Clinical Trial Details
Return to Clinical Trials Home| Actively Enrolling | Yes |
| Primary Investigator | Dunn, David |
| Title | The Evaluation of LAMICTAL™ as an Add-on Treatment for Bipolar I Disorder in Children and Adolescents, 10 to 17 Years of Age |
| Date Published | May 27th, 2010 |
| Contact Name | Alisha Baker |
| Contact Phone | 317-278-3481 |
| Compensation | Yes |
| Disease | Bipolar I Disorder |
| Healthy Volunteers | No |
| Inclusion / Exclusion | Inclusion criteria –Open-Label
Phase: 1. Subject is male or female between the ages of 10 and 17 years, inclusive. 2. Subject has a diagnosis of bipolar I disorder and is currently experiencing a manic/hypomanic, depressed, or mixed mood episode a...Inclusion criteria –Open-Label Phase: 1. Subject is male or female between the ages of 10 and 17 years, inclusive. 2. Subject has a diagnosis of bipolar I disorder and is currently experiencing a manic/hypomanic, depressed, or mixed mood episode as defined by Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text revision (DSM-IV-TR) criteria and based on the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime Version (K-SADS-PL), and, as assessed* by a physician with adequate training in child and adolescent psychiatry (e.g., Board Certification or board eligible in Child and Adolescent Psychiatry). *Assessment by a physician with adequate training in psychiatry must include face to-face evaluation of the subject, but may be aided by subject evaluation conducted by a healthcare professional with a clinically relevant qualification (e.g., psychiatric nurses or psychologists) and a minimum of two years documented experience assessing child and adolescent patients with bipolar disorder. 3. Subject is currently receiving a stable treatment regimen. For the purpose of this study, a stable treatment regimen is defined as one or two of the allowed conventional bipolar treatments (mood stabilizer[s] and/or antipsychotic[s]; (see Section 5.6.1) that has been taken at a therapeutic dose(s) and/or blood level(s) for at least four weeks prior to the Screen Visit (visit 1). 4. Subject is symptomatic and has at least moderate disease severity at the Screen (visit 1) and the Baseline Visit (visit 2) as indicated by a CGI-BP(S) score ≥4 and one of the following, as appropriate, for the diagnosed index mood episode*: • QIDS- A17-C ≥11, YMRS ≤11 (e.g., depressed) • YMRS ≥12; QIDS- A17-C ≤10 (e.g., manic/hypomanic) • YMRS ≥16, QIDS- A17-C score ≥11 (e.g., mixed) *Subjects meeting criteria for Bipolar II or Bipolar, not otherwise specified, (NOS) are not eligible for this study. 5. Female subjects must have a negative pregnancy test (i.e. serum beta hCG test) at the Screen Visit (visit 1) and at the Baseline Visit (visit 2) (i.e. urine pregnancy test) and be of: a. non-childbearing potential (i.e. physiologically incapable of becoming pregnant).OR b. childbearing potential and agrees to commit to one of the protocol-approved methods of contraception (i.e., meeting the criterion of a highly effectively contraception method with a failure rate of <1%), when used consistently and in accordance with both the product label and the instructions of a physician, as indicated below: • complete abstinence from intercourse, when considered achievable and in line with the lifestyle of the subject, starting for two weeks before exposure to the investigational product, throughout the study, and for one week following the last dose of investigational product, OR • oral contraceptive (combined or progestin only), and the same oral contraceptive regimen has been used for at least two months prior to investigational product administration, and the same method continues throughout the study, and for one week following the last dose of investigational product , OR • progesterone implanted rods inserted for at least two months prior to investigational product administration (but not beyond the third successive year following insertion), and is continued throughout the study, and for one week following the last dose of investigational product, OR • an estrogenic vaginal ring, from at least two weeks prior to the Screen Visit (visit 1),throughout the study, and for one week following the last dose of investigational product, OR • an IUD, inserted by a qualified clinician, with published data showing that the highest expected failure rate is less than 1% per year (not all IUDs meet this criterion). The device must be inserted at least two weeks prior to the Screen Visit (visit 1), and remain throughout the study, and for one week following the last dose of investigational product, OR • injectable medroxyprogesterone acetate and is on a stable dose for two months prior to the Screen Visit (visit 1), throughout the study, and for one week following the last dose of investigational product, OR • double barrier method if comprised of a spermicide with either a condom or diaphragm from at least two weeks prior to the Screen Visit (visit 1), throughout the study, and for one week following the last dose of investigational product. 