A Long-Term Safety Study of ALKS 5461

• Sponsor: Alkermes, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02141399
• Collaborator: (none)
• Enrollment: 1,485
• Locations: 158
• Arm: 1
• Actual Duration (Months): 42.7
• Patients Per Site: 9.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a 52-week open-label study to evaluate the safety and tolerability of ALKS 5461.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: ALKS 5461	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1485 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Multicenter Study of the Long-Term Safety and Tolerability of ALKS 5461 for the Adjunctive Treatment of Major Depressive Disorder in Adults Who Have an Inadequate Response to Antidepressant Therapy (the FORWARD-2 Study)
• Actual Study Start Date: May 1, 2014
• Actual Primary Completion Date: Nov 20, 2017
• Actual Study Completion Date: Nov 20, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ALKS 5461	Drug: ALKS 5461; Sublingual tablet, taken daily

Outcome Measures

Primary Outcome Measures

1. Incidence of Adverse Events (AEs) [Up to 56 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Agree to use an approved method of contraception for the duration of the study

• Have the potential to safely benefit from the administration of ALKS 5461

• Have a diagnosis of major depressive disorder (MDD)

• Additional criteria may apply

Exclusion Criteria:

• Have a positive test for drugs of abuse

• Currently pregnant or breastfeeding

• Have a current primary Axis-I disorder other than MDD

• Have used opioid agonists (eg, codeine, oxycodone, tramadol, morphine) or opioid antagonists (eg, naloxone, naltrexone) within 14 days

• Have received electroconvulsive therapy treatment within the last 2 years, or received more than 1 course of electroconvulsive treatment during their lifetime

• Have attempted suicide within the past 2 years

• Have a history of intolerance, allergy, or hypersensitivity to buprenorphine or opioid antagonists (eg, naltrexone, naloxone)

