Agitation with Dementia of the Alzheimer's Type MedDRA version: 20.0 Level: PT Classification code 10012271 Term: Dementia Alzheimer's type System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
Suven Life Sciences Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 2.Is male or female =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 3.Has onset of agitation symptoms at least 2 weeks prior to Visit1 4.Has confirmed agitation using the IPA Consensus Provisional Definition of Agitation in Cognitive Disorders 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 Alzheimer's type and without any other clinically significant comorbid pathologies 6.Has a score between 5 and 26 (inclusive) on MMSE at Visit 1. Participant can be rescreened after 1 month if MMSE is not within range and can be rescreened more than once with agreement of the medical monitor 7.Has a clinically significant agitation/aggression (score of =4) as measured by the NPI-12 A/A at Visits 1 and 2 8.Must be receiving treatment with stable doses of either a cholinesterase inhibitor or memantine or both for =3 months prior to Visit1 and likely to be maintained on his/her current dose of cholinesterase inhibitor for the entire duration of the study 9.Inclusion criterion #9 was deleted in Protocol Amendment 2 10.Has no change to medications targeting behavioral manifestations of AD within 4 weeks prior to Visit 2 including starting, stopping, or dosage modifications. Concomitant medications should be reviewed to determine their effects on behavioral manifestations of AD with agreement of the medical monitor prior to randomization. Oral lorazepam as rescue medication is allowed for the short-term treatment of symptoms of agitation if deemed necessary by the investigator. 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 the regularly scheduled telephone visits between the caregiver and site staff. Any use or increase in dose of lorazepam will be documented as a rescue medication, even if given to participants for symptoms other than agitation and aggression. Lorazepam must not be administered within 12 hours prior to the efficacy and safety assessments. If lorazepam is not available, another intermediate-acting benzodiazepine may be used at doses equivalent to lorazepam doses. 11.Is permitted to use low-dose trazodone (up to 100 mg/day),eszopiclone, zolpidem, zopiclone, or zaleplon for nighttime management of insomnia. If a bedtime dose of a sleep agent for insomnia is being taken on a regular basis prior to screening a stable dose (=4 weeks) of the sleep agent may be continued as needed during the study. If a sleep agent has not been previously taken prior to screening and needs to be initiated medication should be limited to a maximum allowable daily dose approved for the treatment of insomnia. Insomnia medications must not be administered within 8 hours prior to the efficacy and/or safety assessments. 12.Is permitted to use anxiolytic medications (including benzodiazepine) and antidepressants (eg selective serotonin re-uptake inhibitors, serotonin norepinephrine re-uptake inhibitors with the exclusion of tricyclic antidepressants) provided they have been on a stable dose f
Exclusion criteria
Exclusion criteria: 1. Female participants who are pregnant or breast feeding 2. Sexually active females of childbearing potential and male participants are not practicing two different methods of birth control with their partner during the study and for 90 days after the last dose of study drug or who will not remain abstinent during the study and for 90 days after the last dose. If employing birth control, each couple must use two of the following precautions: vasectomy, tubal ligation, vaginal diaphragm, intrauterine device, birth control pill, birth control implant, birth control depot injections, condom with spermicide, or sponge with spermicide 3. Has history of confirmed COVID-19 within 3 months prior to Visit 1 4. Has a diagnosis of dementia due to other causes including vascular disease, (large infarct [>10 mm] cortical/subcortical), Parkinson's disease, Lewy Body disease, AIDS, Creutzfeldt-Jakob disease, frontotemporal dementia, Huntington's disease, major head trauma, primary or secondary cerebral neoplasia, or other non-Alzheimer disorders. 5. Has a history of stroke, documented TIAs and/or pulmonary embolism within the last 12 months 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. Participants with history of MDD who are currently treated and controlled on medication for =3 months may be enrolled 7. Has symptoms of agitation that are not secondary to AD 8. Has symptoms of delirium or history of delirium within 1 month prior to Visit 1. 9. Has used or will continue to use MAOIs, linezolid, tricyclic antidepressants, or intravenous methylene blue within 14 days prior to Visit 1. 10. Has uncontrolled cardiac disease or hypertension. This includes participants with history of congestive heart failure, history of unstable angina or myocardial infarction within 6 months of Visit 1, clinically significant ECG findings at Visits 1 or 2, and participants whose hypertension has not been controlled on medication for =3 months prior to Visit 1. 11. All antipsychotics are prohibited and should be discontinued as appropriate (2 weeks or at least 5 half-lives [whichever is longer] prior to Visit 2). 12. Exclusion Criterion #12 was deleted in Protocol Amendment 2 13. Centrally-acting anticholinergic medications are prohibited and should be tapered off and discontinued at least 2 weeks prior to Visit 2. 14. CYP3A4 substrates with narrow therapeutic index are prohibited and should be discontinued as appropriate (2 weeks or at least 5 half-lives [whichever is longer] prior to Visit 2). 15. Use of any medications, herbal supplements and/or ingestion of foods with known inhibitory /inducer effects on CYP3A4 should be discontinued from screening through EOT visit. 16. Use of herbal and dietary supplements that cause liver injury (eg, supplements that contain aloe vera, black cohosh, cascara, chaparral, comfrey, ephedra, or kava). 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. 17. Has a history or current evidence of QT prolongation syndrome, QTcF =450 msec (for male participants) or = 470 msec (for female participants), or Torsade de Pointes, as determined by ECG at Visits 1 or 2. 18. Has bradycardia (100 bpm) on the ECG at Visits
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of masupirdine (50 mg and 100 mg) compared to placebo for agitation as measured by the CMAI items score aligning to the IPA agitation criteria domains (physical aggression, excessive motor activity, and verbal aggression) after 12 weeks of treatment.;Secondary Objective: To measure whether the effects of masupirdine (50 mg and 100 mg) are substantial enough to be detected by a skilled and experienced clinician based on a direct examination of the participant and an interview of the participant's primary caregiver.;Primary end point(s): Change in CMAI items score aligning to the IPA agitation criteria domains from baseline to Week 12;Timepoint(s) of evaluation of this end point: Evaluated at Day 1; 15 (+/- 3 days); 29 (+/- 3 days); 57 (+/- 3 days); 85 (+/- 3 days) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Improvement in mADCS-CGI-C at Week 12;Timepoint(s) of evaluation of this end point: Evaluated at Day 1; 15 (+/- 3 days); 29 (+/- 3 days); 57 (+/- 3 days); 85 (+/- 3 days) | — |
Countries
Croatia, Poland, Serbia, United States
Contacts
Public ContactProject Managament
PPD
Outcome results
None listed