Study Evaluating Intepirdine (RVT-101) in Subjects With Mild to Moderate Alzheimer's Disease on Donepezil: MINDSET Study
- Registration Number
- NCT02585934
- Lead Sponsor
- Axovant Sciences Ltd.
- Brief Summary
This study seeks to confirm a demonstrated treatment effect of intepirdine (RVT-101) as an adjunctive therapy to donepezil for the treatment of subjects with Alzheimer's disease.
- Detailed Description
This Phase 3 study seeks to confirm a demonstrated treatment effect of intepirdine (RVT-101) on both cognition and activities of daily living when added to stable donepezil treatment in subjects with mild-to-moderate Alzheimer's disease after 24 weeks of double-blind treatment. This study will also provide further information on the safety and tolerability of the 35-mg dose of intepirdine (RVT-101) when used in combination with donepezil compared to donepezil alone. This study is being conducted under the agreement of a Special Protocol Assessment by FDA. Subjects completing this study will be eligible to enroll in a 12 month open-label study of RVT-101 (RVT-101-3002) in which concomitant medications for the treatment of Alzheimer's disease including memantine will be allowed.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1315
- Male or female subject with AD
- Ongoing donepezil therapy for AD
- An MMSE score 12 to 24 inclusive at Screening; MMSE score 10-26 inclusive at Baseline
- Hachinski Ischaemia score less than or equal to 4 at Screening.
- If female, subject must be: a. of non-childbearing potential or surgically sterile; or, b. willing to use an adequate methods of birth control. Male subjects who are sexually active will also be required to use an adequate form of birth control.
- Subject has the ability to comply with procedures for cognitive and other testing in the opinion of the investigator.
- Subject has a reliable caregiver who is willing to report on subject's status throughout the study.
Other Causes for Dementia
- Diagnosis of vascular dementia
- Atypical clinical features or clinical course of dementia that would lead the investigator to conclude symptoms are more likely due to an alternate dementia diagnosis including, but not limited to, frontotemporal dementia, Lewy body dementia, or others.
Confounding Medical Conditions
- History of significant psychiatric illness such as schizophrenia or bipolar affective disorder or any other significant psychiatric illness that in the opinion of the investigator would interfere with participation in the study;
- Any clinically relevant concomitant disease, which, in the opinion of the investigator, makes the subject unsuitable for inclusion in the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description RVT-101 RVT-101 RVT-101 adjunct to 5 mg or 10 mg donepezil Placebo Placebo Placebo adjunct to 5 mg or 10 mg donepezil
- Primary Outcome Measures
Name Time Method Alzheimer's Disease Assessment Scale - Cognitive Subscale 11 Items (ADAS-Cog-11) Score Change From Baseline to Week 24 Baseline, 24 weeks The 11-item ADAS-Cog assesses a range of cognitive abilities including memory, comprehension, orientation in time and place, and spontaneous speech. The ADAS-Cog-11 total score range is from 0 to 70, with a higher score indicating more severe cognitive impairment.
Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Score Change From Baseline to Week 24 Baseline, 24 weeks The ADCS-ADL scale measures functional impairment in terms of activities of daily living. The score ranges from 0 to 78. The lower the score, the greater the impairment; higher scores indicate better (more desirable) function
- Secondary Outcome Measures
Name Time Method Clinical Global Impression of Change - Plus Caregiver Interview (CIBIC+) Score at Week 24 24 weeks The CIBIC+ assessment measures the global functioning of the subject. The CIBIC+ is scored as a seven-point categorical rating, ranging from a score of 1 (indicating "very much improved"), to a score of 4 (indicating "no change"), or to a score of 7 (indicating "very much worse.") Lower CIBIC+ scores indicate better (more desirable) function
The Dependence Scale (DS) Score Change From Baseline to Week 24 Baseline, 24 weeks The DS measures the amount of assistance patients with dementia require in performing daily activities. The scale consists of 13 items, representing a range of severity from mild to severe levels of dependency. The score range is from 0 to 15 with higher scores indicating greater dependency.
