Study Evaluating Intepirdine (RVT-101) in Subjects With D... | NCT02669433

Label	Type	Description	Intervention Names
RVT-101 35 mg	Experimental	RVT-101 35 mg once daily	Drug: RVT-101 35 mg
RVT-101 70 mg	Experimental	RVT-101 70 mg once daily	Drug: RVT-101 70 mg
Placebo	Placebo Comparator	Placebo	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
RVT-101 35 mg	Drug	once daily, oral, 35-mg tablets	RVT-101 35 mg
RVT-101 70 mg

Measure	Description	Time Frame
Unified Parkinson's Disease Rating Scale-Part III (UPDRS-III) Change From Baseline at Week 24	The primary endpoint was to assess the effects of intepirdine versus placebo on the UPDRS Part III after 24 weeks of treatment. UPDRS Part III scores range from 0 to 108, with higher scores indicating worse outcome.	Change from Baseline at 24 weeks

Measure	Description	Time Frame
Alzheimer's Disease Assessment Scale - Cognitive Subscale 11 Items (ADAS-Cog-11) Change From Baseline at 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.	Change from Baseline at 24 weeks

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female subject with probable DLB
Mini Mental State Examination (MMSE) score of 14-26 inclusive at Screening and Baseline
Patient has the ability to comply with procedures for cognitive and other testing in the opinion of the investigator
Patient has a reliable caregiver who is willing to report on the subject's status throughout the study
Patients currently receiving therapy for DLB are eligible for enrollment

Exclusion Criteria:

Atypical clinical features or clinical course that would lead the investigator to conclude primary symptoms are more likely explained by an alternate dementia diagnosis.
Any clinically relevant concomitant disease that, in the opinion of the investigator, makes the patient unsuitable for inclusion in the study.

Name	Affiliation	Role
Ilise Lombardo, MD	Axovant Sciences Inc., Senior Vice President, Clinical Research	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
US138		Phoenix	Arizona	85006	United States
US108

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Subjects dosed with two Placebo tablets Placebo: once daily, oral, matching tablets
FG001	RVT-101 35 mg	Subjects dosed with one Placebo tablet + 1 35 mg tablet of RVT-101 RVT-101 35 mg: once daily, oral, 35-mg tablets

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 15, 2017	Dec 17, 2018

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Unified Parkinson's Disease Rating Scale-Part III (UPDRS-III) Change From Baseline at Week 24

The primary endpoint was to assess the effects of intepirdine versus placebo on the UPDRS Part III after 24 weeks of treatment. UPDRS Part III scores range from 0 to 108, with higher scores indicating worse outcome.

UPDRS Primary Population

Posted

Least Squares Mean

Standard Error

units on a scale

Change from Baseline at 24 weeks

ID	Title	Description
OG000	Placebo	Subjects dosed with two Placebo tablets Placebo: once daily, oral, matching tablets
OG001	RVT-101 35 mg	Subjects dosed with one Placebo tablet + 1 35 mg tablet of RVT-101 RVT-101 35 mg: once daily, oral, 35-mg tablets
OG002	RVT-101 70 mg	Subjects dosed with two RVT-101 35 mg tablets RVT-101 70 mg: once daily, oral, 35-mg tablets

Units	Counts
Participants	OG00072 OG00172 OG00269

Title

Denominators

Categories

Title	Measurements
	OG000-0.55± 1.039 OG0011.45± 1.025 OG002-1.29± 1.056

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Models Analysis		0.158	The threshold for statistical significance was p=0.05	Mean Difference (Final Values)	-2.01			2-Sided	95	-4.80	0.79			Placebo - active		Superiority
OG000 OG002		Mixed Models Analysis

Secondary

Alzheimer's Disease Assessment Scale - Cognitive Subscale 11 Items (ADAS-Cog-11) Change From Baseline at 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.

ITT Population

Posted

Least Squares Mean

Standard Error

units on a scale

Change from Baseline at 24 weeks

ID	Title	Description
OG000	Placebo	Subjects dosed with two Placebo tablets Placebo: once daily, oral, matching tablets
OG001	RVT-101 35 mg	Subjects dosed with one Placebo tablet + 1 35 mg tablet of RVT-101 RVT-101 35 mg: once daily, oral, 35-mg tablets
OG002	RVT-101 70 mg	Subjects dosed with two RVT-101 35 mg tablets RVT-101 70 mg: once daily, oral, 35-mg tablets

Units	Counts

Secondary

Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC+) Change From Baseline at Week 24

To assess the effects of RVT-101 versus placebo on global function as measured by the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC+) after 24 weeks of treatment. CIBIC+ is recorded on a 7-point scale with a score of 4 indicating no change, scores above 4 indicating worsening, and scores below 4 indicating improvement.

ITT Population

Posted

Least Squares Mean

Standard Error

units on a scale

Change from Baseline at 24 weeks

ID	Title	Description
OG000	Placebo	Subjects dosed with two Placebo tablets Placebo: once daily, oral, matching tablets
OG001	RVT-101 35 mg	Subjects dosed with one Placebo tablet + 1 35 mg tablet of RVT-101 RVT-101 35 mg: once daily, oral, 35-mg tablets
OG002	RVT-101 70 mg	Subjects dosed with two RVT-101 35 mg tablets RVT-101 70 mg: once daily, oral, 35-mg tablets

