Alzheimer's Disease
Conditions
Keywords
adjunctive therapy, moderate, Alzheimer's disease, apolipoprotein E, mild, rosiglitazone, cognition
Brief summary
Rosiglitazone (RSG) has been tested in clinical studies and is approved by the FDA as a treatment for type II diabetes mellitus, a disease that occurs when the body is unable to effectively use glucose. RSG XR, the investigational drug used in this study, is an extended-release form of RSG. This study tests whether RSG XR safely provides clinical benefit to people with mild to moderate Alzheimer's disease (AD) when combined with one of the currently approved AD medications, Aricept®, Razadyne® or Exelon®. RSG XR is a new approach to AD therapy and this study tests a new way to treat AD by testing whether one's genetic makeup affects the response to the study drug. Clinical data suggesting that RSG may benefit AD patients was first seen in a small study performed at the University of Washington and then from a larger GSK study conducted in Europe and New Zealand. In the first study, subjects receiving RSG once daily for 6 months scored significantly better on 3 tests of memory and thought than those who did not receive RSG. In the GSK study, those that appeared to benefit most from treatment with RSG XR had a specific genetic pattern. They did not have the gene that caused them to produce the protein apolipoprotein E e4 (APOE e4). Subjects who have the APOE e4 gene may have two copies, one from each parent, or they may have only one APOE e4 gene meaning that they inherited either the APOE e2 or APOE e3 version of the gene, instead of APOE e4, from one of their parents. Subjects with one copy of the APOE e4 gene remained at their same level of thinking ability while those with two copies of the APOE e4 gene, continued to worsen during the 6-month treatment. The current study will more directly test the effectiveness or RSG XR on people who either have or lack the APOE e4 gene.
Detailed description
A 54-week, double-blind, randomized, placebo-controlled, parallel-group study to investigate the effects of rosiglitazone (extended release tablets) as adjunctive therapy to acetylcholinesterase inhibitors on cognition and overall clinical response in APOE e4-stratified subjects with mild to moderate Alzheimer's disease (REFLECT-3)
Interventions
Rosiglitazone Extended Release 2mg OD
Rosiglitazone Extended Release 8mg OD
OTHERPlacebo
Placebo
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
A subject will be eligible for inclusion in this study only if all of the following criteria apply: * Male or female subject with a clinical diagnosis of probable Alzheimer's disease in accordance with NINCDS-ADRDA criteria (Appendix 2). (Note: National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and Alzheimer's Disease and Related Disorders Association (ADRDA).) * Subject has mild to moderate Alzheimer's disease as defined by a MMSE score 10 to 26 inclusive at Screening. * Hachinski Ischemia Score ≤ 4 at Screening (See Appendix 3). * Age ≥50 and ≤90 years. * At least 6 months of ongoing acetylcholinesterase inhibitor therapy for Alzheimer's disease, with stable dosing for at least the last 2 months (and with no intent to change for the duration of the study). * Current use of medication is in accordance with the criteria listed in Table 2 (Permitted Medications, Section 8.1). * Female subjects must be post-menopausal (i.e. \>1 year without menstrual period), surgically sterile, or agree to use adequate method of contraception (Appendix 4) for the duration of the study. Female subjects who are pre-menopausal or who have been post-menopausal for \<1 year must undertake pregnancy testing (urine test) at Visit 1, which must be negative. * Brain CT or MRI scan performed within the past 12 months or at Screening, showing no evidence of any other potential cause of dementia other than Alzheimer's disease. (Note: Questionable CT or MRI scans should be discussed with the medical monitor, using central imaging guidelines.) * Neurological exam without focal changes (excluding changes attributable to AD or peripheral trauma). * Subject has the ability to comply with procedures for cognitive and other testing. * Subject lives with (or has substantial periods of contact with) a regular caregiver who is willing to attend all visits, oversee the subject's compliance with protocol-specified procedures and study medication, and report on subject's status. (Note: A non-cohabiting caregiver must spend sufficient time with the subject so that, in the opinion of the Investigator, the caregiver can reliably assess cognitive function, activities and behavior, and report on the subject's compliance and health. As caregiver time spent with a potential subject is anticipated to be highly variable across countries and cultures, GSK will consider a variety of different measures by which this stipulation may be met, and GSK should be consulted if adequacy of a caregiver situation is in doubt. However, as guidance, the ability for a caregiver to meet his/her expected responsibilities for this study would normally be possible when the caregiver spends no less than 10 hours per week with the subject, divided over multiple days.) * Subject has provided full written informed consent prior to the performance of any protocol-specified procedure; or if unable to provide informed consent due to cognitive status, full written informed consent on behalf of the subject has been provided by a legally acceptable representative. (Note: Consent by legally acceptable representative is allowed where this is in accordance with local laws, regulations and ethics committee policy.) * Caregiver has provided full written informed consent on his/her own behalf prior to the performance of any protocol-specified procedure. * Subjects considered for enrolment must have a QTc (either QTc B (Bazett's correction) or QTc F (Fridericia's correction)) \<450msec at Visit 1, with the exception of subjects with bundle branch block (for whom either QTc B or QTc F must be \<480msec). (Note: For the purposes of these criteria, QTc B is defined as (QT interval \[msec\]) / (square root of RR interval \[seconds\]); and QTc F is defined as (QT interval \[msec\]) / (cube root of RR interval \[seconds\]).)
Exclusion criteria
A subject will not be eligible for inclusion in this study if any of the following criteria apply: * Diagnosis of possible, probable, or definite vascular dementia in accordance with NINDS-AIREN criteria (Appendix 5). (Note: National Institute of Neurological Disorders and Stroke (NINDS) and Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN).) * History or evidence of any other CNS disorder that could be interpreted as a cause of dementia: e.g. cerebrovascular disease (stroke, hemorrhage), structural abnormality, epilepsy, infectious or inflammatory/demyelinating CNS conditions, Parkinson's disease. * Evidence of the following disorders: current vitamin B12 deficiency, positive syphilis serology, or active thyroid dysfunction (particularly that suggestive of hypothyroidism), including abnormally high or low serum levels of thyroid stimulating hormone (TSH), that are clinically significant in the opinion of the investigator. (Note: Testing is required for each parameter only when no result is available from previous 12 months.) * History of Type 1 diabetes mellitus or secondary diabetes mellitus. * Type 2 diabetes mellitus where the subject is being treated with insulin, a PPARγ agonist, or an insulin secretagogue (e.g. a sulfonylurea or glitinide). * Any patient with an HbA1c ≥8.5%. (See Section 6.3.8.4 for Safety Measures for Enrolled Subjects with Type 2 Diabetes Mellitus.) * History or clinical/investigational evidence of congestive heart failure defined by the New York Heart Association criteria (Class I to IV cardiac status; Appendix 6). * History of cardiovascular event within the last 6 months (i.e. intervention, percutaneous coronary intervention, vascular surgery, acute coronary syndrome \[non Q-wave myocardial infarction, Q-wave myocardial infarction, unstable angina\] or significant arrhythmia; or major intervention (e.g. cardiac surgery or angiography plus stenting) scheduled). * History of significant psychiatric illness such as schizophrenia or bipolar affective disorder that in the opinion of the Investigator would interfere with participation in the study, major depressive disorder (according to DSM-IV) in the past year, or current active depression requiring initiation of treatment. (Note: If not currently treated, but active depression is suspected, the Cornell Scale for Depression in Dementia (CSDD, Appendix 7) can be used by the Investigator as a guide for deciding whether a prospective subject requires treatment. If the subject has a CSDD score \>7, the Investigator should decide if the subject has depression in need of prescribed medication, and a CSDD \>12 is considered a strong indicator that treatment is needed. Subjects will be allowed to re-screen after their depression has been adequately managed for \>3 months.) * History or presence of gastro-intestinal, hepatic, or renal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs, or any other clinically relevant abnormality, medical or psychiatric condition, which, in the opinion of the Investigator, makes the subject unsuitable for inclusion in the study. * Clinically significant peripheral edema at the time of screening. * Current or recent drug or alcohol abuse or dependence (defined by DSM-IV criteria for substance-related disorders), or recent or remote history of the same if that could be a contributing factor to the dementia. * Systolic blood pressure \>165 or \<90 mmHg or diastolic blood pressure \>95 or \<60 mmHg at the time of screening. * Clinically significant anemia (i.e. hemoglobin \<11 g/dL for males or \<10 g/dL for females) or presence of hemoglobinopathies which would prevent accurate assessment of HbA1c. * Abnormal kidney function tests (\>1.5 times the upper limit of normal (ULN)). * ALT, AST, or alkaline phosphatase values \>2.5 times the ULN, total bilirubin values \>1.5 times the ULN, or history of severe hepatobiliary disease (e.g. hepatitis B or C, or cirrhosis, Child-Pugh Class B/C). (Note: For subjects with a diagnosis of Gilberts Syndrome and an isolated increase in total bilirubin \>1.5 ULN, fractionation should be performed. If all of the following conditions are met, the patient may enter or remain in the study, even if total bilirubin \>1.5 ULN: * an elevated unconjugated (indirect) bilirubin; * the percentage of direct bilirubin \<35%; * ALT, AST, and alkaline phosphatase \<2.5 ULN if subject is in screening (\<2.0 ULN for Canadian subjects only), or ≤3 ULN if subject is already randomized into the study) * History of a bone marrow transplant. * Subject is unable (with assistance, if appropriate) to take study medication as prescribed throughout the study or is at risk of non-compliance with study medication or procedures. * Subject is an immediate family member or employee of the participating Investigator, of any of the participating site staff, or of GSK. * In France, a subject is neither affiliated with nor a beneficiary of a social security category. * The French subject has participated in any study using an investigational drug during the previous 30 days or 5 half-lives (whichever is longer). * Cognitive tasks prescribed for cognitive rehabilitation and performed under medical supervision are prohibited for 6 months prior to Screening, as well as for the duration of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 48, as a Function of APOE ε4 Status in APOE4 Negatives Cohort | Baseline (Week 0) and Week 48 | The 11-item ADAS-Cog assessed 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. Scores range from 0 to 70 with higher scores indicating greater dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. A hierarchical testing procedure was used to control for statistical tests in the two RSG dose groups and the genetic subgroups. |
| Change From Baseline in ADAS-Cog Total Score at Week 48, as a Function of APOE ε4 Status in All Except E4/E4s Cohort | Baseline (Week 0) and Week 48 | The 11-item ADAS-Cog assessed 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. Scores range from 0 to 70 with higher scores indicating greater dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. A hierarchical testing procedure was used to control for statistical tests in the two RSG dose groups and the genetic subgroups. |
| Change From Baseline in ADAS-Cog Total Score at Week 48, as a Function of APOE ε4 Status in Full Population Cohort | Baseline (Week 0) and Week 48 | The 11-item ADAS-Cog assessed 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. Scores range from 0 to 70 with higher scores indicating greater dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. A hierarchical testing procedure was used to control for statistical tests in the two RSG dose groups and the genetic subgroups. |
| Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score at Week 48, as a Function of APOE ε4 Status in APOE4 Negatives Cohort | Baseline (Week 0) and Week 48 | The CDR-SB was a validated clinical assessment of global function in patients with AD. Impairment was scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or box scores, can be added together to give the CDR-Sum of Boxes which ranges from 0 to 18 (severe impairment). Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Primary inference will be based on the week 48 treatment differences obtained from the MMRM model. A hierarchical testing procedure was used to control for statistical tests in the two RSG dose groups and the genetic subgroups. |
| Change From Baseline in CDR-SB Score at Week 48, as a Function of APOE ε4 Status in All Except E4/E4s Cohort | Baseline (Week 0) and Week 48 | The CDR-SB was a validated clinical assessment of global function in patients with AD. Impairment was scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or box scores, can be added together to give the CDR-Sum of Boxes which ranges from 0 to 18 (severe impairment). Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Primary inference will be based on the week 48 treatment differences obtained from the MMRM model. A hierarchical testing procedure was used to control for statistical tests in the two RSG dose groups and the genetic subgroups. |
| Change From Baseline in CDR-SB Score at Week 48, as a Function of APOE ε4 Status in Full Population Cohort | Baseline (Week 0) and Week 48 | The CDR-SB was a validated clinical assessment of global function in patients with AD. Impairment was scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or box scores, can be added together to give the CDR-Sum of Boxes which ranges from 0 to 18 (severe impairment). Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Primary inference will be based on the week 48 treatment differences obtained from the MMRM model. A hierarchical testing procedure was used to control for statistical tests in the two RSG dose groups and the genetic subgroups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Scale Total Score- Thermometer Score | Baseline (Week 0) and Week 12, 36, 48 | The EQ-5D Proxy is an assessment of quality of life and utility benefit. The EQ-5D Proxy is composed of two parts: part two is the visual analogue scale 'Thermometer'. Caregivers are asked to respond as they feel the participant would on dimensions of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 'Thermometer' has endpoints of 100 (best imaginable health state) and 0 (worst imaginable health state). Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Full population data was presented. |
| Change From Baseline in EQ-5D Scale Total Score- Utility Score | Baseline (Week 0) and Week 12, 36, 48 | The EQ-5D Proxy is an assessment of quality of life and utility benefit. The EQ-5D Proxy is composed of two parts: part one is the five dimensional Health State Classification. The Utility score is a caregiver rating of health status on dimensions of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Answers to each question were responded to on a 3-point scale which indicates the level of impairment (level 1= no problem; level 2=some or moderate problem(s) and level 3=unable, or extreme problem with higher scores indicating greater dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Full population data was presented. |
| Change From Baseline in Alzheimer's Carer's Quality of Life Instrument (ACQLI) Score | Baseline (Week 0) and Week 12, 36, 48 | The ACQLI is an assessment of caregiver quality of life. This instrument consisted of 30 questions exploring various aspects of carer's quality of life. Each of the questions had two point response, and the 30 questions were summed to provide a total score. Items were assumed to be unidimensional (i.e., represent a single variable) and were scored 0/1 (false/true) before summation into a total score with a 0-30 range. To ease comparisons between scales, ACQLI scores were transformed to range between 0-100 (100: worse). Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Full population data was presented. |
