Clinical trial NCT00250705
Conditions: Conduct Disorder
Keywords: Aripiprazole
Sponsor: University of Iowa
Start date: 2004-11-17; Completion date: 2009-03-23
Enrollment: 12 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The proposed study will be a 6-week open label study evaluating aripiprazole in the treatment of 12 male post-pubertal adolescents (13-17 years, Tanner Stage 4) diagnosed with conduct disorder. The initial dose depending on the weight of the patient will be as follows: \< 25 kg = 1 mg/d; 25-50 kg = 2 mg/d; 50-70 kg = 5 mg/d; \> 70 kg = 10 mg/d (Data on File, 2003, Bristol-Myers Squibb). For the first two weeks of the study, the dose will be flexible based on response and tolerance and thereafter will remain fixed.

Detailed description:
The use of atypical antipsychotics in children began in 1992 with several small case series with clozapine. Since that time, five other atypical agents, risperidone, olanzapine, quetiapine, ziprasidone and aripiprazole have been introduced into the US market. The newer atypical agents are not associated with agranulocytosis that has limited the usefulness of clozapine. Among the atypical antipsychotics, risperidone has remained the most extensively studied in children and adolescents, for a variety of problems, including Tourette's disorder, conduct disorder, schizophrenia, aggression, and pervasive development disorder. Risperidone has been shown to be an effective treatment in many of these disorders. However, weight gain, hyperprolactinemia, and extrapyramidal symptoms (EPS) are troublesome adverse effects more commonly associated with risperidone such that the drug's utility in this aged patient population is limited. We expect that the utility of aripiprazole in treating the pediatric population will not be limited by adverse effects like the other atypical antipsychotics.

Arms: arm 1: All subjects were male and had a diagnosis of conduct disorder. All subjects were offered treatment with aripiprazole.
Interventions: intervention 1: Aripiprazole
Intervention descriptions: intervention 1: The initial dose depending on the weight of the patient will be as follows: \< 25 kg = 1 mg/d; 25-50 kg = 2 mg/d; 50-70 kg = 5 mg/d; \> 70 kg = 10 mg/d (Data on File, 2003, Bristol-Myers Squibb). Thereafter the dose will be flexible based on response and tolerance for the duration of the 6 week study. All subjects initially received either a 5 or 10 mg/d (7.0 ± 2.6 mg/d) dose of aripiprazole. Thereafter the dose was individualized based on response and tolerance. Maximum dose was 20 mg.

Protocol documents:
ICF_002.pdf: 
FOR IRB USE ONLY 
$STAMP_IRB 
$STAMP_IRB_ID 
$STAMP_APPRV_DT 
$STAMP_EXP_DT 
 
 
 
Page 1 of 7 
 
INFORMED CONSENT DOCUMENT 
 
Project Title: 
An Open Label Trial of Aripiprazole in the Treatment of Conduct Disorder in 
 
Adolescents 
 
Research Team: Samuel Kuperman, MD, Chadi Calarge, MD, Anne Kolar, MD,  
 
Timothy Holman, MA 
 
 
• If you are the parent/guardian of a child under 18 years old who is being invited to be in this study, 
the word “you” in this document refers to your child.  You will be asked to read and sign this 
document to give permission for your child to participate.   
• If you are a teenager reading this document because you are being invited to be in this study, the 
word “you” in this document refers to you.  You will be asked to read and sign this document to 
indicate your willingness to participate. 
 
 
This consent form describes the research study to help you decide if you want to participate.  This form 
provides important information about what you will be asked to do during the study, about the risks and 
benefits of the study, and about your rights as a research subject.   
• If you have any questions about or do not understand something in this form, you should ask 
the research team for more information.   
• You should discuss your participation with anyone you choose such as family or friends.   
• Do not sign this form unless the study research team has answered your questions and you 
decide that you want to be part of this study.  
 
WHAT IS THE PURPOSE OF THIS STUDY? 
This is a research study.  We are inviting you to participate in this research study because you are a male 
between the ages of 13 and 17 and have been diagnosed with Conduct Disorder. 
 
