Masupirdine for Alzheimer's disease dementia with agitation

Inclusion criteria

• {"criterion_text":"- 1. Participant and/or the participant’s LAR/caregiver can understand the written informed consent, provide signed and witnessed written informed consent, and agree to comply with protocol requirements prior to beginning any study procedures.\n- 2. Is ≥50 years of age at Visit 1 and has a diagnosis of dementia of the Alzheimer’s type according to the NIA-AA 2011 criteria. Biomarkers will not be considered for eligibility.\n- 3. Has onset of agitation symptoms at least 2 weeks prior to Visit 1.\n- 4. Has confirmed agitation using the IPA Consensus Provisional Definition of Agitation in Cognitive Disorders.\n- 5. Has an MRI or CT scan performed after onset of Alzheimer's disease symptoms and prior to randomization with findings consistent with the diagnosis of dementia of the Protocol CTP3S1502HT6, Page 49 and without any other clinically significant comorbid pathologies.\n- 6. Has a score between 5 and 26 (both inclusive) on MMSE at Visit 1.\n- 7. Has a clinically significant agitation/aggression (score of ≥4) as measured by the NPI-12 A/A at Visits 1 and 2.\n- 8. Must be receiving treatment with stable doses of either a cholinesterase inhibitor or memantine or both for ≥3 months prior to Visit 1 and likely to be maintained on his/her current dose for the duration of the study.\n- 9. Has no change to medications targeting behavioral manifestations of AD within 4 weeks prior to Visit 2. Lorazepam can be administered in a dose ≤1.5 mg/day and not to exceed 3 days in a 7-day period. Concomitant use of lorazepam must be recorded during visits.\n- 10. Is permitted to use low-dose trazodone (up to 100 mg/day), eszopiclone, zolpidem, zopiclone, or zaleplon for nighttime management of insomnia. Insomnia medications must not be administered within 8 hours prior to the efficacy and/or safety assessments.\n- 11. Is permitted to use anxiolytic medications (including benzodiazepine), and antidepressants (with the exclusion of tricyclic antidepressants), provided they have been on a stable dose for ≥4 weeks prior to Visit 1.\n- 12. Is permitted to use supplements, medical foods, or pharmaceuticals specifically for the treatment of dementia, agitation, or sleep, containing omega-3 fatty acids, melatonin, vitamin B12, folate, or valerian root. However, the dose should be stable for ≥4 weeks prior to Visit 1 and must remain stable throughout the study. All stable supplements require review and approval by the medical monitor prior to randomization.\n- 13. Has a person (ie, caregiver) who is qualified, willing, and able to provide accurate information regarding the participant's cognitive and functional abilities and will accompany the participant to study visits. The caregiver should have face-to-face contact with the participant for a minimum of approximately 8 hours per week spread over 3 to 5 days during the week.\n- 14. Participants who are independent living, having in-home services, or living in assisted living or nursing homes. The participant can participate in this study if his/her caregiver ensures the administration of the study drug.\n- 15. Has vision and hearing (corrected) sufficient to comply with the testing procedures. Both participant and caregiver must be able to read and understand the written information and have literacy skills to ensure compliance with the visit procedures.\n- 16. Has no clinically significant abnormalities in general health, physical examination, neurological examination, ECG recording, or laboratory assessments. For ALT, AST, or TBL, clinically significant is defined as greater than 1.5 times the upper limit of normal.\n- 17. Has a BMI >18.5 kg/m2 at Visit 1.\n- 18. Is willing and able to participate in all aspects of study design including blood sampling (PK and laboratory tests).\n- 19. Has ability to travel to the study site at the scheduled visit times (except participants living in nursing homes)."}