| Change in ADAS-Cog Total Score for Observed Cases at Week 54 Compared to Week 48 | Week 48 and Week 54 | The 11-item ADAS-Cog assessed 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. Scores range from 0 to 70 with higher scores indicating greater dysfunction. It was of interest to compare the single blind phase data between the treatment groups defined based on the double blind treatment group. This analysis only included participants who received at least one dose of single-blind medication. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Full population data was presented. |
| Change in CDR-SB Total Score for Observed Cases at Week 54 Compared to Week 48 | Week 48 and Week 54 | The CDR-SB was a validated clinical assessment of global function in participants with AD. Impairment was scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or box scores, can be added together to give the CDR-Sum of Boxes which ranges from 0 to 18 (severe impairment). It was of interest to compare the single blind phase data between the treatment groups defined based on the double blind treatment group. This analysis only included participants who received at least one dose of single-blind medication. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Full population data was presented. |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 48 | Baseline (Week 0) and Week 48 | Blood samples were collected for assessments of HbA1c levels at Baseline and up to Week 48. Change from Baseline was calculated as value at scheduled time point minus Baseline value . Baseline was defined as value at Week 0. Endpoint treatment differences which were adjusted to take account of missing data are derived. Full population data was presented. |
| Number of Participants With On-treatment Adverse Events (AEs), Serious Adverse Events (SAEs) and Severity of AEs | Upto Week 48 | AE was defined as any untoward medical occurrence in a participant temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE was any untoward medical occurrence that, at any dose results in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect or was considered as medically significant. |
| Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Weight | Upto Week 54 | Body weight was measured at all visits, without shoes and wearing light clothing. The assessment was performed a t Baseline and up to Week 54. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Full population data was presented. |
| Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Upto Week 54 | SBP and DBP of participants were recorded in sitting posture as vital sign at each visit. The blood pressure (BP) values were identified as of potential clinical concern if the values were out of the reference range (for SBP, 90 to 140 mmHg and DBP, 50 to 90 mmHg) or meet a change from baseline criterion. The change from baseline criterion for SBP, was increase from Baseline (high) if increased by more than or equal to (\>=) 40 mm Hg from Baseline; decrease from Baseline (low) if decreased by \>= 30 mmHg from Baseline. For DBP, increase from baseline (high) if increased by \>=30 mmHg from baseline; decrease from Baseline (low) if decreased by \>= 20 mmHg from Baseline. Baseline was defined as value at Week 0. |
| Change From Baseline in ADAS-Cog Total Score at Weeks 8, 16, 24 and 36 | Baseline (Week 0) and Week 8, 16, 24, 36 | The 11-item ADAS-Cog assessed 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. Scores range from 0 to 70 with higher scores indicating greater dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. It was calculated at Weeks 8, 16, 24 and 36. Full population data was presented. |
| Change From Baseline in Weight | Baseline (Week 0) and Weeks 4, 8, 12, 16, 24, 36, 48, 54 | Body weight was measured at all visits, without shoes and wearing light clothing. The assessment was performed at Baseline, Weeks 4, 8, 12, 16, 24, 36, 48, 54. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Full population data was presented. |
| Change From Baseline in Hemoglobin | Baseline (Week 0) and Weeks 4, 16, 36, 48 | Hematology parameters were assessed at Baseline, Weeks 4, 16, 36, 48. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Full population data was presented. |
| Change From Baseline in Hematocrit | Baseline (Week 0) and Weeks 4, 16, 36, 48 | Hematology parameters were assessed at Baseline and up to Week 48. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. |
| Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Up to Week 48 | Haematology parameters were identified as of PCC (high \[H\], low \[L\]), if the values were out of the reference range (RR). The range for parameters was: platelet (100AV-500AV), red blood cell (RBC , 0.8-1.2), hemoglobin (L: female \[F\]:10, male \[M\]:11; H: F:16.5-AV, M:18), hematocrit (0.8-1.2), white blood cell (WBC, 3-15), Total neutrophils (ANC- absolute Neutrophil count) (0.75-1.5), lymphocytes (0.75-1.5), monocyte s (0.75-2), eosinophils (none -2), basophils (none -2), mean corpuscle volume (MCV, 0.8-1.2), mean corpuscular hemoglobin (MCH, 0.8-1.2), mean corpuscular hemoglobin concentration (MCHC , 0.8-1.2), red cell distribution width (RDW, 0.8-1.2), Neutrophil bands (none-1) and segmented neutrophils (0.75-1.3). Full population data was presented. |
| Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Upto Week 48 | Clinical chemistry parameters were identified as of PCC (High, Low), if values were out of RR: Alanine amino transferase (ALT,none-120 \[250percent upper limit of RR, ULRR \]),Album in (0.75-2),Aldolase(1.1-1.1),Aspartate amino transferase (AST,none-105 (3-64y),137.5(65+y),\>250 percent ULRR), Alkaline phosphatase(ALP,none-312.5 (20+y),\>250percent ULRR),blood urea nitrogen(BUN)/Creatinine ratio(none-1.25),BUN(none-11),Chloride(80-115),Calcium (0.75-1.25),Carbon dioxide(CO2,15-40) content,Creatinine (22,\<50percent lower limit of RR \[LLRR \]-155, \>125percent ULRR),Creatine phosphokinase(CPK,none-1.25),Gamma glutamyl transferase(GGT,none-2.5),Glucose (3.6-7.8),HbA1C, High density lipoprotein (HDL,0.65-none),Lactate dehydrogenase (LDH,none -2), Low density lipoprotein(LDL,none-1.25),Magnesium (0.5-2),Potassium (3-5.5),Phosphorus inorganic(0.5-1.5), Sodium (130-150), Total protein (0.8-1.5),Total cholesterol(none -1.5),Direct Billirubin. |
| Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Baseline (Week 0) and Weeks 4, 8, 16, 24, 36, 48, 54 | Triplicate 12-lead ECG measures was obtained digitally, approximately one minute apart after the participant had rested in the supine position in a quiet room (no TV, minimal talking) for atleast 10 minutes. The ECG parameters includes HR. The assessments were performed at Baseline and up to Week 54. Change from Baseline was calculated as value at scheduled time point minus Baseline value . Baseline was defined as value at Week 0. Full population data was presented. |
| Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | Baseline (Week 0) and Weeks 4, 8, 16, 24, 36, 48, 54 | Triplicate 12-lead ECG measures was obtained digitally, approximately one minute apart after the participant had rested in the supine position in a quiet room (no TV, minimal talking) for atleast 10 minutes. The ECG parameters includes PR interval, QRS duration, QT - uncorrected interval, QTc Bazett (QTcB), QTc Fridericia (QTcF) and RR interval. The assessments were performed at Baseline and up to Week 54. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Full population data was presented. |
| Change From Baseline in HbA1c up to Week 54 | Baseline (Week 0) and Weeks 12, 24, 36, 48, 54 | Blood samples were collected for assessments of HbA1c levels at Baseline, Weeks 12, 24, 36, 48, 54. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. |
| Change From Baseline in Short Term Memory Assessment | Baseline (Week 0) and upto Week 48 | The 11-item ADAS-Cog assessed 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. Scores range from 0 to 70 with higher scores indicating greater dysfunction. Questions 1 (word recall) and 7 (word recognition) of ADAS-Cog questionnaire was summed to get a short term memory assessment. The score for Question 1 was calculated as the mean number of words not recalled over the trials for which data was available. If data for all three trials was missing, or if the score for Question 7 was missing then the short term memory score will also be set to missing. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. |
| Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Heart Rate (HR) | Upto Week 54 | HR of participants were recorded in sitting posture as vital sign at each visit. The HR values were identified as of potential clinical concern if the values were out of the reference range (50 to 100 beats per minute) or meet a change from baseline criterion. The change from baseline criterion for HR, was increase from Baseline (high) if increased by more than or equal to (\>=) 30 from Baseline; decrease from Baseline (low) if decreased by \>= 30 from Baseline. Baseline was defined as value at Week 0. Full population data was presented. |
| Change From Baseline in CDR-SB Score at Weeks 12, 24 and 36 | Baseline (Week 0) and Week 12, 24, 36 | The CDR-SB was a validated clinical assessment of global function in patients with AD. Impairment was scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or box scores, can be added together to give the CDR-Sum of Boxes which ranges from 0 to 18 (severe impairment). Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. It was calculated at Weeks 12, 24 and 36. Full population data was presented. |
| Change From Screening in Mini Mental State Examination (MMSE) Total Score | Screening (Week -4) and Week 48 | The MMSE consists of 11 tests of orientation, memory (recent and immediate), concentration, language and praxis. Scores range from 0 to 30, with lower scores indicating greater cognitive impairment. The scale is completed by the investigator, based on the performance of the participant. Change from screening was calculated as value at scheduled time point minus screening value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Full population data was presented. |
| Change From Baseline in Disability Assessment for Dementia (DAD) Total Score | Baseline (Week 0) and Week 8, 16, 24, 48 | The DAD assessed the ability of a participant to execute basic and instrumental activities of daily living (ADL) and leisure activities. The scale consists of 40 questions assessing basic and instrumental ADLs. This scale assessed a participants' ability to initiate, plan, and perform activities related to hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. Each item was scored as yes: 1, no: 0 and N/A: not applicable. Higher scores indicate less disability with a score of 100 indicating no disability and 0 indicating no functional ability. The percentage score was calculated as (DAD Total score /Total number of applicable items) multiplied by 100. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Full population data was presented. |
| Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Baseline (Week 0) and Week 8, 16, 24, 48 | NPI is an assessment of frequency and severity of behavioral disturbances in dementia that comprised of 10 dimensions: delusions, hallucinations, dysphoria, apathy, euphoria, disinhibition, aggressiveness and agitation, irritability, anxiety, aberrant motor activity. Participant's caregiver asked about behavior in participant. If Yes, informant then rated both severity on a 3-point scale, 1-mild to 3-severe (total range: 0-36) and frequency using a 4-point scale, 1-occasionally to 4-very frequently. Total score was frequency × severity. Distress was scored on 5-point scale, 0-no distress to 5-very severe or extreme. Total NPI score was calculated by adding all domain scores; NPI total score: 0-144 and NPI distress score: 0-60, higher scores indicated more severe behavioral disturbance. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Adjusted means were presented. Full population data was presented. |
| Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Baseline (Week 0) and Week 12, 24, 36, 48 | The RUD instrument was developed as a comprehensive tool to assess the amount of resource use among demented patients. RUD assessd both formal and informal resource use of the patient and the primary caregiver, making it possible to calculate costs from a societal perspective. Q1 corresponds to the number of hours during the last month the caregiver spent assisting the patient with toilet visits, eating, dressing, grooming, walking and bathing and Q2 corresponds to the number of hours during the last month the caregiver spent assisting the patient with shopping, food preparation, housekeeping, laundry, transportation, taking medication and managing financial matters. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Full population data was presented. |
Countries
Australia, Belgium, Bulgaria, Canada, Czechia, Finland, France, Germany, Hong Kong, Malaysia, Netherlands, Philippines, Poland, Singapore, Slovakia, Slovenia, South Africa, South Korea, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
A total of 1485 participants with Alzheimer's disease (AD) who were being treated with an approved Acetylcholinesterase inhibitor (AChEI) were randomized in the study and stratified by Apolipoprotein E gene (APOE) ε4 allele status. Total of 1468 were included in safety population and 1429 in the intent-to-treat population (ITT).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54) | 487 |
| RSG XR 2mg Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54) | 490 |
| RSG XR 8mg Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54) | 491 |
| Total | 1,468 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Abnormal ECG | 0 | 1 | 3 |
| Overall Study | Administration related | 3 | 1 | 1 |
| Overall Study | Adverse Event | 46 | 49 | 78 |
| Overall Study | Caregiver related | 4 | 7 | 3 |
| Overall Study | Conditional medication increased dose | 1 | 0 | 0 |
| Overall Study | Decided to discontinue on their own | 1 | 4 | 1 |
| Overall Study | Disease progression | 1 | 2 | 5 |
| Overall Study | Efficacy related | 1 | 1 | 0 |
| Overall Study | Exclusion criteria met | 0 | 0 | 1 |
| Overall Study | Increased risk of cardiac infarction | 0 | 1 | 0 |
| Overall Study | Investigator decided to discontinue | 4 | 1 | 4 |
| Overall Study | Lost to Follow-up | 4 | 4 | 4 |
| Overall Study | Memory declined | 0 | 0 | 1 |
| Overall Study | Non-compliance | 8 | 13 | 5 |
| Overall Study | Participant at risk due to study drug | 2 | 0 | 0 |
| Overall Study | Participant died | 0 | 1 | 0 |
| Overall Study | Participant hospitalised | 3 | 0 | 0 |
| Overall Study | Participant unwell | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 12 | 13 | 14 |
| Overall Study | Screen failure | 1 | 0 | 0 |
| Overall Study | Serious adverse event | 0 | 1 | 0 |
| Overall Study | Unmet inclusion-exclusion criteria | 1 | 0 | 1 |
| Overall Study | Use of prohibited drug | 1 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 32 | 40 | 40 |
Baseline characteristics
| Characteristic | Placebo | RSG XR 2mg | RSG XR 8mg | Total |
|---|---|---|---|---|
| Age, Continuous | 72.8 Years STANDARD_DEVIATION 8.19 | 73.4 Years STANDARD_DEVIATION 8.19 | 73.6 Years STANDARD_DEVIATION 8.4 | 73.3 Years STANDARD_DEVIATION 8.26 |
| Race/Ethnicity, Customized Hispanic or Latino | 16 Participants | 14 Participants | 18 Participants | 48 Participants |
| Race/Ethnicity, Customized Missing | 4 Participants | 3 Participants | 3 Participants | 10 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 467 Participants | 473 Participants | 470 Participants | 1410 Participants |
| Sex: Female, Male Female | 272 Participants | 276 Participants | 268 Participants | 816 Participants |
| Sex: Female, Male Male | 215 Participants | 214 Participants | 223 Participants | 652 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 9 / 487 | 11 / 490 | 11 / 491 |
| other Total, other adverse events | 11 / 487 | 42 / 490 | 100 / 491 |
| serious Total, serious adverse events | 60 / 487 | 58 / 490 | 66 / 491 |
Outcome results
Primary
Change From Baseline in ADAS-Cog Total Score at Week 48, as a Function of APOE ε4 Status in All Except E4/E4s Cohort
The 11-item ADAS-Cog assessed 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. Scores range from 0 to 70 with higher scores indicating greater dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. A hierarchical testing procedure was used to control for statistical tests in the two RSG dose groups and the genetic subgroups.
