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

• Sponsor: Axovant Sciences Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02585934
• Collaborator: (none)
• Enrollment: 1,315
• Locations: 197
• Arms: 2
• Actual Duration (Months): 23
• Patients Per Site: 6.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Drug: RVT-101; Drug: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1315 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Oct 1, 2015
• Actual Primary Completion Date: Sep 1, 2017
• Actual Study Completion Date: Sep 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RVT-101 RVT-101 adjunct to 5 mg or 10 mg donepezil	Drug: RVT-101; once daily, oral, 35 mg tablets
Placebo Comparator: Placebo Placebo adjunct to 5 mg or 10 mg donepezil	Drug: Placebo; once daily, oral, pill manufactured to match RVT-101 35 mg tablet

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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

1. 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

2. 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.

3. 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.

4. 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.

5. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	US112	Phoenix	Arizona	United States	85005
2	US220	Tucson	Arizona	United States	85704
3	US168	Encino	California	United States	91436
4	US117	Fullerton	California	United States	92835
5	US214	Los Angeles	California	United States	90024
6	US189	Pasadena	California	United States	91105
7	US096	Rancho Mirage	California	United States	92270
8	US0195	Santa Ana	California	United States	92705
9	US016	Simi Valley	California	United States	93065
10	US106	Temecula	California	United States	92591
11	US179	Hamden	Connecticut	United States	06518
12	US171	Norwich	Connecticut	United States	06360
13	US088	Atlantis	Florida	United States	33462
14	US007	Brooksville	Florida	United States	34601
15	US002	Hallandale Beach	Florida	United States	33009
16	US140	Hialeah	Florida	United States	33012
17	US216	Miami	Florida	United States	33137
18	US110	Miami	Florida	United States	33165
19	US172	North Palm Beach	Florida	United States	33408
20	US003	Orlando	Florida	United States	32806
21	US256	Pensacola	Florida	United States	32502
22	US037	Tampa	Florida	United States	33613
23	US042	Tampa	Florida	United States	33613
24	US004	The Villages	Florida	United States	32162
25	US048	Atlanta	Georgia	United States	30331
26	US046	Atlanta	Georgia	United States	30342
27	US217	Columbus	Georgia	United States	31909
28	US111	Baton Rouge	Louisiana	United States	70808
29	US095	Shreveport	Louisiana	United States	71104
30	US116	Newton	Massachusetts	United States	02459
31	US174	Quincy	Massachusetts	United States	02169
32	US144	Hattiesburg	Mississippi	United States	39401
33	US094	Las Vegas	Nevada	United States	89113
34	US135	Berlin	New Jersey	United States	08009
35	US197	Lawrenceville	New Jersey	United States	08648
36	US057	Manchester	New Jersey	United States	08759
37	US215	Mount Arlington	New Jersey	United States	07856
38	US209	Toms River	New Jersey	United States	08755
39	US036	West Long Branch	New Jersey	United States	07764
40	US001	Albany	New York	United States	12208
41	US049	Brooklyn	New York	United States	11235
42	US097	New Hyde Park	New York	United States	11040
43	US177	New Windsor	New York	United States	12553
44	US142	New York	New York	United States	10021
45	US044	New York	New York	United States	10022
46	US150	Chapel Hill	North Carolina	United States	27599
47	US185	Charlotte	North Carolina	United States	28270
48	US113	Beachwood	Ohio	United States	44122
49	US136	Cincinnati	Ohio	United States	45220
50	US008	Cincinnati	Ohio	United States	45227
51	US119	Shaker Heights	Ohio	United States	44122
52	US134	Portland	Oregon	United States	97210
53	US169	Media	Pennsylvania	United States	19063
54	US187	Philadelphia	Pennsylvania	United States	19102
55	US162	Plains	Pennsylvania	United States	18075
56	US148	Willow Grove	Pennsylvania	United States	19001
57	US115	Houston	Texas	United States	77074
58	US043	San Antonio	Texas	United States	78229
59	US143	Orem	Utah	United States	84058
60	US149	Charlottesville	Virginia	United States	22903
61	US170	Spokane	Washington	United States	99202
62	AR130	La Plata	Buenos Aires	Argentina	A1902AJU
63	AR041	La Plata	Buenos Aires	Argentina	B1900BOM
64	AR101	Buenos Aires		Argentina	B1828CKR
65	AR060	Buenos Aires		Argentina	C1199ABB
66	AR084	Ciudad Autónoma de Buenos Aire		Argentina	C1012AAR
67	AR027	Ciudad Autónoma de Buenos Aire		Argentina	C1058AAJ
68	AR012	Ciudad Autónoma de Buenos Aire		Argentina	C1111AAL
69	AR160	Ciudad Autónoma de Buenos Aire		Argentina	C1117ABH
70	AR040	Ciudad Autónoma de Buenos Aire		Argentina	C1405BCK
71	AR028	Ciudad Autónoma de Buenos Aire		Argentina	C1406BOA
