Trial Outcomes & Findings for A Multicenter Study of NAP (AL-108) in Schizophrenia (NCT NCT00505765)

NCT ID: NCT00505765

Last Updated: 2017-03-10

Results Overview

The MATRICS Consensus Cognitive Battery (MCCB) measures functioning across various cognitive domains and is comprised of ten tests that assess seven cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition) Its measurements are based on timed paper-and-pencil, computerized, and orally-administered tests, as well as spatial tests using geometric cubes. MCCB composite T scores are between 40 and 60 (normal range) and \< 40 (below normal range).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 63 participants
• Primary outcome timeframe: Baseline, week 6
• Results posted on: 2017-03-10

Participant Flow

6 of 69 randomized participants were excluded prior to starting medication

Participant milestones

Measure	AL-108, 30 mg/Day AL-108, 30 mg/day- 3 sprays in each nostril, twice per day	AL-108, 5 mg/Day AL-108, 5 mg/day- one spray in each nostril once per day	Placebo Placebo, low-dose: 1 puff administered in each nostril daily (QD) Placebo, high-dose: 3 puffs administered twice daily in each nostril (BID) Data were combined across placebo conditions for analysis
Overall Study STARTED	21	20	22
Overall Study Mid-Point Assessment	20	19	21
Overall Study COMPLETED	19	17	19
Overall Study NOT COMPLETED	2	3	3

Reasons for withdrawal

Measure	AL-108, 30 mg/Day AL-108, 30 mg/day- 3 sprays in each nostril, twice per day	AL-108, 5 mg/Day AL-108, 5 mg/day- one spray in each nostril once per day	Placebo Placebo, low-dose: 1 puff administered in each nostril daily (QD) Placebo, high-dose: 3 puffs administered twice daily in each nostril (BID) Data were combined across placebo conditions for analysis
Overall Study Withdrawal by Subject	1	0	0
Overall Study Adverse Event	1	2	0
Overall Study Noncompliance	0	1	3

Baseline Characteristics

A Multicenter Study of NAP (AL-108) in Schizophrenia

Baseline characteristics by cohort

Measure	AL-108, 30 mg/Day n=21 Participants AL-108, 30 mg/day- 3 sprays in each nostril, twice per day	AL-108, 5 mg/Day n=20 Participants AL-108, 5 mg/day- one spray in each nostril once per day	Placebo n=22 Participants Placebo, low-dose: 1 puff administered in each nostril daily (QD) Placebo, high-dose: 3 puffs administered twice daily in each nostril (BID) Data were combined across placebo conditions for analysis	Total n=63 Participants Total of all reporting groups
Age, Continuous	45.2 years STANDARD_DEVIATION 8.2 • n=5 Participants	43.2 years STANDARD_DEVIATION 10.5 • n=7 Participants	41.4 years STANDARD_DEVIATION 10.4 • n=5 Participants	43.4 years STANDARD_DEVIATION 10.2 • n=4 Participants
Sex/Gender, Customized Female	7 participants n=5 Participants	7 participants n=7 Participants	8 participants n=5 Participants	22 participants n=4 Participants
Sex/Gender, Customized Male	14 participants n=5 Participants	13 participants n=7 Participants	14 participants n=5 Participants	41 participants n=4 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	22 Participants n=4 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	13 Participants n=7 Participants	14 Participants n=5 Participants	41 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic	0 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Race/Ethnicity, Customized Non-Hispanic	21 Participants n=5 Participants	17 Participants n=7 Participants	21 Participants n=5 Participants	59 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, week 6

Population: Only participants with completed MCCB at both baseline and 6 weeks were included in analysis

The MATRICS Consensus Cognitive Battery (MCCB) measures functioning across various cognitive domains and is comprised of ten tests that assess seven cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition) Its measurements are based on timed paper-and-pencil, computerized, and orally-administered tests, as well as spatial tests using geometric cubes. MCCB composite T scores are between 40 and 60 (normal range) and < 40 (below normal range).