Time frame: Baseline (Week 0) and Week 48
Population: ITT population. Number of participants with observed data contributing to the analysis have been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in ADAS-Cog Total Score at Week 48, as a Function of APOE ε4 Status in All Except E4/E4s Cohort | 3.8 Scores on a scale | Standard Error 0.38 |
| RSG XR 2mg | Change From Baseline in ADAS-Cog Total Score at Week 48, as a Function of APOE ε4 Status in All Except E4/E4s Cohort | 3.6 Scores on a scale | Standard Error 0.35 |
| RSG XR 8mg | Change From Baseline in ADAS-Cog Total Score at Week 48, as a Function of APOE ε4 Status in All Except E4/E4s Cohort | 3.8 Scores on a scale | Standard Error 0.41 |
p-value: 0.78395% CI: [-1.1, 0.9]Mixed model for repeated measures
p-value: 0.9495% CI: [-1.1, 1.1]Mixed model for repeated measures
Primary
Change From Baseline in ADAS-Cog Total Score at Week 48, as a Function of APOE ε4 Status in Full Population Cohort
The 11-item ADAS-Cog assessed 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. Scores range from 0 to 70 with higher scores indicating greater dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. A hierarchical testing procedure was used to control for statistical tests in the two RSG dose groups and the genetic subgroups.
Time frame: Baseline (Week 0) and Week 48
Population: ITT population. Number of participants with observed data contributing to the analysis have been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in ADAS-Cog Total Score at Week 48, as a Function of APOE ε4 Status in Full Population Cohort | 3.9 Scores on a scale | Standard Error 0.35 |
| RSG XR 2mg | Change From Baseline in ADAS-Cog Total Score at Week 48, as a Function of APOE ε4 Status in Full Population Cohort | 3.8 Scores on a scale | Standard Error 0.33 |
| RSG XR 8mg | Change From Baseline in ADAS-Cog Total Score at Week 48, as a Function of APOE ε4 Status in Full Population Cohort | 3.8 Scores on a scale | Standard Error 0.36 |
p-value: =0.76395% CI: [-1.1, 0.8]Mixed model for repeated measures
p-value: =0.895% CI: [-1.1, 0.9]Mixed model for repeated measures
Primary
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 48, as a Function of APOE ε4 Status in APOE4 Negatives Cohort
The 11-item ADAS-Cog assessed 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. Scores range from 0 to 70 with higher scores indicating greater dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. A hierarchical testing procedure was used to control for statistical tests in the two RSG dose groups and the genetic subgroups.
Time frame: Baseline (Week 0) and Week 48
Population: ITT population comprised of all participants randomized to treatment, who had taken at least one dose of study medication and who had at least one post baseline efficacy assessment. Number of participants with observed data contributing to the analysis have been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 48, as a Function of APOE ε4 Status in APOE4 Negatives Cohort | 3.2 Scores on a scale | Standard Error 0.54 |
| RSG XR 2mg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 48, as a Function of APOE ε4 Status in APOE4 Negatives Cohort | 3.5 Scores on a scale | Standard Error 0.53 |
| RSG XR 8mg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 48, as a Function of APOE ε4 Status in APOE4 Negatives Cohort | 4.0 Scores on a scale | Standard Error 0.63 |
p-value: 0.73995% CI: [-1.2, 1.8]Mixed model for repeated measures
p-value: 0.34395% CI: [-0.8, 2.4]Mixed model for repeated measures
Primary
Change From Baseline in CDR-SB Score at Week 48, as a Function of APOE ε4 Status in All Except E4/E4s Cohort
The CDR-SB was a validated clinical assessment of global function in patients with AD. Impairment was scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or box scores, can be added together to give the CDR-Sum of Boxes which ranges from 0 to 18 (severe impairment). Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Primary inference will be based on the week 48 treatment differences obtained from the MMRM model. A hierarchical testing procedure was used to control for statistical tests in the two RSG dose groups and the genetic subgroups.
Time frame: Baseline (Week 0) and Week 48
Population: ITT population. Number of participants with observed data contributing to the analysis have been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in CDR-SB Score at Week 48, as a Function of APOE ε4 Status in All Except E4/E4s Cohort | 1.8 Scores on a scale | Standard Error 0.13 |
| RSG XR 2mg | Change From Baseline in CDR-SB Score at Week 48, as a Function of APOE ε4 Status in All Except E4/E4s Cohort | 1.8 Scores on a scale | Standard Error 0.13 |
| RSG XR 8mg | Change From Baseline in CDR-SB Score at Week 48, as a Function of APOE ε4 Status in All Except E4/E4s Cohort | 1.7 Scores on a scale | Standard Error 0.13 |
p-value: 0.91395% CI: [-0.4, 0.3]Mixed model for repeated measures
p-value: 0.48195% CI: [-0.5, 0.2]Mixed model for repeated measures
Primary
Change From Baseline in CDR-SB Score at Week 48, as a Function of APOE ε4 Status in Full Population Cohort
The CDR-SB was a validated clinical assessment of global function in patients with AD. Impairment was scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or box scores, can be added together to give the CDR-Sum of Boxes which ranges from 0 to 18 (severe impairment). Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Primary inference will be based on the week 48 treatment differences obtained from the MMRM model. A hierarchical testing procedure was used to control for statistical tests in the two RSG dose groups and the genetic subgroups.
Time frame: Baseline (Week 0) and Week 48
Population: ITT population. Number of participants with observed data contributing to the analysis have been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in CDR-SB Score at Week 48, as a Function of APOE ε4 Status in Full Population Cohort | 1.9 Scores on a scale | Standard Error 0.12 |
| RSG XR 2mg | Change From Baseline in CDR-SB Score at Week 48, as a Function of APOE ε4 Status in Full Population Cohort | 1.8 Scores on a scale | Standard Error 0.13 |
| RSG XR 8mg | Change From Baseline in CDR-SB Score at Week 48, as a Function of APOE ε4 Status in Full Population Cohort | 1.8 Scores on a scale | Standard Error 0.12 |
p-value: 0.55795% CI: [-0.4, 0.2]Mixed model for repeated measures
p-value: 0.40495% CI: [-0.5, 0.2]Mixed model for repeated measures
Primary
Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score at Week 48, as a Function of APOE ε4 Status in APOE4 Negatives Cohort
The CDR-SB was a validated clinical assessment of global function in patients with AD. Impairment was scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or box scores, can be added together to give the CDR-Sum of Boxes which ranges from 0 to 18 (severe impairment). Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Primary inference will be based on the week 48 treatment differences obtained from the MMRM model. A hierarchical testing procedure was used to control for statistical tests in the two RSG dose groups and the genetic subgroups.
Time frame: Baseline (Week 0) and Week 48
Population: ITT population. Number of participants with observed data contributing to the analysis have been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score at Week 48, as a Function of APOE ε4 Status in APOE4 Negatives Cohort | 1.8 Scores on a scale | Standard Error 0.2 |
| RSG XR 2mg | Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score at Week 48, as a Function of APOE ε4 Status in APOE4 Negatives Cohort | 1.7 Scores on a scale | Standard Error 0.2 |
| RSG XR 8mg | Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score at Week 48, as a Function of APOE ε4 Status in APOE4 Negatives Cohort | 1.7 Scores on a scale | Standard Error 0.17 |
p-value: 0.61195% CI: [-0.7, 0.4]Mixed model for repeated measures
p-value: 0.74195% CI: [-0.6, 0.4]Mixed model for repeated measures
Secondary
Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range
Clinical chemistry parameters were identified as of PCC (High, Low), if values were out of RR: Alanine amino transferase (ALT,none-120 \[250percent upper limit of RR, ULRR \]),Album in (0.75-2),Aldolase(1.1-1.1),Aspartate amino transferase (AST,none-105 (3-64y),137.5(65+y),\>250 percent ULRR), Alkaline phosphatase(ALP,none-312.5 (20+y),\>250percent ULRR),blood urea nitrogen(BUN)/Creatinine ratio(none-1.25),BUN(none-11),Chloride(80-115),Calcium (0.75-1.25),Carbon dioxide(CO2,15-40) content,Creatinine (22,\<50percent lower limit of RR \[LLRR \]-155, \>125percent ULRR),Creatine phosphokinase(CPK,none-1.25),Gamma glutamyl transferase(GGT,none-2.5),Glucose (3.6-7.8),HbA1C, High density lipoprotein (HDL,0.65-none),Lactate dehydrogenase (LDH,none -2), Low density lipoprotein(LDL,none-1.25),Magnesium (0.5-2),Potassium (3-5.5),Phosphorus inorganic(0.5-1.5), Sodium (130-150), Total protein (0.8-1.5),Total cholesterol(none -1.5),Direct Billirubin.
