Behavior Seen With Short-term (Eight Weeks) Treatment of Children Are Maintained Over a Twelve Month Period. Visit 10	31.88 units on a scale Interval 24.94 to 38.63

SECONDARY outcome

Timeframe: 12 months or study duration

Population: Measurements of height were not consistently obtained on all subjects.

Height measured in centimeters at the time of each visit as part of the vital signs.

Outcome measures

Measure	Atomoxetine HCL (Strattera) n=26 Participants Treatment of children with fetal alcohol syndrome and ADHD with Atomoxetine HCL (Strattera)
Compare Growth While on Atomoxetine With Growth Before Entry Into Study. Visit 1	121.67 cm Standard Deviation 9.84
Compare Growth While on Atomoxetine With Growth Before Entry Into Study. Visit 8	123.27 cm Standard Deviation 4.01
Compare Growth While on Atomoxetine With Growth Before Entry Into Study. Visit 10	132.13 cm Standard Deviation 8.77

Adverse Events

Atomoxetine HCL (Strattera)

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Atomoxetine HCL (Strattera) n=26 participants at risk The subjects received 7 days of atomoxetine at 0.5 mg/kg/day. The children were seen weekly for assessment for 4 weeks then every two weeks until the eight week double blind period was completed. After each week of treatment, response was reassessed and the dose was increased to 1.0 then 1.4 mg/kg/d unless there were excessive side effects. The subjects were then invited to continue for 1 year to assess safety and efficacy
Respiratory, thoracic and mediastinal disorders Cough	34.6% 9/26 • Number of events 204 • 1 year All-Ccause Mortality and Serious Adverse Events were monitored.
Gastrointestinal disorders Vomiting	30.8% 8/26 • Number of events 204 • 1 year All-Ccause Mortality and Serious Adverse Events were monitored.
Nervous system disorders Headache	30.8% 8/26 • Number of events 204 • 1 year All-Ccause Mortality and Serious Adverse Events were monitored.
Gastrointestinal disorders Stomachache	26.9% 7/26 • Number of events 204 • 1 year All-Ccause Mortality and Serious Adverse Events were monitored.
Nervous system disorders Sleepy or Sleep Trouble	26.9% 7/26 • Number of events 204 • 1 year All-Ccause Mortality and Serious Adverse Events were monitored.
General disorders Nasal Congestion or Rhinorrhea	23.1% 6/26 • Number of events 204 • 1 year All-Ccause Mortality and Serious Adverse Events were monitored.
Psychiatric disorders Irritability	15.4% 4/26 • Number of events 204 • 1 year All-Ccause Mortality and Serious Adverse Events were monitored.
Renal and urinary disorders Enuresis	15.4% 4/26 • Number of events 204 • 1 year All-Ccause Mortality and Serious Adverse Events were monitored.
General disorders Fever	15.4% 4/26 • Number of events 204 • 1 year All-Ccause Mortality and Serious Adverse Events were monitored.
Infections and infestations Upper Respiratory or Sinus Infection	15.4% 4/26 • Number of events 204 • 1 year All-Ccause Mortality and Serious Adverse Events were monitored.
General disorders Dizziness	11.5% 3/26 • Number of events 204 • 1 year All-Ccause Mortality and Serious Adverse Events were monitored.
Gastrointestinal disorders Diarrhea	11.5% 3/26 • Number of events 204 • 1 year All-Ccause Mortality and Serious Adverse Events were monitored.
Ear and labyrinth disorders Ear Infection	11.5% 3/26 • Number of events 204 • 1 year All-Ccause Mortality and Serious Adverse Events were monitored.
Skin and subcutaneous tissue disorders Skin Rash or Redness	7.7% 2/26 • Number of events 204 • 1 year All-Ccause Mortality and Serious Adverse Events were monitored.
Infections and infestations Sore Throat	7.7% 2/26 • Number of events 204 • 1 year All-Ccause Mortality and Serious Adverse Events were monitored.
Gastrointestinal disorders Decreased Appetite	7.7% 2/26 • Number of events 204 • 1 year All-Ccause Mortality and Serious Adverse Events were monitored.
Respiratory, thoracic and mediastinal disorders Asthma or Wheezing	7.7% 2/26 • Number of events 204 • 1 year All-Ccause Mortality and Serious Adverse Events were monitored.
General disorders Fatigue	7.7% 2/26 • Number of events 204 • 1 year All-Ccause Mortality and Serious Adverse Events were monitored.
Psychiatric disorders Sad and Angry or Mood Swings	7.7% 2/26 • Number of events 204 • 1 year All-Ccause Mortality and Serious Adverse Events were monitored.

Additional Information

Mark Wolraich, M.D.

University of Oklahoma Health Sciences Center

Phone: (405) 271-5700

Email: mark-wolraich@ouhsc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place