Study Evaluating Intepirdine (RVT-101) in Subjects With Mild to Moderate Alzheimer's Disease on Donepezil: MINDSET Study

Alzheimer's Disease Clinical Trial

Official title:

A Phase 3, Double-blind, Randomized Study of RVT-101 Versus Placebo When Added to Existing Stable Donepezil Treatment in Subjects With Mild to Moderate Alzheimer's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02585934
• Other study ID #: RVT-101-3001
• Status: Completed
• Phase: Phase 3
• Start date: October 2015
• Est. completion date: September 2017

Study information

• Verified date: November 2018
• Source: Axovant Sciences Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 1315
• Est. completion date: September 2017
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

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.

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• RVT-101
once daily, oral, 35 mg tablets
• Placebo
once daily, oral, pill manufactured to match RVT-101 35 mg tablet

Locations

Country	Name	City	State
Argentina	AR060	Buenos Aires
Argentina	AR101	Buenos Aires
Argentina	AR012	Ciudad Autónoma de Buenos Aire
Argentina	AR027	Ciudad Autónoma de Buenos Aire
Argentina	AR028	Ciudad Autónoma de Buenos Aire
Argentina	AR035	Ciudad Autónoma de Buenos Aire
Argentina	AR040	Ciudad Autónoma de Buenos Aire
Argentina	AR081	Ciudad Autónoma de Buenos Aire
Argentina	AR084	Ciudad Autónoma de Buenos Aire
Argentina	AR160	Ciudad Autónoma de Buenos Aire
Argentina	AR051	Cordoba
Argentina	AR137	Cordoba
Argentina	AR041	La Plata	Buenos Aires
Argentina	AR130	La Plata	Buenos Aires
Argentina	AR210	Mendoza
Argentina	AR219	Mendoza
Argentina	AR059	Santiago del Estero
Australia	AU227	Caulfield
Australia	AU079	Chermside
Australia	AU032	Heidelberg West
Australia	AU062	Herston
Australia	AU011	Hornsby
Australia	AU138	West Perth
Bulgaria	BU125	Ruse
Bulgaria	BU131	Sofia
Bulgaria	BU198	Sofia
Bulgaria	BU073	Varna
Canada	CA236	Gatineau	Quebec
Canada	CA120	Kamloops	British Columbia
Canada	CA054	Kelowna	British Columbia
Canada	CA188	Kelowna	British Columbia
Canada	CA151	Medicine Hat	Alberta
Canada	CA147	Newmarket	Ontario
Canada	CA196	North York	Ontario
Canada	CA186	Penticton	British Columbia
Canada	CA237	Toronto	Ontario
Canada	CA141	West Vancouver	British Columbia
Chile	CH212	Antofagasta	II Región
Chile	CH061	Santiago	Región Metropolitana
Chile	CH075	Santiago	Región Metropolitana
Chile	CH076	Santiago	Region Metropolitana
Croatia	CR068	Zagreb
Croatia	CR069	Zagreb
Croatia	CR070	Zagreb
Croatia	CR083	Zagreb
Croatia	CR122	Zagreb
Czechia	CZ128	Praha 10
Czechia	CZ207	Praha 10
Czechia	CZ132	Praha 2
Czechia	CZ129	Praha 6
Czechia	CZ161	Rychnov nad Kneznou
France	FR231	Lille Cedex
France	FR182	Marseille Cedex 5
France	FR221	Paris Cedex
France	FR202	Villeurbanne
Germany	GE206	Bad Homburg
Germany	GE071	Berlin
Germany	GE091	Berlin
Germany	GE139	Berlin
Germany	GE230	Cologne
Germany	GE252	Ellwangen
Germany	GE180	Leipzig
Germany	GE228	Mannheim
Germany	GE017	Munchen
Germany	GE157	Nürnberg
Germany	GE098	Ulm
Germany	GE251	Westerstede
Italy	IT053	Brescia
Italy	IT124	Cefalù
Italy	IT030	Pavia
Italy	IT103	Perugia
Italy	IT029	Roma
Italy	IT072	Roma
Italy	IT183	Roma
Italy	IT175	Rome
Italy	IT085	Torino
Korea, Republic of	SK066	Busan
Korea, Republic of	SK067	Seoul
Korea, Republic of	SK190	Seoul
Poland	PO013	Bialystok
Poland	PO010	Bydgoszcz
Poland	PO024	Bydgoszcz
Poland	PO092	Katowice
Poland	PO107	Katowice
Poland	PO023	Krakow
Poland	PO025	Krakow
Poland	PO009	Poznan
Poland	PO014	Szczecin
Poland	PO074	Warszawa
Serbia	SE090	Belgrade
Serbia	SE164	Belgrade
Serbia	SE166	Belgrade
Serbia	SE193	Belgrade
Serbia	SE155	Kragujevac
Serbia	SE031	Novi Knezevac
Serbia	SE165	Vrsac
Singapore	SI026	Singapore
Singapore	SI052	Singapore
Slovakia	SL056	Banska Bystrica
Slovakia	SL192	Bratislava
Slovakia	SL200	Dubnica nad Váhom
Slovakia	SL191	Kosice
Slovakia	SL078	Krompachy
Slovakia	SL077	Svidnik
Spain	SP249	Alicante
Spain	SP021	Barcelona
Spain	SP022	Barcelona
Spain	SP176	Barcelona
Spain	SP250	Barcelona
Spain	SP019	Ceuta
Spain	SP194	Donostia
Spain	SP222	Getxo
Spain	SP018	Madrid
Spain	SP093	Madrid
Spain	SP184	Sant Cugat del Vallès
Spain	SP020	Terrassa
Taiwan	TA065	Kaohsiung
Taiwan	TA086	Taipei
Taiwan	TA121	Taoyuan
United Kingdom	UK063	Bath
United Kingdom	UK038	Blackpool
United Kingdom	UK233	Cambridge
United Kingdom	UK033	Cannock
