Double-blind, Placebo-Controlled Divalproex Sodium ER in Bipolar I or Bipolar II Depression

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00194116

Enrollment

Registered

2005-09-19

Start date

2004-09-30

Completion date

2008-02-29

Last updated

2019-07-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Bipolar Disorder

Brief summary

Double-Blind, Placebo-Controlled Divalproex Sodium ER in Bipolar I or Bipolar II Depression Previously Diagnosed and Treated as Recurrent Major Depression: This study recruits males and females aged 18 - 70 who currently meet diagnostic criteria for bipolar I or bipolar II disorder and are currently experiencing an episode of major depression. Patients are randomized to double-blind treatment with divalproex sodium ER or placebo and remain in the study for up to six weeks. This six-week double-blind treatment period is followed by an open-label treatment period of six months duration. This study is sponsored by Abbott Laboratories.

Interventions

DRUGDivalproex Sodium ER

Tablets will be available in 250mg and 500mg strengths. Divalproex will be titrated to a minimum blood level of 50 mg/L. However, the investigators will titrate divalproex to the maximum tolerable dose with an expected average dose of 2000mg per day. By dosing in this manner, all subjects will have a minimum blood level of 50 mg/L, but the mean level is likely to be considerably higher.

DRUGPlacebo

. Tablets will be available in 250mg and 500mg strengths. Divalproex will be titrated to a minimum blood level of 50 mg/L. However, the investigators will titrate divalproex to the maximum tolerable dose with an expected average dose of 2000mg per day. By dosing in this manner, all subjects will have a minimum blood level of 50 mg/L, but the mean level is likely to be considerably higher.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

16 Years to 65 Years

Healthy volunteers

Yes

Inclusion criteria

* Subject must give consent to participate in the study and sign and date the IRB approved written informed consent form prior to the initiation of any study procedures * Subject must be between the ages of 18 and 70 * Subject must have a diagnosis of bipolar I or II. * Subject must be currently depressed as confirmed by the Mini-International Neuropsychiatric Interview (MINI) * Subject must have a baseline Montgomery-Asberg Depression Scale (MADRS) score of \>19 and Young Mania Rating Scale (YMRS) score of \<12 * Women of childbearing potential must be nonpregnant/nonlactating and using adequate contraception if sexually active * Subject must not be using any concomitant psychotropic medications during the acute phase except prn benzodiazepines

Exclusion criteria

* Subjects lacks the capacity to provide informed consent * Subject has currently or previously used divalproex or Dvpx-ER * Subject is a serious suicide risk or has medically unstable conditions as judged by the investigators * Subject has any alcohol, cocaine, or cannabis dependence within 3 months of study entry * Subject has any cocaine, hallucinogens, opiates, crystal methamphetamine, or MMDA abuse within 3 months of study entry

Design outcomes

Primary

Measure	Time frame	Description
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score	Acute phase (week0-week6)	MADRS total scores range from 0-60, where higher scores are indicative of more depression.

Secondary

Measure	Time frame	Description
Change in General Behavior Inventory (GBI) Depression Scale Score	Acute phase (week0-week6)	GBI Depression Scale Scores range from 46-184, where higher scores are indicative of more depression.
Change in General Behavior Inventory (GBI) Hypomanic/Biphasic Scale Score	Acute phase (week0-week6)	GBI Hypomanic/Biphasic Scale scores range from 28-112, where higher scores are indicative of more hypomanic/manic symptoms.
Change in Young Mania Rating Scale (YMRS) Total Score	Acute phase (week0-week6)	YMRS Scores range from 0 to 60 where higher scores are indicative of more mania.
Change in Short Form Health Survey (SF-36) Mental Component Summary Score	Acute phase (week0-week6)	SF-36 Mental Component Summary scores range from 0-100, with a higher score indicating better mental health.
Change in Hamilton Anxiety Rating Scale (HAMA) Total Score	Acute phase (week0-week6)	HAMA Scores range from 0 to 56 where higher scores are indicative of more anxiety.
Change in Short Form Health Survey (SF-36) Physical Component Summary Score	Acute phase (week0-week6)	SF-36 Physical Component Summary scores range from 0-100, with a higher score indicating better physical health.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Divalproex Sodium ER Divalproex Sodium ER: Tablets will be available in 250mg and 500mg strengths. Divalproex will be titrated to a minimum blood level of 50 mg/L. However, the investigators will titrate divalproex to the maximum tolerable dose with an expected average dose of 2000mg per day. By dosing in this manner, all subjects will have a minimum blood level of 50 mg/L, but the mean level is likely to be considerably higher.	26
Placebo Placebo: . Tablets will be available in 250mg and 500mg strengths. Divalproex will be titrated to a minimum blood level of 50 mg/L. However, the investigators will titrate divalproex to the maximum tolerable dose with an expected average dose of 2000mg per day. By dosing in this manner, all subjects will have a minimum blood level of 50 mg/L, but the mean level is likely to be considerably higher.	28
Total	54

Baseline characteristics

Characteristic	Placebo	Total	Divalproex Sodium ER
Age, Continuous	38.8 years STANDARD_DEVIATION 14.4	39.2 years STANDARD_DEVIATION 12.5	39.7 years STANDARD_DEVIATION 10.3
DSM-IV Diagnosis Bipolar I Disorder	10 Participants	20 Participants	10 Participants
DSM-IV Diagnosis Bipolar II Disorder	18 Participants	34 Participants	16 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	2 Participants	2 Participants
Race (NIH/OMB) Black or African American	6 Participants	9 Participants	3 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) White	22 Participants	42 Participants	20 Participants
Sex: Female, Male Female	16 Participants	31 Participants	15 Participants
Sex: Female, Male Male	12 Participants	23 Participants	11 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 26	0 / 28
other Total, other adverse events	13 / 26	5 / 28
serious Total, serious adverse events	0 / 26	0 / 28