• Have had a significant blood loss or blood donation within the past 60 days

• Additional criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alkermes Investigational Site	Birmingham	Alabama	United States	35226
2	Alkermes Investigational Site	Birmingham	Alabama	United States	35294
3	Alkermes Investigational Site	Tucson	Arizona	United States	85712
4	Alkermes Investigational Site	Little Rock	Arkansas	United States	72211
5	Alkermes Investigational Site	Bellflower	California	United States	90706
6	Alkermes Investigational Site	Beverly Hills	California	United States	90210
7	Alkermes Investigational Site	Carson	California	United States	90746
8	Alkermes Investigational Site	Garden Grove	California	United States	92845
9	Alkermes Investigational Site	Glendale	California	United States	91206
10	Alkermes Investigational Site	Los Alamitos	California	United States	90720
11	Alkermes Investigational Site	Los Angeles	California	United States	90024
12	Alkermes Investigational Site	National City	California	United States	91950
13	Alkermes Investigational Site	Oakland	California	United States	94612
14	Alkermes Investigational Site	Oceanside	California	United States	92056
15	Alkermes Investigational Site	Orange	California	United States	92868
16	Alkermes Investigational Site	Pico Rivera	California	United States	90660
17	Alkermes Investigational Site	Redlands	California	United States	92374
18	Alkermes Investigational Site	San Gabriel	California	United States	91776
19	Alkermes Investigational Site	Sherman Oaks	California	United States	91403
20	Alkermes Investigational Site	Temecula	California	United States	92591
21	Alkermes Investigational Site	Torrance	California	United States	90502
22	Alkermes Investigational Site	Upland	California	United States	91786
23	Alkermes Investigational Site	Colorado Springs	Colorado	United States	80910
24	Alkermes Investigational Site	Denver	Colorado	United States	80209
25	Alkermes Investigational Site	Hartford	Connecticut	United States	06106
26	Alkermes Investigational Site	Norwich	Connecticut	United States	06360
27	Alkermes Investigational Site	Bradenton	Florida	United States	34201
28	Alkermes Investigational Site	Coral Springs	Florida	United States	33067
29	Alkermes Investigational Site	Fort Myers	Florida	United States	33912
30	Alkermes Investigational Site	Gainesville	Florida	United States	32607
31	Alkermes Investigational Site	Hallandale Beach	Florida	United States	33009
32	Alkermes Investigational Site	Hialeah	Florida	United States	33016
33	Alkermes Investigational Site	Jacksonville	Florida	United States	32256
34	Alkermes Investigational Site	Lauderhill	Florida	United States	33319
35	Alkermes Investigational Site	Maitland	Florida	United States	32751
36	Alkermes Investigational Site	Melbourne	Florida	United States	32901
37	Alkermes Investigational Site	North Miami	Florida	United States	33161
38	Alkermes Investigational Site	Oakland Park	Florida	United States	33334
39	Alkermes Investigational Site	Orlando	Florida	United States	32801
40	Alkermes Investigational Site	Tampa	Florida	United States	33613
41	Alkermes Investigational Site	The Villages	Florida	United States	32162
42	Alkermes Investigational Site	West Palm Beach	Florida	United States	33407
43	Alkermes Investigational Site	Winter Haven	Florida	United States	33880
44	Alkermes Investigational Site	Alpharetta	Georgia	United States	30005
45	Alkermes Investigational Site	Atlanta	Georgia	United States	30308
46	Alkermes Investigational Site	Decatur	Georgia	United States	30030
47	Alkermes Investigational Site	Smyrna	Georgia	United States	30080
48	Alkermes Investigational Site	Chicago	Illinois	United States	60634
49	Alkermes Investigational Site	Chicago	Illinois	United States	60640
50	Alkermes Investigational Site	Deerfield	Illinois	United States	60015
51	Alkermes Investigational Site	Hoffman Estates	Illinois	United States	60169
52	Alkermes Investigational Site	Joliet	Illinois	United States	60435
53	Alkermes Investigational Site	Oak Brook	Illinois	United States	60523
54	Alkermes Investigational Site	Skokie	Illinois	United States	60076
55	Alkermes Investigational Site	Indianapolis	Indiana	United States	46260
56	Alkermes Investigational Site	Lafayette	Indiana	United States	47905
57	Alkermes Investigational Site	Newburgh	Indiana	United States	47630
58	Alkermes Investigational Site	Valparaiso	Indiana	United States	46383
59	Alkermes Investigational Site	Edgewood	Kentucky	United States	41017
60	Alkermes Investigational Site	Owensboro	Kentucky	United States	42301
61	Alkermes Investigational Site	Baltimore	Maryland	United States	21204
62	Alkermes Investigational Site	Baltimore	Maryland	United States	21208
63	Alkermes Investigational Site	Washington D.C.	Maryland	United States	20016
64	Alkermes Investigational Site	Belmont	Massachusetts	United States	02478
65	Alkermes Investigational Site	Brockton	Massachusetts	United States	02301
66	Alkermes Investigational Site	Watertown	Massachusetts	United States	02472
67	Alkermes Investigational Site	Worcester	Massachusetts	United States	01655
68	Alkermes Investigational Site	Flowood	Mississippi	United States	39232
69	Alkermes Investigational Site	O'Fallon	Missouri	United States	63368
70	Alkermes Investigational Site	Saint Charles	Missouri	United States	63304
71	Alkermes Investigational Site	Saint Louis	Missouri	United States	63109
72	Alkermes Investigational Site	Saint Louis	Missouri	United States	63141
73	Alkermes Investigational Site	Berlin	New Jersey	United States	80091
74	Alkermes Investigational Site	Cherry Hill	New Jersey	United States	08002
75	Alkermes Investigational Site	Princeton	New Jersey	United States	08540