United Kingdom	UK211	Epping
United Kingdom	UK234	Guildford
United Kingdom	UK055	Leeds
United Kingdom	UK039	London
United Kingdom	UK034	Manchester
United Kingdom	UK229	Norwich
United Kingdom	UK087	Oxford
United Kingdom	UK235	Plymouth
United Kingdom	UK100	Sheffield
United Kingdom	UK064	Southampton
United Kingdom	UK152	Southampton
United Kingdom	UK153	Swindon
United Kingdom	UK154	Warrington
United States	US001	Albany	New York
United States	US046	Atlanta	Georgia
United States	US048	Atlanta	Georgia
United States	US088	Atlantis	Florida
United States	US111	Baton Rouge	Louisiana
United States	US113	Beachwood	Ohio
United States	US135	Berlin	New Jersey
United States	US049	Brooklyn	New York
United States	US007	Brooksville	Florida
United States	US150	Chapel Hill	North Carolina
United States	US185	Charlotte	North Carolina
United States	US149	Charlottesville	Virginia
United States	US008	Cincinnati	Ohio
United States	US136	Cincinnati	Ohio
United States	US217	Columbus	Georgia
United States	US168	Encino	California
United States	US117	Fullerton	California
United States	US002	Hallandale Beach	Florida
United States	US179	Hamden	Connecticut
United States	US144	Hattiesburg	Mississippi
United States	US140	Hialeah	Florida
United States	US115	Houston	Texas
United States	US094	Las Vegas	Nevada
United States	US197	Lawrenceville	New Jersey
United States	US214	Los Angeles	California
United States	US057	Manchester	New Jersey
United States	US169	Media	Pennsylvania
United States	US110	Miami	Florida
United States	US216	Miami	Florida
United States	US215	Mount Arlington	New Jersey
United States	US097	New Hyde Park	New York
United States	US177	New Windsor	New York
United States	US044	New York	New York
United States	US142	New York	New York
United States	US116	Newton	Massachusetts
United States	US172	North Palm Beach	Florida
United States	US171	Norwich	Connecticut
United States	US143	Orem	Utah
United States	US003	Orlando	Florida
United States	US189	Pasadena	California
United States	US256	Pensacola	Florida
United States	US187	Philadelphia	Pennsylvania
United States	US112	Phoenix	Arizona
United States	US162	Plains	Pennsylvania
United States	US134	Portland	Oregon
United States	US174	Quincy	Massachusetts
United States	US096	Rancho Mirage	California
United States	US043	San Antonio	Texas
United States	US0195	Santa Ana	California
United States	US119	Shaker Heights	Ohio
United States	US095	Shreveport	Louisiana
United States	US016	Simi Valley	California
United States	US170	Spokane	Washington
United States	US037	Tampa	Florida
United States	US042	Tampa	Florida
United States	US106	Temecula	California
United States	US004	The Villages	Florida
United States	US209	Toms River	New Jersey
United States	US220	Tucson	Arizona
United States	US036	West Long Branch	New Jersey
United States	US148	Willow Grove	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Axovant Sciences Ltd.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Bulgaria,  Canada,  Chile,  Croatia,  Czechia,  France,  Germany,  Italy,  Korea, Republic of,  Poland,  Serbia,  Singapore,  Slovakia,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Alzheimer's Disease Assessment Scale - Cognitive Subscale 11 Items (ADAS-Cog-11) Score Change From Baseline to Week 24	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.	Baseline, 24 weeks
Primary	Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Score Change From Baseline to Week 24	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	Baseline, 24 weeks
Secondary	Clinical Global Impression of Change - Plus Caregiver Interview (CIBIC+) Score at Week 24	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	24 weeks
Secondary	The Dependence Scale (DS) Score Change From Baseline to Week 24	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.	Baseline, 24 weeks
Secondary	Neuropsychiatric Inventory (NPI) Score Change From Baseline to 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.	Baseline and Week 24
Secondary	ADAS-Cog-13 Score Change From Baseline to Week 24	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.	Baseline, 24 weeks
Secondary	Measurement of Concentrations of RVT-101 (Intepirdine) in Plasma	Measurement collected at timepoints Week 6, Week 12, Week 18, and Week 24	Week 6, Week 12, Week 18, Week 24

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