Trial Outcomes & Findings for A Study of ALKS 3831 in Adults With Acute Exacerbation of Schizophrenia (the ENLIGHTEN-1 Study) (NCT NCT02634346)

Last Updated: 2018-06-27

Results Overview

This scale consists of symptom constructs (7 positive, 7 negative, 16 general psychopathology), each to be rated on a 7-point Likert-type scale of severity with 1 being absent to 7 being extreme. Minimum scores (best outcome) equals 30 (total scale); maximum scores (worst outcome) equals 210 (total scale). Change is calculated between the baseline visit and Week 4.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

403 participants

Primary outcome timeframe

4 weeks

Results posted on

2018-06-27

Participant Flow

Disposition is shown for the safety population - subjects who were randomized and received at least 1 dose of study drug. 1 subject in the placebo group and 1 subject in the olanzapine-only group were randomized but not treated, and thus were not included in the safety population.

Participant milestones

Participant milestones
Measure	ALKS 3831 Olanzapine + samidorphan; administered as a coated bilayer tablet ALK3831: Daily dosing	Olanzapine Administered as a coated bilayer tablet Olanzapine: Daily dosing	Placebo Administered as a coated bilayer tablet Placebo: Daily dosing
Overall Study STARTED	134	133	134
Overall Study COMPLETED	122	119	111
Overall Study NOT COMPLETED	12	14	23

Reasons for withdrawal

Reasons for withdrawal
Measure	ALKS 3831 Olanzapine + samidorphan; administered as a coated bilayer tablet ALK3831: Daily dosing	Olanzapine Administered as a coated bilayer tablet Olanzapine: Daily dosing	Placebo Administered as a coated bilayer tablet Placebo: Daily dosing
Overall Study Withdrawal by Subject	8	9	8
Overall Study Adverse Event	2	2	7
Overall Study Lack of Efficacy	1	2	8
Overall Study Lost to Follow-up	1	0	0
Overall Study Protocol Violation	0	1	0

Baseline Characteristics

A Study of ALKS 3831 in Adults With Acute Exacerbation of Schizophrenia (the ENLIGHTEN-1 Study)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ALKS 3831 n=134 Participants Administered as a coated bilayer tablet ALK3831: Daily dosing	Olanzapine n=133 Participants Administered as a coated bilayer tablet Olanzapine: Daily dosing	Placebo n=134 Participants Administered as a coated bilayer tablet Placebo: Daily dosing	Total n=401 Participants Total of all reporting groups
Age, Continuous	40.8 years STANDARD_DEVIATION 12.55 • n=93 Participants	41.5 years STANDARD_DEVIATION 10.89 • n=4 Participants	41.1 years STANDARD_DEVIATION 10.59 • n=27 Participants	41.1 years STANDARD_DEVIATION 11.35 • n=483 Participants
Sex: Female, Male Female	49 Participants n=93 Participants	52 Participants n=4 Participants	56 Participants n=27 Participants	157 Participants n=483 Participants
Sex: Female, Male Male	85 Participants n=93 Participants	81 Participants n=4 Participants	78 Participants n=27 Participants	244 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=93 Participants	7 Participants n=4 Participants	4 Participants n=27 Participants	13 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	132 Participants n=93 Participants	126 Participants n=4 Participants	130 Participants n=27 Participants	388 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=483 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants	0 Participants n=4 Participants	3 Participants n=27 Participants	4 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants
Race (NIH/OMB) Black or African American	42 Participants n=93 Participants	33 Participants n=4 Participants	38 Participants n=27 Participants	113 Participants n=483 Participants
Race (NIH/OMB) White	87 Participants n=93 Participants	99 Participants n=4 Participants	91 Participants n=27 Participants	277 Participants n=483 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	5 Participants n=483 Participants
Region of Enrollment United States	55 participants n=93 Participants	50 participants n=4 Participants	49 participants n=27 Participants	154 participants n=483 Participants
Region of Enrollment Ukraine	24 participants n=93 Participants	26 participants n=4 Participants	29 participants n=27 Participants	79 participants n=483 Participants
Region of Enrollment Bulgaria	44 participants n=93 Participants	38 participants n=4 Participants	45 participants n=27 Participants	127 participants n=483 Participants
Region of Enrollment Serbia	11 participants n=93 Participants	19 participants n=4 Participants	11 participants n=27 Participants	41 participants n=483 Participants

PRIMARY outcome

Timeframe: 4 weeks

Population: Subjects that received at least 1 dose of study drug and had at least 1 post-baseline PANSS assessment.