72	AR081	Ciudad Autónoma de Buenos Aire		Argentina	C1425AHQ
73	AR035	Ciudad Autónoma de Buenos Aire		Argentina	C1428AQK
74	AR051	Cordoba		Argentina	X5000DCE
75	AR137	Cordoba		Argentina	X5000FJF
76	AR210	Mendoza		Argentina	M5501ACP
77	AR219	Mendoza		Argentina	M5502AHV
78	AR059	Santiago del Estero		Argentina	G4200DND
79	AU227	Caulfield		Australia	VIC3162
80	AU079	Chermside		Australia	QLD 4032
81	AU032	Heidelberg West		Australia	VIC 3081
82	AU062	Herston		Australia	QLD 4209
83	AU011	Hornsby		Australia	NSW 2077
84	AU138	West Perth		Australia	WA 6005
85	BU125	Ruse		Bulgaria	7003
86	BU131	Sofia		Bulgaria	1431
87	BU198	Sofia		Bulgaria	1632
88	BU073	Varna		Bulgaria	9000
89	CA151	Medicine Hat	Alberta	Canada	T1B4E7
90	CA120	Kamloops	British Columbia	Canada	V2C 1K7
91	CA054	Kelowna	British Columbia	Canada	V1Y 1Z9
92	CA188	Kelowna	British Columbia	Canada	V1Y 4N7
93	CA186	Penticton	British Columbia	Canada	V2A 5C8
94	CA141	West Vancouver	British Columbia	Canada	V7T 2Z3
95	CA147	Newmarket	Ontario	Canada	L3Y 5G8
96	CA196	North York	Ontario	Canada	M3B 2S7
97	CA237	Toronto	Ontario	Canada	M4G 0A1
98	CA236	Gatineau	Quebec	Canada	J8T8JI
99	CH212	Antofagasta	II Región	Chile	1270244
100	CH076	Santiago	Region Metropolitana	Chile	7560356
101	CH061	Santiago	Región Metropolitana	Chile	7510186
102	CH075	Santiago	Región Metropolitana	Chile	7520338
103	CR069	Zagreb		Croatia	10000
104	CR122	Zagreb		Croatia	10000
105	CR068	Zagreb		Croatia	10090
106	CR070	Zagreb		Croatia	10090
107	CR083	Zagreb		Croatia	10090
108	CZ128	Praha 10		Czechia	100 00
109	CZ207	Praha 10		Czechia	109 00
110	CZ132	Praha 2		Czechia	120 00
111	CZ129	Praha 6		Czechia	160 00
112	CZ161	Rychnov nad Kneznou		Czechia	516 01
113	FR231	Lille Cedex		France	59037
114	FR182	Marseille Cedex 5		France	13385
115	FR221	Paris Cedex		France	75013
116	FR202	Villeurbanne		France	69 100
117	GE206	Bad Homburg		Germany	61348
118	GE091	Berlin		Germany	10117
119	GE071	Berlin		Germany	12203
120	GE139	Berlin		Germany	13125
121	GE230	Cologne		Germany	50937
122	GE252	Ellwangen		Germany	73479
123	GE180	Leipzig		Germany	04107
124	GE228	Mannheim		Germany	68165
125	GE017	Munchen		Germany	81675
126	GE157	Nürnberg		Germany	90402
127	GE098	Ulm		Germany	89081
128	GE251	Westerstede		Germany	26655
129	IT053	Brescia		Italy	25125
130	IT124	Cefalù		Italy	90015
131	IT030	Pavia		Italy	27100
132	IT103	Perugia		Italy	06156
133	IT072	Roma		Italy	00168
134	IT183	Roma		Italy	00179
135	IT029	Roma		Italy	00189
136	IT175	Rome		Italy	00185
137	IT085	Torino		Italy	10 126
138	SK066	Busan		Korea, Republic of	49201
139	SK067	Seoul		Korea, Republic of	06351
140	SK190	Seoul		Korea, Republic of	07061
141	PO013	Bialystok		Poland	15-756
142	PO024	Bydgoszcz		Poland	85-080
143	PO010	Bydgoszcz		Poland	85-796
144	PO107	Katowice		Poland	40-123
145	PO092	Katowice		Poland	40-749
146	PO023	Krakow		Poland	30-349
147	PO025	Krakow		Poland	35-505
148	PO009	Poznan		Poland	61-853
149	PO014	Szczecin		Poland	70-111
150	PO074	Warszawa		Poland	01-697
151	SE164	Belgrade		Serbia	11 000
152	SE090	Belgrade		Serbia	11000
153	SE166	Belgrade		Serbia	11000
154	SE193	Belgrade		Serbia	11000
155	SE155	Kragujevac		Serbia	34000
156	SE031	Novi Knezevac		Serbia	23330
157	SE165	Vrsac		Serbia	26300
158	SI052	Singapore		Singapore	119074
159	SI026	Singapore		Singapore	308433
160	SL056	Banska Bystrica		Slovakia	97404
161	SL192	Bratislava		Slovakia	820 07
162	SL200	Dubnica nad Váhom		Slovakia	01841
163	SL191	Kosice		Slovakia	040 17
164	SL078	Krompachy		Slovakia	05342
165	SL077	Svidnik		Slovakia	08901
166	SP249	Alicante		Spain	03690
167	SP176	Barcelona		Spain	08003
168	SP022	Barcelona		Spain	08028
169	SP021	Barcelona		Spain	08035
170	SP250	Barcelona		Spain	08036
171	SP019	Ceuta		Spain	51003
172	SP194	Donostia		Spain	20014
173	SP222	Getxo		Spain	48993
174	SP018	Madrid		Spain	28040
175	SP093	Madrid		Spain	28046
176	SP184	Sant Cugat del Vallès		Spain	08190
177	SP020	Terrassa		Spain	08221
178	TA065	Kaohsiung		Taiwan	833
179	TA086	Taipei		Taiwan	100
180	TA121	Taoyuan		Taiwan	333
181	UK063	Bath		United Kingdom	BA1 3NG
182	UK038	Blackpool		United Kingdom	FY2 0JH
183	UK233	Cambridge		United Kingdom	CB21 5EF
184	UK033	Cannock		United Kingdom	WS11 0BN
185	UK211	Epping		United Kingdom	CM16 6TN
186	UK234	Guildford		United Kingdom	GU2 7YD
187	UK055	Leeds		United Kingdom	LS10 1DU
188	UK039	London		United Kingdom	W1G 9JF
189	UK034	Manchester		United Kingdom	M13 9NQ
190	UK229	Norwich		United Kingdom	NR2 3TD
191	UK087	Oxford		United Kingdom	OX3 9DU
192	UK235	Plymouth		United Kingdom	PL5 8BT
193	UK100	Sheffield		United Kingdom	S5 7JT
194	UK064	Southampton		United Kingdom	SO16 6YD
195	UK152	Southampton		United Kingdom	SO30 3JB
196	UK153	Swindon		United Kingdom	SN3 6BW
197	UK154	Warrington		United Kingdom	WA22 8WA