Neuropsychiatric Inventory (NPI) Score Change From Baseline to Week 24 Baseline and Week 24 The NPI is a behavior rating scale composed of a 12-item structured interview of the caregiver that is scored from 0 to 144 (the higher the score, the greater the psychiatric disturbance). It assesses 12 behavioral disturbances occurring in dementia patients: delusions, hallucinations, agitation, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor activity, night-time behavior disturbances, and eating disturbances. Both the frequency and the severity of each behavior are determined.
ADAS-Cog-13 Score Change From Baseline to Week 24 Baseline, 24 weeks 13-item ADAS-Cog assesses a range of cognitive abilities including memory, comprehension, orientation in time and place, and spontaneous speech. Most items are evaluated by tests, but some are dependent on clinician ratings on a 5-point scale. The ADAS-Cog-13 is the ADAS-Cog-11 with 2 additional items: delayed word recall and total digit cancellation. Scores for the ADAS-Cog-13 range from 0 to 85 with higher scores indicating greater dysfunction.
Measurement of Concentrations of RVT-101 (Intepirdine) in Plasma Week 6, Week 12, Week 18, Week 24 Measurement collected at timepoints Week 6, Week 12, Week 18, and Week 24
Trial Locations
- Locations (197)
US046
🇺🇸Atlanta, Georgia, United States
US117
🇺🇸Fullerton, California, United States
US094
🇺🇸Las Vegas, Nevada, United States
US008
🇺🇸Cincinnati, Ohio, United States
US115
🇺🇸Houston, Texas, United States
PO023
🇵🇱Krakow, Poland
PO014
🇵🇱Szczecin, Poland
SE090
🇷🇸Belgrade, Serbia
CA120
🇨🇦Kamloops, British Columbia, Canada
SL077
🇸🇰Svidnik, Slovakia
CH075
🇨🇱Santiago, Región Metropolitana, Chile
US119
🇺🇸Shaker Heights, Ohio, United States
US187
🇺🇸Philadelphia, Pennsylvania, United States
US116
🇺🇸Newton, Massachusetts, United States
US142
🇺🇸New York, New York, United States
US044
🇺🇸New York, New York, United States
US113
🇺🇸Beachwood, Ohio, United States
US185
🇺🇸Charlotte, North Carolina, United States
US162
🇺🇸Plains, Pennsylvania, United States
US170
🇺🇸Spokane, Washington, United States
US143
🇺🇸Orem, Utah, United States
AR040
🇦🇷Ciudad Autónoma de Buenos Aire, Argentina
AR219
🇦🇷Mendoza, Argentina
AR137
🇦🇷Cordoba, Argentina
AR051
🇦🇷Cordoba, Argentina
AU227
🇦🇺Caulfield, Australia
AU079
🇦🇺Chermside, Australia
AU062
🇦🇺Herston, Australia
BU125
🇧🇬Ruse, Bulgaria
CA188
🇨🇦Kelowna, British Columbia, Canada
CA186
🇨🇦Penticton, British Columbia, Canada
BU073
🇧🇬Varna, Bulgaria
CA151
🇨🇦Medicine Hat, Alberta, Canada
CA196
🇨🇦North York, Ontario, Canada
CA147
🇨🇦Newmarket, Ontario, Canada
CA141
🇨🇦West Vancouver, British Columbia, Canada
CA237
🇨🇦Toronto, Ontario, Canada
CH212
