6.1 Clinical Trial Data Sources
NAMENDA XR was eva luated in a double-blind placebo-controlled trial treating a total of 676 patients with moderate to severe dementia of the Alzheimer's type (341 patients treated with NAMENDA XR 28 mg/day dose and 335 patients treated with placebo) for a treatment period up to 24 weeks.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
6.2 Adverse Reactions Leading to Discontinuation
In the placebo-controlled clinical trial of NAMENDA XR [See Clinical Studies (14)], which treated a total of 676 patients, the proportion of patients in the NAMENDA XR 28 mg/day dose and placebo groups who discontinued treatment due to adverse events were 10.0% and 6.3%, respectively. The most common adverse reaction in the NAMENDA XR treated group that led to treatment discontinuation in this study was dizziness at a rate of 1.5%.
6.3 Most Common Adverse Reactions
The most commonly observed adverse reactions seen in patients administered NAMENDA XR in the controlled clinical trial, defined as those occurring at a frequency of at least 5% in the NAMENDA XR group and at a higher frequency than placebo were headache, diarrhea and dizziness.
Table 1 lists treatment-emergent adverse reactions that were observed at an incidence of ≥ 2% in the NAMENDA XR treated group and occurred at a rate greater than placebo.
6.4 Vital Sign Changes
NAMENDA XR and placebo groups were compared with respect to (1) mean change from baseline in vital signs (pulse, systolic blood pressure, diastolic blood pressure, and weight) and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. There were no clinically important changes in vital signs in patients treated with NAMENDA XR. A comparison of supine and standing vital sign measures for NAMENDA XR and placebo in Alzheimer's patients indicated that NAMENDA XR treatment is not associated with orthostatic changes.
6.5 Laboratory Changes
NAMENDA XR and placebo groups were compared with respect to (1) mean change from baseline in various serum chemistry, hematology, and urinalysis variables and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses revealed no clinically important changes in laboratory test parameters associated with NAMENDA XR treatment.
6.6 ECG Changes
NAMENDA XR and placebo groups were compared with respect to (1) mean change from baseline in various ECG parameters and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses revealed no clinically important changes in ECG parameters associated with NAMENDA XR treatment.
6.7 Other Adverse Reactions Observed During Clinical Trials of NAMENDA XR
Following is a list of treatment-emergent adverse reactions reported from 750 patients treated with NAMENDA XR for periods up to 52 weeks in double-blind or open-label clinical trials. The listing does not include those events already listed in Table 1, those events for which a drug cause was remote, those events for which descriptive terms were so lacking in specificity as to be uninformative, and those events reported only once which did not have a substantial probability of being immediately life threatening. Events are categorized by body system.
Blood and Lymphatic System Disorders: anemia.
Cardiac Disorders: bradycardia, myocardial infarction.
Gastrointestinal Disorders: fecal incontinence, nausea.
General Disorders: asthenia, fatigue, gait disturbance, irritability, peripheral edema, pyrexia.
Infections and Infestations: bronchitis, nasopharyngitis, pneumonia, upper respiratory tract infection, urinary tract infection.
Injury, Poisoning and Procedural Complications: fall.
Investigations: weight decreased.
Metabolism and Nutrition Disorders: anorexia, dehydration, decreased appetite, hyperglycemia.
Musculoskeletal and Connective Tissue Disorders: arthralgia, pain in extremity.
Nervous System Disorders: convulsion, dementia Alzheimer's type, syncope, tremor.
Psychiatric Disorders: agitation, confusional state, delirium, delusion, disorientation, hallucination, insomnia, restlessness.
Respiratory, Thoracic
