MAGELLAN: Melatonin Agonist Effects of Tasimelteon Versus Placebo in Patients With Major Depressive Disorder

• Sponsor: Vanda Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01428661
• Collaborator: (none)
• Enrollment: 507
• Locations: 40
• Arms: 2
• Duration (Months): 20
• Patients Per Site: 12.7
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of an 8-week double-masked treatment of tasimelteon or placebo in male and female subjects with Major Depressive Disorder.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: tasimelteon; Drug: placebo	Phase 2/Phase 3

Detailed Description

This is a randomized, parallel, double-masked, placebo-controlled, multicenter outpatient study comparing tasimelteon with placebo in the treatment of subjects with Major Depressive Disorder (MDD).

The study has three phases: the pre-randomization phase, the randomization phase, and an open-label extension phase. The pre-randomization phase comprises a screening visit where subject's initial eligibility will be evaluated. The randomization phase is comprised of an 8-week double-masked segment. Subjects meeting all entry criteria for the study will enter the randomization phase. During this phase, subjects will be asked to take either 20 mg tasimelteon or placebo for 8 weeks in a double-masked fashion. At the end of the 8-week double-masked phase, those subjects who completed the 8-week treatment phase will be offered to enroll into a 52-week open-label extension where each subject will receive daily doses of 20 mg tasimelteon.

Study Design

• Study Type: Interventional
• Actual Enrollment: 507 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: MAGELLAN: A Multicenter, Randomized, Double-Masked, Placebo-Controlled, Parallel Study to Investigate the Safety and Efficacy of 20 Mg Tasimelteon Versus Placebo in Adult Subjects With Major Depressive Disorder Followed by a 52-Week Open-Label Extension
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: tasimelteon	Drug: tasimelteon; 20 mg once daily
Placebo Comparator: placebo	Drug: placebo; once daily

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Endpoint at Week 8 Using the Total Score of the Hamilton Depression Rating Scale (HAM-D) [8 weeks]

   Hamilton Rating Scale for Depression (HAM-D) assesses the range of symptoms that are most frequently observed in subjects with major depressive disorder (MDD) on a scale from 0 to 52. Higher HAM-D scores indicate more severe levels of depressive symptoms, thus, a negative change from baseline indicates a reduction (or improvement) in depressive symptoms.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Subjects with diagnosis of MDD, single or recurrent episode, according to DSM-IV TR criteria;

• Current episode ≥4 weeks and ≤1 year;

• CGI-Severity score ≥4 at screening and baseline.

Exclusion Criteria:

• Lifetime history of bipolar disorder (I or II), schizophrenia, schizoaffective disorder, eating disorder, or obsessive-compulsive disorder;

• Any other current Axis I (except general anxiety disorder as long as it is not considered the primary disorder) or Axis II disorder;

• A positive test for drugs of abuse at the screening visit and/or history of drug or alcohol abuse/dependence as defined in DSM-IV TR, Diagnostic Criteria for Drug and Alcohol Abuse and Dependence, within the past 12 months;

• Formal psychotherapy within 3 months of the screening visit. General supportive psychotherapy is acceptable;