Sponsors and Collaborators

• Axovant Sciences Ltd.

Investigators

• Study Director: Ilise Lombardo, MD, Axovant Sciences, Inc., Vice President, Clinical Research

Study Documents (Full-Text)

• Study Protocol: Protocol - Apr 13, 2016
• Statistical Analysis Plan: Statistical Analysis Plan Document - Aug 9, 2017
• Statistical Analysis Plan: Statistical Analysis Plan Addendum Document - Sep 19, 2017

More Information

Publications

None provided.

• Responsible Party: Axovant Sciences Ltd.
• ClinicalTrials.gov Identifier: NCT02585934
• Other Study ID Numbers: RVT-101-3001
• First Posted: Oct 26, 2015
• Last Update Posted: Dec 5, 2018
• Last Verified: Nov 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Axovant Sciences Ltd.: Alzheimer's disease; RVT-101; donepezil; intepirdine; dementia
• Additional relevant MeSH terms: Alzheimer Disease

Study Results

Participant Flow

Pre-assignment Detail	2173 participants signed consent and were screened for participation. Of these, 1470 entered a 3-week single-blind placebo run-in period with treatment with placebo qd + stable dose of donepezil 5 or 10 mg qd. There was an overlap between the participants from the run-in period and the participants that were randomized during the treatment period.

