Trial Outcomes & Findings for Nuedexta in Treatment-Resistant Major Depression (NCT NCT01882829)

NCT ID: NCT01882829

Last Updated: 2018-06-11

Results Overview

The Montgomery-Asberg Depression Rating Scale is a 10-item instrument used for the evaluation of depressive symptoms in adults and for the assessment of any changes to those symptoms. Each of the 10 items is s scored 0 (normal) to 6 (severe depression) with overall score ranges from 0 (normal) to 60 (severe depression). Primary outcome is change in MADRS at Visit 6 (Week 10). Higher values represent a worse outcome.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 20 participants
• Primary outcome timeframe: At baseline and visit 6 (week 10)
• Results posted on: 2018-06-11

Participant Flow

Recruitment period from October 2013 to December 2015

Participant milestones

Measure	Nuedexta (Dextromethorphan/Quinidine) 45/10 mg every 12 hours x 8 weeks dextromethorphan/quinidine: up to 45/10 mg every 12 hours in patients with TRD with a short 7 day tapering period in which subjects are tapered off 45/10 mg dose from twice a day to once daily for an additional 7 days at post 8-week treatment period to minimize the potential for discontinuation effects
Overall Study STARTED	20
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Measure	Nuedexta (Dextromethorphan/Quinidine) 45/10 mg every 12 hours x 8 weeks dextromethorphan/quinidine: up to 45/10 mg every 12 hours in patients with TRD with a short 7 day tapering period in which subjects are tapered off 45/10 mg dose from twice a day to once daily for an additional 7 days at post 8-week treatment period to minimize the potential for discontinuation effects
Overall Study Adverse Event	4
Overall Study Protocol Violation	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Nuedexta in Treatment-Resistant Major Depression

Baseline characteristics by cohort

Measure	Nuedexta (Dextromethorphan/Quinidine) n=20 Participants up to 45/10 mg every 12 hours x 8 weeks then once a day for 1 week
Age, Continuous	49.4 years STANDARD_DEVIATION 7.7 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants
Montgomery-Asberg Depression Scale (MADRS)	32.5 units on a scale STANDARD_DEVIATION 3.9 • n=5 Participants
Clinical Global Impression - Severity (CGI-S)	4.5 units on a scale STANDARD_DEVIATION 0.5 • n=5 Participants

PRIMARY outcome

Timeframe: At baseline and visit 6 (week 10)

The Montgomery-Asberg Depression Rating Scale is a 10-item instrument used for the evaluation of depressive symptoms in adults and for the assessment of any changes to those symptoms. Each of the 10 items is s scored 0 (normal) to 6 (severe depression) with overall score ranges from 0 (normal) to 60 (severe depression). Primary outcome is change in MADRS at Visit 6 (Week 10). Higher values represent a worse outcome.

Outcome measures

Measure	Nuedexta (Dextromethorphan/Quinidine) n=20 Participants up to 45/10 mg every 12 hours x 8 weeks then once a day for 1 week
Montgomery-Asberg Depression Rating Scale	-13.0 change in units on a scale Standard Deviation 11.5

SECONDARY outcome

Timeframe: At baseline and Visit 6 (week 10)

The Quality of Life Enjoyment and Satisfaction Questionnaire Short Form is a reliable and valid self-report measure designed to obtain sensitive measures of the degree of enjoyment and satisfaction experienced by individuals. The raw total score ranges from 14 to 70. Higher scores reflect better oucomes.

Outcome measures

Measure	Nuedexta (Dextromethorphan/Quinidine) n=20 Participants up to 45/10 mg every 12 hours x 8 weeks then once a day for 1 week
Quality of Life Enjoyment and Satisfaction Questionnaire Short Form	0.1 change in units on a scale Standard Deviation 0.2

SECONDARY outcome

Timeframe: At baseline and Visit 6 (week 10)

Population: missing data on 2 participants

The Range of Impaired Functioning Tool a brief scale for assessing functional impairment related to medical or psychiatric illness and has been demonstrated to possess good psychometric properties. The LIFE-RIFT has a total score and individual domain scores for the following areas of functioning: household duties, work, recreation, relationships with family, relationships with friends, schoolwork, and global life satisfaction (the satisfaction item is patient rated).

