Safety and Efficacy Study of ELND005 as an Adjunctive Maintenance Treatment in Bipolar I Disorder

• Sponsor: OPKO Health, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01674010
• Collaborator: Elan Pharmaceuticals (Industry)
• Enrollment: 309
• Locations: 82
• Arms: 2
• Duration (Months): 22
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary purpose of this study is to determine whether ELND005 is effective in the maintenance treatment of bipolar 1 disorder when added to other therapies.

Condition or Disease	Intervention/Treatment	Phase
Bipolar 1 Disorder	Drug: ELND005; Drug: Lamotrigine; Drug: Valproic acid; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 309 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Prospective, Randomized, Double-Blind, Placebo-Controlled, Phase 2 Safety and Efficacy Study of Oral ELND005 as an Adjunctive Maintenance Treatment in Patients With Bipolar I Disorder
• Study Start Date: Aug 1, 2012
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lamotrigine or Valproic acid + ELND005 Lamotrigine or valproic acid plus ELND005 film coated tablets, 500mg BID for up to 48 weeks	Drug: ELND005; Other Names: Scyllo-inositol ; Drug: Lamotrigine; Drug: Valproic acid
Placebo Comparator: Lamotrigine or Valproic acid + placebo Lamotrigine or valproic acid plus matched placebo BID for up to 48 weeks	Drug: Lamotrigine; Drug: Valproic acid; Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Treatment Emergent Adverse Events [up to 48 weeks]

   The study was terminated early so no efficacy analysis was done, safety data are reported.

Secondary Outcome Measures

1. Proportion of Study Participants With Recurrence of Any Mood Episode [up to 48 weeks]

2. Time to Recurrence of a Depressive Episode [up to 48 weeks]

3. Time to Recurrence of a Manic/Hypomanic or a Mixed Episode [up to 48 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Meets the DSM-IV-TR criteria for BPD I by the SCID, prior to the Screening Visit.

• Has a history in the last 3 years of ≥ 1 manic or mixed episodes of sufficient severity that required hospitalization and/or treatment with a mood stabilizer or antipsychotic, or confirmed by a family member or medical records to ensure the episode fulfills the DSM-IV-TR criteria.

• Has experienced a mood episode of any polarity within 4 months prior to the Screening Visit and responded to StOC therapy.

• Is euthymic at the Screening Visit (ie, score of ≤ 12 on the MADRS and a score of ≤ 12 on the Y-MRS).

• Is receiving maintenance treatment for his or her BPD I with either LTG or VPA; on stable doses for past 4 weeks and therapeutic drug levels (total VPA 50--125 µg/mL and LTG 10-50 µmol/L or as deemed appropriate by the investigator). Dose adjustments made for tolerability reasons will be acceptable.

A study patient must meet the following additional criteria to be eligible for randomization in the Double-blind Randomization Phase of this study:

• Maintained in a stable euthymic state during Phase 1, defined as Y-MRS and MADRS scores of ≤ 12, with the following exceptions: a maximum of 2 nonconsecutive excursions will be allowed throughout Phase 1. Excursions are defined as Y-MRS or MADRS scores >12 but ≤ 16.

Exclusion Criteria:

• Woman of childbearing potential who is unwilling or unable to use an acceptable method of birth control or is using a prohibited contraceptive method.

• Is found to be actively suicidal on the C-SSRS (answer of "yes" to question 4 or 5 [current or over the last 30 days]) or a score of ≥4 on the MADRS item 10 at the Screening Visit.

• Has suboptimally treated thyroid disease as evidenced by thyroid-stimulating hormone (TSH) >3 mIU/L at the Screening Visit.

• Has received electroconvulsive therapy (ECT) during the current episode or within 6 months prior to the Screening Visit.

• Has an estimated glomerular filtration rate <40 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease formula.

A study patient who meets ANY of the above and ANY of the criteria below will not be eligible for enrollment in the Double-blind Randomization Phase of this study:

• Has current signs or symptoms of psychosis.