Arm/Group Title	RVT-101	Placebo
Arm/Group Description	RVT-101 adjunct to 5 mg or 10 mg donepezil RVT-101: once daily, oral, 35 mg tablets for up to 27 weeks	Placebo adjunct to 5 mg or 10 mg donepezil Placebo: once daily, oral, pill manufactured to match RVT-101 35 mg tablet for up to 27 weeks
Period Title: Overall Study
STARTED	661	654
Safety Population	656	651
Intent to Treat (ITT)	643	633
Per Protocol (PP)	603	582
COMPLETED	592	581
NOT COMPLETED	69	73

Baseline Characteristics

Arm/Group Title	RVT-101	Placebo	Total
Arm/Group Description	RVT-101 adjunct to 5 mg or 10 mg donepezil RVT-101: once daily, oral, 35 mg tablets for up to 27 weeks	Placebo adjunct to 5 mg or 10 mg donepezil Placebo: once daily, oral, pill manufactured to match RVT-101 35 mg tablet for up to 27 weeks	Total of all reporting groups
Overall Participants	643	633	1276
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	72.7	72.5	72.6
Age, Customized (Count of Participants)
< 74 years	309 48.1%	312 49.3%	621 48.7%
>/= 74 years	334 51.9%	321 50.7%	655 51.3%
< 65 years	98 15.2%	97 15.3%	195 15.3%
>/=65 years	545 84.8%	536 84.7%	1081 84.7%
Sex: Female, Male (Count of Participants)
Female	386 60%	394 62.2%	780 61.1%
Male	257 40%	239 37.8%	496 38.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	120 18.7%	108 17.1%	228 17.9%
Not Hispanic or Latino	518 80.6%	519 82%	1037 81.3%
Unknown or Not Reported	5 0.8%	6 0.9%	11 0.9%
Race/Ethnicity, Customized (Count of Participants)
White	595 92.5%	592 93.5%	1187 93%
Black or African American	12 1.9%	10 1.6%	22 1.7%
Asian	27 4.2%	20 3.2%	47 3.7%
American Indian or Alaska Native	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.2%	1 0.1%
Others	2 0.3%	1 0.2%	3 0.2%
Not Applicable	3 0.5%	5 0.8%	8 0.6%
Missing	4 0.6%	4 0.6%	8 0.6%
BMI (kg/m^2) [Mean (Full Range) ]
Mean (Full Range) [kg/m^2]	26.4	26.5	26.4

Outcome Measures

1. Primary Outcome

Title	Alzheimer's Disease Assessment Scale - Cognitive Subscale 11 Items (ADAS-Cog-11) Score Change From Baseline to Week 24
Description	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.
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

ITT Population with data at both timepoints.

Arm/Group Title	RVT-101	Placebo
Arm/Group Description	RVT-101 adjunct to 5 mg or 10 mg donepezil RVT-101: once daily, oral, 35 mg tablets	Placebo adjunct to 5 mg or 10 mg donepezil Placebo: once daily, oral, pill manufactured to match RVT-101 35 mg tablet
Measure Participants	584	577
Least Squares Mean (Standard Error) [units on a scale]	0.39 (0.211)	0.75 (0.213)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RVT-101, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2249
	Comments	the threshold for statistical significance was p=0.05
	Method	Mixed Models Analysis
	Comments	Statistical Method: Mixed model for repeated measures
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-0.36
	Confidence Interval	(2-Sided) 95%; -0.95 to 0.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Score Change From Baseline to Week 24
Description	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
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

ITT Population with data at both endpoints

Arm/Group Title	RVT-101	Placebo
Arm/Group Description	RVT-101 adjunct to 5 mg or 10 mg donepezil RVT-101: once daily, oral, 35 mg tablets	Placebo adjunct to 5 mg or 10 mg donepezil Placebo: once daily, oral, pill manufactured to match RVT-101 35 mg tablet
Measure Participants	588	575
Least Squares Mean (Standard Error) [units on a scale]	-1.06 (0.289)	-0.97 (0.293)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RVT-101, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8260
	Comments	the threshold for statistical significance was p=0.05
	Method	Mixed Models Analysis
	Comments	Statistical Method: Mixed model for repeated measures
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-0.09
	Confidence Interval	(2-Sided) 95%; -0.90 to 0.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Clinical Global Impression of Change - Plus Caregiver Interview (CIBIC+) Score at Week 24
Description	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
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