Higher scores indicate poorer functioning; scores ≥2 reflect impaired functioning in that domain. Results are reported for the total sum with full range from 3 (no impairment) to 60 (severe impairment), which is based on all individual domain scores.

Outcome measures

Measure	Nuedexta (Dextromethorphan/Quinidine) n=18 Participants up to 45/10 mg every 12 hours x 8 weeks then once a day for 1 week
Range of Impaired Functioning Tool	-3.7 change in units on a scale Standard Deviation 4.1

SECONDARY outcome

Timeframe: At baseline and Visit 6 (week 10)

The Sheehan Disability Scale (SDS) is a self-rated scale which assesses illness-related disability in three areas of functioning: work, social and family. The SDS assess disability or functional impairment across three domains: work/school, social life/leisure activities and family life/home responsibilities. Each domain is scored from 0 (not at all) to 10 (very severely). The three domains can be summarized to evaluate global functional impairment by adding the scores of each of the three domains, resulting in global SDS score ranges from 0 (unimpaired) to 30 (highly impaired).

Outcome measures

Measure	Nuedexta (Dextromethorphan/Quinidine) n=20 Participants up to 45/10 mg every 12 hours x 8 weeks then once a day for 1 week
Sheehan Disability Scale	-4.3 change in units on a scale Standard Deviation 7.4

SECONDARY outcome

Timeframe: up to 12 weeks

Frequency of observed adverse events over the study treatment period as captured by the PRISE. The Patient Rated Inventory of Side Effects (PRISE) assesses the presence of treatment side effects in nine organ/function systems (gastrointestinal, nervous system, heart, eyes/ears, skin, genital/urinary, sleep, sexual functioning, and other).

Outcome measures

Measure	Nuedexta (Dextromethorphan/Quinidine) n=20 Participants up to 45/10 mg every 12 hours x 8 weeks then once a day for 1 week
Patient Rated Inventory of Side Effects (PRISE)	25 events

SECONDARY outcome

Timeframe: up to 12 weeks

Population: missing data on one participant

The Columbia-Suicide Severity Rating Scale (C-SSRS) is a comprehensive, semi-structured interview measure that uniquely measures the full spectrum of suicidality including passive and active suicidal ideation, suicidal intent as well as suicidal behaviors. Full range from 0 (low intensity suicidal ideation to 9 (high intensity suicidal ideation).

Outcome measures

Measure	Nuedexta (Dextromethorphan/Quinidine) n=19 Participants up to 45/10 mg every 12 hours x 8 weeks then once a day for 1 week
Columbia-Suicide Severity Rating Scale (C-SSRS)	0.1 change in units on a scale Standard Deviation 0.5

SECONDARY outcome

Timeframe: up to 12 weeks

The Quick Inventory of Depressive Symptomatology, Self Report (QIDS-SR) is a 16-item self rated instrument designed to assess the severity of depressive symptoms (30). The 16 items cover the nine symptom domains of major depression, and are rated on a scale of 0-3. Total score ranges from 0 to 27, with ranges of 0-5 (normal), 6-10 (mild), 11-15 (moderate), 16-20 (moderate to severe), and 21+ (severe).

Outcome measures

Measure	Nuedexta (Dextromethorphan/Quinidine) n=20 Participants up to 45/10 mg every 12 hours x 8 weeks then once a day for 1 week
Quick Inventory of Depressive Symptomatology, Self Report (QIDS-SR)	-5.9 change in units on a scale Standard Deviation 6.6

SECONDARY outcome

Timeframe: up to 12 weeks

The Clinical Global Impression (CGI) scale assesses overall treatment response in psychiatric patients and has good reliability and validity metrics. The administration time is 2 minutes. This scale consists of three items: Severity of Illness (item 1); Global Improvement (item 2); and Efficacy Index (item 3). Item 1 is rated on a seven-point scale (1 = normal, 7 = among the most extremely ill patients) as is item 2 (1 = very much improved, 7 = very much worse). Full scale is 1 to 14.