Outcome measures

Outcome measures
Measure	ALKS 3831 n=132 Participants Administered as a coated bilayer tablet ALK3831: Daily dosing	Olanzapine n=132 Participants Administered as a coated bilayer tablet Olanzapine: Daily dosing	Placebo n=133 Participants Administered as a coated bilayer tablet Placebo: Daily dosing
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4	-23.9 units on a scale Standard Error 1.28	-22.8 units on a scale Standard Error 1.29	-17.5 units on a scale Standard Error 1.32

SECONDARY outcome

Timeframe: 4 weeks

Population: Subjects who received at least 1 dose of study drug and had at least 1 post-baseline PANSS assessment.

The CGI-S is a 7-point scale that requires the clinician to assess how mentally ill the patient is in a specific point in time. Results indicate participants evaluated at one of the following categories: "1: normal, not at all ill"; "2: borderline mentally ill"; "3: mildly ill"; "4: moderately ill"; "5: markedly ill"; "6: severely ill"; and "7: among the most extremely ill patients". Results indicate a change in CGI-S score from baseline to Week 4 based on the observed data. Change is calculated between the baseline visit and Week 4.

Outcome measures

Outcome measures
Measure	ALKS 3831 n=132 Participants Administered as a coated bilayer tablet ALK3831: Daily dosing	Olanzapine n=132 Participants Administered as a coated bilayer tablet Olanzapine: Daily dosing	Placebo n=133 Participants Administered as a coated bilayer tablet Placebo: Daily dosing
Change From Baseline in Clinical Global Impressions-Severity (CGIS) Score at Week 4	-1.21 units on a scale Standard Error 0.082	-1.27 units on a scale Standard Error 0.083	-0.84 units on a scale Standard Error 0.085

SECONDARY outcome

Timeframe: Approximately 4 weeks

Population: Number of subjects who received study drug and had a treatment-emergent adverse event

Outcome measures

Outcome measures
Measure	ALKS 3831 n=134 Participants Administered as a coated bilayer tablet ALK3831: Daily dosing	Olanzapine n=133 Participants Administered as a coated bilayer tablet Olanzapine: Daily dosing	Placebo n=134 Participants Administered as a coated bilayer tablet Placebo: Daily dosing
Incidence of Adverse Events	73 Participants	73 Participants	60 Participants

Adverse Events

ALKS 3831

Serious events: 1 serious events

Other events: 50 other events

Deaths: 0 deaths

Olanzapine

Serious events: 1 serious events

Other events: 45 other events

Deaths: 1 deaths

Placebo

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ALKS 3831 n=134 participants at risk Administered as a coated bilayer tablet ALK3831: Daily dosing	Olanzapine n=133 participants at risk Administered as a coated bilayer tablet Olanzapine: Daily dosing	Placebo n=134 participants at risk Administered as a coated bilayer tablet Placebo: Daily dosing
Psychiatric disorders Catatonia	0.75% 1/134 • Number of events 1 • Treatment emergent adverse events (TEAEs) are presented for the double-blind treatment period (4 weeks). The safety population includes all subjects who received at least 1 dose of study drug.	0.00% 0/133 • Treatment emergent adverse events (TEAEs) are presented for the double-blind treatment period (4 weeks). The safety population includes all subjects who received at least 1 dose of study drug.	0.00% 0/134 • Treatment emergent adverse events (TEAEs) are presented for the double-blind treatment period (4 weeks). The safety population includes all subjects who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Toxicity to Various Agents	0.00% 0/134 • Treatment emergent adverse events (TEAEs) are presented for the double-blind treatment period (4 weeks). The safety population includes all subjects who received at least 1 dose of study drug.	0.75% 1/133 • Number of events 1 • Treatment emergent adverse events (TEAEs) are presented for the double-blind treatment period (4 weeks). The safety population includes all subjects who received at least 1 dose of study drug.	0.00% 0/134 • Treatment emergent adverse events (TEAEs) are presented for the double-blind treatment period (4 weeks). The safety population includes all subjects who received at least 1 dose of study drug.