ITT population at the Week 24 timepoint

Arm/Group Title	RVT-101	Placebo
Arm/Group Description	RVT-101 adjunct to 5 mg or 10 mg donepezil RVT-101: once daily, oral, 35 mg tablets	Placebo adjunct to 5 mg or 10 mg donepezil Placebo: once daily, oral, pill manufactured to match RVT-101 35 mg tablet
Measure Participants	577	568
Least Squares Mean (Standard Error) [units on a scale]	4.18 (0.037)	4.30 (0.037)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RVT-101, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0234
	Comments	the threshold for statistical significance was p=0.05
	Method	Mixed Models Analysis
	Comments	Statistical Method: Mixed model for repeated measures
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95%; -0.22 to -0.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	The Dependence Scale (DS) Score Change From Baseline to Week 24
Description	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.
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

ITT population at both timepoints

Arm/Group Title	RVT-101	Placebo
Arm/Group Description	RVT-101 adjunct to 5 mg or 10 mg donepezil RVT-101: once daily, oral, 35 mg tablets	Placebo adjunct to 5 mg or 10 mg donepezil Placebo: once daily, oral, pill manufactured to match RVT-101 35 mg tablet
Measure Participants	580	568
Least Squares Mean (Standard Error) [units on a scale]	0.30 (0.070)	0.17 (0.071)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RVT-101, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2096
	Comments	the threshold for statistical significance was p=0.05
	Method	Mixed Models Analysis
	Comments	Statistical Method: Mixed model for repeated measures
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	0.12
	Confidence Interval	(2-Sided) 95%; -0.07 to 0.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Neuropsychiatric Inventory (NPI) Score Change From Baseline to Week 24
Description	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.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

ITT Population at both timepoints

Arm/Group Title	RVT-101	Placebo
Arm/Group Description	RVT-101 adjunct to 5 mg or 10 mg donepezil RVT-101: once daily, oral, 35 mg tablets	Placebo adjunct to 5 mg or 10 mg donepezil Placebo: once daily, oral, pill manufactured to match RVT-101 35 mg tablet
Measure Participants	583	570
Least Squares Mean (Standard Error) [units on a scale]	-0.08 (0.339)	0.06 (0.344)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RVT-101, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7650
	Comments	the threshold for statistical significance was p=0.05
	Method	Mixed Models Analysis
	Comments	Statistical Method: Mixed model for repeated measures
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 95%; -1.09 to 0.80
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	ADAS-Cog-13 Score Change From Baseline to Week 24
Description	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.
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

ITT at both timepoints

Arm/Group Title	RVT-101	Placebo
Arm/Group Description	RVT-101 adjunct to 5 mg or 10 mg donepezil RVT-101: once daily, oral, 35 mg tablets	Placebo adjunct to 5 mg or 10 mg donepezil Placebo: once daily, oral, pill manufactured to match RVT-101 35 mg tablet
Measure Participants	583	576
Least Squares Mean (Standard Error) [units on a scale]	0.26 (0.233)	0.64 (0.236)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RVT-101, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2472
	Comments	the threshold for statistical significance was p=0.05
	Method	Mixed Models Analysis
	Comments	Statistical Method: Mixed model for repeated measures
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-0.38
	Confidence Interval	(2-Sided) 95%; -1.03 to 0.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Measurement of Concentrations of RVT-101 (Intepirdine) in Plasma
Description	Measurement collected at timepoints Week 6, Week 12, Week 18, and Week 24
Time Frame	Week 6, Week 12, Week 18, Week 24

Outcome Measure Data

Analysis Population Description

PK population at specified timepoints: Week 6, Week 12, Week 18, and Week 24

Arm/Group Title	RVT-101
Arm/Group Description	RVT-101 adjunct to 5 mg or 10 mg donepezil RVT-101: once daily, oral, 35 mg tablets for up to 27 weeks
Measure Participants	656
Summary Statistics at Week 6	201.11
Summary Statistics at Week 12	170.95
Summary Statistics at Week 18	198.69
Summary Statistics at Week 24	193.36