🇨🇱Antofagasta, II Región, Chile
CH076
🇨🇱Santiago, Region Metropolitana, Chile
CH061
🇨🇱Santiago, Región Metropolitana, Chile
CR070
🇭🇷Zagreb, Croatia
CA236
🇨🇦Gatineau, Quebec, Canada
CR069
🇭🇷Zagreb, Croatia
CR083
🇭🇷Zagreb, Croatia
CR122
🇭🇷Zagreb, Croatia
CZ128
🇨🇿Praha 10, Czechia
CZ207
🇨🇿Praha 10, Czechia
FR182
🇫🇷Marseille Cedex 5, France
CR068
🇭🇷Zagreb, Croatia
CZ132
🇨🇿Praha 2, Czechia
CZ129
🇨🇿Praha 6, Czechia
FR221
🇫🇷Paris Cedex, France
FR202
🇫🇷Villeurbanne, France
FR231
🇫🇷Lille Cedex, France
GE139
🇩🇪Berlin, Germany
GE252
🇩🇪Ellwangen, Germany
GE091
🇩🇪Berlin, Germany
GE206
🇩🇪Bad Homburg, Germany
GE230
🇩🇪Cologne, Germany
GE180
🇩🇪Leipzig, Germany
GE228
🇩🇪Mannheim, Germany
GE098
🇩🇪Ulm, Germany
GE017
🇩🇪Munchen, Germany
GE157
🇩🇪Nürnberg, Germany
GE251
🇩🇪Westerstede, Germany
IT053
🇮🇹Brescia, Italy
IT029
🇮🇹Roma, Italy
IT124
🇮🇹Cefalù, Italy
IT030
🇮🇹Pavia, Italy
IT072
🇮🇹Roma, Italy
IT175
🇮🇹Rome, Italy
SK067
🇰🇷Seoul, Korea, Republic of
PO024
🇵🇱Bydgoszcz, Poland
PO010
🇵🇱Bydgoszcz, Poland
SK190
🇰🇷Seoul, Korea, Republic of
IT085
🇮🇹Torino, Italy
PO092
🇵🇱Katowice, Poland
PO025
🇵🇱Krakow, Poland
PO107
🇵🇱Katowice, Poland
PO009
🇵🇱Poznan, Poland
PO074
🇵🇱Warszawa, Poland
SE164
🇷🇸Belgrade, Serbia
SE031
🇷🇸Novi Knezevac, Serbia
SE193
🇷🇸Belgrade, Serbia
SE165
🇷🇸Vrsac, Serbia
SI052
🇸🇬Singapore, Singapore
SL200
🇸🇰Dubnica nad Váhom, Slovakia
SI026
🇸🇬Singapore, Singapore
SL056
🇸🇰Banska Bystrica, Slovakia
SL192
🇸🇰Bratislava, Slovakia
SP022
🇪🇸Barcelona, Spain
SP249
🇪🇸Alicante, Spain
SP194
🇪🇸Donostia, Spain
SL078
🇸🇰Krompachy, Slovakia
SP021
🇪🇸Barcelona, Spain
SP176
🇪🇸Barcelona, Spain
SP093
🇪🇸Madrid, Spain
SP019
🇪🇸Ceuta, Spain
SP020
🇪🇸Terrassa, Spain
SP250
🇪🇸Barcelona, Spain
SP018
🇪🇸Madrid, Spain
SP222
🇪🇸Getxo, Spain
SP184
🇪🇸Sant Cugat del Vallès, Spain
TA065
🇨🇳Kaohsiung, Taiwan
TA086
🇨🇳Taipei, Taiwan
TA121
🇨🇳Taoyuan, Taiwan
UK211
🇬🇧Epping, United Kingdom
UK063
🇬🇧Bath, United Kingdom
UK038
🇬🇧Blackpool, United Kingdom
UK233
🇬🇧Cambridge, United Kingdom
UK033
🇬🇧Cannock, United Kingdom
UK055
🇬🇧Leeds, United Kingdom
UK034
🇬🇧Manchester, United Kingdom
UK039
🇬🇧London, United Kingdom
UK234
🇬🇧Guildford, United Kingdom
UK100
🇬🇧Sheffield, United Kingdom
UK154
🇬🇧Warrington, United Kingdom
UK229
🇬🇧Norwich, United Kingdom
UK087
🇬🇧Oxford, United Kingdom
UK064
🇬🇧Southampton, United Kingdom
UK153
🇬🇧Swindon, United Kingdom
UK152
🇬🇧Southampton, United Kingdom
UK235
🇬🇧Plymouth, United Kingdom
SK066
🇰🇷Busan, Korea, Republic of
US168
🇺🇸Encino, California, United States
US220
🇺🇸Tucson, Arizona, United States
US214
🇺🇸Los Angeles, California, United States
US096
🇺🇸Rancho Mirage, California, United States
US016
🇺🇸Simi Valley, California, United States
US0195
🇺🇸Santa Ana, California, United States
US106