76	Alkermes Investigational Site	Albuquerque	New Mexico	United States	87109
77	Alkermes Investigational Site	Brooklyn	New York	United States	11241
78	Alkermes Investigational Site	Jamaica	New York	United States	11432
79	Alkermes Investigational Site	Mount Kisco	New York	United States	10549
80	Alkermes Investigational Site	New York	New York	United States	10019
81	Alkermes Investigational Site	New York	New York	United States	10023
82	Alkermes Investigational Site	New York	New York	United States	10029
83	Alkermes Investigational Site	New York	New York	United States	10128
84	Alkermes Investigational Site	New York	New York	United States	10168
85	Alkermes Investigational Site	Staten Island	New York	United States	10305
86	Alkermes Investigational Site	Staten Island	New York	United States	10312
87	Alkermes Investigational Site	Charlotte	North Carolina	United States	28204
88	Alkermes Investigational Site	High Point	North Carolina	United States	27265
89	Alkermes Investigational Site	Beachwood	Ohio	United States	44122
90	Alkermes Investigational Site	Canton	Ohio	United States	44718
91	Alkermes Investigational Site	Cincinnati	Ohio	United States	45215
92	Alkermes Investigational Site	Cincinnati	Ohio	United States	45227
93	Alkermes Investigational Site	Dayton	Ohio	United States	45417
94	Alkermes Investigational Site	Mason	Ohio	United States	45040
95	Alkermes Investigational Site	Middleburg Heights	Ohio	United States	44130
96	Alkermes Investigational Site	Oklahoma City	Oklahoma	United States	73103
97	Alkermes Investigational Site	Oklahoma City	Oklahoma	United States	73112
98	Alkermes Investigational Site	Portland	Oregon	United States	97210
99	Alkermes Investigational Site	Portland	Oregon	United States	97214
100	Alkermes Investigational Site	Salem	Oregon	United States	97301
101	Alkermes Investigational Site	Allentown	Pennsylvania	United States	18104
102	Alkermes Investigational Site	Media	Pennsylvania	United States	19063
103	Alkermes Investigational Site	Philadelphia	Pennsylvania	United States	19104
104	Alkermes Investigational Site	Philadelphia	Pennsylvania	United States	19107
105	Alkermes Investigational Site	Lincoln	Rhode Island	United States	02865
106	Alkermes Investigational Site	Charleston	South Carolina	United States	29407
107	Alkermes Investigational Site	Memphis	Tennessee	United States	38119
108	Alkermes Investigational Site	Austin	Texas	United States	78731
109	Alkermes Investigational Site	Dallas	Texas	United States	75231
110	Alkermes Investigational Site	Dallas	Texas	United States	75390
111	Alkermes Investigational Site	DeSoto	Texas	United States	75115
112	Alkermes Investigational Site	Houston	Texas	United States	77081
113	Alkermes Investigational Site	Houston	Texas	United States	77098
114	Alkermes Investigational Site	San Antonio	Texas	United States	78229
115	Alkermes Investigational Site	Sugar Land	Texas	United States	77478
116	Alkermes Investigational Site	Wichita Falls	Texas	United States	76309
117	Alkermes Investigational Site	Clinton	Utah	United States	84015
118	Alkermes Investigational Site	Woodstock	Vermont	United States	05091
119	Alkermes Investigational Site	Bellevue	Washington	United States	98007
120	Alkermes Investigational Site	Seattle	Washington	United States	98104
121	Alkermes Investigational Site	Spokane	Washington	United States	99204
122	Alkermes Investigational Site	Middleton	Wisconsin	United States	53562
123	Alkermes Investigational Site	Waukesha	Wisconsin	United States	53188
124	Alkermes Investigational Site	Towong	Queensland	Australia	4066
125	Alkermes Investigational Site	Frankston	Victoria	Australia	3199
126	Alkermes Investigational Site	Melbourne	Victoria	Australia	3004
127	Alkermes Investigational Site	Bourgas		Bulgaria	8001
128	Alkermes Investigational Site	Kazanlak		Bulgaria	6100
129	Alkermes Investigational Site	Sofia		Bulgaria	1113
130	Alkermes Investigational Site	Sofia		Bulgaria	1431
131	Alkermes Investigational Site	Sofia		Bulgaria	1632
132	Alkermes Investigational Site	Varna		Bulgaria	9020
133	Alkermes Investigational Site	Veliko Turnovo		Bulgaria	5000
134	Alkermes Investigational Site	Vratza		Bulgaria	3000
135	Alkermes Investigational Site	Penticton	British Columbia	Canada	V2A 4M4
136	Alkermes Investigational Site	Halifax	Nova Scotia	Canada	B3S 1L8
137	Alkermes Investigational Site	Gatineau	Quebec	Canada	J8T 8JL
138	Alkermes Investigational Site	Quebec		Canada	G3K 2P8
139	Alkermes Investigational Site	Oranienburg	Brandenburg	Germany	16515
140	Alkermes Investigational Site	Achim		Germany	28832
141	Alkermes Investigational Site	Berlin		Germany	10245
142	Alkermes Investigational Site	Berlin		Germany	10365
143	Alkermes Investigational Site	Berlin		Germany	10629
144	Alkermes Investigational Site	Ellwangen		Germany	73479
145	Alkermes Investigational Site	Freiburg		Germany	79104
146	Alkermes Investigational Site	Hannover		Germany	30159
147	Alkermes Investigational Site	Mainz		Germany	55131
148	Alkermes Investigational Site	Schwerin		Germany	19053
149	Alkermes Investigational Site	Stralsund		Germany	18439
150	Alkermes Investigational Site	Budapest		Hungary	1053
151	Alkermes Investigational Site	Budapest		Hungary	1135
152	Alkermes Investigational Site	Budapest		Hungary	1137
153	Alkermes Investigational Site	Bialystok		Poland	15-879
154	Alkermes Investigational Site	Gdansk		Poland	80-438
155	Alkermes Investigational Site	Gdansk		Poland	80-546
156	Alkermes Investigational Site	Gorlice		Poland	38-300
157	Alkermes Investigational Site	San Juan		Puerto Rico	00918
158	Alkermes Investigational Site	San Juan		Puerto Rico	00926