Outcome measures

Measure	Nuedexta (Dextromethorphan/Quinidine) n=20 Participants up to 45/10 mg every 12 hours x 8 weeks then once a day for 1 week
Clinical Global Impression (CGI) Scale	-1.5 change in units on a scale Standard Deviation 1.3

SECONDARY outcome

Timeframe: At baseline and Visit 6 (week 10)

The Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) is a brief scale to measure cognitive and executive dysfunction in mood and anxiety disorders, and possesses good reliability and validity. The Massachusetts General Hospital CPFQ was developed to assess each of the 7 most common complaints of depressed patients reporting fatigue or cognitive/executive problems. The CPFQ consists of 7 questions, each rated on a scale from 1 to 6, with 1 indicating greater than normal functioning, 2 indicating normal functioning and with higher numbers indicating poorer functioning. Total score range from 7 (greater than normal function) to 42 (poor function).

Outcome measures

Measure	Nuedexta (Dextromethorphan/Quinidine) n=20 Participants up to 45/10 mg every 12 hours x 8 weeks then once a day for 1 week
Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ)	-4.1 change in units on a scale Standard Deviation 6.5

SECONDARY outcome

Timeframe: Baseline and Week 10

Change in Hamilton Anxiety Rating Scale (HAM-A) score from baseline to Week 10. It consists of 14 items, each defined by a series of symptoms. Each item is rated on a 5-point scale, ranging from 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and >25-30 moderate to severe.

Outcome measures

Measure	Nuedexta (Dextromethorphan/Quinidine) n=20 Participants up to 45/10 mg every 12 hours x 8 weeks then once a day for 1 week
HAM-A	-5.7 change in units on a scale Standard Deviation 5.9

SECONDARY outcome

Timeframe: Baseline and Week 10

Mean change in Brief Inventory Symptom from baseline to week 10. The BSS is a self-report 19-item scale preceded by five screening items. The BSS and its screening items are intended to assess a patient's thoughts, plans and intent to commit suicide. All 24 items are rated on a three-point scale (0 to 2). In this study, scores from the five screening items were included in the overall score. Therefore, total scores could range from 0 to 48, with higher scores reflecting more severe symptoms.

Outcome measures

Measure	Nuedexta (Dextromethorphan/Quinidine) n=20 Participants up to 45/10 mg every 12 hours x 8 weeks then once a day for 1 week
Beck Scale for Suicidal Ideation (BSI)	-2.5 change in units on a scale Standard Deviation 5.1

Adverse Events

Nuedexta (Dextromethorphan/Quinidine)

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Measure	Nuedexta (Dextromethorphan/Quinidine) n=20 participants at risk up to 45/10 mg every 12 hours x 8 weeks then once a day for 1 week
Psychiatric disorders Insomnia	5.0% 1/20

Other adverse events

Measure	Nuedexta (Dextromethorphan/Quinidine) n=20 participants at risk up to 45/10 mg every 12 hours x 8 weeks then once a day for 1 week
Cardiac disorders Palpitations	5.0% 1/20
Eye disorders Vision blurred	5.0% 1/20
Gastrointestinal disorders Constipation	15.0% 3/20
Gastrointestinal disorders Dry Mouth	10.0% 2/20
Gastrointestinal disorders Flatulence	5.0% 1/20
Gastrointestinal disorders Nausea	10.0% 2/20
General disorders Fatigue	5.0% 1/20
General disorders Malaise	5.0% 1/20
Metabolism and nutrition disorders Decreased appetitie	5.0% 1/20
Nervous system disorders Headache	5.0% 1/20
Nervous system disorders Dizziness	10.0% 2/20
Nervous system disorders Sedation	10.0% 2/20
Nervous system disorders Somnolence	5.0% 1/20
Psychiatric disorders Anxiety	5.0% 1/20
Psychiatric disorders Depression	5.0% 1/20
Psychiatric disorders Libido decreased	5.0% 1/20
Psychiatric disorders Mental Status Changes	5.0% 1/20
Psychiatric disorders Restlesness	5.0% 1/20

Additional Information

Dr. James W Murrough

Icahn School of Medicine at Mount Sinai

Phone: 212-241-7574

Email: james.murrough@mssm.edu

Results disclosure agreements

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