Time frame: Upto Week 48
Population: Safety population. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Urea/BUN- High | 27 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Magnesium- Low | 1 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Creatinine- High | 10 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | ALT- High | 2 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Lactate Dehydrogenase- High | 0 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Direct Bilirubin- High | 1 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | AST- High | 1 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | LDL Cholesterol calculation- High | 65 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | GGT- High | 6 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Troponin I- High | 1 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | HDL Cholesterol, direct- Low | 0 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Glucose- High | 81 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Sodium- Low | 4 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Glycosylated Hemoglobin A1C | 1 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Glucose- Low | 14 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | BUN/Creatinine ratio- High | 17 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Aldolase- Low | 2 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Sodium- High | 2 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Calcium- Low | 1 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Aldolase- High | 2 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Potassium- Low | 3 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Carbondioxide content/BicarbonateLow | 0 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Total Bilirubin- High | 5 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Potassium- High | 11 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Cholesterol- High | 21 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Alkaline Phosphatase- High | 2 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Phosphorus, inorganic- High | 2 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Creatine Kinase- High | 33 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Sodium- Low | 6 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | ALT- High | 1 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Aldolase- High | 2 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Aldolase- Low | 1 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Alkaline Phosphatase- High | 0 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | AST- High | 1 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | BUN/Creatinine ratio- High | 25 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Calcium- Low | 0 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Carbondioxide content/BicarbonateLow | 0 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Cholesterol- High | 32 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Creatine Kinase- High | 63 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Creatinine- High | 12 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Direct Bilirubin- High | 0 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | GGT- High | 2 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Glucose- High | 60 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Glucose- Low | 22 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Glycosylated Hemoglobin A1C | 1 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | HDL Cholesterol, direct- Low | 0 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | LDL Cholesterol calculation- High | 106 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Lactate Dehydrogenase- High | 0 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Magnesium- Low | 0 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Phosphorus, inorganic- High | 0 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Potassium- High | 12 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Potassium- Low | 1 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Sodium- High | 0 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Total Bilirubin- High | 1 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Troponin I- High | 1 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Urea/BUN- High | 40 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Lactate Dehydrogenase- High | 1 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Creatine Kinase- High | 69 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | ALT- High | 1 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Magnesium- Low | 1 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Cholesterol- High | 61 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Total Bilirubin- High | 1 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Phosphorus, inorganic- High | 0 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Carbondioxide content/BicarbonateLow | 3 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Aldolase- High | 0 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Potassium- High | 12 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Calcium- Low | 0 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Urea/BUN- High | 48 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Potassium- Low | 0 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | BUN/Creatinine ratio- High | 40 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Troponin I- High | 1 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Sodium- High | 2 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Glucose- Low | 22 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Glucose- High | 55 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | AST- High | 2 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Glycosylated Hemoglobin A1C | 0 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | GGT- High | 5 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Alkaline Phosphatase- High | 0 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | HDL Cholesterol, direct- Low | 3 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Direct Bilirubin- High | 1 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Sodium- Low | 2 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | LDL Cholesterol calculation- High | 162 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Creatinine- High | 15 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range | Aldolase- Low | 0 Participants |
Secondary
Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range
Haematology parameters were identified as of PCC (high \[H\], low \[L\]), if the values were out of the reference range (RR). The range for parameters was: platelet (100AV-500AV), red blood cell (RBC , 0.8-1.2), hemoglobin (L: female \[F\]:10, male \[M\]:11; H: F:16.5-AV, M:18), hematocrit (0.8-1.2), white blood cell (WBC, 3-15), Total neutrophils (ANC- absolute Neutrophil count) (0.75-1.5), lymphocytes (0.75-1.5), monocyte s (0.75-2), eosinophils (none -2), basophils (none -2), mean corpuscle volume (MCV, 0.8-1.2), mean corpuscular hemoglobin (MCH, 0.8-1.2), mean corpuscular hemoglobin concentration (MCHC , 0.8-1.2), red cell distribution width (RDW, 0.8-1.2), Neutrophil bands (none-1) and segmented neutrophils (0.75-1.3). Full population data was presented.
Time frame: Up to Week 48
Population: Safety population. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | MCH- High | 0 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | MCV- High | 0 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Eosinophils- High | 3 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Total Neutrophils (ANC)- High | 4 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Lymphocytes- Low | 11 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Hematocrit- Low | 3 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | White Blood Cell count- High | 5 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Lymphocytes- High | 3 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Hemoglobin- High | 1 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | RDW- Low | 1 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Hemoglobin- Low | 9 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Platelet count- High | 3 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Red Blood Cell count- High | 0 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Platelet count- Low | 3 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Monocytes- Low | 44 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Red Blood Cell count- Low | 3 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Total Neutrophils (ANC)- Low | 4 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | MCV- Low | 0 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | MCH- Low | 1 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | White Blood Cell count- Low | 4 Participants |
| Placebo | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | RDW- High | 11 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Platelet count- High | 2 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | RDW- Low | 0 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Total Neutrophils (ANC)- High | 0 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Total Neutrophils (ANC)- Low | 2 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | White Blood Cell count- High | 2 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Red Blood Cell count- High | 0 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Red Blood Cell count- Low | 3 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | White Blood Cell count- Low | 3 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Eosinophils- High | 1 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Hematocrit- Low | 3 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Hemoglobin- High | 3 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Hemoglobin- Low | 14 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Lymphocytes- High | 1 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Lymphocytes- Low | 3 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | MCH- High | 0 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | MCH- Low | 3 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | MCV- High | 0 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | MCV- Low | 1 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Monocytes- Low | 21 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Platelet count- Low | 0 Participants |
| RSG XR 2mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | RDW- High | 18 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Platelet count- High | 4 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | MCH- High | 1 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | White Blood Cell count- High | 0 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Total Neutrophils (ANC)- High | 0 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | MCH- Low | 3 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | MCV- High | 1 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Red Blood Cell count- Low | 11 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Platelet count- Low | 2 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | MCV- Low | 1 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Red Blood Cell count- High | 1 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | RDW- High | 50 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Hemoglobin- High | 1 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Monocytes- Low | 44 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Hemoglobin- Low | 36 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Hematocrit- Low | 6 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | RDW- Low | 0 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Lymphocytes- High | 1 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Eosinophils- High | 1 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Total Neutrophils (ANC)- Low | 10 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | Lymphocytes- Low | 7 Participants |
| RSG XR 8mg | Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range | White Blood Cell count- Low | 12 Participants |
Secondary
Change From Baseline in ADAS-Cog Total Score at Weeks 8, 16, 24 and 36
The 11-item ADAS-Cog assessed 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. Scores range from 0 to 70 with higher scores indicating greater dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. It was calculated at Weeks 8, 16, 24 and 36. Full population data was presented.
Time frame: Baseline (Week 0) and Week 8, 16, 24, 36
Population: ITT population. Number of participants with observed data contributing to the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in ADAS-Cog Total Score at Weeks 8, 16, 24 and 36 | Week 24 | 1.1 Scores on a scale | Standard Error 0.26 |
| Placebo | Change From Baseline in ADAS-Cog Total Score at Weeks 8, 16, 24 and 36 | Week 36 | 2.6 Scores on a scale | Standard Error 0.31 |
| Placebo | Change From Baseline in ADAS-Cog Total Score at Weeks 8, 16, 24 and 36 | Week 8 | 0.1 Scores on a scale | Standard Error 0.23 |
| Placebo | Change From Baseline in ADAS-Cog Total Score at Weeks 8, 16, 24 and 36 | Week 16 | 0.2 Scores on a scale | Standard Error 0.24 |
| RSG XR 2mg | Change From Baseline in ADAS-Cog Total Score at Weeks 8, 16, 24 and 36 | Week 24 | 1.5 Scores on a scale | Standard Error 0.28 |
| RSG XR 2mg | Change From Baseline in ADAS-Cog Total Score at Weeks 8, 16, 24 and 36 | Week 16 | 0.3 Scores on a scale | Standard Error 0.23 |
| RSG XR 2mg | Change From Baseline in ADAS-Cog Total Score at Weeks 8, 16, 24 and 36 | Week 36 | 2.8 Scores on a scale | Standard Error 0.29 |
| RSG XR 2mg | Change From Baseline in ADAS-Cog Total Score at Weeks 8, 16, 24 and 36 | Week 8 | 0.2 Scores on a scale | Standard Error 0.23 |
| RSG XR 8mg | Change From Baseline in ADAS-Cog Total Score at Weeks 8, 16, 24 and 36 | Week 36 | 2.6 Scores on a scale | Standard Error 0.31 |
| RSG XR 8mg | Change From Baseline in ADAS-Cog Total Score at Weeks 8, 16, 24 and 36 | Week 8 | 0.3 Scores on a scale | Standard Error 0.23 |
| RSG XR 8mg | Change From Baseline in ADAS-Cog Total Score at Weeks 8, 16, 24 and 36 | Week 16 | 0.2 Scores on a scale | Standard Error 0.24 |
| RSG XR 8mg | Change From Baseline in ADAS-Cog Total Score at Weeks 8, 16, 24 and 36 | Week 24 | 1.1 Scores on a scale | Standard Error 0.27 |
Comparison: For Week 8p-value: 0.63395% CI: [-0.5, 0.8]Mixed model for repeated measures
Comparison: For Week 8p-value: 0.57595% CI: [-0.4, 0.8]Mixed model for repeated measures
Comparison: For Week 16p-value: 0.8295% CI: [-0.6, 0.7]Mixed model for repeated measures
Comparison: For Week 16p-value: 0.90895% CI: [-0.7, 0.6]Mixed model for repeated measures
Comparison: For Week 24p-value: 0.29295% CI: [-0.3, 1.1]Mixed model for repeated measures
Comparison: For Week 24p-value: 0.97895% CI: [-0.7, 0.7]Mixed model for repeated measures
Comparison: For Week 36p-value: 0.69195% CI: [-0.6, 1]Mixed model for repeated measures
Comparison: For Week 36p-value: 0.84995% CI: [-0.9, 0.8]Mixed model for repeated measures
Secondary
Change From Baseline in Alzheimer's Carer's Quality of Life Instrument (ACQLI) Score
The ACQLI is an assessment of caregiver quality of life. This instrument consisted of 30 questions exploring various aspects of carer's quality of life. Each of the questions had two point response, and the 30 questions were summed to provide a total score. Items were assumed to be unidimensional (i.e., represent a single variable) and were scored 0/1 (false/true) before summation into a total score with a 0-30 range. To ease comparisons between scales, ACQLI scores were transformed to range between 0-100 (100: worse). Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Full population data was presented.
Time frame: Baseline (Week 0) and Week 12, 36, 48
Population: ITT population. Number of participants with observed data contributing to the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Alzheimer's Carer's Quality of Life Instrument (ACQLI) Score | Week 36 | 1.2 Scores on a scale | Standard Error 0.24 |
| Placebo | Change From Baseline in Alzheimer's Carer's Quality of Life Instrument (ACQLI) Score | Week 12 | 0.3 Scores on a scale | Standard Error 0.19 |
| Placebo | Change From Baseline in Alzheimer's Carer's Quality of Life Instrument (ACQLI) Score | Week 48 | 1.1 Scores on a scale | Standard Error 0.27 |
| RSG XR 2mg | Change From Baseline in Alzheimer's Carer's Quality of Life Instrument (ACQLI) Score | Week 36 | 0.8 Scores on a scale | Standard Error 0.25 |
| RSG XR 2mg | Change From Baseline in Alzheimer's Carer's Quality of Life Instrument (ACQLI) Score | Week 12 | 0.1 Scores on a scale | Standard Error 0.19 |
| RSG XR 2mg | Change From Baseline in Alzheimer's Carer's Quality of Life Instrument (ACQLI) Score | Week 48 | 1.3 Scores on a scale | Standard Error 0.29 |
| RSG XR 8mg | Change From Baseline in Alzheimer's Carer's Quality of Life Instrument (ACQLI) Score | Week 12 | 0.2 Scores on a scale | Standard Error 0.21 |
| RSG XR 8mg | Change From Baseline in Alzheimer's Carer's Quality of Life Instrument (ACQLI) Score | Week 48 | 1.2 Scores on a scale | Standard Error 0.27 |
| RSG XR 8mg | Change From Baseline in Alzheimer's Carer's Quality of Life Instrument (ACQLI) Score | Week 36 | 1.4 Scores on a scale | Standard Error 0.25 |
Comparison: Week 12p-value: 0.52995% CI: [-0.7, 0.3]Mixed model for repeated measures
Comparison: Week 12p-value: 0.6295% CI: [-0.7, 0.4]Mixed model for repeated measures
Comparison: Week 36p-value: 0.28495% CI: [-1, 0.3]Mixed model for repeated measures
Comparison: Week 36p-value: 0.48895% CI: [-0.4, 0.9]Mixed model for repeated measures
Comparison: Week 48p-value: 0.54995% CI: [-0.5, 1]Mixed model for repeated measures
Comparison: For Week 48p-value: 0.7895% CI: [-0.6, 0.9]Mixed model for repeated measures
Secondary
Change From Baseline in CDR-SB Score at Weeks 12, 24 and 36
The CDR-SB was a validated clinical assessment of global function in patients with AD. Impairment was scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or box scores, can be added together to give the CDR-Sum of Boxes which ranges from 0 to 18 (severe impairment). Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. It was calculated at Weeks 12, 24 and 36. Full population data was presented.