Sponsors and Collaborators

• Alkermes, Inc.

Investigators

• Study Director: Sanjeev Pathak, MD, Alkermes, Inc.

Study Documents (Full-Text)

• Study Protocol - Mar 3, 2016
• Statistical Analysis Plan - Sep 15, 2017

More Information

Publications

None provided.

• Responsible Party: Alkermes, Inc.
• ClinicalTrials.gov Identifier: NCT02141399
• Other Study ID Numbers: ALK5461-208
• First Posted: May 19, 2014
• Last Update Posted: Dec 14, 2018
• Last Verified: Nov 1, 2018

• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major

Study Results

Participant Flow

Recruitment Details	Subjects were entered into the study in one of 3 ways, based upon previous experience with a prior ALKS 5461 study: Subjects continuing from a prior ALKS 5461 study; Subjects who participated in the prospective lead-in for a prior ALKS 5461 study, but did not meet the entrance criteria; Subjects who did not participate in a prior ALKS 5461 study.
Pre-assignment Detail	All subjects received ALKS 5461 during the course of the study as an adjunctive treatment for major depressive disorder. In addition all subjects were treated with background antidepressant therapy prescribed by the investigator.

Arm/Group Title	ALKS 5461
Arm/Group Description	ALKS 5461 adjunctive treatment
Period Title: Overall Study
STARTED	1485
COMPLETED	741
NOT COMPLETED	744

Baseline Characteristics

Arm/Group Title	ALKS 5461
Arm/Group Description	ALKS 5461 adjunctive treatment
Overall Participants	1485
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.5 (12.27)
Sex: Female, Male (Count of Participants)
Female	964 64.9%
Male	521 35.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	197 13.3%
Not Hispanic or Latino	1288 86.7%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	7 0.5%
Asian	28 1.9%
Native Hawaiian or Other Pacific Islander	8 0.5%
Black or African American	362 24.4%
White	1080 72.7%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
Canada	54 3.6%
Hungary	5 0.3%
United States	1204 81.1%
Poland	33 2.2%
Australia	35 2.4%
Bulgaria	88 5.9%
Germany	66 4.4%

Outcome Measures

1. Primary Outcome

Title	Incidence of Adverse Events (AEs)
Time Frame	Up to 56 weeks

Outcome Measure Data

Analysis Population Description

The safety population included all subjects who received at least 1 dose of study drug.

Arm/Group Title	ALKS 5461
Arm/Group Description	ALKS 5461 adjunctive treatment
Measure Participants	1485
Count of Participants [Participants]	1124 75.7%