Other adverse events

Other adverse events
Measure	ALKS 3831 n=134 participants at risk Administered as a coated bilayer tablet ALK3831: Daily dosing	Olanzapine n=133 participants at risk Administered as a coated bilayer tablet Olanzapine: Daily dosing	Placebo n=134 participants at risk Administered as a coated bilayer tablet Placebo: Daily dosing
Investigations Weight increased	18.7% 25/134 • Number of events 25 • Treatment emergent adverse events (TEAEs) are presented for the double-blind treatment period (4 weeks). The safety population includes all subjects who received at least 1 dose of study drug.	14.3% 19/133 • Number of events 19 • Treatment emergent adverse events (TEAEs) are presented for the double-blind treatment period (4 weeks). The safety population includes all subjects who received at least 1 dose of study drug.	3.0% 4/134 • Number of events 4 • Treatment emergent adverse events (TEAEs) are presented for the double-blind treatment period (4 weeks). The safety population includes all subjects who received at least 1 dose of study drug.
Nervous system disorders Somnolence	9.0% 12/134 • Number of events 12 • Treatment emergent adverse events (TEAEs) are presented for the double-blind treatment period (4 weeks). The safety population includes all subjects who received at least 1 dose of study drug.	9.8% 13/133 • Number of events 13 • Treatment emergent adverse events (TEAEs) are presented for the double-blind treatment period (4 weeks). The safety population includes all subjects who received at least 1 dose of study drug.	2.2% 3/134 • Number of events 3 • Treatment emergent adverse events (TEAEs) are presented for the double-blind treatment period (4 weeks). The safety population includes all subjects who received at least 1 dose of study drug.
Gastrointestinal disorders Dry mouth	7.5% 10/134 • Number of events 10 • Treatment emergent adverse events (TEAEs) are presented for the double-blind treatment period (4 weeks). The safety population includes all subjects who received at least 1 dose of study drug.	5.3% 7/133 • Number of events 8 • Treatment emergent adverse events (TEAEs) are presented for the double-blind treatment period (4 weeks). The safety population includes all subjects who received at least 1 dose of study drug.	0.75% 1/134 • Number of events 1 • Treatment emergent adverse events (TEAEs) are presented for the double-blind treatment period (4 weeks). The safety population includes all subjects who received at least 1 dose of study drug.
Psychiatric disorders Anxiety	6.0% 8/134 • Number of events 8 • Treatment emergent adverse events (TEAEs) are presented for the double-blind treatment period (4 weeks). The safety population includes all subjects who received at least 1 dose of study drug.	5.3% 7/133 • Number of events 7 • Treatment emergent adverse events (TEAEs) are presented for the double-blind treatment period (4 weeks). The safety population includes all subjects who received at least 1 dose of study drug.	6.0% 8/134 • Number of events 12 • Treatment emergent adverse events (TEAEs) are presented for the double-blind treatment period (4 weeks). The safety population includes all subjects who received at least 1 dose of study drug.
Nervous system disorders Headache	6.0% 8/134 • Number of events 8 • Treatment emergent adverse events (TEAEs) are presented for the double-blind treatment period (4 weeks). The safety population includes all subjects who received at least 1 dose of study drug.	5.3% 7/133 • Number of events 9 • Treatment emergent adverse events (TEAEs) are presented for the double-blind treatment period (4 weeks). The safety population includes all subjects who received at least 1 dose of study drug.	3.0% 4/134 • Number of events 7 • Treatment emergent adverse events (TEAEs) are presented for the double-blind treatment period (4 weeks). The safety population includes all subjects who received at least 1 dose of study drug.
Psychiatric disorders Schizophrenia	0.75% 1/134 • Number of events 1 • Treatment emergent adverse events (TEAEs) are presented for the double-blind treatment period (4 weeks). The safety population includes all subjects who received at least 1 dose of study drug.	1.5% 2/133 • Number of events 2 • Treatment emergent adverse events (TEAEs) are presented for the double-blind treatment period (4 weeks). The safety population includes all subjects who received at least 1 dose of study drug.	6.0% 8/134 • Number of events 8 • Treatment emergent adverse events (TEAEs) are presented for the double-blind treatment period (4 weeks). The safety population includes all subjects who received at least 1 dose of study drug.

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