Trial Outcomes & Findings for A Study of ALKS 5461 for the Treatment of Major Depressive Disorder (MDD) - the FORWARD-3 Study (NCT NCT02158546)

Last Updated: 2019-06-25

Results Overview

The MADRS-10 scale is a clinician-administered questionnaire comprised of 10 items used to measure the severity of MDD symptoms. Scores range from 0 (no apparent symptoms) to 60 (most severe symptoms). Individual questionnaire items include: Apparent Sadness, Reported Sadness, Inner Tension, Reduced Sleep, Reduced Appetite, Concentration Difficulties, Lassitude, Inability to Feel, Pessimistic Thoughts, and Suicidal Thoughts.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

447 participants

Primary outcome timeframe

Baseline and week 6

Results posted on

2019-06-25

Participant Flow

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.

2 cohorts of subjects were enrolled: Group 1- subjects with baseline HAM-D17 score ≥ 20; Group 2- subjects with baseline HAM-D17 score 18-19. Only Group 1 was included in the efficacy analysis. Study included a 4-week pbo run-in period prior to the 6-week treatment period. In Group 1, 102 subjects did not meet criteria for randomization.

Participant milestones

Participant milestones
Measure	Group 1 - ALKS 5461 2mg/2mg Randomized to ALKS 5461 2mg/2mg	Group 1 - Placebo Randomized to Placebo	Group 2 ALKS 5461 2mg/2mg Randomized to ALKS 5461 2mg/2mg	Group 2 - Placebo Randomized to placebo
Overall Study STARTED	152	153	18	19
Overall Study COMPLETED	133	136	14	13
Overall Study NOT COMPLETED	19	17	4	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Group 1 - ALKS 5461 2mg/2mg Randomized to ALKS 5461 2mg/2mg	Group 1 - Placebo Randomized to Placebo	Group 2 ALKS 5461 2mg/2mg Randomized to ALKS 5461 2mg/2mg	Group 2 - Placebo Randomized to placebo
Overall Study Physician Decision	0	1	0	0
Overall Study Non-compliance	0	1	0	1
Overall Study Failure to meet eligibility criteria	0	1	0	0
Overall Study Lack of Efficacy	1	1	0	0
Overall Study Adverse Event	2	2	0	0
Overall Study Withdrawal by Subject	6	2	1	0
Overall Study Lost to Follow-up	5	4	0	1
Overall Study Site Excluded	5	5	3	4

Baseline Characteristics

A Study of ALKS 5461 for the Treatment of Major Depressive Disorder (MDD) - the FORWARD-3 Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1 ALKS 5461 2mg/2mg n=147 Participants Randomized to ALKS 5461 2mg/2mg	Group 1 Placebo n=148 Participants Randomized to placebo	Group 2 ALKS 5461 2mg/2mg n=15 Participants Randomized to ALKS 5461 2mg/2mg	Group 2 Placebo n=15 Participants Randomized to placebo	Total n=325 Participants Total of all reporting groups
Age, Continuous	47.4 years STANDARD_DEVIATION 12.31 • n=5 Participants	48.1 years STANDARD_DEVIATION 12.51 • n=7 Participants	47.5 years STANDARD_DEVIATION 12.63 • n=5 Participants	45.9 years STANDARD_DEVIATION 11.44 • n=4 Participants	47.7 years STANDARD_DEVIATION 12.33 • n=21 Participants
Sex: Female, Male Female	88 Participants n=5 Participants	94 Participants n=7 Participants	8 Participants n=5 Participants	7 Participants n=4 Participants	197 Participants n=21 Participants
Sex: Female, Male Male	59 Participants n=5 Participants	54 Participants n=7 Participants	7 Participants n=5 Participants	8 Participants n=4 Participants	128 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	23 Participants n=5 Participants	29 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	55 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	124 Participants n=5 Participants	119 Participants n=7 Participants	13 Participants n=5 Participants	14 Participants n=4 Participants	270 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Black or African American	33 Participants n=5 Participants	33 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	71 Participants n=21 Participants
Race (NIH/OMB) White	106 Participants n=5 Participants	115 Participants n=7 Participants	12 Participants n=5 Participants	13 Participants n=4 Participants	246 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment United States	118 Participants n=5 Participants	128 Participants n=7 Participants	14 Participants n=5 Participants	12 Participants n=4 Participants	272 Participants n=21 Participants
Region of Enrollment Bulgaria	29 Participants n=5 Participants	20 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	53 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline and week 6

Population: The Full Analysis Set (FAS) consists of subjects in the Group 1 Safety Population who have at least 1 post-randomization assessment of MADRS total score.