The purpose of this research study is to evaluate the safety and effectiveness of a drug called 
aripiprazole as a treatment for conduct disorder.  Aripiprazole was recently approved by the US Food 
and Drug Administration (FDA) for use in adults as a treatment for psychotic disorders.  However, it has 
not been approved for use in people under the age of 18 or as a treatment for conduct disorder.  
Therefore it is considered investigational.   
HOW MANY PEOPLE WILL PARTICIPATE? 
Approximately 20 people will take part in this study at the University of Iowa 
 
HOW LONG WILL I BE IN THIS STUDY? 
If you agree to take part in this study, your involvement will last for to 7 weeks.  If you complete the 
study there will be a total of 6 visits.  Each of the first 5 visits will last about one hour.  The last visit 
will last about 2 hours.  The second, third and fourth visits will be weekly.  The fifth visit will be 2 
weeks after the fourth visit.  The final visit will be 2 weeks after the fifth visit.  


FOR IRB USE ONLY 
$STAMP_IRB 
$STAMP_IRB_ID 
$STAMP_APPRV_DT 
$STAMP_EXP_DT 
 
 
 
Page 2 of 7 
WHAT WILL HAPPEN DURING THIS STUDY? 
The first thing that will happen in this study is the study doctor will perform a physical examination and 
discuss your medical and psychiatric history with you.  Your vital signs (blood pressure and pulse) will 
be recorded. Measurements of your height, weight, and the distance around your waist, hips and arms 
will be recorded in order to calculate your body mass index (BMI).  A blood sample will be taken for 
routine tests and you will be required to provide a urine sample for drugs of abuse testing.  You will also 
have an electro-cardiogram (ECG), which is a routine heart test.  All of these tests are to make sure you 
don’t have a physical problem that would prevent you from taking part in the rest of the study. 
 
If you are eligible to continue in the study you will be invited back for a second visit.  This is called the 
“baseline” visit.  Your vital signs and BMI will again be recorded.  The study doctor and one of the 
other investigators will interview you about your symptoms of Conduct Disorder.  Medication side 
effect ratings will be also be done.  One of your parents or guardians will also be asked to fill out 3 
questionnaires about your symptoms.  All of the information at the baseline visit is to determine your 
level of functioning before your first dose of aripiprazole.  At the end of this visit aripiprazole will be 
dispensed to you.  The study doctor will explain how and when to take the medication. 
 
One week later you will return for the third visit.  Your vital signs and BMI will again be recorded.  The 
study doctor and one of the other investigators will interview you about your symptoms of Conduct 
Disorder.  Medication side effect ratings will be also be done.  One of your parents or guardians will 
again be asked to fill out 3 questionnaires about your symptoms. The aripiprazole dose may be increased 
at this visit, depending on whether you report any side effects from the medication. 
 
One week later you will return for a fourth visit.  Your vital signs and BMI will again be recorded.  The 
study doctor and one of the other investigators will interview you about your symptoms of Conduct 
Disorder.  Medication side effect ratings will be again be done.  One of your parents or guardians will 
again be asked to fill out 3 questionnaires about your symptoms. The aripiprazole dose may again be 
increased at this visit, or decreased depending on whether you report any side effects from the 
medication. 
 
Two weeks later you will return for a fifth visit.  All of the things that were done at the fourth visit will 
be repeated.  The aripiprazole dose may again be increased at this visit, or decreased depending on 
whether you report any side effects from the medication. 
  
Two weeks later you will return for the sixth and final visit.  The study doctor will repeat the physical 
examination that was performed at the first visit.  An ECG will be repeated.  Blood will be collected for 
routine laboratory tests.  Urine will be collected for drugs of abuse testing.  Your vital signs and BMI 
will again be recorded.  The study doctor and one of the other investigators will interview you about 
your symptoms of conduct disorder.  Medication side effect ratings will be also be done.  One of your 
parents or guardians will again be asked to fill out 3 questionnaires about your symptoms. The study 
doctor will discuss with you and at least one of your parents or guardians whether you should continue 
to take aripiprazole.  He will also discuss alternative treatments, if applicable.  The schedule of events 
for the study is summarized in the following table: 
 
 
 


FOR IRB USE ONLY 
$STAMP_IRB 
$STAMP_IRB_ID 
$STAMP_APPRV_DT 
$STAMP_EXP_DT 
 
 
 
Page 3 of 7 
Procedure 
Screening visit 
baseline week 1 week 2 week 4 week 6 
 
 
 
 
 
 
 
Time until next visit 
2-7 days 
7 days 
7days 
14 days 14 days 
 
 
 
 
 
 
 
 
Physical Exam 
X 
 
 
 
 
X 
ECG 
X 
 
 
 
