An International, Multicenter, Double-blind, Randomized, Placebo-controlled, Phase IV Study of the Safety and Efficacy of Lithium versus Placebo as an add on to SEROQUEL XR™ (Quetiapine Fumarate) in Adult Patients with Acute Mania

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-007190-20-BG
• Date of registration: 01/06/2009
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: An International, Multicenter, Double-blind, Randomized, Placebo-controlled, Phase IV Study of the Safety and Efficacy of Lithium versus Placebo as an add on to SEROQUEL XR™ (Quetiapine Fumarate) in Adult Patients with Acute Mania
• Scientific title: An International, Multicenter, Double-blind, Randomized, Placebo-controlled, Phase IV Study of the Safety and Efficacy of Lithium versus Placebo as an add on to SEROQUEL XR™ (Quetiapine Fumarate) in Adult Patients with Acute Mania
• Date of first enrolment: 02/06/2009
• Target sample size: 350
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-007190-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Bulgaria, Germany

Key inclusion & exclusion criteria

Inclusion criteria:
1. Provision of informed consent prior to any study-specific procedures.
2. Male and female subjects aged 18 to 65 years, inclusive.
3. Documented clinical diagnosis meeting the DSM-IV-TR (American Psychiatric Association 2000) criteria for bipolar I disorder, most recent episode manic (296.4x) or mixed (296.6x).
4. YMRS total score =20 and =4 on 2 of 4 core items (irritability, speech, content, disruptive/aggressive behavior) at enrollment (Visit 1) and randomization (Visit 2).
5. Subjects must have a CGI-BP =4 (moderately ill) at enrollment (Visit 1) and at randomization (Visit 2).
6. Subjects must have experienced =1 manic or mixed episode (other than the current episode) in the past 5 years.
7. Female subjects of childbearing potential must have a negative serum pregnancy test at enrollment (Visit 1) and be willing to use a reliable method of birth control, i.e., double-barrier method, oral contraceptive, implant, dermal contraception, long term injectable contraceptive, intrauterine device, or tubal ligation.
8. Subjects must be able to understand and comply with the requirements of the study, as judged by the investigator.
9. Subjects may be outpatients or inpatients at enrollment (Visit 1), but all subjects must be inpatients when randomized (Visit 2) and remain inpatients until discharged at the discretion of the investigator.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Subjects must not have another current, major DSM-IV-TR Axis I disorder that is symptomatic or has required treatment within 6 months of enrollment, other than the bipolar disorder under study.
2. Subjects with >8 mood episodes during the past 12 months.
3. Subjects with a mania-like syndrome that is a physiological consequence of a medical condition, a medication, a treatment, substance abuse, or withdrawal.
4. Subjects that are continuously hospitalized for acute bipolar mania for >3 weeks immediately prior to randomization (Visit 2).
5. Subject with alcohol or other substance dependence or abuse as defined by DSM IV-TR criteria at enrollment (Visit 1) that is not in sustained full or sustained partial remission (12 months or longer), except caffeine and nicotine dependence. Subjects with a positive urine toxicology screen are not excluded unless they satisfy DSM-IV-TR criteria for abuse or dependence, except that subjects are excluded with a single urine toxicology screen positive for cocaine, heroin, or PCP.
6. Subjects who use or need to use, within 2 weeks prior to randomization, drugs that strongly induce or inhibit the hepatic metabolizing cytochrome 3A4 enzymes. Examples of inducers are carbamazepine, phenytoin, barbiturates, rifampin, rigabutin, glucocorticoids, thioridazine, and St. John’s wort. Examples of inhibitors are ketoconazole (except for topical use), itraconazole, fluconazole, erythromycin, clarithromycin, indinavir, nelfinavir, ritonavir, and saquinavir.
7. Subjects with evidence of a clinical disorder or clinical finding problematic to the study, as judged by the investigator, such as renal (serum creatinine =1.5 mg/dL) or hepatic impairment (alanine transaminase [ALT] or aspartate transaminase [AST] 3 times the upper limit of normal), significant coronary artery disease, cerebrovascular disease, active viral hepatitis B or chronic active hepatitis C, or Acquired Immunodeficiency Syndrome (AIDS).
8. Subject with clinical findings that, in the opinion of the investigator, suggest unstable medical conditions, or that might be negatively affected by the study medication or that would negatively affect the study medication. Examples of unstable conditions are poorly controlled hypertension or unstable angina.
9. Subjects with conditions that could affect absorption or metabolism of the investigational product (e.g., malabsorption syndrome, severe liver disease), as judged by the investigator.
10. Subjects with current or past diagnosis of stroke or medically documented transient ischemic attacks (TIA).
11. Subjects with a history of seizure disorder, except febrile convulsions.
12. Subjects using any of the following medications:
- Antipsychotic use (other than SEROQUEL) within 7 days prior to randomization (Visit 2).
- Antidepressant, anxiolytic, hypnotic, or other psychoactive drugs within 7 days prior to randomization (Visit 2), with the exception of lorazepam (or locally available equivalent approved by the Sponsor), if needed, up to a maximum dose of 6 mg which can be used up to the day prior to randomization.
- Mood stabilizers (other than lithium) within 2 days prior to randomization (Visit 2).
- Fluoxetine within 28 days prior to randomization (Visit 2).
- A depot antipsychotic injection within 1 dosing interval (for the depot) prior to randomization (Visit 2).
- Irreversible monoamine oxidase inhibitors (MAOI) within 14 days prior to randomization (Visit 2).
- Lithium within 14 days prior to randomiz

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Acut mania in subjects with bipolar I disorder
MedDRA version: 9.1 Level: PT Classification code 10004939 Term: Bipolar I disorder

Intervention(s)

Trade Name: Seroquel XR 200 mg
Product Name: Seroquel XR 200 mg
Pharmaceutical Form: Capsule*
INN or Proposed INN: quetiapine fumarate
CAS Number: 111974-69-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Trade Name: Lithium carbonate capsule, USP
Product Name: Lithium
Pharmaceutical Form: Capsule*
INN or Proposed INN: Lithium carbonate
CAS Number: 554132
Other descriptive name: Lithium
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Trade Name: Seroquel XR 300 mg
Product Name: Seroquel XR 300 mg
Pharmaceutical Form: Capsule*
INN or Proposed INN: quetiapine fumarate
CAS Number: 111974-69-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-

Primary Outcome(s)

Main Objective: The primary objective is to evaluate the effectiveness of lithium compared to placebo as an add on to quetiapine XR in the treatment of acute mania in subjects with bipolar I disorder, as assessed by the change from baseline to final assessment (Day 43) in Young Mania Rating Scale (YMRS) total score.

Primary end point(s): The primary efficacy variable is change from badeline to final assessment (day 43) in Young Mania Rating Scale (YMRS) total score.

Secondary Objective: The secondary objectives are to compare effectiveness of Lithium compared to placebo as an add-on to quetiapineXR reduction from baseline using different scales (e.g. YMRS, MADRS,CIG-BP, PANSS). Short time safety of Lithium as add-on to quetiapine XR.
Blood samples for optionl exploratory genetic studies focusing in identifications of genes that influence the disposition, efficacy, safety and tolerability of quetiapine XR in subjects with bipolar I disorder.

Secondary ID(s)

2008-007190-20-DE

D144AC00003