Time frame: Baseline (Week 0) and Week 12, 24, 36
Population: ITT population. Number of participants with observed data contributing to the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in CDR-SB Score at Weeks 12, 24 and 36 | Week 24 | 0.9 Scores on a scale | Standard Error 0.1 |
| Placebo | Change From Baseline in CDR-SB Score at Weeks 12, 24 and 36 | Week 12 | 0.3 Scores on a scale | Standard Error 0.07 |
| Placebo | Change From Baseline in CDR-SB Score at Weeks 12, 24 and 36 | Week 36 | 1.4 Scores on a scale | Standard Error 0.11 |
| RSG XR 2mg | Change From Baseline in CDR-SB Score at Weeks 12, 24 and 36 | Week 24 | 0.8 Scores on a scale | Standard Error 0.1 |
| RSG XR 2mg | Change From Baseline in CDR-SB Score at Weeks 12, 24 and 36 | Week 12 | 0.4 Scores on a scale | Standard Error 0.08 |
| RSG XR 2mg | Change From Baseline in CDR-SB Score at Weeks 12, 24 and 36 | Week 36 | 1.3 Scores on a scale | Standard Error 0.11 |
| RSG XR 8mg | Change From Baseline in CDR-SB Score at Weeks 12, 24 and 36 | Week 12 | 0.3 Scores on a scale | Standard Error 0.07 |
| RSG XR 8mg | Change From Baseline in CDR-SB Score at Weeks 12, 24 and 36 | Week 36 | 1.3 Scores on a scale | Standard Error 0.1 |
| RSG XR 8mg | Change From Baseline in CDR-SB Score at Weeks 12, 24 and 36 | Week 24 | 0.9 Scores on a scale | Standard Error 0.09 |
Comparison: For Week 12p-value: 0.93895% CI: [-0.2, 0.2]Mixed model for repeated measures
Comparison: For Week 12p-value: 0.88795% CI: [-0.2, 0.2]Mixed model for repeated measures
Comparison: For Week 24p-value: 0.46595% CI: [-0.4, 0.2]Mixed model for repeated measures
Comparison: For Week 24p-value: 0.59695% CI: [-0.2, 0.3]Mixed model for repeated measures
Comparison: For Week 36p-value: 0.45295% CI: [-0.4, 0.2]Mixed model for repeated measures
Comparison: For Week 36p-value: 0.42995% CI: [-0.4, 0.2]Mixed model for repeated measures
Secondary
Change From Baseline in Disability Assessment for Dementia (DAD) Total Score
The DAD assessed the ability of a participant to execute basic and instrumental activities of daily living (ADL) and leisure activities. The scale consists of 40 questions assessing basic and instrumental ADLs. This scale assessed a participants' ability to initiate, plan, and perform activities related to hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. Each item was scored as yes: 1, no: 0 and N/A: not applicable. Higher scores indicate less disability with a score of 100 indicating no disability and 0 indicating no functional ability. The percentage score was calculated as (DAD Total score /Total number of applicable items) multiplied by 100. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Full population data was presented.
Time frame: Baseline (Week 0) and Week 8, 16, 24, 48
Population: ITT population. Number of participants with observed data contributing to the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Disability Assessment for Dementia (DAD) Total Score | Week 8 | -2.3 Scores on a scale | Standard Error 0.5 |
| Placebo | Change From Baseline in Disability Assessment for Dementia (DAD) Total Score | Week 16 | -3.0 Scores on a scale | Standard Error 0.57 |
| Placebo | Change From Baseline in Disability Assessment for Dementia (DAD) Total Score | Week 24 | -4.6 Scores on a scale | Standard Error 0.6 |
| Placebo | Change From Baseline in Disability Assessment for Dementia (DAD) Total Score | Week 48 | -9.5 Scores on a scale | Standard Error 0.81 |
| RSG XR 2mg | Change From Baseline in Disability Assessment for Dementia (DAD) Total Score | Week 48 | -9.4 Scores on a scale | Standard Error 0.81 |
| RSG XR 2mg | Change From Baseline in Disability Assessment for Dementia (DAD) Total Score | Week 8 | -1.2 Scores on a scale | Standard Error 0.5 |
| RSG XR 2mg | Change From Baseline in Disability Assessment for Dementia (DAD) Total Score | Week 24 | -2.8 Scores on a scale | Standard Error 0.62 |
| RSG XR 2mg | Change From Baseline in Disability Assessment for Dementia (DAD) Total Score | Week 16 | -2.3 Scores on a scale | Standard Error 0.55 |
| RSG XR 8mg | Change From Baseline in Disability Assessment for Dementia (DAD) Total Score | Week 48 | -10.4 Scores on a scale | Standard Error 0.82 |
| RSG XR 8mg | Change From Baseline in Disability Assessment for Dementia (DAD) Total Score | Week 16 | -3.9 Scores on a scale | Standard Error 0.59 |
| RSG XR 8mg | Change From Baseline in Disability Assessment for Dementia (DAD) Total Score | Week 24 | -4.7 Scores on a scale | Standard Error 0.63 |
| RSG XR 8mg | Change From Baseline in Disability Assessment for Dementia (DAD) Total Score | Week 8 | -2.3 Scores on a scale | Standard Error 0.46 |
Comparison: For Week 8p-value: 0.0995% CI: [-0.2, 2.5]Mixed model for repeated measures
Comparison: For Week 8p-value: 0.95795% CI: [-1.3, 1.3]Mixed model for repeated measures
Comparison: For Week 16p-value: 0.39595% CI: [-0.9, 2.2]Mixed model for repeated measures
Comparison: For Week 16p-value: 0.27595% CI: [-2.5, 0.7]Mixed model for repeated measures
Comparison: For Week 24p-value: 0.03995% CI: [0.1, 3.4]Mixed model for repeated measures
Comparison: For Week 24p-value: 0.89595% CI: [-1.8, 1.6]Mixed model for repeated measures
Comparison: For Week 48p-value: 0.91495% CI: [-2.1, 2.3]Mixed model for repeated measures
Comparison: For Week 48p-value: 0.4395% CI: [-3.2, 1.3]Mixed model for repeated measures
Secondary
Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours
The RUD instrument was developed as a comprehensive tool to assess the amount of resource use among demented patients. RUD assessd both formal and informal resource use of the patient and the primary caregiver, making it possible to calculate costs from a societal perspective. Q1 corresponds to the number of hours during the last month the caregiver spent assisting the patient with toilet visits, eating, dressing, grooming, walking and bathing and Q2 corresponds to the number of hours during the last month the caregiver spent assisting the patient with shopping, food preparation, housekeeping, laundry, transportation, taking medication and managing financial matters. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Full population data was presented.
Time frame: Baseline (Week 0) and Week 12, 24, 36, 48
Population: ITT population. Number of participants with observed data contributing to the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Q1 Week 12 | -2.4 Caregiver hours | Standard Error 2.72 |
| Placebo | Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Q1 Week 24 | 7.4 Caregiver hours | Standard Error 3.43 |
| Placebo | Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Q1 Week 36 | 11.2 Caregiver hours | Standard Error 4.36 |
| Placebo | Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Q1 Week 48 | 15.7 Caregiver hours | Standard Error 4.14 |
| Placebo | Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Q2 Week 12 | -1.1 Caregiver hours | Standard Error 4.06 |
| Placebo | Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Q2 Week 24 | 5.6 Caregiver hours | Standard Error 4.41 |
| Placebo | Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Q2 Week 36 | 16.4 Caregiver hours | Standard Error 5.52 |
| Placebo | Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Q2 Week 48 | 21.8 Caregiver hours | Standard Error 5.62 |
| RSG XR 2mg | Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Q1 Week 36 | 12.7 Caregiver hours | Standard Error 3.7 |
| RSG XR 2mg | Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Q2 Week 36 | 23.4 Caregiver hours | Standard Error 6.1 |
| RSG XR 2mg | Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Q1 Week 48 | 19.7 Caregiver hours | Standard Error 4.06 |
| RSG XR 2mg | Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Q2 Week 12 | 5.8 Caregiver hours | Standard Error 3.7 |
| RSG XR 2mg | Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Q2 Week 24 | 15.6 Caregiver hours | Standard Error 4.9 |
| RSG XR 2mg | Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Q1 Week 12 | 1.8 Caregiver hours | Standard Error 2.56 |
| RSG XR 2mg | Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Q1 Week 24 | 9.0 Caregiver hours | Standard Error 2.92 |
| RSG XR 2mg | Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Q2 Week 48 | 26.0 Caregiver hours | Standard Error 5.69 |
| RSG XR 8mg | Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Q1 Week 36 | 13.4 Caregiver hours | Standard Error 4.09 |
| RSG XR 8mg | Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Q1 Week 24 | 10.9 Caregiver hours | Standard Error 3.69 |
| RSG XR 8mg | Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Q1 Week 12 | 3.5 Caregiver hours | Standard Error 2.68 |
| RSG XR 8mg | Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Q1 Week 48 | 19.2 Caregiver hours | Standard Error 4.54 |
| RSG XR 8mg | Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Q2 Week 36 | 15.2 Caregiver hours | Standard Error 4.53 |
| RSG XR 8mg | Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Q2 Week 24 | 12.3 Caregiver hours | Standard Error 4.79 |
| RSG XR 8mg | Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Q2 Week 12 | 6.4 Caregiver hours | Standard Error 4.04 |
| RSG XR 8mg | Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours | Q2 Week 48 | 21.6 Caregiver hours | Standard Error 4.92 |
Comparison: Q1 Week 12p-value: 0.25195% CI: [-2.9, 11.2]Mixed model for repeated measures
Comparison: Q1 Week 12p-value: 0.11395% CI: [-1.4, 13.2]Mixed model for repeated measures
Comparison: Q1 Week 24p-value: 0.72395% CI: [-7.1, 10.2]Mixed model for repeated measures
Comparison: Q1 Week 24p-value: 0.48295% CI: [-6.3, 13.2]Mixed model for repeated measures
Comparison: Q1 Week 36p-value: 0.78595% CI: [-9.5, 12.6]Mixed model for repeated measures
Comparison: Q1 Week 36p-value: 0.71195% CI: [-9.4, 13.8]Mixed model for repeated measures
Comparison: Q1 Week 48p-value: 0.48495% CI: [-7.2, 15.2]Mixed model for repeated measures
Comparison: Q1 Week 48p-value: 0.57295% CI: [-8.5, 15.4]Mixed model for repeated measures
Comparison: Q2 Week 12p-value: 0.19795% CI: [-3.6, 17.3]Mixed model for repeated measures
Comparison: Q2 Week 12p-value: 0.18395% CI: [-3.5, 18.4]Mixed model for repeated measures
Comparison: Q2 Week 24p-value: 0.12195% CI: [-2.6, 22.6]Mixed model for repeated measures
Comparison: Q2 Week 24p-value: 0.29195% CI: [-5.8, 19.3]Mixed model for repeated measures
Comparison: Q2 Week 36p-value: 0.38995% CI: [-8.9, 22.9]Mixed model for repeated measures
Comparison: Q2 Week 36p-value: 0.86595% CI: [-15, 12.6]Mixed model for repeated measures
Comparison: Q2 Week 48p-value: 0.59695% CI: [-11.3, 19.6]Mixed model for repeated measures
Comparison: Q2 Week 48p-value: 0.97595% CI: [-14.7, 14.2]Mixed model for repeated measures
Secondary
Change From Baseline in EQ-5D Scale Total Score- Utility Score
The EQ-5D Proxy is an assessment of quality of life and utility benefit. The EQ-5D Proxy is composed of two parts: part one is the five dimensional Health State Classification. The Utility score is a caregiver rating of health status on dimensions of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Answers to each question were responded to on a 3-point scale which indicates the level of impairment (level 1= no problem; level 2=some or moderate problem(s) and level 3=unable, or extreme problem with higher scores indicating greater dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Full population data was presented.
