Efficacy, Safety and Tolerability Study of AVP-923 (Dextromethorphan/Quinidine) for Treatment of Symptoms of Agitation in Participants With Alzheimer's Disease
Agitation · Alzheimer's Disease
Bottom Line
View on ClinicalTrials.gov: NCT01584440 ↗Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- AVP-923-20 (Drug); Placebo (Drug); AVP-923-30 (Drug)
- Age
- Adult, Older Adult · 50+ yrs
- Sex
- All
- Sponsor
- Avanir Pharmaceuticals
- Primary completion
- Jul 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 |
-1.7; -3.3; -0.8; -2.0 | <=0.001 sig |
| SECONDARY Number of Participants With the Indicated Type of Adverse Event |
93; 55; 8; 4; 0; 0 | — |
| SECONDARY Change in the Total NPI Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 |
-8.5; -13.5; -2.5; -6.0 | 0.014 sig |
| SECONDARY Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 |
-0.6; -0.8; -0.1; 0.2; -1.0; -0.9 | 0.444 |
| SECONDARY Change in the Sum of the Agitation/Aggression, Irritability/Lability, Disinhibition, and Aberrant Motor Behavior NPI Domain (NPI4D) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 |
-4.0; -7.6; -1.9; -4.6 | <=0.001 sig |
| SECONDARY Change in the Sum of the Agitation/Aggression, Irritability/Lability, Anxiety, and Aberrant Motor Behavior NPI Domain (NPI4A) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 |
-4.5; -7.3; -1.4; -4.8 | 0.001 sig |
| SECONDARY Change in the Total Neuropsychiatric Inventory-Caregiver Distress Score (NPI-CDS) From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 |
-3.6; -6.6; -2.0; -2.6 | 0.014 sig |
| SECONDARY Change in the NPI-CDS for the Agitation/Aggression Domain From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 |
-0.6; -1.4; -0.7; -0.5 | 0.010 sig |
| SECONDARY Change in the NPI-CDS NPI4D Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 |
-1.5; -3.3; -1.2; -1.8 | 0.002 sig |
| SECONDARY Change in the NPI-CDS NPI4A Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 |
-1.7; -3.3; -1.0; -1.5 | 0.008 sig |
| SECONDARY Change in the Caregiver Strain Index (CSI) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 |
-0.6; -1.2; 0.1; -0.2 | 0.050 |
| SECONDARY Change in the Cornell Scale for Depression in Dementia (CSDD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 |
0.6; -1.0; -0.7; -0.9 | 0.020 sig |
| SECONDARY Change in the Mini-Mental State Examination (MMSE) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline), as Analyzed by the Specified SPCD Methodology |
-0.3; 0.2; -0.5; 0.3 | 0.053 |
| SECONDARY Change in the Quality of Life-Alzheimer's Disease (QoL-AD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 |
0.3; 0.4; 0.9; -0.3; -0.0; 1.3 | 0.469 |
| SECONDARY Change in the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 |
-0.8; -0.9; -0.6; -2.0 | 0.163 |
| SECONDARY Change in the NPI Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 8 and Day 22 and From Day 36 (Stage 2 Baseline) to Day 43 and Day 57 |
-1.4; -2.2; -1.6; -2.7; -1.3; -0.5 | 0.279 |
| SECONDARY Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) |
1; 8; 13; 22; 43; 28 | 0.0001 sig |
| SECONDARY Number of Participants With the Indicated Response on the mADCS-CGIC Scale Agitation Domain at Day 70 Compared to Their Response at Day 36 (Stage 2 Baseline) |
4; 0; 2; 11; 8; 15 | 0.0266 sig |
| SECONDARY Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) |
2; 10; 23; 24; 30; 20 | 0.002 sig |
| SECONDARY Number of Participants With the Indicated Categorical Response on the PGI-C for the Caregiver Domain at Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) |
5; 9; 9; 26; 17; 25 | 0.0048 sig |
| SECONDARY Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use |
9; 8; 13; 1; 0; 1 | — |
| SECONDARY Number of Participants Using Rescue Medications |
5; 11; 7; 0; 3; 1 | — |
Summary
Eligibility Criteria
Key Inclusion Criteria
Diagnosis of probable Alzheimer's disease (AD).
The participant has clinically significant symptoms of agitation secondary to AD, that interfere with daily routine and for which a prescription medication is deemed indicated, in the opinion of the investigator.
Either out-patients or residents of an assisted-living facility or a skilled nursing home.
CGI-S score is ≥ 4 (moderately ill) at screening and baseline.
Mini Mental State Examination (MMSE) score at screening between 8 and 28 (inclusive).
Caregiver who is able and willing to comply with all required study procedures, ensuring that the participant attends all study visits and takes the study medication as instructed. In order to qualify as a caregiver for this study, the individual should spend time with the participant for a minimum of 4 hours on 4 separate days per week.
Key Exclusion Criteria
Participant has other type of dementia (e.g., vascular dementia, frontotemporal dementia, Parkinson's disease, substance-induced dementia).
Participant with co-existent clinically significant or unstable systemic diseases that could confound the interpretation of the safety results of the study (e.g. malignancy, poorly controlled diabetes, poorly controlled hypertension, unstable pulmonary, renal or hepatic disease, unstable ischemic cardiac disease, dilated cardiomyopathy, certain cardiac conduction abnormalities including QTc prolongation, or unstable valvular heart disease).
Participant with myasthenia gravis.
Data sourced from ClinicalTrials.gov (NCT01584440). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.