Safety, Tolerability and Efficacy of AVP-786 for the Treatment of Disinhibition

• Sponsor: Avanir Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02534038
• Collaborator: (none)
• Enrollment: 1
• Location: 1
• Arms: 2
• Actual Duration (Months): 22.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Treatment of disinhibition syndrome in participants with Neurodegenerative Disorder.

Condition or Disease	Intervention/Treatment	Phase
Disinhibition Syndrome	Drug: AVP-786; Drug: Placebo	Phase 2

Detailed Description

Eligible participants for this study must have a diagnosis of Neurodegenerative Disorder and must exhibit disinhibition syndrome of sufficient severity to warrant treatment.

This is a multicenter, randomized, double-blind, placebo-controlled, cross-over study consisting of two 6-week treatment periods.

Approximately 12 participants will be enrolled at approximately 2 centers in the United States.

Following screening procedures for assessment of inclusion and exclusion criteria, eligible participants will be randomized into the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability, and Efficacy of AVP-786 for the Treatment of Disinhibition in Patients With Neurodegenerative Disorders
• Actual Study Start Date: Dec 1, 2015
• Actual Primary Completion Date: Oct 3, 2017
• Actual Study Completion Date: Oct 3, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo drug to be taken twice a day for 6 weeks	Drug: Placebo; matching placebo
Active Comparator: AVP-786 Participants randomized to AVP-786 will take one dose of AVP-786 once a day and one dose of placebo once a day for the first 7 days; from day 8, participants will receive AVP-786 twice a day for 5 weeks.	Drug: AVP-786; d6-DM/Q; Other Names: Deuterated (d6)-dextromethorphan (DM)/Quinidine (Q)

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Disinhibition Domain of the Neuropsychiatric Inventory (NPI) [Baseline; Week 6, Week 8, and Week 14]

Secondary Outcome Measures

1. Change From Baseline for the Total NPI Score [Baseline; Week 6, Week 8, and Week 14]

2. Change From Baseline for the NPI Total Caregiver Distress [Baseline; Week 6, Week 8, and Week 14]

3. Change From Baseline for the NPI Disinhibition Domain Caregiver Distress [Baseline; Week 1, Week 3, Week 6, Week 8, Week 9, Week 11, and Week 14]

4. Change From Baseline for the Frontal Behavioral Inventory (FBI) Total Score [Baseline; Week 1, Week 3, Week 6, Week 8, Week 9, Week 11, and Week 14]

5. Change From Baseline for the FBI Disinhibition Domain Score [Baseline; Week 1, Week 3, Week 6, Week 9, Week 11, and Week 14]

6. Change From the First Assessment for the Modified Clinical Global Impression of Change (mCGIC) Scale [Week 3, Week 6, Week 11, and Week 14]

7. Change From the First Assessment for the Patient Global Impression of Change (PGIC) Scale [Week 3, Week 6, Week 11, and Week 14]

8. Change From Baseline for the Quality of Relationships (QoR) Scale [Baseline; Week 6, Week 8, and Week 14]

9. Change From Baseline for the Quality of Life (QoL) Scale [Baseline; Week 6, Week 8, and Week 14]

10. Change From Baseline for the Interpersonal Reactivity Index (IRI) [Baseline; Week 6, Week 8, and Week 14]

11. Change From Baseline for the Center for Neurologic Study-Lability Scale (CNS-LS) [Baseline; Week 6, Week 8, and Week 14]

12. Change From Baseline for the Mini-Mental State Examination (MMSE) [Baseline; Week 6, Week 8, and Week 14]

13. Change From Baseline for the Cornell Scale for Depression in Dementia (CSDD) [Baseline; Week 6, Week 8, and Week 14]

14. Change From Baseline for the Stroop Color and Word Task [Baseline; Week 6, Week 8, and Week 14]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Documented diagnosis of a Neurodegenerative Disorder including frontotemporal dementia, Alzheimer's disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), dementia with Lewy bodies (DBL), vascular cognitive disorders, or Huntington's disease, at least 3 months prior to Baseline

• The participant has behavior from 2 of the 3 categories of disinhibited behavior from the definition of the behavioral variant of frontotemporal dementia

• The behavioral changes are not due to a pre-existing major psychiatric disorder (e.g., schizophrenia, bipolar disease, etc.) and are not due to the direct effect of systemic illness, drug action, or substance use

