SOLMANIA - Comparison of Valproate-Amisulpride and Valproate-Haloperidol in Bipolar I Patients

A 3-Month, Open, Randomised Trial Comparing the Efficacy and Safety of the Association Valproate-Amisulpride to the Association Valproate-Haloperidol in Bipolar I Patients Suffering From a Manic Episode

The primary objective is:

• To compare the efficacy of the association valproate-amisulpride (400 to 800 mg/day) to the association valproate-haloperidol (5 to 15 mg/day) in bipolar I patients suffering from a manic episode according to DSM IV TR (American Psychiatric Association [APA] 2000) and treated for a 3-month period.

The secondary objectives are:

• To evaluate the clinical and biological safety of the association valproate-amisulpride to the association valproate-haloperidol;
• To assess the patient status 3 weeks and 3 months after inclusion; and
• To assess patient satisfaction at 3 months.

Study Overview

• Status: Completed
• Conditions: Bipolar Disorder
• Intervention / Treatment: Drug: Amisulpride

• Study Type: Interventional
• Enrollment: 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czech Republic
  • Prague, Czech Republic
    • Sanofi-Aventis
• France
  • Paris, France
    • Sanofi-Aventis
• Poland
  • Warsaw, Poland
    • Sanofi-Aventis
• Slovakia
  • Bratislava, Slovakia
    • Sanofi-Aventis
• Spain
  • Barcelona, Spain
    • Sanofi-Aventis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Pre-Inclusion Criteria on D-3:

• In-patients
• From 18 to 65 years old
• Able to comply with the protocol
• Having given their written informed consent (with a legal representative or a person of trust)
• Current diagnosis of bipolar I disorder according to DSM IV TR (APA 2000)
• Having had at least one manic episode in the past
• Currently suffering from a manic episode according to DSM IV TR (APA 2000)
• A minimum total score of 20 on the Young Mania Rating Scale (Y-MRS) at D-3

Inclusion Criteria on D0:

• Having completed at least one day of the one to three-day washout period
• A minimum total score of 20 on the Young Mania Rating Scale at D0
• A score of > or = 3 for 2 of the following Y-MRS items: elevated mood; increased motor activity energy; sleep; content (grandiosity).
• A score of > or = 5 on the Clinical Global Impression Severity Scale for the severity of mania items at D0
• Using an effective contraception method (women of childbearing age only)

Exclusion Criteria:

Exclusion Criteria on D-3:

• Having participated in a clinical trial within the three previous months
• Pregnant or breast-feeding. Female patients should therefore be using reliable contraceptive methods (oral or parenteral contraception, intra-uterine device or surgical sterilisation)
• Uncontrolled gastro-intestinal, renal, hepatic, endocrine, cardiovascular, pulmonary, immunological or hematological disease
• Central nervous system (CNS) neoplasm; demyelinating disease; degenerative neurological disorder; active CNS infection; or any progressive disorder that may confound interpretation of the study results
• Prolactin-dependant tumor
• Past or current pancreatitis
• Acute hepatitis, chronic hepatitis, or family history of severe hepatitis, especially drug related, hepatic porphyry
• Current or recent (within 3 months) DSM IV diagnosis of substance dependence (with the exception of nicotine or caffeine dependence); or substance abuse with stimulants including, but not limited to, cocaine, crack, amphetamines, pseudoephedrine, cold medications with phenylephrine, or other stimulants. Alcohol and marijuana abuse prior to study entry would be acceptable if related to the current manic episode, based on the investigator's judgement
• Parkinson's disease
• Phaeochromocytoma
• History of epilepsy
• History of allergy or hypersensitivity to haloperidol or benzamides or valproate
• Treated with fluoxetin within the past 4 weeks
• Treated with injectable long-acting neuroleptics if, for the patient, the interval between 2 injection periods has not elapsed before pre-inclusion (D-3)
• Treated with a mood stabiliser (other than valproate) at effective dose for less than 7 days preceding D-3 and for whom a modification is not justified
• Bradycardia < 55 beats per minute (bpm)
• Known hypokaliaemia
• Congenital prolongation of the QT interval
• Treated with any of the following medications: Class Ia antiarrhythmic agents such as quinidine, disopyramide/Class III antiarrhythmic agents such as amiodarone, sotalol; Drugs like: beperidil, cisapride, sultopride, thioridazine, intravenous (IV) erythromycin, IV vincamine, halofantrine, pentamidine, or sparfloxacin.

Exclusion Criteria on D0:

• Potentially significant alterations of laboratory tests on D0:

  • ASAT or ALAT > 2 upper limit of normal (ULN). If ASAT or ALAT values range between 1.5 ULN and 2 ULN, the patient can be randomized and a new test will be performed 7 days after randomization;
  • Alkaline phosphatase levels or bilirubin levels not within normal reference range.
• QTc prolongation on D0; QTc Bazett > 450ms in male patients and QTc > 470ms in female patients on electrocardiogram (ECG).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Combination of the percentage of responders defined by a decrease of at least 50% of the Y-MRS (Young Mania Rating Scale) between D0 and D END and the completion of the 3-month treatment period.

Secondary Outcome Measures

Outcome Measure
Other efficacy criteria (such as the changes in Y-MRS scores between D0 and D 21, between D0 and D END.The percentage of remission defined as the Y-MRS < or = 12 at D END...). Safety data (clinical, ECG and laboratory data)

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Gilles Perdriset, MD, Sanofi

Study record dates

Study Major Dates

• Study Start: May 1, 2004

Study Registration Dates

• First Submitted: July 18, 2005
• First Submitted That Met QC Criteria: August 1, 2005
• First Posted (Estimate): August 2, 2005

Study Record Updates

• Last Update Posted (Estimate): April 10, 2008
• Last Update Submitted That Met QC Criteria: April 8, 2008
• Last Verified: April 1, 2008

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Bipolar and Related Disorders; Bipolar Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Dopamine Agents; Dopamine Antagonists; Antidepressive Agents, Second-Generation; Amisulpride
• Other Study ID Numbers: C_8428