• Participation in a previous tasimelteon trial. Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vanda Investigational Site	Garden Grove	California	United States	92845
2	Vanda Investigational Site	Irvine	California	United States	92617
3	Vanda Investigational Site	Los Alamitos	California	United States	90720
4	Vanda Investigational Site	Oakland	California	United States	94612
5	Vanda Investigational Site	Oceanside	California	United States	92056
6	Vanda Investigational Site	San Diego	California	United States	92102
7	Vanda Investigational Site	Sherman Oaks	California	United States	91403
8	Vanda Investigational Site	Torrance	California	United States	90502
9	Vanda Investigational Site	Denver	Colorado	United States	80239
10	Vanda Investigational Site	Bradenton	Florida	United States	34201
11	Vanda Investigational Site	Jacksonville	Florida	United States	32216
12	Vanda Investigational Site	Maitland	Florida	United States	32751
13	Vanda Investigational Site	N. Miami	Florida	United States	33161
14	Vanda Investigational Site	Orlando	Florida	United States	32806
15	Vanda Investigational Site	Atlanta	Georgia	United States	30308
16	Vanda Investigational Site	Atlanta	Georgia	United States	30328
17	Vanda Investigational Site	Chicago	Illinois	United States	60640
18	Vanda Investigational Site	Joliet	Illinois	United States	60435
19	Vanda Investigational Site	Prairie Village	Kansas	United States	66205
20	Vanda Investigational Site	Baltimore	Maryland	United States	21208
21	Vanda Investigational Site	Boston	Massachusetts	United States	02135
22	Vanda Investigational Site	Omaha	Nebraska	United States	68198
23	Vanda Investigational Site	Las Vegas	Nevada	United States	89102
24	Vanda Investigational Site	Toms River	New Jersey	United States	08755
25	Vanda Investigational Site	Willingboro	New Jersey	United States	08046
26	Vanda Investigational Site	Brooklyn	New York	United States	11235
27	Vanda Investigational Site	Mt. Kisco	New York	United States	10549
28	Vanda Investigational Site	New York	New York	United States	10168
29	Vanda Investigational Site	Rochester	New York	United States	14618
30	Vanda Investigational Site	Staten Island	New York	United States	10312
31	Vanda Investigational Site	Cincinnati	Ohio	United States	45267
32	Vanda Investigational Site	Dayton	Ohio	United States	45417
33	Vanda Investigational Site	Portland	Oregon	United States	97210
34	Vanda Investigational Site	Lincoln	Rhode Island	United States	02865
35	Vanda Investigational Site	Memphis	Tennessee	United States	38119
36	Vanda Investigational Site	Austin	Texas	United States	78731
37	Vanda Investigational Site	Dallas	Texas	United States	75231
38	Vanda Investigational Site	Salt Lake City	Utah	United States	84106
39	Vanda Investigational Site	Seattle	Washington	United States	98104
40	Vanda Investigational Site	Brown Deer	Wisconsin	United States	53223

Sponsors and Collaborators

• Vanda Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Vanda Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01428661
• Other Study ID Numbers: VP-VEC-162-2301
• First Posted: Sep 5, 2011
• Last Update Posted: Jun 19, 2015
• Last Verified: Jun 1, 2015

• Keywords provided by Vanda Pharmaceuticals: tasimelteon; Major Depressive Disorder; MDD; depression
• Additional relevant MeSH terms: Disease; Depressive Disorder; Depression; Depressive Disorder, Major

Study Results

Participant Flow

Pre-assignment Detail	*Tasi: subject left country (1); Placebo: sponsor request (1), subject moved (1), IMP schedule (1), subject incarcerated (1), withdrawn after receipt of medical records (1), visit schedule (1) **Tasi: surgery (1), visit schedule (3), +UDS (2), IMP schdule (2), prohibited meds (1), withdrew consent (1), sponsor terminated trial (175)

Arm/Group Title	Tasimelteon	Placebo	Open Label Tasimelteon
Arm/Group Description	20 mg tasimelteon capsules, PO daily for 8 weeks	Placebo capsules, PO daily for 8 weeks	20 mg capsules, PO daily for 52 weeks
Period Title: Double-Masked Phase
STARTED	254	253	0
COMPLETED	197	204	0
NOT COMPLETED	57	49	0
Period Title: Double-Masked Phase
STARTED	0	0	339
COMPLETED	0	0	19
NOT COMPLETED	0	0	320

