A Study of the Safety and Efficacy of Memantine in Modera... | NCT00322153

Status Module

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Oral administration, once daily.	Drug: Placebo
Memantine ER	Active Comparator	28mg, once daily. Oral administration for 24 weeks.	Drug: memantine ER

Name	Type	Description	Arm Group Labels	Other Names
memantine ER	Drug	28mg(7mg capsules) once daily and oral administration for 24 weeks.	Memantine ER

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Severe Impairment Battery (SIB) at Week 24 (LOCF)	The SIB was developed for the evaluation of cognitive function in patients with more advanced dementia, and evaluates the areas of memory, language, praxis, orientation, and attention. The SIB test items consist of simple, one-step commands presented with gestural cues that are repeated if necessary. The test contains 51 items, and the range of possible scores is 0 to 100 (with 0 being the worst result). The SIB has been shown to be a valid and reliable instrument sensitive to longitudinal change.	Baseline to week 24
Clinician's Interview-Based Impression of Change With Caregiver Input (CIBIC-plus) at Week 24 (LOCF)	The CIBIC-Plus is a measure of an overall clinical effect and is based on a comprehensive evaluation at Baseline and later visits of four domains: general (overall clinical status), functional (including activities of daily living), cognitive, and behavioral. A skilled clinician interviews the patient, and includes information supplied by a knowledgeable caregiver. The CIBIC-Plus is a rating of the patient's global status relative to Baseline, ranging from a score of 1, indicating "marked improvement" to a score of 4, indicating "no change" to a score of 7, indicating "marked worsening."	Week 24

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in the 19-Item Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL19) Scale at Week 24 (LOCF)	The ADCS-ADL19 modified inventory consists of 19 items used to measure the functional capabilities of patients with moderate to severe dementia. Each activity-of-daily-living (ADL) item comprises a series of hierarchical subquestions ranging from the highest level of independent performance to complete loss of ability to perform the ADL Inventory. The inventory is performed by interviewing a person in close contact with the patient and covers the most usual and consistent performance of the patient over the preceding 4 weeks. Response range is 0 (total disability) to 54 (total independence).

Eligibility Module

Name	Affiliation	Role
Stephen M Graham, PhD	Forest Laboratories	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Forest Investigative Site 010		Phoenix	Arizona	85004	United States
Forest Investigative Site 062

PubMed Identifier	Type	Citation	Retractions
29771687	Derived	Grossberg GT, Alva G, Hendrix S, Ellison N, Kane MC, Edwards J. Memantine ER Maintains Patient Response in Moderate to Severe Alzheimer's Disease: Post Hoc Analyses From a Randomized, Controlled, Clinical Trial of Patients Treated With Cholinesterase Inhibitors. Alzheimer Dis Assoc Disord. 2018 Jul-Sep;32(3):173-178. doi: 10.1097/WAD.0000000000000261.

Results Section

Participant Flow Module

ID	Title	Description
FG000	Placebo	Matching placebo oral administration once daily for 24 weeks.
FG001	Memantine ER	28mg once daily oral administration for 24 weeks.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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

Change From Baseline in Severe Impairment Battery (SIB) at Week 24 (LOCF)

The SIB was developed for the evaluation of cognitive function in patients with more advanced dementia, and evaluates the areas of memory, language, praxis, orientation, and attention. The SIB test items consist of simple, one-step commands presented with gestural cues that are repeated if necessary. The test contains 51 items, and the range of possible scores is 0 to 100 (with 0 being the worst result). The SIB has been shown to be a valid and reliable instrument sensitive to longitudinal change.

Primary efficacy analysis was based on the Intent-to-Treat (ITT) Population. The ITT Population was consisted of all patients in the Safety Population who completed at least one post-Baseline efficacy assessment in SIB or CIBIC-Plus. The last-observation-carried-forward approach was used to impute missing post-Baseline values.

Posted

Least Squares Mean

Standard Error

Units on a scale

Baseline to week 24

ID	Title	Description
OG000	Placebo	Matching placebo oral administration once daily for 24 weeks.
OG001	Memantine ER	28mg once daily oral administration for 24 weeks.

Units	Counts
Participants	OG000327 OG001332

Title

Denominators

Categories

Title	Measurements
	OG000-0.4± 0.65 OG0012.2± 0.65

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	The co-primary efficacy parameter was change from Baseline to Week 24 in SIB total score. Missing SIB total scores at Week 24 were imputed using the last-observation-carried-forward (LOCF) approach.	ANCOVA	Least-squares mean (-0.4 in placebo and 2.2 in memantine ER) are controlled for center and adjusted for SIB baseline value.	0.001		Mean Difference (Final Values)	2.6			2-Sided	95	1.0	4.2				No	Superiority or Other

Primary

Clinician's Interview-Based Impression of Change With Caregiver Input (CIBIC-plus) at Week 24 (LOCF)

The CIBIC-Plus is a measure of an overall clinical effect and is based on a comprehensive evaluation at Baseline and later visits of four domains: general (overall clinical status), functional (including activities of daily living), cognitive, and behavioral. A skilled clinician interviews the patient, and includes information supplied by a knowledgeable caregiver. The CIBIC-Plus is a rating of the patient's global status relative to Baseline, ranging from a score of 1, indicating "marked improvement" to a score of 4, indicating "no change" to a score of 7, indicating "marked worsening."

