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Paliperidone Palmitate Efficacy and Safety in Bipolar Disorder Complicated by Alcoholism

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ClinicalTrials.gov Identifier: NCT01211704
Recruitment Status : Withdrawn (lack of funding)
First Posted : September 29, 2010
Last Update Posted : November 21, 2014
Sponsor:
Collaborator:
Ortho-McNeil, Inc.
Information provided by (Responsible Party):
Ihsan Salloum, University of Miami

Brief Summary:
The primary specific aim is to examine the efficacy of Paliperidone extended release Paliperidone Palmitate Injection (INVEGA® SUSTENNA™) compared to placebo in decreasing manic symptoms in patients with comorbid DSM-IV bipolar disorder and alcohol dependence. The investigators hypothesize that the Paliperidone Palmitate Injection (INVEGA® SUSTENNA™) treated group will have a statistically significant advantage on improvement in manic symptoms. They will also have higher rate of treatment response and remission.

Condition or disease Intervention/treatment Phase
Bipolar Disorder Drug: Paliperidone Palmitate Drug: Placebo Phase 4

Detailed Description:

Subjects who meet study inclusion criteria will be randomized to receive an add-on Paliperidone Palmitate ( INVEGA® SUSTENNA™ ) according to the following schedule described in the medication prescribing information: INVEGA® SUSTENNA™ (PALIPERIDONE PALMITATE) Extended-Release Injectable Suspension ). Tolerability of the paliperidone will be established by either 1) a documented history of having taken either paliperidone or risperidone in the past without any untoward effects or allergic reactions, or 2) by prescribing oral paliperidone 6mg per day for three days with absence of any allergic or severe untoward side effects for those with no prior history of having taken these medications, prior to initiating treatment with INVEGA® SUSTENNA™ according to the manufacturers' recommendations.

Eligible patients will be randomized to INVEGA® SUSTENNA™ or placebo in equivalent ml doses according to the following schedule: Day 1: INVEGA® SUSTENNA™ 234mg vs. placebo injection (equivalent ml); Day 8 (week 1) INVEGA® SUSTENNA™ 156mg vs. placebo injection (equivalent ml); Day 36 (week 5): INVEGA® SUSTENNA™ 117 mg vs. placebo injection (equivalent ml) ( this latter dose could range from 39mg to 156mg according to tolerability and clinical symptoms of bipolar disorder); Day 64 (week 9) no injection; weeks 10 and 11 safety assessment follow-up ( see Study Schematics below). Both treatment groups will participate in standardized individual medication adherence counseling. Subjects with bipolar disorder and who are actively drinking will be recruited into the study. Subjects who have been stable on treatment as usual medications for bipolar disorder for at least three weeks, and who meet all the inclusion criteria will be randomized to receive the double blind study medication consistent of either Paliperidone Palmitate injection ( INVEGA® SUSTENNA™ )or placebo (1:1 ratio). To optimize the likelihood of balanced groups, the investigators will use urn randomization with the following variables: Gender (males vs. females), treatment as usual medication (divalproex sodium vs. other mood stabilizers), presenting bipolar subtype (manic vs mixed) and baseline drinking severity (< vs. > 50% heavy drinking days (> 4 standard drinks for females and > 5 standard drinks per males) in the month prior to enrollment). After randomization, subjects will be assessed weekly at weeks 1, 2, 3, 4, 5, 6, 7, 8,9 of the double-blind treatment phase a and at week 10 and 11 for safety observation follow-up.. The investigators propose to test the above hypotheses in 75 subjects at three sites (25 subjects per site) All subjects will receive a weekly Standardized supportive individual medication adherence counseling session.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Paliperidone Palmitate Efficacy and Safety in Bipolar Disorder Complicated by Alcoholism: A Double-blind, Placebo-controlled, Randomized, Parallel Groups, Multi-center Study.
Study Start Date : October 2010
Estimated Primary Completion Date : December 2011
Estimated Study Completion Date : February 2012

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo, Counceling
Placebo
Drug: Placebo
Placebo in equivalent ml doses to experimental intervention (Paliperidone Palmitate)

Experimental: Paliperidone Palmitate
Paliperidone Palmitate
Drug: Paliperidone Palmitate
NVEGA® SUSTENNA™ or placebo in equivalent ml doses according to the following schedule: Day 1: INVEGA® SUSTENNA™ 234mg vs. placebo injection (equivalent ml); Day 8 (week 1) INVEGA® SUSTENNA™ 156mg vs. placebo injection (equivalent ml); Day 36 (week 5): INVEGA® SUSTENNA™ 117 mg vs. placebo injection (equivalent ml) ( this latter dose could range from 39mg to 156mg according to tolerability and clinical symptoms of bipolar disorder). Treatment with INVEGA® SUSTENNA™ /Placebo will last 5 weeks.
Other Name: INVEGA® SUSTENNA™