Outcome measures

Measure	AL-108, 30 mg/Day n=19 Participants AL-108, 30 mg/day- 3 sprays in each nostril, twice per day	AL-108, 5 mg/Day n=19 Participants AL-108, 5 mg/day- one spray in each nostril once per day	Placebo n=20 Participants Placebo, low-dose: 1 puff administered in each nostril daily (QD) Placebo, high-dose: 3 puffs administered twice daily in each nostril (BID) Data were combined across placebo conditions for analysis
Change in MATRICS Consensus Cognitive Battery Composite Score Change	1.3 units on a scale Standard Deviation 4.6	2.3 units on a scale Standard Deviation 4.6	-0.2 units on a scale Standard Deviation 5.6

PRIMARY outcome

Timeframe: Baseline, 12 weeks

Population: Only participants with completed MCCB at both Baseline and 12 weeks were included in analysis

The MATRICS Consensus Cognitive Battery (MCCB) measures functioning across various cognitive domains and is comprised of ten tests that assess seven cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition) Its measurements are based on timed paper-and-pencil, computerized, and orally-administered tests, as well as spatial tests using geometric cubes. MCCB composite T scores are between 40 and 60 (normal range) and < 40 (below normal range).

Outcome measures

Measure	AL-108, 30 mg/Day n=18 Participants AL-108, 30 mg/day- 3 sprays in each nostril, twice per day	AL-108, 5 mg/Day n=17 Participants AL-108, 5 mg/day- one spray in each nostril once per day	Placebo n=19 Participants Placebo, low-dose: 1 puff administered in each nostril daily (QD) Placebo, high-dose: 3 puffs administered twice daily in each nostril (BID) Data were combined across placebo conditions for analysis
Change in MATRICS Consensus Cognitive Battery (MCCB)	3.9 units on a scale Standard Deviation 4.6	4.6 units on a scale Standard Deviation 7.2	3.2 units on a scale Standard Deviation 4.9

SECONDARY outcome

Timeframe: Baseline, week 6

Population: Only participants with UPSA scores at both Baseline and 6 weeks were included in this analysis

UPSA includes 5 skill areas (subscales) with scores that each range from 0-20. The UPSA yields an overall total score which is the sum of the five subscales and ranges from 0-100. Higher scores are associated with more independent living.

Outcome measures

Measure	AL-108, 30 mg/Day n=20 Participants AL-108, 30 mg/day- 3 sprays in each nostril, twice per day	AL-108, 5 mg/Day n=19 Participants AL-108, 5 mg/day- one spray in each nostril once per day	Placebo n=19 Participants Placebo, low-dose: 1 puff administered in each nostril daily (QD) Placebo, high-dose: 3 puffs administered twice daily in each nostril (BID) Data were combined across placebo conditions for analysis
Change in UCSD Performance-Based Skills Assessment (UPSA) Summary Scores	2.9 units on a scale Standard Deviation 7.6	7.2 units on a scale Standard Deviation 7.3	-0.9 units on a scale Standard Deviation 9.0

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Only participants with UPSA scores at both Baseline and 12 weeks were included in this analysis

UPSA includes 5 skill areas (subscales) with scores that each range from 0-20. The UPSA yields an overall total score which is the sum of the five subscales and ranges from 0-100. Higher scores are associated with more independent living.

Outcome measures

Measure	AL-108, 30 mg/Day n=19 Participants AL-108, 30 mg/day- 3 sprays in each nostril, twice per day	AL-108, 5 mg/Day n=17 Participants AL-108, 5 mg/day- one spray in each nostril once per day	Placebo n=18 Participants Placebo, low-dose: 1 puff administered in each nostril daily (QD) Placebo, high-dose: 3 puffs administered twice daily in each nostril (BID) Data were combined across placebo conditions for analysis
Change in UCSD Performance-Based Skills Assessment (UPSA) Summary Scores	4.9 units on a scale Standard Deviation 19	8.9 units on a scale Standard Deviation 6.6	0.3 units on a scale Standard Deviation 8.5

SECONDARY outcome

Timeframe: Baseline, 6 weeks

Population: Participants administered SCoRS at both Baseline and 6 weeks were included in analysis

Schizophrenia Cognition Rating Scale (SCoRS) assessed functional capacity by completing a 20-question rating scale via interviews with the subject and an informant, focusing on cognitive impairment and its impact on daily functioning. After the interview, the interviewer rated subject's overall difficulty on a Global Scale of 1-10. Higher scores indicate greater cognitive impairment.