Posted

Mean

Standard Error

Units on a scale

Week 24

ID	Title	Description
OG000	Placebo	Matching placebo oral administration once daily for 24 weeks.
OG001	Memantine ER	28mg once daily oral administration for 24 weeks.

Secondary

Change From Baseline in the 19-Item Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL19) Scale at Week 24 (LOCF)

The ADCS-ADL19 modified inventory consists of 19 items used to measure the functional capabilities of patients with moderate to severe dementia. Each activity-of-daily-living (ADL) item comprises a series of hierarchical subquestions ranging from the highest level of independent performance to complete loss of ability to perform the ADL Inventory. The inventory is performed by interviewing a person in close contact with the patient and covers the most usual and consistent performance of the patient over the preceding 4 weeks. Response range is 0 (total disability) to 54 (total independence).

The secondary efficacy analysis was based on the ITT Population. The last-observation-carried-forward approach was used to impute missing post-Baseline values.

Posted

Least Squares Mean

Standard Error

Units on a scale

Baseline to week 24

ID	Title	Description
OG000	Placebo	Matching placebo oral administration once daily for 24 weeks.
OG001	Memantine ER	28mg once daily oral administration for 24 weeks.

Units	Counts

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrioventricular block complete	Cardiac disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Bradycardia	Cardiac disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected335 at risk EG0011 affected341 at risk
Sinus bradycardia	Cardiac disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Cardiac Arrest	Cardiac disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected335 at risk EG0010 affected341 at risk
Cardiac Failure Congestive	Cardiac disorders	MedDRA 10.1	Systematic Assessment	EG0003 affected335 at risk EG0010 affected341 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 10.1	Systematic Assessment	EG0002 affected335 at risk EG0010 affected341 at risk
Myocardial infarction	Cardiac disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected335 at risk EG0010 affected341 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Rectal Prolapse	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Toothache	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Vomiting	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Chest Pain	General disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
General physical health deterioration	General disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Drowning	General disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected335 at risk EG0010 affected341 at risk
Pneumonia	Infections and infestations	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0012 affected341 at risk
Urinary tract infection	Infections and infestations	MedDRA 10.1	Systematic Assessment	EG0003 affected335 at risk EG0012 affected341 at risk
Lobar Pneumonia	Infections and infestations	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Meningitis bacterial	Infections and infestations	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Bacteraemia	Infections and infestations	MedDRA 10.1	Systematic Assessment	EG0001 affected335 at risk EG0010 affected341 at risk
Herpes zoster	Infections and infestations	MedDRA 10.1	Systematic Assessment	EG0001 affected335 at risk EG0010 affected341 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 10.1	Systematic Assessment	EG0005 affected335 at risk EG0012 affected341 at risk
Pneumothorax traumatic	Injury, poisoning and procedural complications	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Skin laceration	Injury, poisoning and procedural complications	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Head Injury	Injury, poisoning and procedural complications	MedDRA 10.1	Systematic Assessment	EG0001 affected335 at risk EG0010 affected341 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA 10.1	Systematic Assessment	EG0003 affected335 at risk EG0010 affected341 at risk
Traumatic brain injury	Injury, poisoning and procedural complications	MedDRA 10.1	Systematic Assessment	EG0001 affected335 at risk EG0010 affected341 at risk
Anticoagulation drug level above therapeutic	Investigations	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected335 at risk EG0010 affected341 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected335 at risk EG0010 affected341 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Cholesteatoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Metastatic carcinoma of the bladder	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Renal neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.1	Systematic Assessment	EG0001 affected335 at risk EG0010 affected341 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0012 affected341 at risk
Syncope	Nervous system disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0012 affected341 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected335 at risk EG0011 affected341 at risk
Dementia Alzheimer's type	Nervous system disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Facial paresis	Nervous system disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected335 at risk EG0011 affected341 at risk
Myoclonus	Nervous system disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Syncope vasovagal	Nervous system disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Convulsion	Nervous system disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected335 at risk EG0010 affected341 at risk
Intracranial haematoma	Nervous system disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected335 at risk EG0010 affected341 at risk
Anxiety disorder due to a general medical condition	Psychiatric disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Delusion	Psychiatric disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Renal failure	Renal and urinary disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Urinary retention	Renal and urinary disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected335 at risk EG0010 affected341 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected335 at risk EG0011 affected341 at risk
Respiratory arrest	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected335 at risk EG0010 affected341 at risk
Excessive skin	Skin and subcutaneous tissue disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Proctocolectomy	Surgical and medical procedures	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected335 at risk EG0011 affected341 at risk
Hypotension	Vascular disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected335 at risk EG0011 affected341 at risk

ID	Term
D003704	Dementia
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D024801	Tauopathies
D019636	Neurodegenerative Diseases
D019965	Neurocognitive Disorders
D001523	Mental Disorders

ID	Term
D000547	Amantadine
D000218	Adamantane
D001952	Bridged-Ring Compounds
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals

ID	Title	Description
BG000	Placebo	Matching placebo oral administration once daily for 24 weeks.
BG001	Memantine ER	28mg once daily oral administration for 24 weeks.
BG002	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	Matching placebo oral administration once daily for 24 weeks.			21	335	70	335
EG001	Memantine ER	28mg once daily oral administration for 24 weeks.			28	341	67	341