6. Subject on a non-enzyme inducing antiepileptic drug (including VPA) must weigh at least 34.1kg (75 pounds) at visit 1 (screening) and baseline. 7. Subject is living with his/her custodial parent(s) or legal guardian(s) and has contact with them on a daily basis. 8. Subject assents (where required) and has a custodial parent’s or legal guardian’s written informed consent before performance of any study-specific procedures, and the subject, and his/her custodial parent(s) or legal guardian(s) have the ability to comprehend the key components of the informed consent form. 9. Subject and his/her custodial parent or legal guardian demonstrate an adequate mastery of the primary language utilized in the study assessments, and must read and write at a level sufficient to complete the study assessment. Exclusion criteria –Open-Label Phase: 1. Subject has been diagnosed with a primary Axis I disorder (with the exception of bipolar I disorder, ADHD, anxiety disorders, oppositional defiant disorder, or conduct disorder) or any Axis II disorder. 2. Subject who has symptoms of the presenting illness that are better accounted for by another diagnosis. 3. Subject currently has signs or symptoms of psychosis or a history of psychosis within the previous four weeks. 4. Subject has been diagnosed with epilepsy, autism, Asperger’s syndrome, or Tourette’s syndrome. 5. Subject has a documented IQ test score < 70 or suspected mental retardation. 6. Subject has an unstable medical disorder; or a disorder that would interfere with the action, absorption, distribution, metabolism or excretion of lamotrigine, that may pose a safety concern, or interfere with the accurate assessment of safety or efficacy. 7. Subject has experienced a serious rash, such as Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis, or a rash otherwise requiring hospitalization. 8. Subject has experienced a rash related to prior lamotrigine use, or for whom lamotrigine treatment was discontinued for clinically significant safety reasons. 9. Subject has received a treatment regimen consisting of three or more drug therapies (simultaneously) for bipolar disorder (e.g., mood stabilizers and/or or antipsychotics) during the four weeks prior to the Screen Visit (visit 1). 10. Subject has received any antidepressant medication, or atomoxetine, during the four weeks prior to the Screen Visit (visit 1). 11. Subject has initiated psychotherapy within 2 months prior to the Screen Visit (visit 1), or plans to initiate psychotherapy during the trial. Subjects who present with their current bipolar episode despite longer-term psychotherapy (i.e., >2 months prior to the Screen Visit (visit 1)) may be included. For subjects who enter the study on psychotherapy, the type and frequency of therapy should remain constant during the study. 12. Subject has been exposed to lamotrigine within six months prior to the Screen Visit (visit 1). 13. Subject has any laboratory or medical abnormality that, in the investigator’s judgment, is considered to be clinically significant and could potentially affect subject safety or study outcome. 14. Subject has a thyroid function test value for Thyroid Stimulating Hormone (TSH) that is outside the normal reference range or has a history of hypothyroidism. 15. Subject has a documented history of hepato-biliary disease including a history of or positive laboratory results for hepatitis (hepatitis B surface antigen and/or hepatitis C antibody) at the Screen Visit (visit 1), and/or clinically significant hepatic enzyme elevation including a value for any one of the following enzymes greater than 1.5 times the upper limit of normal (ULN) at the Screen Visit (visit 1): • Alanine aminotransferase (ALT) • Aspartate aminotransferase (AST) • Total or direct bilirubin > 1.5 times the ULN at Screening, unless consistent with presumed or diagnosed Gilbert’s disease. 