 
X 
Vitals, Height, Weight, BMI 
X 
X 
X 
X 
X 
X 
Urine Collection 
X 
 
 
 
 
X 
Blood collection 
X 
 
 
 
 
X 
Interview with study doctor 
X 
X 
X 
X 
X 
X 
Interview with study team 
 
X 
X 
X 
X 
X 
Parent/Guardian questionnaires 
 
X 
X 
X 
X 
X 
 
 
WHAT ARE THE RISKS OF THIS STUDY? 
There may be some risks from being in this study.  The most common side effects seen with aripiprazole 
in adults were headache, feeling slowed down, fever, upset stomach, vomiting, constipation, anxiety, 
trouble sleeping, lightheadedness, sleepiness, restlessness, tremor, cold symptoms, coughing, rash and 
blurred vision.  
 
Blood collection involves a needle stick that may cause pain, bleeding, bruising, fainting and in rare 
cases an infection.   
 
The interviews and questionnaires may cause emotional discomfort.  You are free not to answer 
questions that cause discomfort. 
 
Are there any Unforeseen Risks? 
In addition to the risks described above, there may be unknown risks, or risks that we did not anticipate, 
associated with being in this study.  Aripiprazole is not approved by the FDA for use in people under the 
age of 18 or for people with Conduct Disorder.  Information about the use of aripiprazole in people 
under the age of 18 is limited.   
 
WHAT ARE THE BENEFITS OF THIS STUDY? 
We don’t know if you will benefit from being in this study.  However, we hope that, in the future, other 
people might benefit from this study because of knowledge gained by the investigators about the use of 
aripiprazole in people age 13 to 17 with Conduct Disorder.  
 
WHAT OTHER TREATMENT OPTIONS ARE THERE? 
Before you decide whether or not to be in this study, your doctor will discuss the other options that are 
available to you.  Instead of being in this study, you could receive counseling; take other medications, or 
both.  
 


FOR IRB USE ONLY 
$STAMP_IRB 
$STAMP_IRB_ID 
$STAMP_APPRV_DT 
$STAMP_EXP_DT 
 
 
 
Page 4 of 7 
WILL IT COST ME ANYTHING TO BE IN THIS STUDY? 
You will not have any costs for being in this research study. You and/or your medical/hospital insurance 
carrier will remain responsible for your regular medical care expenses. 
 
WILL I BE PAID FOR PARTICIPATING? 
You will be paid for being in this research study. You will be paid $50 for each completed visit.  
Payment will be by a check issued by the University of Iowa in the name of the minor participant (the 
person who actually receives the study drug), not the parent or guardian.  It usually takes 1 to 2 weeks 
after a visit before you receive payment.  If you complete all 6 visits the total payment will be $300.   
You will need to provide your social security number (SSN) in order for us to pay you. You may also 
need to provide your address if a check will be mailed to you.  
 
WHO IS FUNDING THIS STUDY? 
Bristol-Myers Squibb Co. is funding this research study.  Bristol-Myers Squibb Co. is the drug company 
that makes aripiprazole.  This means that the University of Iowa is receiving payments from Bristol-
Myers Squibb Co. to support the activities that are required to conduct the study.  No one on the 
research team will receive a direct payment or an increase in salary from for conducting this study.   
 
 
WHAT IF I AM INJURED AS A RESULT OF THIS STUDY? 
 
• If you are injured or become ill from taking part in this study, medical treatment is available at the 
University of Iowa Hospitals and Clinics. 
• No compensation for treatment of research-related illness or injury is available from the University 
of Iowa unless it is proven to be the direct result of negligence by a University employee. 
• If you experience a research-related illness or injury, sustained from the administration of the study 
drugs in accordance with the protocol, sponsor, BMS will pay for the all hospital and medical costs 
required for diagnosis and treatment provided that such costs are not covered by any third party or 
governmental programs providing such coverage. 
 
WHAT ABOUT CONFIDENTIALITY? 
We will keep your participation in this research study confidential to the extent permitted by law.  
However, it is possible that other people may become aware of your participation in this study.  For 
example, federal government regulatory agencies, the U.S. Food and Drug Administration, Bristol-
Myers, Squibb Co. auditing departments of the University of Iowa and the University of Iowa 
Institutional Review Board (a committee that reviews and approves research studies) may inspect and 
copy records pertaining to this research.  Some of these records could contain information that 
personally identifies you.    
   
