A Multi-centre, Double-blind, Randomised-Withdrawal, Parallel-group, Placebo-controlled Phase III Study of the Efficacy and Safety of Quetiapine Fumarate Sustained Release (Seroquel SR™) as Monotherapy in the Maintenance Treatment of Patients with Generalised Anxiety Disorder Following an Open-Label Stabilisation Period (PLATINUM STUDY) - PLATINUM STUDY

• Register: EUCTR
• Last refreshed on: 3 April 2012
• Main ID: EUCTR2005-005055-18-DE
• Date of registration: 22/02/2007
• Prospective Registration: No
• Primary sponsor: AstraZeneca AB
• Public title: A Multi-centre, Double-blind, Randomised-Withdrawal, Parallel-group, Placebo-controlled Phase III Study of the Efficacy and Safety of Quetiapine Fumarate Sustained Release (Seroquel SR™) as Monotherapy in the Maintenance Treatment of Patients with Generalised Anxiety Disorder Following an Open-Label Stabilisation Period (PLATINUM STUDY) - PLATINUM STUDY
• Scientific title: A Multi-centre, Double-blind, Randomised-Withdrawal, Parallel-group, Placebo-controlled Phase III Study of the Efficacy and Safety of Quetiapine Fumarate Sustained Release (Seroquel SR™) as Monotherapy in the Maintenance Treatment of Patients with Generalised Anxiety Disorder Following an Open-Label Stabilisation Period (PLATINUM STUDY) - PLATINUM STUDY
• Date of first enrolment: 15/05/2006
• Target sample size: 1055
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-005055-18
• 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: no Other: no

Countries of recruitment

Finland, Germany, Hungary, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1.Provision of informed consent before initiation of any study- related procedures.
2.Male or female aged 18 to 65 years (inclusive).
3.A documented clinical diagnosis of GAD according to DSM-IV criteria 300.02 as assessed by the MINI. Patients with/without comorbid simple phobia or
comorbid panic attacks (who do not meet criteria for DSM-IV Axis I Panic disorder) are
eligible to enter the study.
4.A HAM-A administered by use of the Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) total score =20 with Item 1 (anxious mood) and Item 2 (tension) scores =2 at enrolment.
5.A CGI-S score =4 at enrolment.
6.Female patients of childbearing potential must have a negative serum pregnancy test at enrolment 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) during the study, as judged by the investigator.
7.Be able to understand and comply with the requirements of the study, as judged by the investigator.
8.Outpatient status at enrolment.