Outcome measures

Measure	AL-108, 30 mg/Day n=16 Participants AL-108, 30 mg/day- 3 sprays in each nostril, twice per day	AL-108, 5 mg/Day n=17 Participants AL-108, 5 mg/day- one spray in each nostril once per day	Placebo n=21 Participants Placebo, low-dose: 1 puff administered in each nostril daily (QD) Placebo, high-dose: 3 puffs administered twice daily in each nostril (BID) Data were combined across placebo conditions for analysis
Change in SCoRS Interviewer Global Rating	0.1 units on a scale Standard Deviation 1.2	-0.6 units on a scale Standard Deviation 1.3	-0.1 units on a scale Standard Deviation 1.0

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Participants administered SCoRS at both Baseline and 12 weeks were included in analysis

Schizophrenia Cognition Rating Scale (SCoRS) assessed functional capacity by completing a 20-question rating scale via interviews with the subject and an informant, focusing on cognitive impairment and its impact on daily functioning. After the interview, the interviewer rated subject's overall difficulty on a Global Scale of 1-10. Higher scores indicate greater cognitive impairment.

Outcome measures

Measure	AL-108, 30 mg/Day n=16 Participants AL-108, 30 mg/day- 3 sprays in each nostril, twice per day	AL-108, 5 mg/Day n=16 Participants AL-108, 5 mg/day- one spray in each nostril once per day	Placebo n=18 Participants Placebo, low-dose: 1 puff administered in each nostril daily (QD) Placebo, high-dose: 3 puffs administered twice daily in each nostril (BID) Data were combined across placebo conditions for analysis
Change in SCoRS Interviewer Global Rating	-0.4 units on a scale Standard Deviation 1.1	-1.2 units on a scale Standard Deviation 1.6	-0.3 units on a scale Standard Deviation 1.5

Adverse Events

AL-108, 30 mg/Day

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

AL-108, 5 mg/Day

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	AL-108, 30 mg/Day n=21 participants at risk AL-108, 30 mg/day- 3 sprays in each nostril, twice per day	AL-108, 5 mg/Day n=20 participants at risk AL-108, 5 mg/day- one spray in each nostril once per day	Placebo n=22 participants at risk Placebo, low-dose: 1 puff administered in each nostril daily (QD) Placebo, high-dose: 3 puffs administered twice daily in each nostril (BID) Data were combined across placebo conditions for analysis
Cardiac disorders Palpitations	4.8% 1/21 • Number of events 1 Of 69 randomized participants, 6 were excluded prior to starting double-blind medication; 63 participants exposed to drug or placebo were included in analyses.	0.00% 0/20 Of 69 randomized participants, 6 were excluded prior to starting double-blind medication; 63 participants exposed to drug or placebo were included in analyses.	0.00% 0/22 Of 69 randomized participants, 6 were excluded prior to starting double-blind medication; 63 participants exposed to drug or placebo were included in analyses.

Other adverse events

Measure	AL-108, 30 mg/Day n=21 participants at risk AL-108, 30 mg/day- 3 sprays in each nostril, twice per day	AL-108, 5 mg/Day n=20 participants at risk AL-108, 5 mg/day- one spray in each nostril once per day	Placebo n=22 participants at risk Placebo, low-dose: 1 puff administered in each nostril daily (QD) Placebo, high-dose: 3 puffs administered twice daily in each nostril (BID) Data were combined across placebo conditions for analysis
Nervous system disorders Restlessness	19.0% 4/21 • Number of events 4 Of 69 randomized participants, 6 were excluded prior to starting double-blind medication; 63 participants exposed to drug or placebo were included in analyses.	45.0% 9/20 • Number of events 9 Of 69 randomized participants, 6 were excluded prior to starting double-blind medication; 63 participants exposed to drug or placebo were included in analyses.	9.1% 2/22 • Number of events 2 Of 69 randomized participants, 6 were excluded prior to starting double-blind medication; 63 participants exposed to drug or placebo were included in analyses.

Additional Information

Stephen R. Marder

Semel Institute at UCLA

Phone: 310-268-3647

Email: marder@ucla.edu

Results disclosure agreements

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