• Disinhibition scale score of ≥4 on the 3 core disinhibition items of the Frontal Behavioral Inventory (FBI) at Screening and Baseline

Exclusion Criteria:

• Participants with symptoms of disinhibition that is not secondary to Neurodegenerative Disorders

• Participants with myasthenia gravis

• Participants with co-existent clinically significant or unstable systemic diseases that could confound the interpretation of the safety results of the study (e.g., malignancy [except skin basal-cell carcinoma or untreated prostate cancer], poorly controlled diabetes, poorly controlled hypertension, unstable pulmonary, renal or hepatic disease, unstable ischemic cardiac disease, dilated cardiomyopathy, or unstable valvular heart disease)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic Lou Ruvo Center for Brain Health	Las Vegas	Nevada	United States	89106

Sponsors and Collaborators

• Avanir Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 1, 2015

More Information

Publications

None provided.

• Responsible Party: Avanir Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02534038
• Other Study ID Numbers: 15-AVP-786-203
• First Posted: Aug 27, 2015
• Last Update Posted: Oct 26, 2020
• Last Verified: Oct 1, 2020

• Keywords provided by Avanir Pharmaceuticals: Disinhibition
• Additional relevant MeSH terms: Quinidine; Dextromethorphan

Study Results

Participant Flow

Arm/Group Title	AVP-786; Placebo	Placebo; AVP-786
Arm/Group Description	In Period 1, participants were randomized to receive AVP-786 (deuterated [d6]-dextromethorphan hydrobromide [d6-DM]/quinidine sulfate [Q]) once a day (OD) in the morning and placebo in the evening for the first 7 days of the study. From Day 8, participants received AVP-786 twice a day (BID) for 14 days. From Day 22, participants received a target dose of d6-DM 28 milligrams (mg)/Q 4.9 mg (AVP-786-28/4.9) BID for the remaining 3 weeks of Period 1. In Period 2, participants were randomized to receive matching placebo. The periods were separated by a 2-week washout period.	In Period 1, participants were randomized to receive matching placebo. In Period 2, participants were randomized to receive AVP-786 OD in the morning and placebo in the evening for the first 7 days of the study. From Day 8, participants received AVP-786 BID for 14 days. From Day 22, participants received a target dose of AVP-786-28/4.9 BID for the remaining 3 weeks of Period 2. The periods were separated by a 2-week washout period.
Period Title: Period 1 (6 Weeks)
STARTED	1	0
COMPLETED	1	0
NOT COMPLETED	0	0
Period Title: Period 1 (6 Weeks)
STARTED	1	0
COMPLETED	1	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	AVP-786; Placebo	Placebo; AVP-786	Total
Arm/Group Description	In Period 1, participants were randomized to receive AVP-786 (deuterated [d6]-dextromethorphan hydrobromide [d6-DM]/quinidine sulfate [Q]) once a day (OD) in the morning and placebo in the evening for the first 7 days of the study. From Day 8, participants received AVP-786 twice a day (BID) for 14 days. From Day 22, participants received a target dose of d6-DM 28 milligrams (mg)/Q 4.9 mg (AVP-786-28/4.9) BID for the remaining 3 weeks of Period 1. In Period 2, participants were randomized to receive matching placebo. The periods were separated by a 2-week washout period.	In Period 1, participants were randomized to receive matching placebo. In Period 2, participants were randomized to receive AVP-786 OD in the morning and placebo in the evening for the first 7 days of the study. From Day 8, participants received AVP-786 BID for 14 days. From Day 22, participants received a target dose of AVP-786-28/4.9 BID for the remaining 3 weeks of Period 2. The periods were separated by a 2-week washout period.	Total of all reporting groups
Overall Participants	1	0	1
Age (Count of Participants)
<=18 years	0 0%	0 NaN
Between 18 and 65 years	0 0%	0 NaN
>=65 years	1 100%	1 Infinity
Sex: Female, Male (Count of Participants)
Female	NA NaN	NA NaN
Male	NA NaN	NA NaN
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	NA NaN	NA NaN
Asian	NA NaN	NA NaN
Native Hawaiian or Other Pacific Islander	NA NaN	NA NaN
Black or African American	NA NaN	NA NaN
White	NA NaN	NA NaN
More than one race	NA NaN	NA NaN
Unknown or Not Reported	NA NaN	NA NaN

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Disinhibition Domain of the Neuropsychiatric Inventory (NPI)
Time Frame	Baseline; Week 6, Week 8, and Week 14

Outcome Measure Data

Analysis Population Description

No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.

