A Study of Different Titration Schedules of ALKS 5461 in Adults With Major Depressive Disorder (MDD)

• Sponsor: Alkermes, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02085135
• Collaborator: (none)
• Enrollment: 66
• Locations: 9
• Arms: 2
• Duration (Months): 7
• Patients Per Site: 7.3
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

This is a Phase 3 study designed to evaluate the safety and tolerability of two titration schedules for ALKS 5461.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 66 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-blind Study to Evaluate the Safety and Tolerability of Two Titration Schedules for ALKS 5461 for the Adjunctive Treatment of Major Depressive Disorder in Adults With an Inadequate Response to Antidepressant Therapy (the FORWARD-1 Study)
• Study Start Date: Feb 1, 2014
• Actual Primary Completion Date: Sep 1, 2014
• Actual Study Completion Date: Sep 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Titration Schedule 1	Drug: ALKS 5461; Sublingual tablet taken once daily
Experimental: Titration Schedule 2	Drug: ALKS 5461; Sublingual tablet taken once daily

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With Adverse Events (AEs) [8 weeks]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Body mass index of 18-40 kg/m2

• Have a diagnosis of MDD

• Have a current major depressive episode (MDE) lasting 8 weeks to 24 months

• Have been treated with an adequate dose of an approved antidepressant during the current MDE for at least 8 weeks

• Have an inadequate response to current antidepressant treatment

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

• Additional criteria may apply

Exclusion Criteria:

• Currently pregnant or breastfeeding

• History of or current infection with Hepatitis B Virus, Hepatitis C Virus or Human Immunodeficiency Virus (HIV)

• Have experienced hallucinations, delusions, or any psychotic symptoms in the current MDE

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

• Have received electroconvulsive therapy treatment within the last 5 years

• 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 with 60 days of screening

• Additional criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alkermes Investigational Site	Jacksonville	Florida	United States	32256
2	Alkermes Investigational Site	Orlando	Florida	United States	32806
3	Alkermes Investigational Site	Atlanta	Georgia	United States	30308
4	Alkermes Investigational Site	Saint Charles	Missouri	United States	63304
5	Alkermes Investigational Site	Staten Island	New York	United States	10305
6	Alkermes Investigational Site	Dayton	Ohio	United States	45417
7	Alkermes Investigational Site	Allentown	Pennsylvania	United States	18104
8	Alkermes Investigational Site	Bellevue	Washington	United States	98007
9	Alkermes Investigational Site	Halifax	Nova Scotia	Canada

Sponsors and Collaborators

• Alkermes, Inc.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alkermes, Inc.
• ClinicalTrials.gov Identifier: NCT02085135
• Other Study ID Numbers: ALK5461-210
• First Posted: Mar 12, 2014
• Last Update Posted: Aug 14, 2019
• Last Verified: Aug 1, 2019

• Keywords provided by Alkermes, Inc.: depression; major depressive disorder; Alkermes; ALKS 5461; samidorphan; buprenorphine
• Additional relevant MeSH terms: Disease; Depressive Disorder; Depression; Depressive Disorder, Major

Study Results

Participant Flow

Recruitment Details	Subjects were diagnosed with major depressive disorder (MDD) and had an inadequate response to 1 or 2 adequate courses of treatment with a commercially available antidepressant therapy (ADT) during the current major depressive episode (MDE). All subjects continued ADT for the duration of the study.

Arm/Group Title	1-Week Titration	2-Week Titration
Arm/Group Description	ALKS 5461: Sublingual tablet taken once daily in ascending doses over a 1-week titration period	ALKS 5461: Sublingual tablet taken once daily in ascending doses over a 2-week titration period
Period Title: Overall Study
STARTED	34	32
COMPLETED	23	23
NOT COMPLETED	11	9

Baseline Characteristics

Arm/Group Title	1-Week Titration	2-Week Titration	Total
Arm/Group Description	ALKS 5461: Sublingual tablet taken once daily in ascending doses over a 1-week titration period	ALKS 5461: Sublingual tablet taken once daily in ascending doses over a 2-week titration period	Total of all reporting groups
Overall Participants	34	32	66
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.7 (12.6)	50.8 (11.3)	49.7 (53)
Sex: Female, Male (Count of Participants)
Female	20 58.8%	21 65.6%	41 62.1%
Male	14 41.2%	11 34.4%	25 37.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 5.9%	5 15.6%	7 10.6%
Not Hispanic or Latino	32 94.1%	27 84.4%	59 89.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 2.9%	1 3.1%	2 3%
Asian	0 0%	1 3.1%	1 1.5%
Native Hawaiian or Other Pacific Islander	0 0%	1 3.1%	1 1.5%
Black or African American	8 23.5%	6 18.8%	14 21.2%
White	24 70.6%	23 71.9%	47 71.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 2.9%	0 0%	1 1.5%
Region of Enrollment (Count of Participants)
Canada	1 2.9%	0 0%	1 1.5%
United States	33 97.1%	32 100%	65 98.5%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Adverse Events (AEs)
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Number of subjects who received at least 1 dose of study drug.

Arm/Group Title	1-Week Titration	2-Week Titration
Arm/Group Description	ALKS 5461: Sublingual tablet taken once daily in ascending doses over a 1-week titration period	ALKS 5461: Sublingual tablet taken once daily in ascending doses over a 2-week titration period
Measure Participants	34	32
Count of Participants [Participants]	27 79.4%	28 87.5%

Adverse Events

Time Frame	Up to 8 weeks
Arm/Group Title	1-Week Titration		2-Week Titration
Arm/Group Description	ALKS 5461: Sublingual tablet taken once daily in ascending doses over a 1-week titration period		ALKS 5461: Sublingual tablet taken once daily in ascending doses over a 2-week titration period
All Cause Mortality
	1-Week Titration		2-Week Titration
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/32 (0%)
Serious Adverse Events
	1-Week Titration		2-Week Titration
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/32 (0%)
Other (Not Including Serious) Adverse Events
	1-Week Titration		2-Week Titration
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/34 (67.6%)		28/32 (87.5%)
Gastrointestinal disorders
Constipation	6/34 (17.6%)	6	11/32 (34.4%)	12
Nausea	9/34 (26.5%)	14	7/32 (21.9%)	7
Dry Mouth	3/34 (8.8%)	3	8/32 (25%)	8
Vomiting	7/34 (20.6%)	7	1/32 (3.1%)	1
Abdominal Pain	2/34 (5.9%)	2	0/32 (0%)	0
Diarrhoea	2/34 (5.9%)	2	0/32 (0%)	0
General disorders
Fatigue	6/34 (17.6%)	6	1/32 (3.1%)	1
Irritability	0/34 (0%)	0	2/32 (6.3%)	2
Infections and infestations
Influenza	0/34 (0%)	0	2/32 (6.3%)	2
Metabolism and nutrition disorders
Decreased appetite	2/34 (5.9%)	2	2/32 (6.3%)	3
Nervous system disorders
Headache	5/34 (14.7%)	12	4/32 (12.5%)	4
Somnolence	3/34 (8.8%)	3	5/32 (15.6%)	7
Dizziness	3/34 (8.8%)	3	2/32 (6.3%)	2
Dysgeusia	4/34 (11.8%)	4	1/32 (3.1%)	1
Sedation	0/34 (0%)	0	4/32 (12.5%)	4
Psychiatric disorders
Insomnia	4/34 (11.8%)	4	4/32 (12.5%)	4

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.