Exclusion criteria

• {"criterion_text":"- 1.Female participants who are pregnant or breast feeding.\n- 2.Sexually active females of childbearing potential and male participants are not practicing two different methods of birth control with their partner.\n- 3.Has history of confirmed COVID-19 within 3 months prior to Visit 1.\n- 4.Has a diagnosis of dementia due to other non-Alzheimer disorders.\n- 5.Has a history of stroke, documented TIAs, and/or pulmonary embolism within the last 12 months.\n- 6.Has a diagnosis of schizophrenia, bipolar disorder, or current untreated/uncontrolled MDD or participants whose C-SDD scores are suggestive of probable depression (ie, scores ≥12) at Visits 1 or 2.\n- 7.Has symptoms of agitation that are not secondary to AD.\n- 8.Has symptoms of delirium or history of delirium within 1 month prior to Visit 1.\n- 9.Has used or will continue to use MAOIs, linezolid, tricyclic antidepressants, or intravenous methylene blue within 14 days prior to Visit 1.\n- 10.Has uncontrolled cardiac disease or hypertension.\n- 11.All antipsychotics are prohibited and should be discontinued as appropriate.\n- 12.Centrally acting anticholinergic medications are prohibited.\n- 13.CYP3A4 substrates with narrow therapeutic index are prohibited and should be discontinued as appropriate.\n- 14.Use of any medications/supplements/foods with known inhibitoryinducer effects on CYP3A4 should be discontinued from screening through EOT visit.\n- 15.Use of herbal and dietary supplements that cause liver injury. Participants on stable use for at least 4 months prior to Visit 1 are allowed; however, herbal and dietary supplement dose changes and new herbal and dietary supplements are not allowed during the study.\n- 16.Has a history or current evidence of QT prolongation syndrome, or Torsade de Pointes, as determined by ECG at Visits 1 or 2.\n- 17.Has bradycardia (100 bpm) on the ECG at Visits 1 or 2.\n- 18.Has uncontrolled type-1 or type-2 diabetes (defined as HbA1c >6.5% at Visit 1).\n- 19.Has cancer, a malignant tumor, or has been treated for an active malignancy within the past 5 years. Participants with stable untreated prostate or cervical cancer, localized squamous cell cancer, or basal cell cancer are permitted.\n- 20.Has clinically significant hepatic impairment.\n- 21.Is treated or likely to require treatment during the study with any medications prohibited by the study protocol.\n- 22.Is at imminent risk of self-harm, based on clinical interview and responses on the C-SSRS, or of harm to others in the opinion of the investigator at Visits 1 or 2.\n- 23.History of significant head injury, seizures, or any other unexplained, recurrent loss of consciousness for more than 15 minutes within 12 months of Visit 1.\n- 24.Poorly controlled psychosis and other psychiatric disorder that, in the opinion of the investigator, would interfere with the participant’s ability to be compliant with the study protocol.\n- 25.Known history of substance use disorder within 1 year prior to first dose of study drug, not including caffeine and nicotine.\n- 26.Current implantable intracranial stimulator or history of intracranial ablation surgery.\n- 27.Repetitive transcranial magnetic stimulation within 3 months prior to Visit 1.\n- 28.Participation in experimental interventional treatments, including immunotherapy, for any aspects of AD in the past 6 months or 5 half-lives of the experimental drug product (whichever is longer), prior to the first dose of study drug. If the participant was on placebo arm of disease-modifying treatments, participation in this study is allowed.\n- 29.Has been previously treated with masupirdine.\n- 30.Use of recreational or medical marijuana within 4 weeks prior to the first dose of study drug or any time during the study.\n- 31.Positive screen for illicit drugs of abuse, including phencyclidine, barbiturates, benzodiazepines, opiates, methadone, cocaine, cannabinoids, and amphetamines.\n- 32.Participant (or caregiver) is deemed otherwise ineligible for participation in this study in the investigator’s judgment."}

Primary endpoints

• {"endpoint_text":"- Change in CMAI items score aligning to the IPA agitation criteria domains from baseline to Week 12","definition_or_measurement_approach":"Change measured by Cohen-Mansfield Agitation Inventory (CMAI) items score aligning to the IPA agitation criteria domains (physical aggression, excessive motor activity, verbal aggression) from baseline to Week 12."}

