Dexmedetomidine Transdermal Systems (DMTS) Treatment for Agitation Associated With Dementia of the Alzheimer's Type

Inclusion Criteria:

1. Voluntarily provide written informed consent (subject or legally authorizedrepresentative [LAR]).

2. Male or female, residing in a care facility.

3. Has a diagnosis of dementia of probable Alzheimer's Disease (AD) based on NationalInstitute on Aging and the Alzheimer's Association (NIA-AA) criteria (2018). Theclinical diagnosis of "probable Alzheimer's Disease (AD)" will be based on the 2018National Institute on Aging-Alzheimer's Association (NIA-AA) diagnostic criteria,which includes patient biomarker data as part of the research diagnosis (Jack etal., 2018). If patient biomarker data are unavailable, per the 2018 NIA-AAdiagnostic criteria, the clinical diagnosis of probable AD will be based on the 2011NIA-AA criteria (McKhann et al., 2011).

4. Had two or more episodes (using a 7-day lookback period) of agitation that impairssocial activities, requires staff or medical intervention, or impairs ability forfunctional activities of daily living at Screening.

5. Had an ABS total score ≥ 22 at least once during Day -4 to Day -1 when assessingeligibility on Day 1 Pre-randomization.

6. Has gone a minimum of 1 week with no change in medication prior to Screening.

7. Has a score of ≤ 23 on the Mini-Mental State Examination (MMSE) at Screening.

8. Female subjects who are:

9. Not pregnant, not lactating, and not planning to become pregnant during thestudy or for 1 menstrual cycle thereafter and

10. Surgically sterile; or postmenopausal (ie, amenorrhea for ≥2 years as reportedby subject/caregiver; postmenopausal status will be confirmed with FSH test);or have a monogamous partner who is surgically sterile; or have a same gendersex partner; or is using double-barrier contraception; or practicingabstinence; or using an insertable, injectable, transdermal, or combinationoral contraceptive for 3 months prior to the study, during the study, and for 1month following the study.

11. Male subjects who have female sex partners of childbearing potential must besurgically sterile or commit to use a reliable method of birth control during thestudy and for 1 month following the study. Reliable contraception is defined as: Atubal ligation, condom with spermicidal gel, an approved hormonal contraceptive suchas oral contraceptives, emergency contraception used as directed, patches, implants,injections, rings, or hormone releasing or copper intrauterine device (IUD).

12. Has a body weight > 50 kg, and body mass index of 20 to 38 kg/m2, inclusive.

13. Subject or LAR able to understand the study procedures, comply with all studyprocedures, and agree to participate in the study program for its full duration.

14. Has lived in facility for at least 7 days prior to screening and will remain infacility through the completion of Follow-Up assessments.

Exclusion Criteria:

1. Has a known sensitivity to dexmedetomidine or any excipient in the DMTS/placebo.

2. Has a skin abnormality (eg, scar, tattoo) or unhealthy skin condition (eg, burns,wounds) at the DMTS/matching placebo application site, according to examination bythe investigator at screening.

3. Has a clinically significant abnormal clinical laboratory test value as determinedby the investigator.

4. Has agitation caused by acute intoxication.

5. Has significant risk of suicide or homicide per investigator's assessment, or anypatient with an answer of "yes" to Items 4 or 5 on the Columbia-Suicide SeverityRating Scale (C-SSRS).

6. Has a history of or positive test results for the human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.

7. Has a clinically significant history or clinically significant manifestation of anyof the following, as determined by the investigator: a renal (including an estimatedglomerular filtration rate [eGFR] below the appropriate age- and gender-specificrange [see Section 8.1.3.2]), hepatic (including any evidence of ascites and/or aChild-Pugh hepatic impairment score > 6 [Appendix G]), cardiovascular, metabolic,neurologic, or psychiatric condition; congestive heart failure, peptic ulcer,gastrointestinal bleeding, or other condition that may preclude participation in thestudy.

8. Has a history of physician-diagnosed migraine, frequent non-vascular headaches (> 5per month), seizures, or are currently taking anticonvulsants.

9. Has a history of syncope or other syncopal attacks.

10. Has present and/or significant history of postural hypotension (determined throughexamination by the investigator or designee) or history of severe dizziness orfainting on standing in the opinion of the investigator.

11. Has evidence of a clinically significant 12-lead ECG abnormality.

12. Has an average heart rate < 60 or > 100 bpm, systolic blood pressure (BP) < 90 or > 140 mmHg, or diastolic BP < 60 or > 90 mmHg, measured in 3 sequential positions (supine after 5 minutes; sitting after 1 minute; and standing after 2 minutes) andafter the sequence has been completed 3 times.

13. Has a history of alcohol abuse or prescription/illicit drug abuse within theprevious 5 years.

14. Has positive results on the urine drug screen or alcohol breath test indicative ofdrugs of abuse or alcohol use at screening.

15. Is receiving concurrent therapy that can interfere with the evaluation of efficacyor safety, such as any drug that in the investigator's opinion may exert significantsynergistic interactions with dexmedetomidine. Medications with potential cardiac effects (eg, hypotension, bradycardia) andmedications that may cause sedation (such as quetiapine [Seroquel®]), arepermissible if the subject has been on a stable dose for a minimum of 30 days priorto Screening and the investigator deems it appropriate. Medications given for the treatment of chronic agitation are permissible if thesubject has been on a stable dose for a minimum of 30 days prior to Screening.

16. Uses any natural health products (including chaparral, comfrey, germander, jin buhuan, kava, pennyroyal, skullcap, St. John's wort, or valerian, and excludingvitamins or mineral supplements) within 7 days prior to study drug administrationand throughout the study, unless in the opinion of the investigator or designee theproduct will not interfere with the study procedures or data integrity or compromisethe safety of the subject.

17. Had symptoms of an upper respiratory tract infection within 7 days prior to dosingof the study drug.

18. Utilized oral or injectable corticosteroids within 7 days prior to dosing of thestudy drug (intranasal and topical corticosteroid use during this time period isallowed).

19. Received any investigational product within 30 days prior to dosing of the studydrug.

20. Received DMTS in a previous clinical trial.

21. Has a Johns Hopkins Fall Risk Assessment Score of > 13.

22. In the opinion of the investigator or designee, is considered unsuitable for studyentry and/or is unlikely to comply with the study protocol for any reason.