Potential beneficial effects of masupirdine (SUVN-502) on agitation/aggression and psychosis in patients with moderate Alzheimer's disease: Exploratory post hoc analyses

Ramakrishna Nirogi, Pradeep Jayarajan, Vijay Benade, Anil Shinde, Vinod Kumar Goyal, Satish Jetta, Jyothsna Ravula, Renny Abraham, Venkata Ramalingayya Grandhi, Ramkumar Subramanian, Santosh Kumar Pandey, Rajesh Kumar Badange, Abdul Rasheed Mohammed, Venkat Jasti, Clive Ballard, Jeffrey Cummings, Ramakrishna Nirogi, Pradeep Jayarajan, Vijay Benade, Anil Shinde, Vinod Kumar Goyal, Satish Jetta, Jyothsna Ravula, Renny Abraham, Venkata Ramalingayya Grandhi, Ramkumar Subramanian, Santosh Kumar Pandey, Rajesh Kumar Badange, Abdul Rasheed Mohammed, Venkat Jasti, Clive Ballard, Jeffrey Cummings

Abstract

Objectives: The effects of masupirdine on the neuropsychiatric symptoms were explored.

Methods: Masupirdine (SUVN-502) was evaluated for its effects on cognition in patients with moderate AD. The prespecified primary outcome showed no drug-placebo difference. Post hoc analyses of domains of the 12-item neuropsychiatric inventory scale were carried out.

Results: In a subgroup of patients (placebo, n = 57; masupirdine 50 mg, n = 53; masupirdine 100 mg, n = 48) with baseline agitation/aggression symptoms ≥1, a statistically significant reduction in agitation/aggression scores was observed in masupirdine 50 mg (95% confidence interval (CI), -1.9 to -0.5, p < 0.001) and masupirdine 100 mg (95% CI, -1.7 to -0.3, p = 0.007) treated arms at Week 13 in comparison to placebo and the effect was sustained for trial duration of 26 weeks in the masupirdine 50 mg treatment arm (95% CI, -2.3 to -0.8, p < 0.001). Similar observations were noted in the subgroup of patients (placebo, n = 29; masupirdine 50 mg, n = 30; masupirdine 100 mg, n = 21) with baseline agitation/aggression symptoms ≥3. In the subgroup of patients (placebo, n = 28; masupirdine 50 mg, n = 28; masupirdine 100 mg, n = 28) who had baseline psychosis symptoms and/or symptom emergence, a significant reduction in psychosis scores was observed in the masupirdine 50 mg (Week 4: 95% CI, -2.8 to -1.4, p < 0.001; Week 13: 95% CI, -3.3 to -1.3, p < 0.001) and masupirdine 100 mg (Week 4: 95% CI, -1.4 to 0, p = 0.046; Week 13: 95% CI, -1.9 to 0.1, p = 0.073) treatment arms in comparison to placebo.

Conclusion: Further research is warranted to explore the potential beneficial effects of masupirdine on NPS.

Keywords: 5-HT6 receptor; Alzheimer's disease; NPI-12; agitation/aggression; clinical trials; masupirdine; psychosis.

Conflict of interest statement

Dr. Cummings has provided consultation to AB Science, Acadia, Alkahest, AlphaCognition, ALZPathFinder, Annovis, AriBio, Artery, Avanir, Biogen, Biosplice, Cassava, Cerevel, Clinilabs, Cortexyme, Diadem, EIP Pharma, Eisai, GatehouseBio, GemVax, Genentech, Green Valley, Grifols, Janssen, Karuna, Lexeo, Lilly, Lundbeck, LSP, Merck, NervGen, Novo Nordisk, Oligomerix, Ono, Otsuka, PharmacotrophiX, PRODEO, Prothena, ReMYND, Renew, Resverlogix, Roche, Signant Health, Suven, Unlearn AI, Vaxxinity, VigilNeuro pharmaceutical, assessment, and investment companies.

Prof. Ballard has received grants and personal fees from Acadia pharmaceutical company, grants and personal fees from Lundbeck, personal fees from Roche, personal fees from Otsuka, personal fees from Biogen, personal fees from Eli Lilly, personal fees from Novo Nordisk, personal fees from AARP, personal fees from Addex, personal fees from Enterin, personal fees from GWPharm, personal fees from Janssen, personal fees from Johnson and Johnson, personal fees from Orion, personal fees from Sunovion, personal fees from tauX pharmaceutical company and from Synexus.

Prof. Ballard and Dr. Cummings did not receive compensation for developing this manuscript.

Ramakrishna Nirogi, Pradeep Jayarajan, Vijay Benade, Anil Shinde, Vinod Kumar Goyal, Satish Jetta, Jyothsna Ravula, Renny Abraham, Venkata Ramalingayya Grandhi, Ramkumar Subramanian, Santosh Kumar Pandey, Rajesh Kumar Badange, Abdul Rasheed Mohammed and Venkat Jasti, are fulltime employees of Suven Life Sciences Ltd.