In the future, Bristol-Myers Squibb Co. may continue to use your health information that is collected as 
part of this study. For example, Bristol-Myers Squibb Co. may combine information from this study 
with the results of other studies to re-analyze the safety and effectiveness of the study medication, to 
evaluate other products or therapies, to develop a better understanding of a disease, or to improve the 
design of future research studies. Bristol-Myers Squibb Co. may also share information from the study 
with regulatory agencies in foreign countries. 
 


FOR IRB USE ONLY 
$STAMP_IRB 
$STAMP_IRB_ID 
$STAMP_APPRV_DT 
$STAMP_EXP_DT 
 
 
 
Page 5 of 7 
To help protect your confidentiality, we will include replacing your name on the interview forms with a 
5-digit number, storing records in a locked file cabinet in a locked room in a building with access 
limited to members of the study team, and storing electronic records on computers that are protected 
with passwords.  Laboratory reports, ECG reports and doctor’s notes will be placed in your hospital 
chart.  If we write a report or article about this study or share the study data set with others, we will do 
so in such a way that you cannot be directly identified. 
 
We are taking some special steps to protect your confidentiality. The University of Iowa Hospitals and 
Clinics generally requires that we put a copy of this Informed Consent Document in your medical record 
chart. Instead of doing that, we’ll ask you to sign another form, called a Record of Consent, which gives 
no specific information about this study. The Record of Consent will be placed in your medical record 
chart. We will keep this Informed Consent Document in our research files; it will not be placed in your 
medical record chart. 
 
To further protect your privacy, the researchers have obtained a Certificate of Confidentiality from the 
Department of Health and Human Services (DHHS).  This Certificate means that the researchers cannot 
be forced (for example by court subpoena) to disclose information that may identify you in any federal, 
state, or local civil, criminal, administrative, legislative, or other proceeding.  However, a Certificate of 
Confidentiality does not prohibit the researcher from disclosing information about you or your 
involvement in this research that you have agreed to disclose or make available.  For example, if you or 
your legally authorized representative request in writing that information about you or your participation 
in the research be released to an insurance company, the researcher may not use the Certificate of 
Confidentiality to withhold this information.  This means that you and your family should actively 
protect your own privacy.  Finally, the researcher is not prevented from taking steps, including reporting 
to appropriate authorities, to prevent serious harm to yourself or others.  You may receive a copy of the 
Certificate of Confidentiality upon request. 
 
WILL MY HEALTH INFORMATION BE USED DURING THIS STUDY? 
The Federal Health Insurance Portability and Accountability Act (HIPAA) requires your health care 
provider to obtain your permission for the research team to access or create “protected health 
information” about you for purposes of this research study.  Protected health information is information 
that personally identifies you and relates to your past, present, or future physical or mental health 
condition or care.  We will access or create health information about you, as described in this document, 
for purposes of this research study and for your treatment.  Once your health care provider has disclosed 
your protected health information to us, it may no longer be protected by the Federal HIPAA privacy 
regulations, but we will continue to protect your confidentiality as described under “Confidentiality.” 
 
We may share your health information related to this study with other parties including federal 
government regulatory agencies, the University of Iowa Institutional Review Boards and support staff, 
and Bristol-Myers Squibb Co.  
 
You cannot participate in this study unless you permit us to use your protected health information.  If 
you choose not to allow us to use your protected health information, we will discuss any non-research 
alternatives available to you.  Your decision will not affect your right to medical care that is not 
research-related.  Your signature on this Consent Document authorizes your health care provider to give 
us permission to use or create health information about you. 


FOR IRB USE ONLY 
$STAMP_IRB 
$STAMP_IRB_ID 
$STAMP_APPRV_DT 
$STAMP_EXP_DT 
 
 
 
Page 6 of 7 
 
Although you may not be allowed to see study information until after this study is over, you may be 
given access to your health care records by contacting your health care provider. Your permission for us 
to access or create protected health information about you for purposes of this study has no expiration 
date. You may withdraw your permission for us to use your health information for this research study by 
sending a written notice to Samuel Kuperman, M.D., 1873 JPP, University of Iowa, Iowa City, Iowa 
52242. However, we may still use your health information that was collected before withdrawing your 
permission.  Also, if we have sent your health information to a third party, such as the study sponsor, or 
we have removed your identifying information, it may not be possible to prevent its future use.  You will 
receive a copy of this signed document. 
 