Baseline Characteristics

Arm/Group Title	Tasimelteon	Placebo	Open Label Tasimelteon	Total
Arm/Group Description	20 mg tasimelteon capsules, PO daily for 8 weeks	Placebo capsules, PO daily for 8 weeks	20 mg capsules, PO daily for 52 weeks	Total of all reporting groups
Overall Participants	254	253	339	846
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.7 (12.61)	42.0 (12.46)	NA (NA)	42.9 (12.54)
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	NA (NA)	NA (NA)	44.1 (12.19)	44.1 (12.19)
Gender (participants) [Number]
Female	161 63.4%	171 67.6%	0 0%	332 39.2%
Male	93 36.6%	82 32.4%	0 0%	175 20.7%
Gender (participants) [Number]
Female	0 0%	0 0%	222 65.5%	222 26.2%
Male	0 0%	0 0%	117 34.5%	117 13.8%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Endpoint at Week 8 Using the Total Score of the Hamilton Depression Rating Scale (HAM-D)
Description	Hamilton Rating Scale for Depression (HAM-D) assesses the range of symptoms that are most frequently observed in subjects with major depressive disorder (MDD) on a scale from 0 to 52. Higher HAM-D scores indicate more severe levels of depressive symptoms, thus, a negative change from baseline indicates a reduction (or improvement) in depressive symptoms.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (ITT) Population included any subject randomized into the study that receives a dose of study medication and that has completed at least one post-baseline efficacy measurement while on study medication.

Arm/Group Title	Tasimelteon	Placebo	Open Label Tasimelteon
Arm/Group Description	20 mg tasimelteon capsules, PO daily for 8 weeks	Placebo capsules, PO daily for 8 weeks	20 mg capsules, PO daily for 52 weeks
Measure Participants	249	243	339
Mean (Standard Error) [units on a scale]	-8.19 (0.45)	-7.83 (0.45)	-13.6 (0.34)

Adverse Events

Adverse Event Reporting Description	One subject randomized to placebo did not take any study drug.
Arm/Group Title	Tasimelteon		Placebo		Open Label Tasimelteon
Arm/Group Description	20 mg tasimelteon capsules, PO daily for 8 weeks		Placebo capsules, PO daily for 8 weeks		20 mg capsules, PO daily for 52 weeks
All Cause Mortality
	Tasimelteon		Placebo		Open Label Tasimelteon
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Tasimelteon		Placebo		Open Label Tasimelteon
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/254 (0.8%)		3/252 (1.2%)		6/339 (1.8%)
General disorders
Non-Cardiac Chest Pain	0/254 (0%)	0	1/252 (0.4%)	1	0/339 (0%)	0
Chest Pain	0/254 (0%)	0	0/252 (0%)	0	2/339 (0.6%)	2
Infections and infestations
Cellulitis	0/254 (0%)	0	0/252 (0%)	0	1/339 (0.3%)	1
Staphylococcal Infection	0/254 (0%)	0	0/252 (0%)	0	1/339 (0.3%)	1
Hepatitis A	0/254 (0%)	0	0/252 (0%)	0	1/339 (0.3%)	1
Hepatitis B	0/254 (0%)	0	0/252 (0%)	0	1/339 (0.3%)	1
Injury, poisoning and procedural complications
Cervical Vertebral Fracture	0/254 (0%)	0	0/252 (0%)	0	1/339 (0.3%)	1
Investigations
Blood Pressure Increased	0/254 (0%)	0	1/252 (0.4%)	1	0/339 (0%)	0
Musculoskeletal and connective tissue disorders
Back Pain	1/254 (0.4%)	1	0/252 (0%)	0	0/339 (0%)	0
Psychiatric disorders
Suicidal Ideation	0/254 (0%)	0	1/252 (0.4%)	1	0/339 (0%)	0
Suicide Attempt	1/254 (0.4%)	1	0/252 (0%)	0	0/339 (0%)	0
Other (Not Including Serious) Adverse Events
	Tasimelteon		Placebo		Open Label Tasimelteon
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/254 (15%)		53/252 (21%)		74/339 (21.8%)
Gastrointestinal disorders
Diarrhoea	15/254 (5.9%)	17	13/252 (5.2%)	15	8/339 (2.4%)	12
Dry Mouth	14/254 (5.5%)	15	10/252 (4%)	10	7/339 (2.1%)	8
Infections and infestations
Upper Respitory Tract Infection	9/254 (3.5%)	9	15/252 (6%)	17	22/339 (6.5%)	29
Nasopharyngitis	9/254 (3.5%)	9	12/252 (4.8%)	12	27/339 (8%)	37
Nervous system disorders
Headache	29/254 (11.4%)	37	24/252 (9.5%)	31	34/339 (10%)	47
Somnolence	17/254 (6.7%)	19	16/252 (6.3%)	19	10/339 (2.9%)	12

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.