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Deep vein Thrombosis	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected91 at risk EG0010 affected89 at risk EG0020 affected88 at risk
Concussion	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0001 affected91 at risk EG0010 affected89 at risk EG0020 affected88 at risk
Facial bones fracture	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0010 affected89 at risk EG0021 affected88 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0011 affected89 at risk EG0020 affected88 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0001 affected91 at risk EG0010 affected89 at risk EG0020 affected88 at risk
Atrial Flutter	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0011 affected89 at risk EG0020 affected88 at risk
Trifascicular block	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0010 affected89 at risk EG0021 affected88 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0002 affected91 at risk EG0010 affected89 at risk EG0020 affected88 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0001 affected91 at risk EG0010 affected89 at risk EG0020 affected88 at risk
Prostatic adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0001 affected91 at risk EG0010 affected89 at risk EG0020 affected88 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0010 affected89 at risk EG0021 affected88 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0011 affected89 at risk EG0021 affected88 at risk
Dementia	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected91 at risk EG0010 affected89 at risk EG0020 affected88 at risk
Encephalopathy	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0011 affected89 at risk EG0020 affected88 at risk
Haemorrhagic stroke	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0011 affected89 at risk EG0020 affected88 at risk
Metabolic encephalopathy	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0011 affected89 at risk EG0020 affected88 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0011 affected89 at risk EG0020 affected88 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0010 affected89 at risk EG0021 affected88 at risk
Delirium	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0002 affected91 at risk EG0010 affected89 at risk EG0020 affected88 at risk
Depression	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0011 affected89 at risk EG0020 affected88 at risk
Hallucination, visual	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0010 affected89 at risk EG0021 affected88 at risk
Mental status change	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected91 at risk EG0010 affected89 at risk EG0020 affected88 at risk
Neuropsychiatric syndrome	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0010 affected89 at risk EG0021 affected88 at risk
Rectal Haemorrhage	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0011 affected89 at risk EG0021 affected88 at risk
Diverticulum intestinal haemorrhagic	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0010 affected89 at risk EG0021 affected88 at risk
Enteritis	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected91 at risk EG0010 affected89 at risk EG0020 affected88 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0010 affected89 at risk EG0021 affected88 at risk
Volvulus	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0011 affected89 at risk EG0020 affected88 at risk
Cholecystitiis acute	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected91 at risk EG0010 affected89 at risk EG0020 affected88 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0011 affected89 at risk EG0021 affected88 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected91 at risk EG0010 affected89 at risk EG0020 affected88 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected91 at risk EG0010 affected89 at risk EG0020 affected88 at risk
Urinary tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0002 affected91 at risk EG0010 affected89 at risk EG0021 affected88 at risk
Pneumonia	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0010 affected89 at risk EG0022 affected88 at risk
Sepsis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 affected91 at risk EG0011 affected89 at risk EG0020 affected88 at risk
Escherichia urinary tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0011 affected89 at risk EG0020 affected88 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 affected91 at risk EG0010 affected89 at risk EG0020 affected88 at risk
Pyelonephritis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0010 affected89 at risk EG0021 affected88 at risk
Urosepsis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0011 affected89 at risk EG0020 affected88 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0011 affected89 at risk EG0020 affected88 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Fall	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG00019 affected91 at risk EG00117 affected89 at risk EG00218 affected88 at risk
Urinary tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0004 affected91 at risk EG0017 affected89 at risk EG0027 affected88 at risk
Constipation	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0005 affected91 at risk EG0019 affected89 at risk EG0026 affected88 at risk
Orthostatic hypotension	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG00012 affected91 at risk EG0013 affected89 at risk EG0025 affected88 at risk
Nasopharygitis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0007 affected91 at risk EG0018 affected89 at risk EG0021 affected88 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0003 affected91 at risk EG0017 affected89 at risk EG0025 affected88 at risk
Hallucination, visual	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0004 affected91 at risk EG0016 affected89 at risk EG0023 affected88 at risk
Confusional state	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0003 affected91 at risk EG0015 affected89 at risk EG0025 affected88 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected91 at risk EG0017 affected89 at risk EG0025 affected88 at risk
Dizziness	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0004 affected91 at risk EG0013 affected89 at risk EG0025 affected88 at risk
Nausea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0002 affected91 at risk EG0014 affected89 at risk EG0025 affected88 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0006 affected91 at risk EG0013 affected89 at risk EG0022 affected88 at risk
Anxiety	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0003 affected91 at risk EG0015 affected89 at risk EG0022 affected88 at risk
Hypertension	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0005 affected91 at risk EG0011 affected89 at risk EG0022 affected88 at risk

ID	Term
D020734	Parkinsonian Disorders
D001480	Basal Ganglia Diseases
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D009069	Movement Disorders
D000080874	Synucleinopathies
D019636	Neurodegenerative Diseases
D019965	Neurocognitive Disorders
D001523	Mental Disorders

ID	Title	Description
BG000	Placebo	Subjects dosed with two Placebo tablets Placebo: once daily, oral, matching tablets
BG001	RVT-101 35 mg	Subjects dosed with one Placebo tablet + 1 35 mg tablet of RVT-101 RVT-101 35 mg: once daily, oral, 35-mg tablets
BG002	RVT-101 70 mg	Subjects dosed with two RVT-101 35 mg tablets RVT-101 70 mg: once daily, oral, 35-mg tablets
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Placebo Placebo: once daily, oral, matching tablets	1	91	11	91	66	91
EG001	RVT-101 35 mg	RVT-101 35 mg once daily RVT-101 35 mg: once daily, oral, 35-mg tablets	1	89	11	89	69	89
EG002	RVT-101 70 mg	RVT-101 70 mg once daily RVT-101 70 mg: once daily, oral, 35-mg tablets	2	88	13	88	59	88