Adverse Events

Time Frame	Screening through post treatment (up to 33 weeks)
Arm/Group Title	RVT-101 Treatment		Placebo Treatment		Screening Period		Run-In Period		RVT-101 Post-Treatment		Placebo Post-Treatment
Arm/Group Description	RVT-101 adjunct to 5 mg or 10 mg donepezil RVT-101: once daily, oral, 35 mg tablets for up to 27 weeks		Placebo adjunct to 5 mg or 10 mg donepezil Placebo: once daily, oral, pill manufactured to match RVT-101 35 mg tablet for up to 27 weeks		Participants screened (0-4 weeks) prior to entering to the first dose of single-blind study medication (ie, prior to the Run-In period)		Placebo adjunct to 5 mg or 10 mg donepezil Placebo: once daily, oral, pill manufactured to match RVT-101 35 mg tablet (for 3 weeks)		Subjects reported adverse events after completing the treatment period. The Post-Treatment period - defined as up to 30 days post-last-dose		Subjects reported adverse events after completing the treatment period. The Post-Treatment period - defined as up to 30 days post-last-dose
All Cause Mortality
	RVT-101 Treatment		Placebo Treatment		Screening Period		Run-In Period		RVT-101 Post-Treatment		Placebo Post-Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/656 (0.5%)		2/651 (0.3%)		1/2173 (0%)		1/1470 (0.1%)		0/656 (0%)		1/651 (0.2%)
Serious Adverse Events
	RVT-101 Treatment		Placebo Treatment		Screening Period		Run-In Period		RVT-101 Post-Treatment		Placebo Post-Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/656 (6.1%)		44/651 (6.8%)		12/2173 (0.6%)		14/1470 (1%)		3/656 (0.5%)		3/651 (0.5%)
Blood and lymphatic system disorders
Anaemia	0/656 (0%)		0/651 (0%)		1/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Cardiac disorders
Myocardial infarction	1/656 (0.2%)		2/651 (0.3%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Atrial Fibrillation	1/656 (0.2%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Angina pectoris	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Angina unstable	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Atrioventricular block	0/656 (0%)		1/651 (0.2%)		1/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Cardiac arrest	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Cardiac failure congestive	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Cardio-respiratory arrest	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Mitral valve prolapse	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Pericardial effusion	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Right ventricular failure	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Sinus node dysfunction	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		1/1470 (0.1%)		0/656 (0%)		0/651 (0%)
Cardiac failure	0/656 (0%)		0/651 (0%)		1/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Ear and labyrinth disorders
Inner ear disorder	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Vertigo positonal	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Gastrointestinal disorders
Duodenal vascular ectasia	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Pancreatitis acute	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Proctitis	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Small intestinal obstruction	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Upper gastrointestinal haemorrhage	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Volvulus	0/656 (0%)		0/651 (0%)		1/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
General disorders
Chest pain	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Hypothermia	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Non-cardiac chest pain	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Asthenia	0/656 (0%)		0/651 (0%)		0/2173 (0%)		1/1470 (0.1%)		0/656 (0%)		0/651 (0%)
Gait disturbance	0/656 (0%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		1/656 (0.2%)		0/651 (0%)
Hepatobiliary disorders
Bile duct stone	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Cholecystitis	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Infections and infestations
Diverticulitis	2/656 (0.3%)		2/651 (0.3%)		0/2173 (0%)		1/1470 (0.1%)		0/656 (0%)		0/651 (0%)
Pneumonia	2/656 (0.3%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Urinary tract infection	1/656 (0.2%)		1/651 (0.2%)		1/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Appendicitis	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Cellulitis	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Gastroenteritis	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
lower respiratory tract infection	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Infected bite	0/656 (0%)		0/651 (0%)		0/2173 (0%)		1/1470 (0.1%)		0/656 (0%)		0/651 (0%)
Sepsis	0/656 (0%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		1/651 (0.2%)
Injury, poisoning and procedural complications
Fall	1/656 (0.2%)		3/651 (0.5%)		1/2173 (0%)		1/1470 (0.1%)		0/656 (0%)		0/651 (0%)
Hip fracture	1/656 (0.2%)		3/651 (0.5%)		2/2173 (0.1%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Contusion	0/656 (0%)		1/651 (0.2%)		1/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Patella fracture	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Pelvic fracture	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Stoma obstruction	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Subdural haematoma	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Upper limb fracture	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Wrist fracture	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Humerus fracture	0/656 (0%)		0/651 (0%)		1/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Foot fracture	0/656 (0%)		0/651 (0%)		0/2173 (0%)		1/1470 (0.1%)		0/656 (0%)		0/651 (0%)