• Has become actively suicidal as defined by C-SSRS answer of "yes" to question 4 or 5 (current or over the last 30 days) and/or has a score of ≥4 on MADRS item 10.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Elan Investigational Site	Birmingham	Alabama	United States	35294
2	Elan Investigational Site	Glendale	Arizona	United States	85306
3	Elan Investigational Site	Phoenix	Arizona	United States	85004
4	Elan Investigational Site	Little Rock	Arkansas	United States	72201
5	Elan Investigational Site	Little Rock	Arkansas	United States	72211
6	Elan Investigational Site	Cerritos	California	United States	90703
7	Elan Investigational Site	Costa Mesa	California	United States	92626
8	Elan Investigational Site	Escondido	California	United States	92025
9	Elan Investigational Site	Garden Grove	California	United States	92845
10	Elan Investigational Site	National City	California	United States	91950
11	Elan Investigational Site	Oceanside	California	United States	92056
12	Elan Investigational Site	Palo Alto	California	United States	94304
13	Elan Investigational Site	Riverside	California	United States	92506
14	Elan Investigational Site	San Diego	California	United States	92121
15	Elan Investigational Site	Santa Ana	California	United States	92701
16	Elan Investigational Site	Stanford	California	United States	94305
17	Elan Investigational Site	Norwich	Connecticut	United States	06360
18	Elan Investigational Site	North Miami	Florida	United States	33161
19	Elan Investigational Site	Oakland Park	Florida	United States	33334
20	Elan Investigational Site	Tampa	Florida	United States	33613
21	Elan Investigational Site	Atlanta	Georgia	United States	30308
22	Elan Investigational Site	Roswell	Georgia	United States	30076
23	Elan Investigational Site	Creve Coeur	Missouri	United States	63141
24	Elan Investigational Site	Saint Louis	Missouri	United States	63118
25	Elan Investigational Site	Saint Louis	Missouri	United States	63128
26	Elan Investigational Site	Lincoln	Nebraska	United States	68526
27	Elan Investigational Site	Marlton	New Jersey	United States	08053
28	Elan Investigational Site	Fresh Meadows	New York	United States	11366
29	Elan Investigational Site	New York	New York	United States	10065
30	Elan Investigational Site	Raleigh	North Carolina	United States	27609
31	Elan Investigational Site	Beachwood	Ohio	United States	44122
32	Elan Investigational Site	Cincinnati	Ohio	United States	45219
33	Elan Investigational Site	Cleveland	Ohio	United States	44106
34	Elan Investigational Site	Oklahoma City	Oklahoma	United States	73112
35	Elan Investigational Site	Philadelphia	Pennsylvania	United States	19139
36	Elan Investigational Site	Charleston	South Carolina	United States	29407
37	Elan Investigational Site	Houston	Texas	United States	77054
38	Elan Investigational Site	Hurst	Texas	United States	76053
39	Elan Investigational Site	San Antonio	Texas	United States	78229
40	Elan Investigational Site	Salt Lake City	Utah	United States	84106
41	Elan Investigational Site	Bellevue	Washington	United States	98007
42	Elan Investigational Site	Kardzhali		Bulgaria	6600
43	Elan Investigational Site	Pazardzhik		Bulgaria	4400
44	Elan Investigational Site	Sofia		Bulgaria	1000
45	Elan Investigational Site	Sofia		Bulgaria	1431
46	Elan Investigational Site	Varna		Bulgaria	9010
47	Elan Investigational Site	Vratsa		Bulgaria	3000
48	Elan Investigational Site	Edmonton	Alberta	Canada	T6L 6W6
49	Elan Investigational Site	Kelowna	British Columbia	Canada	V1Y 1Z9
50	Elan Investigational Site	Halifax	Nova Scotia	Canada	B3H 2E2
51	Elan Investigational Site	Chatham	Ontario	Canada	N7M 5L9
52	Elan Investigational Site	Kingston	Ontario	Canada	K7L 4X3
53	Elan Investigational Site	London	Ontario	Canada	N6A 4H1
54	Elan Investigational Site	Toronto	Ontario	Canada	M4N 3M5
55	Elan Investigational Site	Toronto	Ontario	Canada	M5T 2S8
56	Elan Investigational Site	Praha		Czechia	100 00
57	Elan Investigational Site	Praha		Czechia	120 00
58	Elan Investigational Site	Praha		Czechia	160 00
59	Elan Investigational Site	Praha		Czechia	18100
60	Elan Investigational Site	Strakonice		Czechia	386 29
61	Elan Investigational Site	Bully-Les-Mines		France	62160
62	Elan Investigational Site	Dole		France	39100
63	Elan Investigational Site	Elancourt		France	78990
64	Elan Investigational Site	Nimes		France	30029
65	Elan Investigational Site	Toulouse		France	31000
66	Elan Investigational Site	Toulouse		France	31200
67	Elan Investigational Site	Bydgoszcz		Poland	85-156
68	Elan Investigational Site	Gdansk		Poland	80-546
69	Elan Investigational Site	Lodz		Poland	91-229
70	Elan Investigational Site	Tuszyn		Poland	95-080
71	Elan Investigational Site	Brasov		Romania	500366
72	Elan Investigational Site	Bucharest		Romania	041914
73	Elan Investigational Site	Craiova		Romania	200473
74	Elan Investigational Site	Sibiu		Romania	550082
75	Elan Investigational Site	Torrevieja	Alicante	Spain	03186
76	Elan Investigational Site	Oviedo	Asturias	Spain	33011
77	Elan Investigational Site	Barcelona		Spain	08036
78	Elan Investigational Site	Vitoria		Spain	01004
79	Elan Investigational Site	Ankara		Turkey	06100
80	Elan Investigational Site	Diyarbakir		Turkey	21280
81	Elan Investigational Site	Edirne		Turkey	22030
82	Elan Investigational Site	Istanbul		Turkey	34098