Outcome measures

Outcome measures
Measure	ALKS 5461 2mg/2mg n=142 Participants Randomized to ALKS 5461 2mg/2mg	Placebo n=146 Participants Randomized to placebo	Group 2 ALKS 5461 2mg/2mg Randomized to ALKS 5461 2mg/2mg	Group 2 Placebo Randomized to placebo
Change From Baseline to End of Treatment (Week 6) in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score	-4.8 units on a scale Standard Error 0.67	-4.6 units on a scale Standard Error 0.66	—	—

SECONDARY outcome

Timeframe: 6 weeks

Population: The FAS consists of subjects in the Group 1 Safety Population who have at least 1 post-randomization assessment of MADRS total score.

The proportion of subjects demonstrating MADRS-10 treatment response, defined as a ≥ 50% reduction in MADRS-10 score from baseline to the end of the efficacy period (week 6).

Outcome measures

Outcome measures
Measure	ALKS 5461 2mg/2mg n=142 Participants Randomized to ALKS 5461 2mg/2mg	Placebo n=146 Participants Randomized to placebo	Group 2 ALKS 5461 2mg/2mg Randomized to ALKS 5461 2mg/2mg	Group 2 Placebo Randomized to placebo
Proportion of Patients Who Exhibited Treatment Response (MADRS-10)	24 Participants	21 Participants	—	—

SECONDARY outcome

Timeframe: 6 weeks

Population: The FAS consists of subjects in the Group 1 Safety Population who have at least 1 post-randomization assessment of MADRS total score.

The proportion of subjects achieving remission, defined as a MADRS-10 score of ≤ 10 at the end of the efficacy period.

Outcome measures

Outcome measures
Measure	ALKS 5461 2mg/2mg n=142 Participants Randomized to ALKS 5461 2mg/2mg	Placebo n=146 Participants Randomized to placebo	Group 2 ALKS 5461 2mg/2mg Randomized to ALKS 5461 2mg/2mg	Group 2 Placebo Randomized to placebo
Remission Rate	20 Participants	18 Participants	—	—

SECONDARY outcome

Timeframe: 6 weeks

Population: Safety population consisted of subjects who were identified as placebo non-responders at the end of the double-blind placebo run-in period and received at least one dose of randomized study drug (ie, placebo or ALKS 5461) subsequent to randomization.

Outcome measures

Outcome measures
Measure	ALKS 5461 2mg/2mg n=147 Participants Randomized to ALKS 5461 2mg/2mg	Placebo n=148 Participants Randomized to placebo	Group 2 ALKS 5461 2mg/2mg n=15 Participants Randomized to ALKS 5461 2mg/2mg	Group 2 Placebo n=15 Participants Randomized to placebo
Number of Subjects With Adverse Events (AEs)	63 Participants	51 Participants	11 Participants	8 Participants

Adverse Events

Group 1 ALKS 5461 2mg/2mg

Serious events: 0 serious events

Other events: 39 other events

Deaths: 0 deaths

Group 1 Placebo

Serious events: 1 serious events

Other events: 24 other events

Deaths: 0 deaths

Group 2 ALKS 5461 2mg/2mg

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Group 2 Placebo

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Group 1 ALKS 5461 2mg/2mg n=147 participants at risk Randomized to ALKS 5461 2mg/2mg	Group 1 Placebo n=148 participants at risk Randomized to placebo	Group 2 ALKS 5461 2mg/2mg n=15 participants at risk Randomized to ALKS 5461 2mg/2mg	Group 2 Placebo n=15 participants at risk Randomized to placebo
Cardiac disorders Atrial fibrillation	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.68% 1/148 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.