Time frame: Baseline (Week 0) and Week 12, 36, 48
Population: ITT population. Number of participants with observed data contributing to the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in EQ-5D Scale Total Score- Utility Score | Utility score Week 36 | -0.03 Scores on a scale | Standard Error 0.011 |
| Placebo | Change From Baseline in EQ-5D Scale Total Score- Utility Score | Ultility score Week 12 | -0.02 Scores on a scale | Standard Error 0.009 |
| Placebo | Change From Baseline in EQ-5D Scale Total Score- Utility Score | Utility score Week 48 | -0.03 Scores on a scale | Standard Error 0.011 |
| RSG XR 2mg | Change From Baseline in EQ-5D Scale Total Score- Utility Score | Utility score Week 36 | -0.03 Scores on a scale | Standard Error 0.011 |
| RSG XR 2mg | Change From Baseline in EQ-5D Scale Total Score- Utility Score | Ultility score Week 12 | -0.01 Scores on a scale | Standard Error 0.009 |
| RSG XR 2mg | Change From Baseline in EQ-5D Scale Total Score- Utility Score | Utility score Week 48 | -0.05 Scores on a scale | Standard Error 0.012 |
| RSG XR 8mg | Change From Baseline in EQ-5D Scale Total Score- Utility Score | Ultility score Week 12 | -0.03 Scores on a scale | Standard Error 0.009 |
| RSG XR 8mg | Change From Baseline in EQ-5D Scale Total Score- Utility Score | Utility score Week 48 | -0.04 Scores on a scale | Standard Error 0.01 |
| RSG XR 8mg | Change From Baseline in EQ-5D Scale Total Score- Utility Score | Utility score Week 36 | -0.06 Scores on a scale | Standard Error 0.01 |
Comparison: Ultility score Week 12p-value: 0.66295% CI: [-0.02, 0.03]Mixed model for repeated measures
Comparison: Ultility score Week 12p-value: 0.50395% CI: [-0.03, 0.02]Mixed model for repeated measures
Comparison: Utility score Week 36p-value: 0.89295% CI: [-0.03, 0.03]Mixed model for repeated measures
Comparison: Utility score Week 36p-value: 0.08395% CI: [-0.05, 0]Mixed model for repeated measures
Comparison: Utility score Week 48p-value: 0.36695% CI: [-0.05, 0.02]Mixed model for repeated measures
Comparison: Utility score Week 48p-value: 0.76995% CI: [-0.03, 0.02]Mixed model for repeated measures
Secondary
Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Scale Total Score- Thermometer Score
The EQ-5D Proxy is an assessment of quality of life and utility benefit. The EQ-5D Proxy is composed of two parts: part two is the visual analogue scale 'Thermometer'. Caregivers are asked to respond as they feel the participant would on dimensions of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 'Thermometer' has endpoints of 100 (best imaginable health state) and 0 (worst imaginable health state). Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Full population data was presented.
Time frame: Baseline (Week 0) and Week 12, 36, 48
Population: ITT population. Number of participants with observed data contributing to the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Scale Total Score- Thermometer Score | Thermometer score Week 36 | 1.7 Scores on a scale | Standard Error 0.87 |
| Placebo | Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Scale Total Score- Thermometer Score | Thermometer score Week 12 | 2.4 Scores on a scale | Standard Error 0.82 |
| Placebo | Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Scale Total Score- Thermometer Score | Thermometer score Week 48 | 2.1 Scores on a scale | Standard Error 0.91 |
| RSG XR 2mg | Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Scale Total Score- Thermometer Score | Thermometer score Week 36 | 1.3 Scores on a scale | Standard Error 0.94 |
| RSG XR 2mg | Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Scale Total Score- Thermometer Score | Thermometer score Week 12 | -0.0 Scores on a scale | Standard Error 0.89 |
| RSG XR 2mg | Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Scale Total Score- Thermometer Score | Thermometer score Week 48 | -0.5 Scores on a scale | Standard Error 1 |
| RSG XR 8mg | Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Scale Total Score- Thermometer Score | Thermometer score Week 12 | 0.1 Scores on a scale | Standard Error 0.87 |
| RSG XR 8mg | Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Scale Total Score- Thermometer Score | Thermometer score Week 48 | -1.4 Scores on a scale | Standard Error 0.96 |
| RSG XR 8mg | Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Scale Total Score- Thermometer Score | Thermometer score Week 36 | -0.4 Scores on a scale | Standard Error 0.95 |
Comparison: Thermometer score Week 12p-value: 0.04395% CI: [-4.7, -0.1]Mixed model for repeated measures
Comparison: Thermometer score Week 12p-value: 0.05695% CI: [-4.5, 0.1]Mixed model for repeated measures
Comparison: Thermometer score Week 36p-value: 0.75895% CI: [-2.8, 2.1]Mixed model for repeated measures
Comparison: Thermometer score Week 36p-value: 0.10995% CI: [-4.5, 0.5]Mixed model for repeated measures
Comparison: Thermometer score Week 48p-value: 0.0595% CI: [-5.2, 0]Mixed model for repeated measures
Comparison: Thermometer score Week 48p-value: 0.00995% CI: [-6, -0.9]Mixed model for repeated measures
Secondary
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 48
Blood samples were collected for assessments of HbA1c levels at Baseline and up to Week 48. Change from Baseline was calculated as value at scheduled time point minus Baseline value . Baseline was defined as value at Week 0. Endpoint treatment differences which were adjusted to take account of missing data are derived. Full population data was presented.
Time frame: Baseline (Week 0) and Week 48
Population: ITT population. Only those participants available at that particular time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 48 | 0.13 Percentage | Standard Error 0.018 |
| RSG XR 2mg | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 48 | 0.18 Percentage | Standard Error 0.019 |
| RSG XR 8mg | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 48 | 0.26 Percentage | Standard Error 0.019 |
p-value: 0.03895% CI: [0, 0.1]ANCOVA
p-value: <0.00195% CI: [0.08, 0.18]ANCOVA
Secondary
Change From Baseline in HbA1c up to Week 54
Blood samples were collected for assessments of HbA1c levels at Baseline, Weeks 12, 24, 36, 48, 54. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0.
Time frame: Baseline (Week 0) and Weeks 12, 24, 36, 48, 54
Population: Safety population. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in HbA1c up to Week 54 | Week 48 | 0.16 Percentage of HbA1c | Standard Deviation 0.394 |
| Placebo | Change From Baseline in HbA1c up to Week 54 | Week 36 | 0.15 Percentage of HbA1c | Standard Deviation 0.398 |
| Placebo | Change From Baseline in HbA1c up to Week 54 | Week 12 | 0.02 Percentage of HbA1c | Standard Deviation 0.3 |
| Placebo | Change From Baseline in HbA1c up to Week 54 | Week 24 | 0.09 Percentage of HbA1c | Standard Deviation 0.37 |
| Placebo | Change From Baseline in HbA1c up to Week 54 | Week 54 | 0.09 Percentage of HbA1c | Standard Deviation 0.346 |
| RSG XR 2mg | Change From Baseline in HbA1c up to Week 54 | Week 36 | 0.19 Percentage of HbA1c | Standard Deviation 0.273 |
| RSG XR 2mg | Change From Baseline in HbA1c up to Week 54 | Week 12 | 0.13 Percentage of HbA1c | Standard Deviation 0.278 |
| RSG XR 2mg | Change From Baseline in HbA1c up to Week 54 | Week 24 | 0.17 Percentage of HbA1c | Standard Deviation 0.415 |
| RSG XR 2mg | Change From Baseline in HbA1c up to Week 54 | Week 48 | 0.19 Percentage of HbA1c | Standard Deviation 0.323 |
| RSG XR 2mg | Change From Baseline in HbA1c up to Week 54 | Week 54 | 0.03 Percentage of HbA1c | Standard Deviation 0.483 |
| RSG XR 8mg | Change From Baseline in HbA1c up to Week 54 | Week 54 | 0.03 Percentage of HbA1c | Standard Deviation 0.338 |
| RSG XR 8mg | Change From Baseline in HbA1c up to Week 54 | Week 48 | 0.27 Percentage of HbA1c | Standard Deviation 0.4 |
| RSG XR 8mg | Change From Baseline in HbA1c up to Week 54 | Week 12 | 0.15 Percentage of HbA1c | Standard Deviation 0.398 |
| RSG XR 8mg | Change From Baseline in HbA1c up to Week 54 | Week 36 | 0.25 Percentage of HbA1c | Standard Deviation 0.418 |
| RSG XR 8mg | Change From Baseline in HbA1c up to Week 54 | Week 24 | 0.17 Percentage of HbA1c | Standard Deviation 0.422 |
Secondary
Change From Baseline in Hematocrit
Hematology parameters were assessed at Baseline and up to Week 48. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0.
Time frame: Baseline (Week 0) and Weeks 4, 16, 36, 48
Population: Safety population. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Hematocrit | Week 48 | -0.0026 Ratio | Standard Deviation 0.02776 |
| Placebo | Change From Baseline in Hematocrit | Week 36 | -0.0017 Ratio | Standard Deviation 0.02428 |
| Placebo | Change From Baseline in Hematocrit | Week 4 | -0.0020 Ratio | Standard Deviation 0.0205 |
| Placebo | Change From Baseline in Hematocrit | Week 16 | -0.0018 Ratio | Standard Deviation 0.0234 |
| RSG XR 2mg | Change From Baseline in Hematocrit | Week 4 | -0.0088 Ratio | Standard Deviation 0.0215 |
| RSG XR 2mg | Change From Baseline in Hematocrit | Week 16 | -0.0166 Ratio | Standard Deviation 0.02442 |
| RSG XR 2mg | Change From Baseline in Hematocrit | Week 36 | -0.0174 Ratio | Standard Deviation 0.02705 |
| RSG XR 2mg | Change From Baseline in Hematocrit | Week 48 | -0.0167 Ratio | Standard Deviation 0.02683 |
| RSG XR 8mg | Change From Baseline in Hematocrit | Week 36 | -0.0300 Ratio | Standard Deviation 0.0288 |
| RSG XR 8mg | Change From Baseline in Hematocrit | Week 4 | -0.0121 Ratio | Standard Deviation 0.02128 |
| RSG XR 8mg | Change From Baseline in Hematocrit | Week 16 | -0.0320 Ratio | Standard Deviation 0.02922 |
| RSG XR 8mg | Change From Baseline in Hematocrit | Week 48 | -0.0303 Ratio | Standard Deviation 0.03015 |
Secondary
Change From Baseline in Hemoglobin
Hematology parameters were assessed at Baseline, Weeks 4, 16, 36, 48. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Full population data was presented.
Time frame: Baseline (Week 0) and Weeks 4, 16, 36, 48
Population: Safety population. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Hemoglobin | Week 4 | -0.5 Gram\Liter (G\L) | Standard Deviation 6.5 |
| Placebo | Change From Baseline in Hemoglobin | Week 48 | -0.7 Gram\Liter (G\L) | Standard Deviation 9.1 |
| Placebo | Change From Baseline in Hemoglobin | Week 36 | -0.7 Gram\Liter (G\L) | Standard Deviation 7.78 |
| Placebo | Change From Baseline in Hemoglobin | Week 16 | -0.6 Gram\Liter (G\L) | Standard Deviation 7.37 |
| RSG XR 2mg | Change From Baseline in Hemoglobin | Week 36 | -6.2 Gram\Liter (G\L) | Standard Deviation 8.73 |
| RSG XR 2mg | Change From Baseline in Hemoglobin | Week 16 | -6.1 Gram\Liter (G\L) | Standard Deviation 7.79 |
| RSG XR 2mg | Change From Baseline in Hemoglobin | Week 48 | -5.8 Gram\Liter (G\L) | Standard Deviation 8.66 |
| RSG XR 2mg | Change From Baseline in Hemoglobin | Week 4 | -2.9 Gram\Liter (G\L) | Standard Deviation 6.76 |
| RSG XR 8mg | Change From Baseline in Hemoglobin | Week 48 | -10.7 Gram\Liter (G\L) | Standard Deviation 10.15 |
| RSG XR 8mg | Change From Baseline in Hemoglobin | Week 4 | -3.9 Gram\Liter (G\L) | Standard Deviation 6.8 |
| RSG XR 8mg | Change From Baseline in Hemoglobin | Week 16 | -11.2 Gram\Liter (G\L) | Standard Deviation 9.37 |
| RSG XR 8mg | Change From Baseline in Hemoglobin | Week 36 | -10.6 Gram\Liter (G\L) | Standard Deviation 9.67 |
Secondary
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score
NPI is an assessment of frequency and severity of behavioral disturbances in dementia that comprised of 10 dimensions: delusions, hallucinations, dysphoria, apathy, euphoria, disinhibition, aggressiveness and agitation, irritability, anxiety, aberrant motor activity. Participant's caregiver asked about behavior in participant. If Yes, informant then rated both severity on a 3-point scale, 1-mild to 3-severe (total range: 0-36) and frequency using a 4-point scale, 1-occasionally to 4-very frequently. Total score was frequency × severity. Distress was scored on 5-point scale, 0-no distress to 5-very severe or extreme. Total NPI score was calculated by adding all domain scores; NPI total score: 0-144 and NPI distress score: 0-60, higher scores indicated more severe behavioral disturbance. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Adjusted means were presented. Full population data was presented.
