Study to Evaluate the Efficacy and Safety of GSK239512 in Alzheimer's Disease
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Randomised, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of the H3 Receptor Antagonist, GSK239512 in Subjects With Mild to Moderate Alzheimer's Disease.|
- Change from Baseline (Day 1) in the executive function/working memory composite score in the Cog State battery at Week 16 [ Time Frame: Baseline (Day 1) and Week 16 ]Executive function/working memory composite score was calculated from the three tasks controlled oral word association (a measure of language fluency, planning and working memory where participants were instructed to generate as many as words as they could think of beginning with a specific letter in one minute. They were then requested to do exactly the same for two furthers letters and a score was given for this activity accuracy), category naming (a measure of semantic fluency, planning and working memory where participants were required to generate as many exemplars of the category 'animals' as they could in one minute), and one-back (a valid measure of working memory where participants were shown a single stimulus of a card in the center of the computer screen and were asked for YES" or "NO" to match the current card with the previous card and the accuracy was noted). Change from Baseline is the value at indicated time point minus the Baseline value.
- Change from Baseline (Day 1) in the episodic memory composite score in the CogState battery at Week 16 [ Time Frame: Baseline (Day 1) and Week 16 ]Episodic memory composite score was calculated from the three tasks International Shopping List Task (ISLT) immediate recall, ISLT delayed recall, and Paired Associate Learning (PAL). The Total Score was calculated by taking the mean of all individual task scores. Change from Baseline is the value at indicated time point minus the Baseline value.
- Change from Baseline (Day 1) in Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) total score at Weeks 8 and 16 [ Time Frame: Baseline (Day 1), Week 8, and 16 ]The ADAS-cog assesses a range of cognitive abilities including memory, comprehension, orientation in time and place, and spontaneous speech. Most items were evaluated by tests, but some were dependent on clinician ratings on a five point scale. Total scores were calculated as the sum of the individual components. The scale ranges from 0 to 70 with higher scores indicating greater dysfunction. Change from Baseline is the value at indicated time point minus the Baseline value.
- Change from Baseline (Day 1) in the attention composite score in the CogState battery at Week 16. [ Time Frame: Baseline (Day 1) and Week 16 ]Attention composite score was calculated from the two tasks Detection and Identification. If one of the Task Scores used in the calculation of a Composite Score was missing, then the Composite Score was calculated as the mean of the non-missing Task Scores. If more than one Task Score was missing, then the Composite Score was be set to missing. Change from Baseline is the value at indicated time point minus the Baseline value.
- Clinician's Interview-Based Impression of Change-plus (CIBIC+) score at Weeks 8 and 16. [ Time Frame: At Week 8 and 16 ]The term CIBIC+ is also measure of change, though a global assessment of change at screening was collected in addition to the post-randomization visits. However, since the scale is a measure of change itself, change from baseline was not to be calculated. The CIBIC+ global functioning assessment comprises a 7-point rating of severity (assessed at baseline) and change (assessed at subsequent time points). The CIBIC+ assessments were performed by an independent rater. The rater was a trained and experienced neurologist, psychiatrist, neuropsychologist and who does not have access to other participant data for this study. The procedure required separate structured 15-20 minute interviews with the participant and the caregiver.
- Change from Baseline (Day 1) to Weeks 8 and 16 of the Disability Assessment for Dementia scale (DAD) total score [ Time Frame: Baseline (Day 1), Week 8, and Week 16 ]The DAD scale has a total of 40 items. A percentage score was calculated using the formula DAD Percentage Score = 100*(DAD total score / number of item with response). Change from Baseline is the value at indicated time point minus the Baseline value.
- Participant's Global Impression of Change (PGIC) score, Carer's Global Impression of Change (CrGIC) score, and Clinician Global Impression of Change (CGIC) at Week 8 and 16 [ Time Frame: Week 8 and 16 ]Global disease change was also scored by the clinician (CGIC), the caregiver (CrGIC) and the patient (PGIC) using a verbal rating scale. The scale was rated from 1 - 7 (Very much improved, much improved, Minimally improved, No change, minimally worse, much worse, very much worse). No data was available for CGIC parameter at Week 8..
- Change from baseline in the Neuropsychiatric Inventory (NPI) at Weeks 8 and 16 [ Time Frame: Baseline (Day 1), Week 8, and 16 ]NPI is an assessment of the frequency and severity of behavioral disturbances in dementia. The inventory comprises 10 dimensions: delusions, hallucinations, dysphoria, apathy, euphoria, disinhibition, aggressiveness and agitation, irritability, anxiety, and aberrant motor activity. Each dimension has a screening question between 7 and 9 follow-up questions relating to symptoms, asked if the answer to the screening question was 'yes'. The NPI took approximately 10 minutes for the investigator to administer by talking to the caregiver. Change from Baseline is the value at indicated time point minus the Baseline value.