Other adverse events

Additional Information

Eva Stroynowski

Alkermes

Phone: 781-609-7000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Group 1 ALKS 5461 2mg/2mg n=147 participants at risk Randomized to ALKS 5461 2mg/2mg	Group 1 Placebo n=148 participants at risk Randomized to placebo	Group 2 ALKS 5461 2mg/2mg n=15 participants at risk Randomized to ALKS 5461 2mg/2mg	Group 2 Placebo n=15 participants at risk Randomized to placebo
Gastrointestinal disorders Nausea	8.8% 13/147 • Number of events 14 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.68% 1/148 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	26.7% 4/15 • Number of events 7 • AE reporting includes the 6-week double-blind, placebo-controlled period.	13.3% 2/15 • Number of events 2 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Gastrointestinal disorders Vomiting	2.7% 4/147 • Number of events 4 • AE reporting includes the 6-week double-blind, placebo-controlled period.	1.4% 2/148 • Number of events 2 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 2 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Gastrointestinal disorders Constipation	2.0% 3/147 • Number of events 3 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.68% 1/148 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	20.0% 3/15 • Number of events 3 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Gastrointestinal disorders Dry mouth	2.0% 3/147 • Number of events 3 • AE reporting includes the 6-week double-blind, placebo-controlled period.	1.4% 2/148 • Number of events 2 • AE reporting includes the 6-week double-blind, placebo-controlled period.	13.3% 2/15 • Number of events 2 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.
General disorders Fatigue	2.7% 4/147 • Number of events 4 • AE reporting includes the 6-week double-blind, placebo-controlled period.	2.0% 3/148 • Number of events 3 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Infections and infestations Upper respiratory tract infection	2.7% 4/147 • Number of events 5 • AE reporting includes the 6-week double-blind, placebo-controlled period.	2.0% 3/148 • Number of events 4 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Infections and infestations Nasopharyngitis	2.0% 3/147 • Number of events 3 • AE reporting includes the 6-week double-blind, placebo-controlled period.	2.0% 3/148 • Number of events 3 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Investigations Blood creatine phosphokinase increased	2.7% 4/147 • Number of events 4 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Musculoskeletal and connective tissue disorders Muscle spasms	2.0% 3/147 • Number of events 3 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Nervous system disorders Headache	4.1% 6/147 • Number of events 7 • AE reporting includes the 6-week double-blind, placebo-controlled period.	3.4% 5/148 • Number of events 7 • AE reporting includes the 6-week double-blind, placebo-controlled period.	26.7% 4/15 • Number of events 4 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Vascular disorders Hypertension	2.0% 3/147 • Number of events 3 • AE reporting includes the 6-week double-blind, placebo-controlled period.	1.4% 2/148 • Number of events 2 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Gastrointestinal disorders Diarrhoea	0.68% 1/147 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	2.0% 3/148 • Number of events 3 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 2 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Nervous system disorders Dizziness	0.68% 1/147 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	2.0% 3/148 • Number of events 3 • AE reporting includes the 6-week double-blind, placebo-controlled period.	13.3% 2/15 • Number of events 2 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Blood and lymphatic system disorders Anaemia	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Cardiac disorders Bradycardia	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Cardiac disorders Palpitations	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Cardiac disorders Tachycardia	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Eye disorders Eyelid oedema	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Gastrointestinal disorders Flatulence	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Gastrointestinal disorders Food poisoning	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Gastrointestinal disorders Gingival pain	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 2 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Infections and infestations Influenza	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Injury, poisoning and procedural complications Epicondylitis	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Injury, poisoning and procedural complications Tooth fracture	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Investigations Blood pressure increased	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Investigations Urine output increased	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Investigations Metabolic syndorome	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Nervous system disorders Somnolence	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	13.3% 2/15 • Number of events 2 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Nervous system disorders Burning sensation	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Nervous system disorders Disturbance in attention	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Nervous system disorders Hypersomnia	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Nervous system disorders Hypoaesthesia	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 2 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Nervous system disorders Memory impairment	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Nervous system disorders Paraesthesia	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 2 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Nervous system disorders Tension headache	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Psychiatric disorders Abnormal dreams	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Psychiatric disorders Insomnia	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Psychiatric disorders Nightmare	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Psychiatric disorders Sleep disorder	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Psychiatric disorders Initial insomnia	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/147 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/148 • AE reporting includes the 6-week double-blind, placebo-controlled period.	6.7% 1/15 • Number of events 1 • AE reporting includes the 6-week double-blind, placebo-controlled period.	0.00% 0/15 • AE reporting includes the 6-week double-blind, placebo-controlled period.