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

• ClinicalTrials.gov Identifier: NCT01428661
• Recruitment Status: Completed
• First Posted: September 5, 2011
• Results First Posted: June 19, 2015
• Last Update Posted: June 19, 2015
• Sponsor: Vanda Pharmaceuticals
• Information provided by (Responsible Party): Vanda Pharmaceuticals

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Major Depressive Disorder
• Interventions: Drug: tasimelteon; Drug: placebo
• Enrollment: 507

Participant Flow

Recruitment Details
Pre-assignment Details	*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subject left country (1); Placebo: sponsor request (1), subject moved (1), IMP schedule (1), subject incarcerated (1), withdrawn after receipt of medical records (1), visit schedule (1) **Tasi: surgery (1), visit schedule (3), +UDS (2), IMP schdule (2), prohibited meds (1), withdrew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 [1]
Completed	197	204	0 [1]
Not Completed	57	49	0
Reason Not Completed
Protocol Violation	9	4	0
Adverse Event	13	4	0
Lost to Follow-up	14	14	0
Withdrawal by Subject	18	20	0
Lack of Efficacy	2	1	0
*Various	1	6	0
[1] Does not apply.
Period Title: Open Label Extension
Started	0 [1]	0 [1]	339
Completed	0 [1]	0 [1]	19
Not Completed	0	0	320
Reason Not Completed
Protocol Violation	0	0	9
Adverse Event	0	0	15
Lost to Follow-up	0	0	38
Withdrawal by Subject	0	0	49
Lack of Efficacy	0	0	24
**Various	0	0	185
[1] Does not apply.

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 Number of Baseline Participants		254	253	339	846
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	254 participants	253 participants	339 participants	846 participants
		43.7 (12.61)	42.0 (12.46)	NA [1] (NA)	42.9 (12.54)
		[1] The 2 phases of the trial are being separated out so the additive total is correct for each phase.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	254 participants	253 participants	339 participants	846 participants
		NA [1] (NA)	NA [1] (NA)	44.1 (12.19)	44.1 (12.19)
		[1] The 2 phases of the trial are being separated out so the additive total is correct for each phase.
Gender; Measure Type: Number; Unit of measure: Participants	Number Analyzed	254 participants	253 participants	339 participants	846 participants
Female		161	171	0	332
Male		93	82	0	175
Gender; Measure Type: Number; Unit of measure: Participants	Number Analyzed	254 participants	253 participants	339 participants	846 participants
Female		0	0	222	222
Male		0	0	117	117

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
Overall Number of Participants Analyzed	249	243	339
Mean (Standard Error); Unit of Measure: units on a scale
	-8.19 (0.45)	-7.83 (0.45)	-13.6 (0.34)

Adverse Events

Time Frame	[Not Specified]
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 (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--
Serious Adverse Events
	Tasimelteon		Placebo		Open Label Tasimelteon
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/254 (0.79%)		3/252 (1.19%)		6/339 (1.77%)
General disorders
Non-Cardiac Chest Pain †	0/254 (0.00%)	0	1/252 (0.40%)	1	0/339 (0.00%)	0
Chest Pain †	0/254 (0.00%)	0	0/252 (0.00%)	0	2/339 (0.59%)	2
Infections and infestations
Cellulitis †	0/254 (0.00%)	0	0/252 (0.00%)	0	1/339 (0.29%)	1
Staphylococcal Infection †	0/254 (0.00%)	0	0/252 (0.00%)	0	1/339 (0.29%)	1
Hepatitis A †	0/254 (0.00%)	0	0/252 (0.00%)	0	1/339 (0.29%)	1
Hepatitis B †	0/254 (0.00%)	0	0/252 (0.00%)	0	1/339 (0.29%)	1
Injury, poisoning and procedural complications
Cervical Vertebral Fracture †	0/254 (0.00%)	0	0/252 (0.00%)	0	1/339 (0.29%)	1
Investigations
Blood Pressure Increased †	0/254 (0.00%)	0	1/252 (0.40%)	1	0/339 (0.00%)	0
Musculoskeletal and connective tissue disorders
Back Pain †	1/254 (0.39%)	1	0/252 (0.00%)	0	0/339 (0.00%)	0
Psychiatric disorders
Suicidal Ideation †	0/254 (0.00%)	0	1/252 (0.40%)	1	0/339 (0.00%)	0
Suicide Attempt †	1/254 (0.39%)	1	0/252 (0.00%)	0	0/339 (0.00%)	0
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Tasimelteon		Placebo		Open Label Tasimelteon
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/254 (14.96%)		53/252 (21.03%)		74/339 (21.83%)
Gastrointestinal disorders
Diarrhoea †	15/254 (5.91%)	17	13/252 (5.16%)	15	8/339 (2.36%)	12
Dry Mouth †	14/254 (5.51%)	15	10/252 (3.97%)	10	7/339 (2.06%)	8
Infections and infestations
Upper Respitory Tract Infection †	9/254 (3.54%)	9	15/252 (5.95%)	17	22/339 (6.49%)	29
Nasopharyngitis †	9/254 (3.54%)	9	12/252 (4.76%)	12	27/339 (7.96%)	37
Nervous system disorders
Headache †	29/254 (11.42%)	37	24/252 (9.52%)	31	34/339 (10.03%)	47
Somnolence †	17/254 (6.69%)	19	16/252 (6.35%)	19	10/339 (2.95%)	12
† Indicates events were collected by systematic assessment

Limitations and 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.

Results Point of Contact

• Name/Title: Curt Wolfgang, Ph.D.
• Organization: Vanda Pharmaceuticals Inc.
• Phone: 202-734-3400
• EMail: curt.wolfgang@vandapharma.com

• Responsible Party: Vanda Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01428661
• Other Study ID Numbers: VP-VEC-162-2301
• First Submitted: August 31, 2011
• First Posted: September 5, 2011
• Results First Submitted: January 6, 2015
• Results First Posted: June 19, 2015
• Last Update Posted: June 19, 2015