🇺🇸Temecula, California, United States
US179
🇺🇸Hamden, Connecticut, United States
US171
🇺🇸Norwich, Connecticut, United States
US088
🇺🇸Atlantis, Florida, United States
US007
🇺🇸Brooksville, Florida, United States
US216
🇺🇸Miami, Florida, United States
US002
🇺🇸Hallandale Beach, Florida, United States
US140
🇺🇸Hialeah, Florida, United States
US172
🇺🇸North Palm Beach, Florida, United States
US110
🇺🇸Miami, Florida, United States
US256
🇺🇸Pensacola, Florida, United States
US048
🇺🇸Atlanta, Georgia, United States
US004
🇺🇸The Villages, Florida, United States
US217
🇺🇸Columbus, Georgia, United States
US095
🇺🇸Shreveport, Louisiana, United States
US111
🇺🇸Baton Rouge, Louisiana, United States
US174
🇺🇸Quincy, Massachusetts, United States
US144
🇺🇸Hattiesburg, Mississippi, United States
US057
🇺🇸Manchester, New Jersey, United States
US197
🇺🇸Lawrenceville, New Jersey, United States
US135
🇺🇸Berlin, New Jersey, United States
US215
🇺🇸Mount Arlington, New Jersey, United States
US209
🇺🇸Toms River, New Jersey, United States
US001
🇺🇸Albany, New York, United States
US049
🇺🇸Brooklyn, New York, United States
US036
🇺🇸West Long Branch, New Jersey, United States
US097
🇺🇸New Hyde Park, New York, United States
US177
🇺🇸New Windsor, New York, United States
US136
🇺🇸Cincinnati, Ohio, United States
US169
🇺🇸Media, Pennsylvania, United States
US148
🇺🇸Willow Grove, Pennsylvania, United States
US149
🇺🇸Charlottesville, Virginia, United States
AR041
🇦🇷La Plata, Buenos Aires, Argentina
AR130
🇦🇷La Plata, Buenos Aires, Argentina
AR101
🇦🇷Buenos Aires, Argentina
AR060
🇦🇷Buenos Aires, Argentina
AR084
🇦🇷Ciudad Autónoma de Buenos Aire, Argentina
AR027
🇦🇷Ciudad Autónoma de Buenos Aire, Argentina
AR160
🇦🇷Ciudad Autónoma de Buenos Aire, Argentina
AR012
🇦🇷Ciudad Autónoma de Buenos Aire, Argentina
AR081
🇦🇷Ciudad Autónoma de Buenos Aire, Argentina
AR028
🇦🇷Ciudad Autónoma de Buenos Aire, Argentina
AR035
🇦🇷Ciudad Autónoma de Buenos Aire, Argentina
AR210
🇦🇷Mendoza, Argentina
AR059
🇦🇷Santiago del Estero, Argentina
AU032
🇦🇺Heidelberg West, Australia
AU011
🇦🇺Hornsby, Australia
AU138
🇦🇺West Perth, Australia
BU131
🇧🇬Sofia, Bulgaria
BU198
🇧🇬Sofia, Bulgaria
CA054
🇨🇦Kelowna, British Columbia, Canada
CZ161
🇨🇿Rychnov nad Kneznou, Czechia
GE071
🇩🇪Berlin, Germany
SE166
🇷🇸Belgrade, Serbia
IT103
🇮🇹Perugia, Italy
IT183
🇮🇹Roma, Italy
PO013
🇵🇱Bialystok, Poland
SE155
🇷🇸Kragujevac, Serbia
SL191
🇸🇰Kosice, Slovakia
US189
🇺🇸Pasadena, California, United States
US037
🇺🇸Tampa, Florida, United States
US042
🇺🇸Tampa, Florida, United States
US112
🇺🇸Phoenix, Arizona, United States
US003
🇺🇸Orlando, Florida, United States
US150
🇺🇸Chapel Hill, North Carolina, United States
US134
🇺🇸Portland, Oregon, United States
US043
🇺🇸San Antonio, Texas, United States