IS BEING IN THIS STUDY VOLUNTARY? 
Taking part in this research study is completely voluntary.  You may choose not to take part at all.  If 
you decide to be in this study, you may stop participating at any time.  If you decide not to be in this 
study, or if you stop participating at any time, you won’t be penalized or lose any benefits for which you 
otherwise qualify. 
 
What if I Decide to Drop Out of the Study? 
If you decide to leave the study early, we will ask you to return for a close out visit in which we will 
conduct all the safety testing and interviews that are scheduled at the final visit.  If you choose not to 
have the safety testing it won’t be possible for the study team to know whether you had any bad effects 
from taking part in the study.  You also would be expected to return all un-used study drug at the end of 
the study or if you choose to stop the study early.   
 
Will I Receive New Information About the Study while Participating? 
If we obtain any new information during this study that might affect your willingness to continue 
participating in the study, we’ll promptly provide you with that information. 
 
Can Someone Else End my Participation in this Study? 
Under certain circumstances, the researchers or the study sponsor might decide to end your participation 
in this research study earlier than planned.  This might happen because the sponsor stops funding the 
study.  This might also happen because the study doctor feels it would not be safe for you to continue or 
because you experience side effects.  
WHAT IF I HAVE QUESTIONS? 
We encourage you to ask questions.  If you have any questions about the research study itself, please 
contact:  Samuel Kuperman, M.D. at 319-356-1482, Anne Kolar, M.D. at 319-356-1182 or Chadi 
Calarge, M.D. at 319-335-8771.  If  you have a problem during evening or weekend hours that you feel 
needs immediate medical attention and neither Dr. Kuperman nor Dr. Kolar nor Dr. Calarge are 
available, you should go to the nearest emergency room.  The University of Iowa Healthcare general 
number is 319-356-1616.  You can ask to speak with the psychiatric resident (who is a medical doctor) 
on call.  
 


FOR IRB USE ONLY 
$STAMP_IRB 
$STAMP_IRB_ID 
$STAMP_APPRV_DT 
$STAMP_EXP_DT 
 
 
 
Page 7 of 7 
If you have questions, concerns, or complaints about  your rights as a research subject or about research 
related injury, please contact the Human Subjects Office, 340 College of Medicine Administration 
Building, The University of Iowa, Iowa City, Iowa, 52242, (319) 335-6564, or e-mail irb@uiowa.edu.  
General information about being a research subject can be found by clicking “Info for Public” on the 
Human Subjects Office web site, http://research.uiowa.edu/hso. 
 
 
This Informed Consent Document is not a contract. It is a written explanation of what will happen 
during the study if you decide to participate. You are not waiving any legal rights by signing this 
Informed Consent Document. Your signature indicates that this research study has been explained to 
you, that your questions have been answered, and that you agree to take part in this study.  You will 
receive a copy of this form. 
 
 
Subject's Name (printed):  __________________________________________________________ 
 
 
__________________________________________ 
_______________________________ 
(Signature of Subject)  
 
 
 
 
(Date) 
 
 
Parent/Guardian or Legally Authorized Representative’s Name and Relationship to Subject: 
 
 
__________________________________________ 
_______________________________ 
(Name - printed) 
 
 
 
 
 
(Relationship to Subject - printed) 
 
 
__________________________________________ 
_______________________________ 
(Signature of Parent/Guardian or 
 
 
 
(Date)  
Legally Authorized Representative) 
 
 
Statement of Person Who Obtained Consent 
 
I have discussed the above points with the subject or, where appropriate, with the subject’s legally 
authorized representative.  It is my opinion that the subject understands the risks, benefits, and 
procedures involved with participation in this research study. 
 
 
__________________________________________ 
_______________________________ 
(Signature of Person who Obtained Consent) 
 
(Date) 
 
 

Prot_000.pdf: 
PROTOCOL: An Open Label Trial of Aripiprazole in the Treatment of Conduct 
Disorder in Adolescents. 
 