16. Subject has any ECG abnormality that may pose a potential safety concern or has a QTc (QT interval corrected) > 450 msec. 17. Subject in the 10-12 year old age group has a Body Mass Index (BMI) ≤ 15 or ≥ 30; a subject in the 13-17 year old age group has a BMI ≤ 17 or ≥ 34. 18. Subject tests positive for illicit drug use at the Screen Visit (visit 1), has a history of alcohol or substance abuse or dependence (other than nicotine dependence) within the past three months, or has a positive blood alcohol level at the Screen Visit (visit 1). 19. Subject, in the investigator’s judgment, poses a current homicidal or serious suicidal risk, has made a suicide attempt within the twelve months preceding the Screen Visit (visit1), has ever been homicidal, or has a score of ≥2 on Question 13 on the QIDSA17-C at Screening (visit 1) or Baseline (visit 2). 20. Female subject is pregnant, lactating, or does not agree to use contraceptive method(s) specified in the protocol to avoid pregnancy during the study. 21. Subject has a history of allergic reaction to, or a medically significant adverse effect from the investigational product or its excipients, or closely related compounds. 22. Subject is currently participating in another clinical study in which the subject is or will be exposed to an investigational or non-investigational drug or device, or has done so within the preceding month for studies unrelated to the current illness, or six months for studies related to the current illness. 23. Subject has been withdrawn from an effective and tolerated treatment regimen for the primary purpose of enrollment into this trial. 24. Subject is, in the opinion of the investigator, at risk of non-compliance with study procedures. Inclusion criteria –Randomized Phase: 1. Subject is currently being treated with at least the minimum dose of open-label, add on lamotrigine (based on the subject’s age group, weight, if applicable, and concomitant bipolar medication). 2. Subject meets stabilization criteria, defined as a period during the Open-label Phase during which the subject had a CGI-BP(S) score of ≤3 for at least six consecutive weeks. 3. The subject has had a stable lamotrigine dose for a minimum of the last two weeks of the six week stabilization period. 4. Subject is living with his/her custodial parent(s) or legal guardian(s) and has contact with them on a daily basis. Exclusion criteria –Randomized Phase: Subjects meeting any of the following criteria should not be enrolled in the Randomized Phase of the study. Subjects may continue into the Randomized Phase of the study pending receipt of the Week 18/Randomization reports from the clinical laboratory and central ECG provider. Upon receipt of the laboratory and ECG reports, if the subject meets any of the below criteria, the subject should be withdrawn from the study. 1. Subject had a change in his/her ADHD medication, or in the ADHD medication dose at any time after the subject had achieved 4 weeks of stability (i.e., CGI-BP(S) score of ≤3 for 4 consecutive weeks). 2. Subject had a change in his/her conventional bipolar therapy medication(s), or in the conventional bipolar medication dose(s) at any time after the subject had achieved 4 weeks of stability (i.e., CGI-BP(S) score of ≤3 for 4 consecutive weeks). 3. Subject has an unstable medical disorder; or a disorder that would interfere with the action, absorption, distribution, metabolism or excretion of lamotrigine; that may pose a safety concern; or interfere with the accurate assessment of safety or efficacy. 4. Subject has any laboratory or medical abnormality that, in the investigator’s judgment, is considered to be clinically significant and could potentially affect subject safety or study outcome. 5. Subject has a thyroid function test value for TSH that is outside the normal reference range. 6. Subject has a clinically significant hepatic enzyme elevation including a value for any one of the following enzymes greater than 1.5 times the ULN: • ALT • AST • Total or direct bilirubin > 1.5 times the ULN, unless consistent with presumed or diagnosed Gilbert’s disease. 7. Subject, in the investigator’s judgment, poses a current homicidal or serious suicidal risk. 8. Subject has any ECG abnormality that may pose a potential safety concern or has a QTc > 450msec that has also increased at least 30msec compared to Screen (visit 1)/Baseline (visit 1) (if repeated). 9. Female subject is pregnant, lactating, or does not agree to use contraceptive method(s) specified in the protocol to avoid pregnancy during the study. 10. Subject is, in the opinion of the investigator, at risk of non-compliance with study procedures. More |