Arm/Group Title	Placebo	AVP-786
Arm/Group Description	Participants received matching placebo in either the first or last 6 weeks of the study.	Participants received up to a target dose of deuterated (d6)-dextromethorphan hydrobromide (d6-DM) 28 milligrams (mg)/quinidine sulfate (Q) 4.9 mg (AVP-786-28/4.9) twice a day (BID) in either the first or last 6 weeks of the study.
Measure Participants	0	0

2. Secondary Outcome

Title	Change From Baseline for the Total NPI Score
Time Frame	Baseline; Week 6, Week 8, and Week 14

Outcome Measure Data

Analysis Population Description

No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.

Arm/Group Title	Placebo	AVP-786
Arm/Group Description	Participants received matching placebo in either the first or last 6 weeks of the study.	Participants received up to a target dose of AVP-786-28/4.9 BID in either the first or last 6 weeks of the study.
Measure Participants	0	0

3. Secondary Outcome

Title	Change From Baseline for the NPI Total Caregiver Distress
Time Frame	Baseline; Week 6, Week 8, and Week 14

Outcome Measure Data

Analysis Population Description

No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.

Arm/Group Title	Placebo	AVP-786
Arm/Group Description	Participants received matching placebo in either the first or last 6 weeks of the study.	Participants received up to a target dose of AVP-786-28/4.9 BID in either the first or last 6 weeks of the study.
Measure Participants	0	0

4. Secondary Outcome

Title	Change From Baseline for the NPI Disinhibition Domain Caregiver Distress
Time Frame	Baseline; Week 1, Week 3, Week 6, Week 8, Week 9, Week 11, and Week 14

Outcome Measure Data

Analysis Population Description

No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.

Arm/Group Title	Placebo	AVP-786
Arm/Group Description	Participants received matching placebo in either the first or last 6 weeks of the study.	Participants received up to a target dose of AVP-786-28/4.9 BID in either the first or last 6 weeks of the study.
Measure Participants	0	0

5. Secondary Outcome

Title	Change From Baseline for the Frontal Behavioral Inventory (FBI) Total Score
Time Frame	Baseline; Week 1, Week 3, Week 6, Week 8, Week 9, Week 11, and Week 14

Outcome Measure Data

Analysis Population Description

No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.

Arm/Group Title	Placebo	AVP-786
Arm/Group Description	Participants received matching placebo in either the first or last 6 weeks of the study.	Participants received up to a target dose of AVP-786-28/4.9 BID in either the first or last 6 weeks of the study.
Measure Participants	0	0

6. Secondary Outcome

Title	Change From Baseline for the FBI Disinhibition Domain Score
Time Frame	Baseline; Week 1, Week 3, Week 6, Week 9, Week 11, and Week 14

Outcome Measure Data

Analysis Population Description

No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.

Arm/Group Title	Placebo	AVP-786
Arm/Group Description	Participants received matching placebo in either the first or last 6 weeks of the study.	Participants received up to a target dose of AVP-786-28/4.9 BID in either the first or last 6 weeks of the study.
Measure Participants	0	0

7. Secondary Outcome

Title	Change From the First Assessment for the Modified Clinical Global Impression of Change (mCGIC) Scale
Time Frame	Week 3, Week 6, Week 11, and Week 14

Outcome Measure Data

Analysis Population Description

No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.

Arm/Group Title	Placebo	AVP-786
Arm/Group Description	Participants received matching placebo in either the first or last 6 weeks of the study.	Participants received up to a target dose of AVP-786-28/4.9 BID in either the first or last 6 weeks of the study.
Measure Participants	0	0

8. Secondary Outcome

Title	Change From the First Assessment for the Patient Global Impression of Change (PGIC) Scale
Time Frame	Week 3, Week 6, Week 11, and Week 14

Outcome Measure Data

Analysis Population Description

No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.

Arm/Group Title	Placebo	AVP-786
Arm/Group Description	Participants received matching placebo in either the first or last 6 weeks of the study.	Participants received up to a target dose of AVP-786-28/4.9 BID in either the first or last 6 weeks of the study.
Measure Participants	0	0

9. Secondary Outcome

Title	Change From Baseline for the Quality of Relationships (QoR) Scale
Time Frame	Baseline; Week 6, Week 8, and Week 14

Outcome Measure Data

Analysis Population Description

No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.