© 2022 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
(A) Mean change in agitation/aggression domain of NPI‐12 (modified intention to treat (mITT)); Error bars represent standard error of mean; NPI‐12: 12‐item Neuropsychiatric Inventory scale; mITT—modified intent to treat population. (B) Mean change in agitation/aggression domain (baseline ≥1) of NPI‐12 (mITT); Error bars represent standard error of mean; NPI‐12: 12‐item Neuropsychiatric Inventory scale; mITT—modified intent to treat population. (C) Mean change in agitation/aggression domain (baseline ≥3) of NPI‐12 (mITT); Error bars represent standard error of mean; NPI‐12: 12‐item Neuropsychiatric Inventory scale; mITT—modified intent to treat population. (D) Mean change in agitation/aggression domain (baseline symptom and/or symptom emergence) of NPI‐12 (mITT); Error bars represent standard error of mean; NPI‐12: 12‐item Neuropsychiatric Inventory scale; mITT—modified intent to treat population
FIGURE 1
FIGURE 1
(A) Mean change in agitation/aggression domain of NPI‐12 (modified intention to treat (mITT)); Error bars represent standard error of mean; NPI‐12: 12‐item Neuropsychiatric Inventory scale; mITT—modified intent to treat population. (B) Mean change in agitation/aggression domain (baseline ≥1) of NPI‐12 (mITT); Error bars represent standard error of mean; NPI‐12: 12‐item Neuropsychiatric Inventory scale; mITT—modified intent to treat population. (C) Mean change in agitation/aggression domain (baseline ≥3) of NPI‐12 (mITT); Error bars represent standard error of mean; NPI‐12: 12‐item Neuropsychiatric Inventory scale; mITT—modified intent to treat population. (D) Mean change in agitation/aggression domain (baseline symptom and/or symptom emergence) of NPI‐12 (mITT); Error bars represent standard error of mean; NPI‐12: 12‐item Neuropsychiatric Inventory scale; mITT—modified intent to treat population
FIGURE 2
FIGURE 2
(A) Mean change in psychosis domain of NPI‐12 (modified intention to treat (mITT)); Error bars represent standard error of mean; NPI‐12: 12‐item Neuropsychiatric Inventory scale; mITT ‐ modified intent to treat population. (B) Mean change in psychosis domain (baseline ≥1) of NPI‐12 (mITT); Error bars represent standard error of mean; NPI‐12: 12‐item Neuropsychiatric Inventory scale; mITT—modified intent to treat population. (C) Mean change in ADAS‐Cog 11 scores in patients with psychosis (baseline ≥1) of NPI‐12 (mITT); Error bars represent standard error of mean; ADAS‐Cog 11: 11 item Alzheimer's Disease Assessment Scale–Cognitive subscale; NPI‐12: 12‐item Neuropsychiatric Inventory scale; mITT—modified intent to treat population. (D) Mean change in psychosis domain (baseline symptom and/or symptom emergence) of NPI‐12 (mITT); Error bars represent standard error of mean; NPI‐12: 12‐item Neuropsychiatric Inventory scale; mITT—modified intent to treat population. (E) Mean change in ADAS‐Cog 11 scores in patients with psychosis (baseline symptom and/or symptom emergence) of NPI‐12 (mITT); Error bars represent standard error of mean; ADAS‐Cog 11: 11 item Alzheimer's Disease Assessment Scale–Cognitive subscale; NPI‐12: 12‐item Neuropsychiatric Inventory scale; mITT—modified intent to treat population
FIGURE 2
FIGURE 2
(A) Mean change in psychosis domain of NPI‐12 (modified intention to treat (mITT)); Error bars represent standard error of mean; NPI‐12: 12‐item Neuropsychiatric Inventory scale; mITT ‐ modified intent to treat population. (B) Mean change in psychosis domain (baseline ≥1) of NPI‐12 (mITT); Error bars represent standard error of mean; NPI‐12: 12‐item Neuropsychiatric Inventory scale; mITT—modified intent to treat population. (C) Mean change in ADAS‐Cog 11 scores in patients with psychosis (baseline ≥1) of NPI‐12 (mITT); Error bars represent standard error of mean; ADAS‐Cog 11: 11 item Alzheimer's Disease Assessment Scale–Cognitive subscale; NPI‐12: 12‐item Neuropsychiatric Inventory scale; mITT—modified intent to treat population. (D) Mean change in psychosis domain (baseline symptom and/or symptom emergence) of NPI‐12 (mITT); Error bars represent standard error of mean; NPI‐12: 12‐item Neuropsychiatric Inventory scale; mITT—modified intent to treat population. (E) Mean change in ADAS‐Cog 11 scores in patients with psychosis (baseline symptom and/or symptom emergence) of NPI‐12 (mITT); Error bars represent standard error of mean; ADAS‐Cog 11: 11 item Alzheimer's Disease Assessment Scale–Cognitive subscale; NPI‐12: 12‐item Neuropsychiatric Inventory scale; mITT—modified intent to treat population
FIGURE 2
FIGURE 2
(A) Mean change in psychosis domain of NPI‐12 (modified intention to treat (mITT)); Error bars represent standard error of mean; NPI‐12: 12‐item Neuropsychiatric Inventory scale; mITT ‐ modified intent to treat population. (B) Mean change in psychosis domain (baseline ≥1) of NPI‐12 (mITT); Error bars represent standard error of mean; NPI‐12: 12‐item Neuropsychiatric Inventory scale; mITT—modified intent to treat population. (C) Mean change in ADAS‐Cog 11 scores in patients with psychosis (baseline ≥1) of NPI‐12 (mITT); Error bars represent standard error of mean; ADAS‐Cog 11: 11 item Alzheimer's Disease Assessment Scale–Cognitive subscale; NPI‐12: 12‐item Neuropsychiatric Inventory scale; mITT—modified intent to treat population. (D) Mean change in psychosis domain (baseline symptom and/or symptom emergence) of NPI‐12 (mITT); Error bars represent standard error of mean; NPI‐12: 12‐item Neuropsychiatric Inventory scale; mITT—modified intent to treat population. (E) Mean change in ADAS‐Cog 11 scores in patients with psychosis (baseline symptom and/or symptom emergence) of NPI‐12 (mITT); Error bars represent standard error of mean; ADAS‐Cog 11: 11 item Alzheimer's Disease Assessment Scale–Cognitive subscale; NPI‐12: 12‐item Neuropsychiatric Inventory scale; mITT—modified intent to treat population

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