Sponsors and Collaborators

• OPKO Health, Inc.
• Elan Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: OPKO Health, Inc.
• ClinicalTrials.gov Identifier: NCT01674010
• Other Study ID Numbers: ELND005-BPD201; 2012-001935-30
• First Posted: Aug 28, 2012
• Last Update Posted: Oct 21, 2019
• Last Verified: Oct 1, 2019

• Additional relevant MeSH terms: Disease; Inositol; Lamotrigine; Valproic Acid

Study Results

Participant Flow

Arm/Group Title	Open Treatment Phase 1 ELND005 500 mg BID	Phase 2 Placebo	Phase 2 ELND005 500 mg BID
Arm/Group Description	ELND005 500mg BID for 16 weeks	Double Blind Randomization (Phase 2)	Randomization Phase 2 ELND005 500 mg BID
Period Title: Open Treatment Phase 1
STARTED	309	0	0
COMPLETED	129	0	0
NOT COMPLETED	180	0	0
Period Title: Open Treatment Phase 1
STARTED	0	65	64
COMPLETED	0	3	3
NOT COMPLETED	0	62	61

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description
Overall Participants	309
Age (years) [Mean (Standard Deviation) ]
Phase 1(n=309)	44.3 (11.09)
Phase 2 Placebo (n=65)	44.5 (10.65)
Phase 2 ELND005 500mg BID(n=64)	44.6 (10.61)
Sex/Gender, Customized (participants) [Number]
Phase 1 Male	146 47.2%
Phase 1 Female	163 52.8%
Phase 2 Placebo Male	34 11%
Phase 2 Placebo Female	31 10%
Phase 2 ELND005 500 BID Male	32 10.4%
Phase 2 ELND005 500 BID Female	32 10.4%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino Phase 1	23 7.4%
Hispanic or Latino Phase 2 Placebo	4 1.3%
Hispanic or Latino Phase 2 ELND005 500 BID	6 1.9%
Not Hispanic or Latino Phase 1	284 91.9%
Not Hispanic or Latino Phase 2 Placebo	60 19.4%
Not Hispanic or Latino Phase 2 ELND005 500 BID	58 18.8%
Unknown Phase 1	2 0.6%
Unknown Phase 2 Placebo	1 0.3%
Unknown Phase 2 ELND005 500 BID	0 0%
Region of Enrollment (participants) [Number]
North America	210 68%
Europe	99 32%

Outcome Measures

1. Primary Outcome

Title	Treatment Emergent Adverse Events
Description	The study was terminated early so no efficacy analysis was done, safety data are reported.
Time Frame	up to 48 weeks

Outcome Measure Data

Analysis Population Description

TEAEs reported for Phase 2 were from the entire study period

Arm/Group Title	Open Treatment Phase 1 ELND005 500 mg BID	Phase 2 Placebo	Phase 2 ELND005 500 mg BID
Arm/Group Description	ELND005 500mg BID for 16 weeks	Double Blind Randomization (Phase 2)	Randomization Phase 2 ELND005 500 mg BID
Measure Participants	309	65	64
Number [participants]	153 49.5%	45 NaN	45 NaN

2. Secondary Outcome

Title	Proportion of Study Participants With Recurrence of Any Mood Episode
Time Frame	up to 48 weeks

Outcome Measure Data

Analysis Population Description

Study was prematurely terminated, no data were collected for this Outcome Measure

Arm/Group Title	Open Treatment Phase 1 ELND005 500 mg BID	Phase 2 Placebo	Phase 2 ELND005 500 mg BID
Arm/Group Description	ELND005 500mg BID for 16 weeks	Double Blind Randomization (Phase 2)	Randomization Phase 2 ELND005 500 mg BID
Measure Participants	0	0	0

3. Secondary Outcome

Title	Time to Recurrence of a Depressive Episode
Time Frame	up to 48 weeks

Outcome Measure Data

Analysis Population Description

Study was prematurely terminated, no data were collected for this Outcome Measure

Arm/Group Title	Open Treatment Phase 1 ELND005 500 mg BID	Phase 2 Placebo	Phase 2 ELND005 500 mg BID
Arm/Group Description	ELND005 500mg BID for 16 weeks	Double Blind Randomization (Phase 2)	Randomization Phase 2 ELND005 500 mg BID
Measure Participants	0	0	0