Rationale: 
 
The use of atypical antipsychotics in children began in 1992 with several small 
case series with clozapine.  Since that time, five other atypical agents, risperidone, 
olanzapine, quetiapine, ziprasidone and aripiprazole have been introduced into the US 
market.  The newer atypical agents are not associated with agranulocytosis that has 
limited the usefulness of clozapine.  Among the atypical antipsychotics, risperidone has 
remained the most extensively studied in children and adolescents, for a variety of 
problems, including Tourette’s disorder, conduct disorder, schizophrenia, aggression, and 
pervasive development disorder.  Risperidone has been shown to be an effective 
treatment in many of these disorders. However, weight gain, hyperprolactinemia, and 
extrapyramidal symptoms (EPS) are troublesome adverse effects more commonly 
associated with risperidone such that the drug’s utility in this aged patient population is 
limited. We expect that the utility of aripiprazole in treating the pediatric population will 
not be limited by adverse effects like the other atypical antipsychotics. 
 
Previous Work: 
 
 
Several small studies have found risperidone to be more effective than placebo in 
treating children and adolescents with either aggression or conduct disorder.  In a 10-
week, randomized, double-blind study (n=20), risperidone was superior to placebo in 
reducing most measures of the Rating of Aggression Against People and/or Property 
Scale (RAAPP), when dosed at an average of 0.028mg/kg/day [range = 0.75-1.50 
mg/day] (Findling et al 2000).  The data also suggested that treatment with risperidone 
was associated with weight gain. The predicted weight gain from a repeated measures 
analysis for the risperidone group of 4.2±0.7kg was greater than the placebo group 
(p=0.003).  There was no difference in the incidence of EPS at endpoint according the 
Simpson-Angus EPS (SAEPS) rating scale. 
 
Buitelaar et al (2001) assessed the efficacy of risperidone in the treatment of 
aggression.  Thirty-eight adolescents were randomized to either risperidone or placebo in 
a double-blind fashion.  The mean daily dose of risperidone at end of treatment (6 weeks) 
was 2.9mg [range = 1.5-4 mg].  Risperidone treatment produced improvement on the 
Clinical Global Impression-Severity (CGI-S) scale (LOCF, p<0.001) and the at-school 
Aberrant Behavior Checklist (ABC) overall and hyperactivity scales (p<0.05). In the 
risperidone group, following a 2-week washout following the 6-week trial worsening on 
all efficacy measures (CGI-S, Overt Aggression Scale-Modified (OAS-M), and the ABC. 
Weight gain was significant in the risperidone group (3.5% body weight increase, range –
1 to +6kg, p<0.05).  Transient tiredness was also noted in 58% of drug-treated subjects, 
and was also the reason for dose reduction in five of the drug-treated subjects.  
Extrapyramidal Side Effect Rating Scale (ESRS) scores increased for Parkinsonism 
(cluster II) at endpoint compared to placebo (p<0.05). 
 


 
Bellinghen et al (2001) compared risperidone (n=6) to placebo (n=7) in the 
treatment of behavioral disturbances in children and adolescents.  Thirteen patients were 
enrolled in a 4-week double-blind, placebo-controlled study.  Risperidone (mean dose = 
0.05mg/kg; mean total dose = 1.2 mg/day) was more effective than placebo in improving 
ABC cluster scores for irritation and hyperactivity, the CGI scale.  No significant 
differences in EPS symptoms or weight gain were seen between the treatment groups.  
The lack of any adverse effect differences is not surprising considering the low dose of 
risperidone and the small number of patients enrolled in the study. 
 
Methods: 
 
Dose and Schedule of Treatment: The proposed study will be a 6-week open label 
study evaluating aripiprazole in the treatment of 12 male post-pubertal adolescents (13-17 
years, Tanner Stage 4) diagnosed with conduct disorder. The initial dose depending on 
the weight of the patient will be as follows:  < 25 kg = 1 mg/d; 25-50 kg = 2 mg/d; 50-70 
kg = 5 mg/d; > 70 kg = 10 mg/d (Data on File, 2003, Bristol-Myers Squibb).  Thereafter 
the dose will be flexible based on response and tolerance. 
 