Pubis fracture	0/656 (0%)		0/651 (0%)		0/2173 (0%)		1/1470 (0.1%)		0/656 (0%)		0/651 (0%)
Investigations
Haemoglobin decreased	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Metabolism and nutrition disorders
Dehydration	0/656 (0%)		0/651 (0%)		0/2173 (0%)		1/1470 (0.1%)		0/656 (0%)		0/651 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	2/656 (0.3%)		3/651 (0.5%)		0/2173 (0%)		3/1470 (0.2%)		0/656 (0%)		0/651 (0%)
Acoustic neuroma	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Breast cancer	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Hepatocellular carcinoma	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Lung neoplasm	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Malignant melanoma	0/656 (0%)		1/651 (0.2%)		1/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Meningioma	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Ovarian cancer	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Prostate cancer	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Squamous cell carcinoma	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		1/1470 (0.1%)		0/656 (0%)		0/651 (0%)
Uterine leiomyoma	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Squamous cell carcinoma of skin	0/656 (0%)		0/651 (0%)		0/2173 (0%)		1/1470 (0.1%)		0/656 (0%)		0/651 (0%)
Nervous system disorders
Cerebrovascular Accident	0/656 (0%)		3/651 (0.5%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Syncope	2/656 (0.3%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Transient ischaemic attack	2/656 (0.3%)		1/651 (0.2%)		1/2173 (0%)		0/1470 (0%)		1/656 (0.2%)		0/651 (0%)
Ischaemic stroke	2/656 (0.3%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Seizure	0/656 (0%)		2/651 (0.3%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Dementia	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Dizziness	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Headache	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Hypoxic-ischaemic encephalopathy	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Lethargy	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Status epilepticus	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Hydrocephalus	0/656 (0%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		1/656 (0.2%)		0/651 (0%)
Psychiatric disorders
Aggression	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Delirium	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Mental status changes	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Mood altered	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Psychotic disorder	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		1/1470 (0.1%)		0/656 (0%)		0/651 (0%)
Somatic symptom disorder	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Agitation	0/656 (0%)		0/651 (0%)		0/2173 (0%)		1/1470 (0.1%)		0/656 (0%)		0/651 (0%)
Renal and urinary disorders
Acute kidney injury	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
invasive ductal breast carcinoma	0/656 (0%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		1/651 (0.2%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/656 (0.3%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Acute respiratory failure	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Pneumonia aspiration	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Pulmonary embolism	1/656 (0.2%)		0/651 (0%)		1/2173 (0%)		1/1470 (0.1%)		0/656 (0%)		1/651 (0.2%)
Pneumothorax spontaneous	0/656 (0%)		0/651 (0%)		0/2173 (0%)		1/1470 (0.1%)		0/656 (0%)		0/651 (0%)
Vascular disorders
Hypertension	0/656 (0%)		1/651 (0.2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Poor peripheral circulation	1/656 (0.2%)		0/651 (0%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Other (Not Including Serious) Adverse Events
	RVT-101 Treatment		Placebo Treatment		Screening Period		Run-In Period		RVT-101 Post-Treatment		Placebo Post-Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	191/656 (29.1%)		166/651 (25.5%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Gastrointestinal disorders
Diarrhoea	13/656 (2%)		17/651 (2.6%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Nausea	17/656 (2.6%)		13/651 (2%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Infections and infestations
Urinary tract infection	25/656 (3.8%)		26/651 (4%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Injury, poisoning and procedural complications
Fall	37/656 (5.6%)		29/651 (4.5%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Musculoskeletal and connective tissue disorders
Back pain	11/656 (1.7%)		15/651 (2.3%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Nervous system disorders
Headache	17/656 (2.6%)		18/651 (2.8%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Dizziness	19/656 (2.9%)		12/651 (1.8%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Respiratory, thoracic and mediastinal disorders
Nasopharyngitis	23/656 (3.5%)		19/651 (2.9%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Bronchitis	14/656 (2.1%)		10/651 (1.5%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)
Cough	15/656 (2.3%)		7/651 (1.1%)		0/2173 (0%)		0/1470 (0%)		0/656 (0%)		0/651 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

All proposed manuscripts, publications or abstracts must be reviewed and approved by the Sponsor 60 days prior to submission for publication. All confidential information identified by the Sponsor must be deleted prior to submission.