Secondary endpoints

• {"endpoint_text":"- Improvement in mADCS-CGI-C at Week 12","definition_or_measurement_approach":"Improvement measured by Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGI-C) at Week 12."}
• {"endpoint_text":"- Change in CGI-S score as related to agitation from baseline to Week 12","definition_or_measurement_approach":"Change measured by Clinical Global Impressions-Severity (CGI-S) related to agitation from baseline to Week 12."}
• {"endpoint_text":"- Change in CaGI-S score as related to agitation from baseline to Week 12","definition_or_measurement_approach":"Change measured by Caregiver's Global Impression-Severity (CaGI-S) related to agitation from baseline to Week 12."}
• {"endpoint_text":"- Improvement in CaGI-C at Week 12","definition_or_measurement_approach":"Improvement measured by Caregiver's Global Impression-Change (CaGI-C) at Week 12."}
• {"endpoint_text":"- Change in behavioral and psychological symptoms as measured by NPI-12 from baseline to Week 12","definition_or_measurement_approach":"Change measured by Neuropsychiatric Inventory (NPI-12) from baseline to Week 12."}
• {"endpoint_text":"- Change in memory and cognitive behaviors as studied using MMSE total score from baseline to Week 12","definition_or_measurement_approach":"Change measured by Mini Mental State Examination (MMSE) total score from baseline to Week 12."}
• {"endpoint_text":"- Change in CMAI items score aligning to the IPA agitation criteria domains from baseline to Weeks 2, 4, and 8","definition_or_measurement_approach":"Change measured by CMAI items score aligning to IPA agitation domains at Weeks 2, 4, and 8 compared with baseline."}
• {"endpoint_text":"- Change in C-SDD from baseline to Week 12","definition_or_measurement_approach":"Change measured by Cornell Scale for Depression in Dementia (C-SDD) from baseline to Week 12."}

Methods

• Website listing (country-specific materials available for Poland and Croatia).
• Social media campaigns and templates (Facebook ads wording/layout, TikTok script, social-media posts) targeted to general public/caregivers in country languages (Polish, Croatian).
• Printed materials: study flyers, study posters, study brochures, study fact sheets and welcome booklets distributed at sites and local outlets.
• Paid media: newspaper ads and other local paid advertising (documents list newspaper ads).
• Physician outreach: PI-to-Physician letters and promotional materials to clinicians to refer eligible participants.
• Site-based recruitment and referrals via clinical sites and hospital clinics listed in each country.
• Use of recruitment vendors and vendors providing recruitment support (Elligo Health Research Inc. listed for recruitment).
• Participant support materials and logistics: transportation advertisements and subject travel service ICFs to support participation.

Poland

Earliest CTIS Part Ii Submission Date

10-06-2024

Latest Decision Or Authorization Date

03-07-2025

Processing Time Days

388

Number Of Sites

9

Number Of Participants

85

Croatia

Earliest CTIS Part Ii Submission Date

10-06-2024

Latest Decision Or Authorization Date

23-03-2026

Processing Time Days

651

Number Of Sites

4

Number Of Participants

72

Primary sponsor

Full Name

Suven Life Sciences Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

India

Contract research organisations

Name

WCG Clinical Inc.

Responsibilities

Regulatory/vendor services (sponsorDuties code 8)

Name

Medidata Solutions Inc.

Responsibilities

Data/clinical technology vendor (sponsorDuties code 7)

Name

PPD Development LP

Responsibilities

Bioanalytics; other clinical development services

Name

PPD Global Central Labs

Responsibilities

Central lab services (sponsorDuties code 4)

Name

Elligo Health Research Inc.

Responsibilities

Recruitment

Name

Bioclinica Inc.

Responsibilities

ECG analysis/review and site services

Name

Signant Health Global LLC

Responsibilities

Electronic patient reported outcomes/services (sponsorDuties code 3)

Third parties

• {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"sponsorDuties: code 8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties: code 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"Bioanalytics (role listed)","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"sponsorDuties: code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Elligo Health Research Inc.","duties_or_roles":"Recruitment","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"ECG analysis/ review (and sponsorDuties codes listed)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"sponsorDuties: code 3","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP (second entry)","duties_or_roles":"sponsorDuties: code 5","organisation_type":"Pharmaceutical company"}