Primary Outcome Measures :
  1. Paliperidone Palmitate Injection (INVEGA® SUSTENNA™) treated group will have a statistically significant advantage on improvement in manic symptoms. [ Time Frame: 5 weeks ]
    This research can increase knowledge about the utility of paliperidone for improving symptoms of bipolar disorder and cravings of alcohol. If proven effective in reducing these symptoms, paliperidone could be a good and safe treatment option for dual diagnosis.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: Patients will be assessed using the Mini International Neuropsychiatric Interview at baseline, which will be carried out at least three days after all acute withdrawal symptoms have cleared. Subjects who meet DSM-IV criteria for alcohol use disorder (abuse or dependence) and a concurrent bipolar I disorder, (Mixed or Mania State) and a score on the YMRS of 16 or above, and without any exclusion criteria will be recruited for the study. The following criteria must be met. A) Abstinent from alcohol not to exceed 21 consecutive days, and a score of <8 on the CIWA-Ar, [Sullivan, 1989 #1412] at the time of randomization. B) An average minimum of > 7 drinks per week for females or > 14 drinks per week for males, over a consecutive 4-week period during the 12-week period prior to baseline. C) A breath alcohol concentration (BAC) of 0 at the time of signing Informed Consent. D) Subject stable on treatment as usual medications for bipolar disorder for at least three weeks prior to randomization.

Exclusion Criteria: Patients with the following disorders will be excluded from the study: 1) Schizophrenia, schizoaffective, and any non-bipolar psychotic disorder, unipolar major depression, primary anxiety disorders, mental retardation, and signs of impaired cognitive functioning (operationalized as a score < 25 on Folstein's Mini-Mental Status Exam). [Folstein, 1975 #1179]. 2) Current DSM-IV criteria for dependence on substances other than alcohol, cannabis, nicotine, or caffeine. 3) Neurological conditions including epilepsy, history of brain injury, encephalitis, or any organic brain syndrome or documented focally abnormal electroencephalograph examination (EEG), or recent history (within the past two years) of alcohol withdrawal seizure. 4) Medical conditions including severe cardiac, liver, kidney, endocrine (e.g. diabetes), hematologic (e.g. porphyria or any bleeding abnormalities), or other impairing medical conditions, or impending surgery. 5) Congenital prolongation of the QT interval (congenital long QT syndrome), and a history of cardiac arrhythmias or other conditions that prolong the QT interval such as bradycardia; hypokalemia or hypomagnesemia; or on concomitant medications known to prolong QTc including Class 1A (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications, antipsychotic medications (e.g., chlorpromazine, thioridazine), antibiotics (e.g., gatifloxacin, moxifloxacin), or any other class of medications known to prolong the QTc interval. 6) Persistent elevation of liver function enzymes indicating active liver disease (elevated t. bilirubin > 1.5 mg/dl, or elevation to three-time normal range of liver enzymes, SGOT, SGPT, or g-GTP). 7) Any medication that is effective for alcohol dependence such as disulfiram, naltrexone, acamprosate, or topiramate. Carbamazepine for potential clinically significant drug-drug interaction. Other exclusion criteria include pregnancy, women who are breastfeeding, inability or unwillingness to use contraceptive methods, and inability to read or understand study forms and agrees to informed consent, or based on the judgment of the investigative team that the study may not be in the best interest of the subject either due to additional safety concerns or other factors that may interfere with study participations.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01211704


Sponsors and Collaborators
University of Miami
Ortho-McNeil, Inc.
Investigators
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Principal Investigator: Ihsan Salloum, MD MPH University of Miami

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Responsible Party: Ihsan Salloum, Professor of Psychiatry, University of Miami
ClinicalTrials.gov Identifier: NCT01211704     History of Changes
Other Study ID Numbers: 20081123
First Posted: September 29, 2010    Key Record Dates
Last Update Posted: November 21, 2014
Last Verified: November 2014

Keywords provided by Ihsan Salloum, University of Miami:
Bipolar, Alcoholism

Additional relevant MeSH terms:
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Paliperidone Palmitate
Disease
Bipolar Disorder
Alcoholism
Pathologic Processes
Bipolar and Related Disorders
Mental Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin 5-HT2 Receptor Antagonists
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Dopamine D2 Receptor Antagonists
Dopamine Antagonists
Dopamine Agents