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.Patients with a current DSM-IV Axis I disorder other than GAD (with or without simple phobia) within 6 months of enrolment.
2.The presence or history of schizophrenia and other psychotic disorders according to DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition), including: Schizophrenia 295.xx;Schizophreniform Disorder 295.xx;Schizoaffective Disorder 295.x;Delusional Disorder 297.1; Brief Psychotic Disorder 298.8;Shared Psychotic Disorder 297.3;Substance-Induced Psychotic Disorder 291.xx, 292.xx;Psychotic Disorder Not Otherwise Specified 298.9;Mood disorder with Psychotic Features: x4 specifier (eg, 296.24 = Major Depressive Disorder, Single Episode, Severe, with Psychotic Features).
3.Patients with a diagnosis of DSM-IV Axis II disorder that is likely to interfere with the patient’s ability to participate in the study as judged by the investigator.
4.Patients suffering from depressive symptoms, defined as having a MADRS total score ³17 at enrolment.
5.Patients who, in the investigator’s judgment, pose a current serious suicidal or homicidal risk or have made a suicide attempt or patients who have a MADRS Item 10 score =4, or have made a suicide attempt within 6 months before enrolment.
6.Evidence of clinically relevant disease, eg, renal or hepatic impairment, significant coronary artery disease, cerebrovascular disease, viral hepatitis B or C, HIV positive or acquired immunodeficiency syndrome (AIDS).
7.A clinical finding that is unstable.
8.Conditions that could affect absorption and metabolism of study medication (e.g. malabsorption syndrome, liver disease).
9.Laboratory values for alanine aminotransferase (ALT) or aspartate aminotransferase (AST) that are 3 times the upper limit of normal.
10.History of seizure disorder, except febrile convulsions.
11.A current diagnosis of cancer, (except basal or squamous cell skin carcinoma or cervical carcinoma in situ), unless in remission for at least 5 years.
12.Current or past diagnosis of stroke or Transient Ischemic Attack (TIA).
13.Substance or alcohol abuse or dependence.
14.Use of the following medications prior to start of Open-label Run-in Treatment Period (Visit 2): antipsychotic, mood stabiliser, anticonvulsant (except carbamazepine; see Exclusion 17) or antidepressant drugs within 7 days before Visit 2;fluoxetine within 28 days before Visit 2;MAO inhibitors within 14 days before Visit 2;anxiolytics (including benzodiazepines) or hypnotics within 7 days before Visit 2;depot antipsychotic injection within two dosing intervals before Visit 2.
15.Receipt of electro convulsive therapy (ECT) within 90 days prior to enrolment.
16.Patients who in the investigators opinion will require psychotherapy (other than supportive psychotherapy) during the study, unless psychotherapy has been ongoing for a minimum of 3 months prior to enrolment.
17.Use of potent cytochrome P450 (CYP) 3A4 inducers (e.g., barbiturates, carbamazepine, glucocorticoids [except for topical use or inhalation], phenytoin, rifampin, rifabutin, thioridazine, and St John’s Wort) within 14 days prior to the OLRT (Visit 2).
18.Use of potent CYP 3A4 inhibitors.
19.A patient with Diabetes Mellitus (DM).
20.Clinically significant deviation from the reference range in clinical laboratory test results at enrolment, as judged by the investigator.
21.If the patient’s CBC with WBC differential shows an ANC = 1.5 x 109/L.
22.A thyroid-stimulating hormone (TSH) concentration more than 10% above the upper lim

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

Health Condition(s) or Problem(s) studied

Maintenance treatment of patients with Generalised Anxiety Disorder.

Intervention(s)

Product Name: Seroquel SR
Product Code: ZD5077
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Quetiapine Fumarate Sustained Release
CAS Number: 111974-72-2
Current Sponsor code: ZD5077
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: Seroquel SR
Product Code: ZD5077
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Quetiapine Fumarate Sustained Release
CAS Number: 111974-72-2
Current Sponsor code: ZD5077
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: 1.To evaluate the effect of quetiapine SR compared to placebo on health-related quality of life in patients with GAD during long-term treatment.
2.To evaluate the efficacy of quetiapine SR compared to placebo in maintaining improvement of anxiety symptoms in patients with GAD during long-term treatment.
3.To evaluate the effect of quetiapine SR compared to placebo on depressive symptoms in patients with GAD during long-term treatment.
4.To evaluate the effect of quetiapine SR compared to placebo on quality of sleep in patients with GAD during long-term treatment.
5.To evaluate the effect of quetiapine SR compared to placebo on suicidal ideation in patients with GAD during long-term treatment.
6.To evaluate the effect of quetiapine SR compared to placebo on functional disability in patients with GAD during long-term treatment.
7.To evaluate if quetiapine SR compared to placebo is safe and well-tolerated in patients with GAD during long-term treatment.

Main Objective: The primary objective of the study is to evaluate the efficacy of quetiapine SR compared to placebo in increasing time from randomisation to a depressed event in patients with Generalised Anxiety Disorder (GAD).

Primary end point(s): The primary objective of this study is to evaluate the efficacy of quetiapine SR compared to placebo in increasing time from randomisation to an anxiety event in patients with generalised anxiety disorder (GAD).

Secondary ID(s)

2005-005055-18-GB

D1448C00012