4. Secondary Outcome

Title	Time to Recurrence of a Manic/Hypomanic or a Mixed Episode
Time Frame	up to 48 weeks

Outcome Measure Data

Analysis Population Description

Study was prematurely terminated, no data were collected for this Outcome Measure

Arm/Group Title	Open Treatment Phase 1 ELND005 500 mg BID	Phase 2 Placebo	Phase 2 ELND005 500 mg BID
Arm/Group Description	ELND005 500mg BID for 16 weeks	Double Blind Randomization (Phase 2)	Randomization Phase 2 ELND005 500 mg BID
Measure Participants	0	0	0

Adverse Events

Time Frame	Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study.
Arm/Group Title	Open Treatment Phase 1 ELND005 500 mg BID		Phase 2 Placebo		Phase 2 ELND005 500 mg BID
Arm/Group Description	ELND005 500mg BID for 16 weeks		Double Blind Randomization (Phase 2)		Randomization Phase 2 ELND005 500 mg BID
All Cause Mortality
	Open Treatment Phase 1 ELND005 500 mg BID		Phase 2 Placebo		Phase 2 ELND005 500 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Open Treatment Phase 1 ELND005 500 mg BID		Phase 2 Placebo		Phase 2 ELND005 500 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/309 (3.9%)		3/65 (4.6%)		3/64 (4.7%)
Blood and lymphatic system disorders
Hemolytic anemia	1/309 (0.3%)		1/65 (1.5%)		0/64 (0%)
Cardiac disorders
Cardiac disorder	1/309 (0.3%)		0/65 (0%)		0/64 (0%)
Embolic stroke	1/309 (0.3%)		0/65 (0%)		0/64 (0%)
Eye disorders
Diplopia	0/309 (0%)		0/65 (0%)		1/64 (1.6%)
Gastrointestinal disorders
Gastroenteritis	1/309 (0.3%)		0/65 (0%)		0/64 (0%)
Infections and infestations
Pneumonia	1/309 (0.3%)		1/65 (1.5%)		0/64 (0%)
Injury, poisoning and procedural complications
Food Poisoning	1/309 (0.3%)		0/65 (0%)		1/64 (1.6%)
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration	0/309 (0%)		1/65 (1.5%)		0/64 (0%)
Psychiatric disorders
Depression	3/309 (1%)		0/65 (0%)		0/64 (0%)
Bipolar I Disorder	1/309 (0.3%)		0/65 (0%)		0/64 (0%)
Impulsive Behaviour	1/309 (0.3%)		0/65 (0%)		0/64 (0%)
Mania	1/309 (0.3%)		0/65 (0%)		1/64 (1.6%)
Suicide attempt	1/309 (0.3%)		0/65 (0%)		0/64 (0%)
Intentional self-injury	0/309 (0%)		1/65 (1.5%)		0/64 (0%)
Reproductive system and breast disorders
Abortion spontaneous	0/309 (0%)		1/65 (1.5%)		0/64 (0%)
Other (Not Including Serious) Adverse Events
	Open Treatment Phase 1 ELND005 500 mg BID		Phase 2 Placebo		Phase 2 ELND005 500 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	153/309 (49.5%)		45/65 (69.2%)		45/64 (70.3%)
Gastrointestinal disorders
Gastrointestinal disorders	29/309 (9.4%)		12/65 (18.5%)		11/64 (17.2%)
General disorders
General disorders and administration site conditions	10/309 (3.2%)		2/65 (3.1%)		5/64 (7.8%)
Infections and infestations
Infections and infestations	47/309 (15.2%)		20/65 (30.8%)		20/64 (31.3%)
Injury, poisoning and procedural complications
Injury poisoning and procedural complications	19/309 (6.1%)		15/65 (23.1%)		11/64 (17.2%)
Investigations
Investigations	13/309 (4.2%)		8/65 (12.3%)		8/64 (12.5%)
Metabolism and nutrition disorders
Metabolism and nutrition disorders	9/309 (2.9%)		2/65 (3.1%)		5/64 (7.8%)
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders	18/309 (5.8%)		11/65 (16.9%)		10/64 (15.6%)
Nervous system disorders
Nervous system disorders	35/309 (11.3%)		13/65 (20%)		11/64 (17.2%)
Psychiatric disorders
Psychiatric disorders	63/309 (20.4%)		15/65 (23.1%)		13/64 (20.3%)
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders	4/309 (1.3%)		4/65 (6.2%)		4/64 (6.3%)
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders	12/309 (3.9%)		3/65 (4.6%)		4/64 (6.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.