Main outcome measures: The primary outcome efficacy measures will be the Rating of 
Aggression Against People and/or Property Scale (RAAPP) (Kemph et al 1993), Overt 
Aggression Scale-Modified (OAS-M) (Kay et al 1988), and Children’s Aggression Scale-
Parent Version (CAS-P) (Halpern et al 2002) while the secondary outcome measure will 
be the CGI severity and improvement scale (NIMH, 1985a).  Safety measures for 
extrapyramidal adverse effects will include the AIMS (NIMH, 1985b) for tardive 
dyskinesia, Barnes Akathisia Scale (Barnes 1989) (BAS) and the Simpson-Angus Scale 
(SAS) (Simpson and Angus 1970).   The UKU (Lingjaerde et al 1987) will be used for 
monitoring non-motor adverse effects.  Height, weight and body mass index 
measurements as well as initial and endpoint fasting blood sugars and lipids will assess 
the effect of weight change.  Obtaining serum prolactin levels as well as screening for the 
sexual dysfunction adverse effects including galactorrhea, gynecomastia, menstrual 
irregularities and changes in libido will assess sexual dysfunction adverse effects.  An 
initial and endpoint ECG will be obtained to monitor patients for any changes in the QT-
corrected interval.  A gamma-GT will be collected to monitor liver function. 
 
Schedule of Events: 
 
Procedure 
screening 
baseline week 1 week 2 week 4 week 6 
 
(-7 to –28days) 
 
 
 
 
 
History-Demographics 
X 
 
 
 
 
 
Physical Exam 
X 
 
 
 
 
X 
ECG 
X 
 
 
 
 
X 
Vitals, Height, Weight, BMI 
X 
X 
X 
X 
X 
X 
Urine Collection 
X 
 
 
 
 
X 
Phlebotomy 
X 
 
 
 
 
X 
Dispense Study Drug 
 
X 
X 
X 
X 
X 
Determine medication compliance 
 
 
X 
X 
X 
X 
 
 
 
 
 
 
 


Laboratory Tests 
 
 
 
 
 
 
 
 
 
 
 
 
 
fasting glucose 
X 
 
 
 
 
X 
fasting lipid profile: 
 
 
 
 
 
 
total cholesterol 
X 
 
 
 
 
X 
HDL-cholesterol 
X 
 
 
 
 
X 
LDL-cholesterol 
X 
 
 
 
 
X 
Triglicerides 
X 
 
 
 
 
X 
Prolactin 
X 
 
 
 
 
X 
Gamma GT 
X 
 
 
 
 
X 
CBC 
X 
 
 
 
 
X 
Urine Drugs of Abuse Screen 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
Psychiatric Rating Scales 
 
 
 
 
 
 
 
 
 
 
 
 
 
RAAPP 
 
X 
X 
X 
X 
X 
CAS-P 
 
X 
X 
X 
X 
X 
OAS 
 
X 
X 
X 
X 
X 
CGI-S 
 
X 
X 
X 
X 
X 
CGI-I 
 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
Side Effect Rating Scales 
 
 
 
 
 
 
 
 
 
 
 
 
 
AIMS 
 
X 
X 
X 
X 
X 
SAS 
 
X 
X 
X 
X 
X 
UKU 
 
X 
X 
X 
X 
X 
BAS 
 
X 
X 
X 
X 
X 
 
 
 
References: 
 
Buitelaar JK, van der Gaag, R, Cohen-Kettenis P, et al (2001).  A randomized controlled 
trial of risperidone in the treatment of aggression in hospitalized adolescents with 
subaverage cognitive abilities.  J Clin Psychiatry 62:239-48. 
 
Barnes TRE (1989).  A rating scale for drug-induced akathisia.  Br j Psychiatry 154:672-
6. 
 
Data on File, 2003, Bristol-Myers Squibb Company, Princeton, NJ 08536 
 
Kemph JO DeVane CL, Levin GM, et al (1993).  Treatment of aggressive children with 
clonidine: results of an open pilot study. Am Acad Child Adolesc Psychiatry 
32:577-81. 
 


Findling RL, McNamara NK, Branicky L, et al (2000).  A double-blind pilot study of 
risperidone in the treatment of conduct disorder.  J Am Acad Child Adolesc 
Psychiatry 39:509-16. 
 
Kay SR, Wolkenfeld F, Murrill LM (1988).  Profiles of aggression among psychiatric 
patients : I. nature and prevalence.  J Nerv Ment Dis 176:539-46. 
 
Lingjaerde O, Ahlfors UG, Bech P, et al (1987).  The UKU side effect rating scale.  A 
new comprehensive rating scale for psychotropic drugs and a cross-section study 
of side effect in neuroleptic-treated patient.  Acta Psychiatr Scand Suppl 334:1-
100. 
 
National Institute of Mental Health (1985a).  CGI (Clinical Global Impression) Scale.  
Psychopharmacol Bull 21:839-43.  
 