Time frame: Baseline (Week 0) and Week 8, 16, 24, 48
Population: ITT population. Number of participants with observed data contributing to the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 8 | -0.0 Scores on a scale | Standard Error 0.32 |
| Placebo | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 16 | 0.1 Scores on a scale | Standard Error 0.34 |
| Placebo | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 24 | 1.3 Scores on a scale | Standard Error 0.43 |
| Placebo | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 48 | 2.6 Scores on a scale | Standard Error 0.52 |
| RSG XR 2mg | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 48 | 1.5 Scores on a scale | Standard Error 0.49 |
| RSG XR 2mg | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 8 | -0.3 Scores on a scale | Standard Error 0.33 |
| RSG XR 2mg | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 24 | 0.3 Scores on a scale | Standard Error 0.41 |
| RSG XR 2mg | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 16 | 0.2 Scores on a scale | Standard Error 0.37 |
| RSG XR 8mg | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 48 | 1.9 Scores on a scale | Standard Error 0.5 |
| RSG XR 8mg | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 16 | 0.1 Scores on a scale | Standard Error 0.37 |
| RSG XR 8mg | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 24 | 0.2 Scores on a scale | Standard Error 0.39 |
| RSG XR 8mg | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 8 | -0.2 Scores on a scale | Standard Error 0.31 |
Comparison: For Week 8p-value: 0.58395% CI: [-1.1, 0.6]Mixed model for repeated measures
Comparison: For Week 8p-value: 0.63195% CI: [-1.1, 0.6]Mixed model for repeated measures
Comparison: For Week 16p-value: 0.81295% CI: [-0.8, 1.1]Mixed model for repeated measures
Comparison: For Week 16p-value: 0.95295% CI: [-0.9, 1]Mixed model for repeated measures
Comparison: For Week 24p-value: 0.11795% CI: [-2.1, 0.2]Mixed model for repeated measures
Comparison: For Week 24p-value: 0.07495% CI: [-2.1, 0.1]Mixed model for repeated measures
Comparison: For Week 48p-value: 0.14195% CI: [-2.4, 0.3]Mixed model for repeated measures
Comparison: For Week 48p-value: 0.33195% CI: [-2.1, 0.7]Mixed model for repeated measures
Secondary
Change From Baseline in Short Term Memory Assessment
The 11-item ADAS-Cog assessed 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. Scores range from 0 to 70 with higher scores indicating greater dysfunction. Questions 1 (word recall) and 7 (word recognition) of ADAS-Cog questionnaire was summed to get a short term memory assessment. The score for Question 1 was calculated as the mean number of words not recalled over the trials for which data was available. If data for all three trials was missing, or if the score for Question 7 was missing then the short term memory score will also be set to missing. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented.
Time frame: Baseline (Week 0) and upto Week 48
Population: ITT population. Number of participants with observed data contributing to the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Short Term Memory Assessment | Week 36 | 0.6 Scores on an scale | Standard Error 0.15 |
| Placebo | Change From Baseline in Short Term Memory Assessment | Week 24 | -0.0 Scores on an scale | Standard Error 0.15 |
| Placebo | Change From Baseline in Short Term Memory Assessment | Week 8 | -0.2 Scores on an scale | Standard Error 0.14 |
| Placebo | Change From Baseline in Short Term Memory Assessment | Week 16 | -0.3 Scores on an scale | Standard Error 0.14 |
| Placebo | Change From Baseline in Short Term Memory Assessment | Week 48 | 0.6 Scores on an scale | Standard Error 0.16 |
| RSG XR 2mg | Change From Baseline in Short Term Memory Assessment | Week 24 | -0.0 Scores on an scale | Standard Error 0.15 |
| RSG XR 2mg | Change From Baseline in Short Term Memory Assessment | Week 8 | -0.2 Scores on an scale | Standard Error 0.14 |
| RSG XR 2mg | Change From Baseline in Short Term Memory Assessment | Week 16 | -0.4 Scores on an scale | Standard Error 0.14 |
| RSG XR 2mg | Change From Baseline in Short Term Memory Assessment | Week 36 | 0.7 Scores on an scale | Standard Error 0.15 |
| RSG XR 2mg | Change From Baseline in Short Term Memory Assessment | Week 48 | 0.6 Scores on an scale | Standard Error 0.17 |
| RSG XR 8mg | Change From Baseline in Short Term Memory Assessment | Week 48 | 0.9 Scores on an scale | Standard Error 0.16 |
| RSG XR 8mg | Change From Baseline in Short Term Memory Assessment | Week 36 | 0.7 Scores on an scale | Standard Error 0.15 |
| RSG XR 8mg | Change From Baseline in Short Term Memory Assessment | Week 8 | -0.1 Scores on an scale | Standard Error 0.13 |
| RSG XR 8mg | Change From Baseline in Short Term Memory Assessment | Week 24 | 0.2 Scores on an scale | Standard Error 0.14 |
| RSG XR 8mg | Change From Baseline in Short Term Memory Assessment | Week 16 | -0.5 Scores on an scale | Standard Error 0.13 |
Comparison: For Week 8p-value: 0.74895% CI: [-0.4, 0.3]Mixed model for repeated measures
Comparison: For Week 8p-value: 0.61795% CI: [-0.3, 0.5]Mixed model for repeated measures
Comparison: Week 16p-value: 0.70895% CI: [-0.5, 0.3]Mixed model for repeated measures
Comparison: Week 16p-value: 0.495% CI: [-0.5, 0.2]Mixed model for repeated measures
Comparison: For Week 24p-value: 0.92895% CI: [-0.4, 0.4]Mixed model for repeated measures
Comparison: For Week 24p-value: 0.17895% CI: [-0.1, 0.7]Mixed model for repeated measures
Comparison: For Week 36p-value: 0.62695% CI: [-0.3, 0.5]Mixed model for repeated measures
Comparison: For Week 36p-value: 0.60895% CI: [-0.3, 0.5]Mixed model for repeated measures
Comparison: For Week 48p-value: 0.86595% CI: [-0.5, 0.4]Mixed model for repeated measures
Comparison: For Week 48p-value: 0.14995% CI: [-0.1, 0.8]Mixed model for repeated measures
Secondary
Change From Baseline in Weight
Body weight was measured at all visits, without shoes and wearing light clothing. The assessment was performed at Baseline, Weeks 4, 8, 12, 16, 24, 36, 48, 54. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Full population data was presented.
Time frame: Baseline (Week 0) and Weeks 4, 8, 12, 16, 24, 36, 48, 54
Population: Safety population. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Weight | Week 4 | -0.1 Kilograms (Kg) | Standard Deviation 1.95 |
| Placebo | Change From Baseline in Weight | Week 8 | 0.1 Kilograms (Kg) | Standard Deviation 2.1 |
| Placebo | Change From Baseline in Weight | Week 12 | 0.0 Kilograms (Kg) | Standard Deviation 2.35 |
| Placebo | Change From Baseline in Weight | Week 16 | 0.0 Kilograms (Kg) | Standard Deviation 2.88 |
| Placebo | Change From Baseline in Weight | Week 24 | 0.1 Kilograms (Kg) | Standard Deviation 2.85 |
| Placebo | Change From Baseline in Weight | Week 36 | -0.0 Kilograms (Kg) | Standard Deviation 4.53 |
| Placebo | Change From Baseline in Weight | Week 48 | 0.1 Kilograms (Kg) | Standard Deviation 3.51 |
| Placebo | Change From Baseline in Weight | Week 54 | 0.1 Kilograms (Kg) | Standard Deviation 3.7 |
| RSG XR 2mg | Change From Baseline in Weight | Week 12 | 0.1 Kilograms (Kg) | Standard Deviation 2.66 |
| RSG XR 2mg | Change From Baseline in Weight | Week 48 | 0.2 Kilograms (Kg) | Standard Deviation 4.33 |
| RSG XR 2mg | Change From Baseline in Weight | Week 16 | 0.2 Kilograms (Kg) | Standard Deviation 2.85 |
| RSG XR 2mg | Change From Baseline in Weight | Week 24 | 0.1 Kilograms (Kg) | Standard Deviation 3.28 |
| RSG XR 2mg | Change From Baseline in Weight | Week 36 | 0.2 Kilograms (Kg) | Standard Deviation 3.69 |
| RSG XR 2mg | Change From Baseline in Weight | Week 4 | 0.1 Kilograms (Kg) | Standard Deviation 1.61 |
| RSG XR 2mg | Change From Baseline in Weight | Week 8 | 0.2 Kilograms (Kg) | Standard Deviation 2.15 |
| RSG XR 2mg | Change From Baseline in Weight | Week 54 | 0.1 Kilograms (Kg) | Standard Deviation 5.88 |
| RSG XR 8mg | Change From Baseline in Weight | Week 12 | 1.2 Kilograms (Kg) | Standard Deviation 2.5 |
| RSG XR 8mg | Change From Baseline in Weight | Week 8 | 0.9 Kilograms (Kg) | Standard Deviation 2.34 |
| RSG XR 8mg | Change From Baseline in Weight | Week 4 | 0.5 Kilograms (Kg) | Standard Deviation 1.7 |
| RSG XR 8mg | Change From Baseline in Weight | Week 16 | 1.3 Kilograms (Kg) | Standard Deviation 2.78 |
| RSG XR 8mg | Change From Baseline in Weight | Week 48 | 1.9 Kilograms (Kg) | Standard Deviation 3.69 |
| RSG XR 8mg | Change From Baseline in Weight | Week 36 | 1.5 Kilograms (Kg) | Standard Deviation 3.28 |
| RSG XR 8mg | Change From Baseline in Weight | Week 24 | 1.2 Kilograms (Kg) | Standard Deviation 3.59 |
| RSG XR 8mg | Change From Baseline in Weight | Week 54 | 1.2 Kilograms (Kg) | Standard Deviation 3.57 |
Secondary
Change From Screening in Mini Mental State Examination (MMSE) Total Score
The MMSE consists of 11 tests of orientation, memory (recent and immediate), concentration, language and praxis. Scores range from 0 to 30, with lower scores indicating greater cognitive impairment. The scale is completed by the investigator, based on the performance of the participant. Change from screening was calculated as value at scheduled time point minus screening value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Full population data was presented.
Time frame: Screening (Week -4) and Week 48
Population: ITT population. Only those participants available at that particular time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Screening in Mini Mental State Examination (MMSE) Total Score | -2.0 Scores on a scale | Standard Error 0.21 |
| RSG XR 2mg | Change From Screening in Mini Mental State Examination (MMSE) Total Score | -2.3 Scores on a scale | Standard Error 0.22 |
| RSG XR 8mg | Change From Screening in Mini Mental State Examination (MMSE) Total Score | -2.0 Scores on a scale | Standard Error 0.22 |
p-value: 0.38695% CI: [-0.8, 0.3]ANCOVA
p-value: 0.99995% CI: [-0.6, 0.6]ANCOVA
Secondary
Change in ADAS-Cog Total Score for Observed Cases at Week 54 Compared to Week 48
The 11-item ADAS-Cog assessed 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. Scores range from 0 to 70 with higher scores indicating greater dysfunction. It was of interest to compare the single blind phase data between the treatment groups defined based on the double blind treatment group. This analysis only included participants who received at least one dose of single-blind medication. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Full population data was presented.
Time frame: Week 48 and Week 54
Population: ITT population. This analysis will only include participants who received at least one dose of single-blind medication. Only those participants available at that particular time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in ADAS-Cog Total Score for Observed Cases at Week 54 Compared to Week 48 | 1.0 Scores on a scale | Standard Error 0.27 |
| RSG XR 2mg | Change in ADAS-Cog Total Score for Observed Cases at Week 54 Compared to Week 48 | 0.4 Scores on a scale | Standard Error 0.28 |
| RSG XR 8mg | Change in ADAS-Cog Total Score for Observed Cases at Week 54 Compared to Week 48 | 0.5 Scores on a scale | Standard Error 0.28 |
p-value: 0.10695% CI: [-1.3, 0.1]ANCOVA
p-value: 0.22995% CI: [-1.2, 0.3]ANCOVA
Secondary
Change in CDR-SB Total Score for Observed Cases at Week 54 Compared to Week 48
The CDR-SB was a validated clinical assessment of global function in participants with AD. Impairment was scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or box scores, can be added together to give the CDR-Sum of Boxes which ranges from 0 to 18 (severe impairment). It was of interest to compare the single blind phase data between the treatment groups defined based on the double blind treatment group. This analysis only included participants who received at least one dose of single-blind medication. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Full population data was presented.
