PMID- 32393412
OWN - NLM
STAT- MEDLINE
DCOM- 20220110
LR  - 20220110
IS  - 1092-8529 (Print)
IS  - 1092-8529 (Linking)
VI  - 26
IP  - 4
DP  - 2021 Aug
TI  - Long-term safety and durability of effect with a combination of olanzapine and 
      samidorphan in patients with schizophrenia: results from a 1-year open-label 
      extension study.
PG  - 383-392
LID - 10.1017/S1092852920001376 [doi]
AB  - BACKGROUND: Combination olanzapine and samidorphan (OLZ/SAM), in development for 
      schizophrenia and bipolar I disorder, is intended to provide the efficacy of 
      olanzapine while mitigating olanzapine-associated weight gain. OLZ/SAM safety, 
      tolerability, and efficacy from a 52-week open-label extension study in patients 
      with schizophrenia are reported. METHODS: Patients previously completing the 
      4-week, double-blind ENLIGHTEN-1 study switched from OLZ/SAM, olanzapine, or 
      placebo to OLZ/SAM. Assessments included adverse events (AEs), weight, vital 
      signs, Positive and Negative Syndrome Scale (PANSS), and Clinical Global 
      Impression-Severity (CGI-S) scores. Baseline was prior to first dose of OLZ/SAM 
      in the extension study. RESULTS: In total, 281 patients enrolled, 277 received >/=1 
      OLZ/SAM dose, and 183 (66.1%) completed 52 weeks. Reasons for discontinuation 
      included patient withdrawal (15.5%), loss to follow-up (6.9%), AEs (5.8%), and 
      lack of efficacy (1.8%). AEs were reported in 136 (49.1%) patients; increased 
      weight (13%) and somnolence (8%) were most common. Ten serious AEs were reported 
      in eight patients (2.9%); none were considered treatment related. There were no 
      deaths. Mean (SD) baseline weight was 79.1 (17.8) kg. Mean weight change from 
      baseline to week 52 was 1.86 kg (2.79% increase). PANSS total and CGI-S scores 
      continued to decline over 52 weeks (mean [95% CI] changes from baseline to week 
      52: -16.2 [-18.5, -14.0] and -0.9 [-1.0, -0.8], respectively). CONCLUSION: 
      OLZ/SAM was generally well tolerated in this extension study; most patients 
      completed the 52-week treatment period with sustained improvement in 
      schizophrenia symptoms. Mean increases in weight stabilized by week 6 with 
      limited subsequent change through end of treatment.
FAU - Yagoda, Sergey
AU  - Yagoda S
AD  - Alkermes, Inc., Waltham, Massachusetts, USA.
FAU - Graham, Christine
AU  - Graham C
AD  - Alkermes, Inc., Waltham, Massachusetts, USA.
FAU - Simmons, Adam
AU  - Simmons A
AD  - Alkermes, Inc., Waltham, Massachusetts, USA.
FAU - Arevalo, Christina
AU  - Arevalo C
AD  - Alkermes, Inc., Waltham, Massachusetts, USA.
FAU - Jiang, Ying
AU  - Jiang Y
AD  - Alkermes, Inc., Waltham, Massachusetts, USA.
FAU - McDonnell, David
AU  - McDonnell D
AD  - Alkermes Pharma Ireland Limited, Dublin, Ireland.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20200512
PL  - United States
TA  - CNS Spectr
JT  - CNS spectrums
JID - 9702877
RN  - 0 (Antipsychotic Agents)
RN  - 5S6W795CQM (Naltrexone)
RN  - 7W2581Z5L8 (3-carboxamido-4-hydroxynaltrexone)
RN  - N7U69T4SZR (Olanzapine)
SB  - IM
MH  - Adult
MH  - Antipsychotic Agents/*therapeutic use
MH  - Drug Therapy, Combination
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Naltrexone/*analogs & derivatives/therapeutic use
MH  - Olanzapine/*therapeutic use
MH  - Schizophrenia/*drug therapy
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Antipsychotic agents
OT  - narcotic antagonists
OT  - olanzapine
OT  - safety
OT  - schizophrenia
EDAT- 2020/05/13 06:00
MHDA- 2022/01/11 06:00
CRDT- 2020/05/13 06:00
PHST- 2020/05/13 06:00 [pubmed]
PHST- 2022/01/11 06:00 [medline]
PHST- 2020/05/13 06:00 [entrez]
AID - S1092852920001376 [pii]
AID - 10.1017/S1092852920001376 [doi]
PST - ppublish
SO  - CNS Spectr. 2021 Aug;26(4):383-392. doi: 10.1017/S1092852920001376. Epub 2020 May 
      12.