Adverse Events

Time Frame	Up to 56 weeks
Arm/Group Title	ALKS 5461
Arm/Group Description	ALKS 5461 adjunctive treatment
All Cause Mortality
	ALKS 5461
	Affected / at Risk (%)	# Events
Total	2/1485 (0.1%)
Serious Adverse Events
	ALKS 5461
	Affected / at Risk (%)	# Events
Total	47/1485 (3.2%)
Blood and lymphatic system disorders
Anaemia	1/1485 (0.1%)	1
Cardiac disorders
Myocardial infarction	2/1485 (0.1%)	2
Atrial fibrillation	1/1485 (0.1%)	1
Cardiac failure congestive	1/1485 (0.1%)	1
Sinus tachycardia	1/1485 (0.1%)	1
Gastrointestinal disorders
Colitis	2/1485 (0.1%)	2
Duodenal ulcer	1/1485 (0.1%)	1
Gastric ulcer haemorrhage	1/1485 (0.1%)	1
Pancreatitis	1/1485 (0.1%)	1
Small intestinal obstruction	1/1485 (0.1%)	1
General disorders
Asthenia	1/1485 (0.1%)	1
Chest pain	1/1485 (0.1%)	1
Pyrexia	1/1485 (0.1%)	1
Hepatobiliary disorders
Cholelithiasis	1/1485 (0.1%)	1
Infections and infestations
Pneumonia	2/1485 (0.1%)	2
Sepsis	2/1485 (0.1%)	2
Appendicitis	1/1485 (0.1%)	1
Cellulitis	1/1485 (0.1%)	1
Meningitis viral	1/1485 (0.1%)	1
Osteomyelitis	1/1485 (0.1%)	1
Otitis media	1/1485 (0.1%)	1
Pyelonephritis	1/1485 (0.1%)	1
Injury, poisoning and procedural complications
Alcohol poisoning	1/1485 (0.1%)	1
Ankle fracture	1/1485 (0.1%)	1
Ligament sprain	1/1485 (0.1%)	1
Post procedural complication	1/1485 (0.1%)	1
Wrist fracture	1/1485 (0.1%)	1
Metabolism and nutrition disorders
Diabetic ketoacidosis	1/1485 (0.1%)	1
Malnutrition	1/1485 (0.1%)	1
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis	1/1485 (0.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma	2/1485 (0.1%)	2
Breast cancer	1/1485 (0.1%)	1
Oesophageal adenocarcinoma	1/1485 (0.1%)	1
Seminoma	1/1485 (0.1%)	1
Nervous system disorders
Cerebral Haemorrhage	1/1485 (0.1%)	1
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	2/1485 (0.1%)	2
Abortion missed	1/1485 (0.1%)	1
Ectopic pregnancy	1/1485 (0.1%)	1
Psychiatric disorders
Depression	3/1485 (0.2%)	3
Suicidal ideation	3/1485 (0.2%)	3
Major depression	2/1485 (0.1%)	2
Conversion disorder	1/1485 (0.1%)	1
Mental status changes	1/1485 (0.1%)	1
Psychotic disorder	1/1485 (0.1%)	1
Suicide attempt	1/1485 (0.1%)	1
Renal and urinary disorders
Tubulointerstitial nephritis	1/1485 (0.1%)	1
Reproductive system and breast disorders
Endometriosis	1/1485 (0.1%)	1
Menometrorrhagia	1/1485 (0.1%)	1
Menorrhagia	1/1485 (0.1%)	1
Uterine prolapse	1/1485 (0.1%)	1
Vaginal prolapse	1/1485 (0.1%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	1/1485 (0.1%)	1
Pulmonary oedema	1/1485 (0.1%)	1
Respiratory arrest	1/1485 (0.1%)	1
Vascular disorders
Phlebitis	1/1485 (0.1%)	1
Other (Not Including Serious) Adverse Events
	ALKS 5461
	Affected / at Risk (%)	# Events
Total	1124/1485 (75.7%)
Gastrointestinal disorders
Nausea	322/1485 (21.7%)	409
Constipation	151/1485 (10.2%)	173
Vomiting	116/1485 (7.8%)	134
Dry mouth	87/1485 (5.9%)	95
General disorders
Fatigue	85/1485 (5.7%)	91
Infections and infestations
Upper respiratory tract infection	83/1485 (5.6%)	98
Nasopharyngitis	80/1485 (5.4%)	88
Nervous system disorders
Headache	156/1485 (10.5%)	198
Dizziness	150/1485 (10.1%)	179
Somnolence	124/1485 (8.4%)	142
Psychiatric disorders
Insomnia	81/1485 (5.5%)	90

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Should an Investigator desire to disclose study results, Sponsor will review the results disclosure prior to public release and can embargo the disclosure for a period of at least 60 days. Revisions to the disclosure will be negotiated in good faith. For a multicenter study the Investigators agree to publish/publicly present the results together with the other sites for the 12 month period after study results are available unless Sponsor grants written permission in advance.