Arm/Group Title	Placebo	AVP-786
Arm/Group Description	Participants received matching placebo in either the first or last 6 weeks of the study.	Participants received up to a target dose of AVP-786-28/4.9 BID in either the first or last 6 weeks of the study.
Measure Participants	0	0

10. Secondary Outcome

Title	Change From Baseline for the Quality of Life (QoL) Scale
Time Frame	Baseline; Week 6, Week 8, and Week 14

Outcome Measure Data

Analysis Population Description

No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.

Arm/Group Title	Placebo	AVP-786
Arm/Group Description	Participants received matching placebo in either the first or last 6 weeks of the study.	Participants received up to a target dose of AVP-786-28/4.9 BID in either the first or last 6 weeks of the study.
Measure Participants	0	0

11. Secondary Outcome

Title	Change From Baseline for the Interpersonal Reactivity Index (IRI)
Time Frame	Baseline; Week 6, Week 8, and Week 14

Outcome Measure Data

Analysis Population Description

No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.

Arm/Group Title	Placebo	AVP-786
Arm/Group Description	Participants received matching placebo in either the first or last 6 weeks of the study.	Participants received up to a target dose of AVP-786-28/4.9 BID in either the first or last 6 weeks of the study.
Measure Participants	0	0

12. Secondary Outcome

Title	Change From Baseline for the Center for Neurologic Study-Lability Scale (CNS-LS)
Time Frame	Baseline; Week 6, Week 8, and Week 14

Outcome Measure Data

Analysis Population Description

No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.

Arm/Group Title	Placebo	AVP-786
Arm/Group Description	Participants received matching placebo in either the first or last 6 weeks of the study.	Participants received up to a target dose of AVP-786-28/4.9 BID in either the first or last 6 weeks of the study.
Measure Participants	0	0

13. Secondary Outcome

Title	Change From Baseline for the Mini-Mental State Examination (MMSE)
Time Frame	Baseline; Week 6, Week 8, and Week 14

Outcome Measure Data

Analysis Population Description

No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.

Arm/Group Title	Placebo	AVP-786
Arm/Group Description	Participants received matching placebo in either the first or last 6 weeks of the study.	Participants received up to a target dose of AVP-786-28/4.9 BID in either the first or last 6 weeks of the study.
Measure Participants	0	0

14. Secondary Outcome

Title	Change From Baseline for the Cornell Scale for Depression in Dementia (CSDD)
Time Frame	Baseline; Week 6, Week 8, and Week 14

Outcome Measure Data

Analysis Population Description

No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.

Arm/Group Title	Placebo	AVP-786
Arm/Group Description	Participants received matching placebo in either the first or last 6 weeks of the study.	Participants received up to a target dose of AVP-786-28/4.9 BID in either the first or last 6 weeks of the study.
Measure Participants	0	0

15. Secondary Outcome

Title	Change From Baseline for the Stroop Color and Word Task
Time Frame	Baseline; Week 6, Week 8, and Week 14

Outcome Measure Data

Analysis Population Description

No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.

Arm/Group Title	Placebo	AVP-786
Arm/Group Description	Participants received matching placebo in either the first or last 6 weeks of the study.	Participants received up to a target dose of AVP-786-28/4.9 BID in either the first or last 6 weeks of the study.
Measure Participants	0	0

Adverse Events

Time Frame	up to 22 weeks
Arm/Group Title	Placebo		AVP-786
Arm/Group Description	Participants received matching placebo for 6 weeks.		Participants received AVP-786 (up to a target dose of d6-DM 28 milligrams [mg]/Q 4.9 mg [AVP-786-28/4.9] twice a day [BID]) for 6 weeks.
All Cause Mortality
	Placebo		AVP-786
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)
Serious Adverse Events
	Placebo		AVP-786
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		AVP-786
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		1/1 (100%)
Investigations
Blood bilirubin increased	0/1 (0%)		1/1 (100%)
Blood creatine phosphokinase increased	0/1 (0%)		1/1 (100%)

Limitations/Caveats

The study was terminated due to lack of enrollment.

More Information

Certain Agreements

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