A Phase 3, multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy, safety, and tolerability of AVP-786 (deudextromethorphan hydrobromide [d6-DM]/quinidine sulfate [Q]) for the treatment of agitation in patients with dementia of the Alzheimer*s type.
- Conditions
- Agitationdue to Alzheimerrestlessness1005716710012272
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 22
1. Males and females 50 to 90 years of age (inclusive) at the time of informed
consent.
2. Diagnosis of probable Alzheimer*s disease according to the 2011 NIA-AA
working groups criteria. Either outpatients or residents of an assisted living
facility, a skilled nursing home, a dementia unit, or any other type of
facility providing long-term care.
3. MMSE score between 8 and 24 (inclusive) at Screening and Baseline.
4. Patient has clinically significant, moderate-to-severe agitation for at
least 2 weeks prior to Screening that interferes with daily routine per the
Investigator*s judgment.
5. Patients who require pharmacotherapy for the treatment of agitation per the
Investigator*s judgment, after:
* An evaluation of reversible factors (eg, pain, infection, or polypharmacy),
and
* A course of nonpharmacological interventions (eg, redirecting behavior, group
activities, music therapy).
6. Diagnosis of agitation must meet the International Psychogeriatric
Association (IPA) provisional definition of agitation.
7. NPI-AA total score (frequency × severity) must be >= 4 at Screening and
Baseline.
8. Patient must meet an additional predetermined blinded eligibility criterion.
9. Patient has stable cardiac, pulmonary, hepatic, and renal function per the
Investigator*s judgment.
10. No clinically significant findings on the Screening ECGs based on central
review and on the Baseline predose ECG based on the machine read and
Investigator*s evaluation.
11. Women who are of childbearing potential and are sexually active must use an
effective method of birth control for at least 1 month prior to the Baseline,
during participation in the study, and for at least 30 days after the last dose
of study drug. The following requirements must be met:
* Women who are of childbearing potential must use 2 of the following
precautions in order to minimize the risk of failure of 1 method of birth
control: vasectomy, tubal ligation, vaginal diaphragm, intrauterine device,
birth control pills, birth control depot injection, birth control implant, or
condom with spermicide or sponge with spermicide. Periodic abstinence (eg,
calendar, ovulation, symptothermal, post-ovulation methods), declaration of
abstinence for the duration of exposure to study drug, or withdrawal are not
acceptable methods of contraception.
* Women who are sterile (ie, had an oophorectomy and/or hysterectomy),
postmenopausal (defined as 12 consecutive months with no menses without an
alternative medical cause), or practice true abstinence (when this method is in
line with the preferred and usual lifestyle of the patient) are exempt from
this requirement.
* Women who are lactating, pregnant, or plan to become pregnant are not
eligible for participation in the study.
12. For restricted and prohibited concomitant medications, patients willing and
able to meet all protocol requirements for duration of stability or washout
prior to study entry and during the study (see protocol Table 3 Restricted and
Prohibited Concomitant Medications and Appendix 1 Prohibited Concomitant
Medications).
13. Caregiver must be willing and able to comply with all study procedures,
including adherence to administering study drug and not administering any
prohibited medications during the study. The caregiver must spend a minimum of
1. Caregiver is unwilling or unable, in the opinion of the Investigator, to
comply with study instructions. 2. Patient has dementia predominantly of
non-Alzheimer*s type (eg, vascular dementia, frontotemporal dementia,
Parkinson*s disease, substance-induced dementia). 3. Patients with symptoms of
agitation that are not secondary to Alzheimer*s dementia (eg, secondary to
pain, other psychiatric disorder, or delirium). 4. Patients who have been
diagnosed with an Axis 1 disorder (Diagnostic and Statistical Manual of Mental
Disorders, 5th Edition, Text Revision [DSM-5] criteria) including, but not
limited to: * Schizophrenia, schizoaffective disorder, or other psychotic
disorders not related to dementia * Bipolar I or II disorder, bipolar disorder
not otherwise specified * Current Major Depressive Episode: Patients with a
history of major depressive disorder, that is currently not symptomatic, are
eligible. Patients currently on a stable dose(s) of allowed antidepressant
medication(s) for at least 3 months prior to the Screening visit are eligible.
5. Patients with myasthenia gravis (contraindication for quinidine). 6.
Patients with any personal history of complete heart block, QTc prolongation,
or torsades de pointes. a. Screening and Baseline predose QT interval corrected
for heart rate using the Fridericia*s formula (QTcF) of > 450 msec for males
and > 470 msec for females unless due to ventricular pacing (See Section
8.1.5). Screening ECGs will be based on central review. Baseline predose ECG
will be based on the machine read and Investigator*s evaluation; if the QTcF
result from the machine read is exclusionary, do not administer study drug and
please contact a Medical Monitor. b. Presence of premature ventricular
contractions (PVCs) as evaluated by a central reader and deemed clinically
significant by the Investigator. 7. Patients with any family history of
congenital QT interval prolongation syndrome. 8. Patients with known
hypersensitivity to DM, Q, opiate drugs (codeine, etc), or any other ingredient
of the study drug. 9. Patients who have ever received DM co-administered with Q
or d6-DM co-administered with Q. 10. Patients who would be likely to require a
prohibited concomitant medication during the study (see Table 3, Restricted and
Prohibited Concomitant Medications and Appendix 1 Prohibited Concomitant
Medications). 11. Patients with co-existent clinically significant or unstable
systemic diseases that could confound the interpretation of the safety results
of the study (eg, malignancy [except skin basal cell carcinoma], poorly
controlled diabetes, poorly controlled hypertension, unstable pulmonary, renal
or hepatic disease, unstable ischemic cardiac disease, dilated cardiomyopathy,
or unstable valvular heart disease). Certain other nonmetastatic cancer may be
allowed. Each case is to be evaluated individually with a Medical Monitor. 12.
Patients who are currently participating in or who have participated in other
interventional (drug or device) clinical study, or found to be a *Virtually
Certain* match in Clinical Trial Subject Database (CTSdatabase) with a patient
who has participated in another interventional drug or device study within 30
days of Baseline. 13. Patients with history of postural syncope or any history
of unexplained syncope (evaluated on
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method