- Change from Baseline (Day 1) in Mini Mental State Examination (MMSE) total score at Week 16 [ Time Frame: Baseline (Day 1) and Week 16 ]The MMSE score scale consists of 11 items covering orientation, memory (recent and immediate), concentration, language and praxis. A Total Score was calculated by adding together the individual items scores. Total Score ranges from 0 to 30, with a lower score indicating greater cognitive impairment. If any item was missing then the total score was set to missing. Change from Baseline is the value at indicated time point minus the Baseline value.
- Change from baseline during the titration phase, and to Weeks 8 and 16 of the Pittsburgh Sleep Quality Inventory (PSQI) and Epworth Sleepiness Scale (ESS) [ Time Frame: At Week 8 and 16 ]The PSQI scale contains 19 self-rated questions from which 7 component scores were calculated; subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. Each component was scored on the scale of 0 (no difficulty) to 3 (severe difficulty). The component scores were summed up to produce a Global Score (range 0 to 21). Higher scores indicate worse sleep quality. ESS is an 8-item questionnaire. A total score is calculated by summing the individual item scores. Total scores range from 0 to 24, with higher scores indicating greater sleepiness. Component or item scores were set to missing if any of the individual items used in the calculation of the score were missing. Similarly, the Global Score was set to missing if any of the Component Scores were missing. Change from Baseline was the value at indicated time point minus the Baseline value.
- Change from Baseline for Bilateral Score from Olfaction Test at Week 16 [ Time Frame: Baseline (Day 1) and Week 16 ]The Sniffin' Sticks Screening-12 Test was used for bilateral testing. During the testing, the participant wore a blind fold (a black sleeping mask was supplied with the kit). It was recommended that testing be performed in a well-ventilated room with little or no odor and no disturbances during testing. This test consists of a total of 12 pens and 12 multiple choice answers. Participants were presented with each of the 12 pens at an interval of 30 seconds between each and asked to identify each odorant. For each odorant, the Participant was able to choose from 4 possible answers as to what the smell was. Participants had to identify the item that best described the presented odor. Participants had to choose an item even when they do not perceive an odor or do not feel that their decision was correct. Items identified by participants were noted on the recording sheet. The number of correct answers were recorded. Change from BL is the value at indicated time point minus the BL value
- Plasma concentrations of GSK239512 over period [ Time Frame: Up to Week 16 ]Plasma drug concentration of GSK239512 was analyzed from Week 1 till Week 16 at different doses of 10 mcg, 20 mcg, 40 mcg and 80 mcg. Blood samples for pharmacokinetic analysis of GSK239512 were collected at each clinic visit. Two PK samples were collected; one sample with 15 minutes prior to the start of the CogState Neuropsychological Test Battery (NTB) and one sample within 15 minutes of completion of the CogState NTB.
- Number of participants with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 18 weeks ]Adverse event (AE) is an unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain time period after the study has ended. This change may or may not be caused by the intervention being studied. Serious adverse event (SAE) is an adverse event that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect. Medical events that do not result in death, are not life-threatening, or do not require hospitalization may be considered serious adverse events if they put the participant in danger or require medical or surgical intervention to prevent one of the results listed above.
- Number of participants with vital signs outside clinical concern range (Systolic blood pressure [SBP], diastolic blood pressure [DBP], and heart rate [HR]) [ Time Frame: Up to Week 18 ]The SBP was considered as of clinical concern if <90 or >140 millimeters of mercury (mm of Hg) and increase from Baseline more than or equal to (>=) 40 mm Hg occurred. For DBP, Increase from baseline >=30 mm of Hg was considered as of clinical concern. For HR, if the values are <50 beats per minute (bpm) or >100 bpm, and increase from baseline >=30 bpm, it was considered as of clinical concern. All readings were taken in sitting position. The Data has been presented only for abnormal vital signs.
- Number of participants with hematological and clinical chemistry parameters outside the reference range up to 16 weeks [ Time Frame: Up to 16 weeks ]The data for number of participants with abnormal values; high (H) or low (L) was reported for on-treatment time span. Only the data outside the reference range has been presented. Baseline was considered to be the last available assessment prior to the study drug.
- Number of participants with abnormal electrocardiogram (ECG) over period [ Time Frame: Up to 18 weeks ]This analysis was accounted for the maximum post-baseline on-treatment QTc observed. Participant was counted once in the most extreme clinical interpretation category they had within a visit. For interpretations, the least to most extreme interpretations were normal; abnormal - not clinically significant; abnormal - clinically significant. The Baseline value was based on the mean of the screening assessment values. ECG measurements were collected on paper or electronically at each investigational center. Only the abnormal values were presented.
|Actual Study Start Date:||November 2, 2009|
|Study Completion Date:||November 10, 2010|
|Primary Completion Date:||November 10, 2010 (Final data collection date for primary outcome measure)|
Histamine H3 Antagonist
Placebo Comparator: Placebo
Placebo to match GSK239512.
Placebo to match GSK239512
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01009255
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01009255
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|Study Director:||GSK Clinical Trials||GlaxoSmithKline|