National Institute of Mental Health (1985b).  AIMS (Abnormal Involuntary Movement 
Scale).  Psychopharmacol Bull 21:839-43.  
 
Simpson GM, Angus JWS (1970).  A rating scale for extrapyramidal side effects.  Acta 
Psychiatr Scand Suppl 212:11-9. 
 
Van Bellinghen M, DeTroch C ( 2001).  Risperidone in the treatment of behavior 
disturbances in children and adolescents with borderline intellectual functioning: 
A double-blind placebo-controlled pilot trial.  J Child Adolesc Psychopharmacol 
11:5-13. 
 


 
Budget: Open label Aripiprazole-Conduct Disorder study  
 
 
 
 
 
 
 
 
 
 
Procedure 
Screening Baseline Week 1 Week 2 Week 4 Week 6 
 
 
 
 
 
 
 
History-Demographics 
50.00  
 
 
 
 
Physical Exam 
100.00  
 
 
 
100.00 
ECG 
125.00  
 
 
 
125.00 
Vitals, Height, Weight, BMI 
10.00 
10.00 
10.00 
10.00 
10.00 
10.00 
Urine Collection 
5.00  
 
 
 
5.00 
Phlebotomy 
10.00  
 
 
 
10.00 
 
 
 
 
 
 
 
Laboratory Tests 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fasting glucose 
12.00  
 
 
 
12.00 
Fasting lipid profile: 
 
 
 
 
 
 
Total cholesterol 
15.00  
 
 
 
15.00 
HDL-cholesterol 
29.00  
 
 
 
29.00 
LDL-cholesterol 
0.00  
 
 
 
0.00 
Triglycerides 
19.00  
 
 
 
19.00 
Prolactin 
53.00  
 
 
 
53.00 
Gamma GT 
21.00  
 
 
 
21.00 
CBC 
27.00  
 
 
 
27.00 
Urine Drugs of Abuse Screen 
85.00  
 
 
 
85.00 
 
 
 
 
 
 
 
Psychiatric Rating Scales 
 
 
 
 
 
 
 
 
 
 
 
 
 
RAAPP 
 
25.00 
25.00 
25.00 
25.00 
25.00 
CAS-P 
 
25.00 
25.00 
25.00 
25.00 
25.00 
OAS 
 
25.00 
25.00 
25.00 
25.00 
25.00 
CGI-S 
 
25.00 
25.00 
25.00 
25.00 
25.00 
CGI-I 
 
25.00 
25.00 
25.00 
25.00 
25.00 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Side Effect Rating Scales 
 
 
 
 
 
 
 
 
 
 
 
 
 
AIMS/BAS/SAS 
 
25.00 
25.00 
25.00 
25.00 
25.00 
UKU 
 
25.00 
25.00 
25.00 
25.00 
25.00 
 
 
 
 
 
 
 
Investigator Fee 
100.00 
100.00 100.00 100.00 100.00 100.00 
Study Coordinator Fee 
50.00 
50.00 
50.00 
50.00 
50.00 
50.00 
Subject Compensation 
25.00 
25.00 
25.00 
25.00 
25.00 
25.00 
 
 
 
 
 
 
 


Total direct costs per visit 
886.00 
360.00 360.00 360.00 360.00 861.00 
Total direct costs per completed subject  
 
 
 
 
3187.00 
 
 
 
 
 
 
 
Total indirect costs per visit (25%) 
184.00 
90.00 
90.00 
90.00 
90.00 215.25 
Total indirect costs per completed 
subject 
 
 
 
 
 
759.25 
 
 
 
 
 
 
 
Total costs per completed subject 
 
 
 
 
 
3796.25 
 

SAP_001.pdf: 
All statistical analyses were conducted using InStat 3.1a (GraphPad Software, La Jolla, CA). A modified intent-to-treat (ITT) population was used for analyses. 
For each outcome variable, the modified ITT population included all subjects with at least one post-baseline psychometric measurement (subjects received at 
least one week of aripiprazole). Demographic data is presented as means and standard deviations while bivariant data were contrasted using paired-t tests. A 
repeated measure analysis of variance (ANOVA) model was used to assess the changes in the psychometric tests. In cases where a subject did not complete the 
entire 6-week trial, the last available observation was carried forward (LOCF) and used for statistical comparisons. A repeated measure analysis of variance was 
used to assess the changes in the psychometric tests. For determining significance of statistical tests 〈 was set at 0.05.