Time frame: Week 48 and Week 54
Population: ITT population. Only those participants available at that particular time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in CDR-SB Total Score for Observed Cases at Week 54 Compared to Week 48 | 0.3 Scores on a scale | Standard Error 0.07 |
| RSG XR 2mg | Change in CDR-SB Total Score for Observed Cases at Week 54 Compared to Week 48 | 0.2 Scores on a scale | Standard Error 0.08 |
| RSG XR 8mg | Change in CDR-SB Total Score for Observed Cases at Week 54 Compared to Week 48 | 0.3 Scores on a scale | Standard Error 0.08 |
p-value: 0.32495% CI: [-0.3, 0.1]ANCOVA
p-value: 0.98795% CI: [-0.2, 0.2]ANCOVA
Secondary
Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration
Triplicate 12-lead ECG measures was obtained digitally, approximately one minute apart after the participant had rested in the supine position in a quiet room (no TV, minimal talking) for atleast 10 minutes. The ECG parameters includes PR interval, QRS duration, QT - uncorrected interval, QTc Bazett (QTcB), QTc Fridericia (QTcF) and RR interval. The assessments were performed at Baseline and up to Week 54. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Full population data was presented.
Time frame: Baseline (Week 0) and Weeks 4, 8, 16, 24, 36, 48, 54
Population: Safety population. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 4, +3hr | 3.8 MSEC | Standard Deviation 22.82 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 0, +2hr | 23.8 MSEC | Standard Deviation 105.24 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 0, +3hr | 3.5 MSEC | Standard Deviation 103.09 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 0, +4hr | -8.8 MSEC | Standard Deviation 91.08 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 4, Pre-Dose | -0.2 MSEC | Standard Deviation 99.28 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 4, +1hr | 23.2 MSEC | Standard Deviation 115.71 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 4, +2hr | 24.0 MSEC | Standard Deviation 123.53 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 4, +3hr | 7.4 MSEC | Standard Deviation 117.68 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 4, +4hr | -2.1 MSEC | Standard Deviation 117.25 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 8 | 0.6 MSEC | Standard Deviation 110.81 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 16 | 9.0 MSEC | Standard Deviation 110.76 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 24 | -1.3 MSEC | Standard Deviation 119.93 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 36 | -8.0 MSEC | Standard Deviation 114.49 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 48 | -8.2 MSEC | Standard Deviation 125.15 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 54 | 10.9 MSEC | Standard Deviation 128.93 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT interval, Week 0, +1hr | 5.2 MSEC | Standard Deviation 18.01 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 0, +2hr | 6.4 MSEC | Standard Deviation 19.64 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 0, +3hr | 2.2 MSEC | Standard Deviation 19.38 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 0, +4hr | -0.3 MSEC | Standard Deviation 18.65 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 4, Pre-Dose | -0.8 MSEC | Standard Deviation 19.18 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 4, +1hr | 3.6 MSEC | Standard Deviation 21.53 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 4, +2hr | 5.2 MSEC | Standard Deviation 22.96 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 0, +1hr | 26.7 MSEC | Standard Deviation 92.91 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 4, +4hr | 1.9 MSEC | Standard Deviation 25.13 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 8 | -1.4 MSEC | Standard Deviation 21.3 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 16 | 2.4 MSEC | Standard Deviation 23.39 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 24 | 1.6 MSEC | Standard Deviation 24.35 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 36 | 0.5 MSEC | Standard Deviation 21.85 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 48 | 2.0 MSEC | Standard Deviation 24.53 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 54 | 2.1 MSEC | Standard Deviation 24.97 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB interval, Week 0, +1hr | -0.4 MSEC | Standard Deviation 13.49 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 0, +2hr | 1.6 MSEC | Standard Deviation 14.35 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 0, +3hr | 1.9 MSEC | Standard Deviation 15.19 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 0, +4hr | 1.7 MSEC | Standard Deviation 13.48 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 4, Pre-Dose | -0.5 MSEC | Standard Deviation 15.98 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 4, +1hr | -0.9 MSEC | Standard Deviation 16.84 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 4, +2hr | 0.4 MSEC | Standard Deviation 17.13 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 4, +3hr | 2.4 MSEC | Standard Deviation 18.56 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 4, +4hr | 2.8 MSEC | Standard Deviation 17.83 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 8 | -1.3 MSEC | Standard Deviation 15.27 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 16 | 1.1 MSEC | Standard Deviation 18.12 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 24 | 2.2 MSEC | Standard Deviation 19.04 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 36 | 2.5 MSEC | Standard Deviation 17.87 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 48 | 4.5 MSEC | Standard Deviation 18.91 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 54 | 0.2 MSEC | Standard Deviation 18.42 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF interval, Week 0, +1hr | 1.5 MSEC | Standard Deviation 11.92 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 0, +2hr | 3.2 MSEC | Standard Deviation 12.5 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 0, +3hr | 1.9 MSEC | Standard Deviation 13.34 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 0, +4hr | 1.0 MSEC | Standard Deviation 12.31 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 4, Pre-Dose | -0.6 MSEC | Standard Deviation 13.82 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 4, +1hr | 0.6 MSEC | Standard Deviation 14.45 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 4, +2hr | 2.0 MSEC | Standard Deviation 14.65 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 4, +3hr | 2.9 MSEC | Standard Deviation 16.15 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 4, +4hr | 2.5 MSEC | Standard Deviation 16.51 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 8 | -1.4 MSEC | Standard Deviation 13.29 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 16 | 1.4 MSEC | Standard Deviation 16.62 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 24 | 2.0 MSEC | Standard Deviation 17.21 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 36 | 1.8 MSEC | Standard Deviation 15.23 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 48 | 3.5 MSEC | Standard Deviation 16.61 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 54 | 0.8 MSEC | Standard Deviation 16.08 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 0, +1hr | 0.6 MSEC | Standard Deviation 10.45 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 0, +2hr | 0.0 MSEC | Standard Deviation 10.82 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 0, +3hr | 0.2 MSEC | Standard Deviation 10.74 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 0, +4hr | 1.8 MSEC | Standard Deviation 12.62 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 1, Pre-dose | -0.2 MSEC | Standard Deviation 12.81 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 1, +1hr | 0.3 MSEC | Standard Deviation 13.5 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 1, +2hr | 0.7 MSEC | Standard Deviation 13.27 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 1, +3hr | 0.7 MSEC | Standard Deviation 14.43 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 1, +4hr | 0.9 MSEC | Standard Deviation 15.31 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 8 | -1.3 MSEC | Standard Deviation 13.2 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 16 | -0.7 MSEC | Standard Deviation 15.22 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 24 | -1.9 MSEC | Standard Deviation 12.43 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 36 | -1.2 MSEC | Standard Deviation 13.87 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 48 | -0.6 MSEC | Standard Deviation 16.83 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 54 | -0.5 MSEC | Standard Deviation 13.66 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 0, +1hr | 0.2 MSEC | Standard Deviation 5.49 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 0, +2hr | 0.2 MSEC | Standard Deviation 5.44 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 0, +3hr | -0.1 MSEC | Standard Deviation 5.3 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 0, +4hr | 0.1 MSEC | Standard Deviation 5.72 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 4, Pre-Dose | 0.6 MSEC | Standard Deviation 7.45 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 4, +1hr | 1.1 MSEC | Standard Deviation 7.17 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 4, +2hr | 1.0 MSEC | Standard Deviation 7.6 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 4, +3hr | 1.3 MSEC | Standard Deviation 8.86 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 4, +4hr | 0.1 MSEC | Standard Deviation 9.19 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 8 | 0.2 MSEC | Standard Deviation 7.17 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 16 | 0.8 MSEC | Standard Deviation 8.91 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 24 | 0.9 MSEC | Standard Deviation 8.72 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 36 | 1.7 MSEC | Standard Deviation 9.14 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 48 | 1.5 MSEC | Standard Deviation 9.52 |
| Placebo | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 54 | 0.8 MSEC | Standard Deviation 9.29 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 48 | 1.3 MSEC | Standard Deviation 11.52 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 0, +1hr | 17.9 MSEC | Standard Deviation 83.58 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF interval, Week 0, +1hr | 2.0 MSEC | Standard Deviation 12.78 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 0, +1hr | 0.0 MSEC | Standard Deviation 10.39 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 0, +2hr | 11.0 MSEC | Standard Deviation 100.67 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 16 | 0.6 MSEC | Standard Deviation 12 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 0, +1hr | 0.6 MSEC | Standard Deviation 6.26 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 0, +3hr | 4.6 MSEC | Standard Deviation 105.04 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 0, +2hr | 2.3 MSEC | Standard Deviation 14.24 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 4, +1hr | 0.4 MSEC | Standard Deviation 8.44 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 0, +4hr | -12.1 MSEC | Standard Deviation 92.98 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 24 | 0.1 MSEC | Standard Deviation 12.28 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 0, +2hr | 0.2 MSEC | Standard Deviation 11.79 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 4, Pre-Dose | -9.6 MSEC | Standard Deviation 104.15 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 4, +4hr | 2.3 MSEC | Standard Deviation 20.3 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 0, +3hr | 2.6 MSEC | Standard Deviation 13.89 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 4, +1hr | 8.7 MSEC | Standard Deviation 115.7 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 4, Pre-Dose | 1.3 MSEC | Standard Deviation 17.14 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 16 | -0.5 MSEC | Standard Deviation 8.42 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 4, +2hr | 6.8 MSEC | Standard Deviation 119.63 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 0, +4hr | 0.2 MSEC | Standard Deviation 17.24 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 0, +3hr | -0.1 MSEC | Standard Deviation 11.02 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 4, +3hr | 8.5 MSEC | Standard Deviation 124.69 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 8 | 0.8 MSEC | Standard Deviation 7.15 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 0, +2hr | 0.8 MSEC | Standard Deviation 6.82 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 4, +4hr | -4.7 MSEC | Standard Deviation 108.17 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 4, Pre-Dose | 0.6 MSEC | Standard Deviation 14.8 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 8 | 0.7 MSEC | Standard Deviation 18.78 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 8 | 0.5 MSEC | Standard Deviation 110.7 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 0, +3hr | 2.4 MSEC | Standard Deviation 15.73 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 0, +4hr | 1.5 MSEC | Standard Deviation 10.47 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 16 | -1.5 MSEC | Standard Deviation 127.38 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 4, +1hr | 1.5 MSEC | Standard Deviation 15.13 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 48 | -2.5 MSEC | Standard Deviation 13.48 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 24 | 2.8 MSEC | Standard Deviation 141.97 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 16 | 0.3 MSEC | Standard Deviation 18.73 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 4, +2hr | 0.7 MSEC | Standard Deviation 7.87 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 36 | -3.7 MSEC | Standard Deviation 127.72 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 4, +2hr | 3.3 MSEC | Standard Deviation 15.1 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 1, Pre-dose | 0.4 MSEC | Standard Deviation 13.78 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 48 | -17.0 MSEC | Standard Deviation 132.82 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 0, +2hr | 1.6 MSEC | Standard Deviation 15.7 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 0, +3hr | 0.8 MSEC | Standard Deviation 6.34 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 54 | 5.4 MSEC | Standard Deviation 119.76 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 4, +3hr | 2.6 MSEC | Standard Deviation 16.19 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 4, +1hr | 0.9 MSEC | Standard Deviation 17.51 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT interval, Week 0, +1hr | 4.5 MSEC | Standard Deviation 17.29 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 24 | 1.5 MSEC | Standard Deviation 18.81 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 1, +1hr | 1.6 MSEC | Standard Deviation 13.43 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 0, +2hr | 3.8 MSEC | Standard Deviation 20.7 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 4, +4hr | 1.7 MSEC | Standard Deviation 17.88 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB interval, Week 0, +1hr | 0.7 MSEC | Standard Deviation 14.41 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 0, +3hr | 3.2 MSEC | Standard Deviation 20.61 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 54 | 0.9 MSEC | Standard Deviation 9.4 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 36 | 1.7 MSEC | Standard Deviation 12.81 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 0, +4hr | -1.6 MSEC | Standard Deviation 20.13 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 8 | 0.6 MSEC | Standard Deviation 15.94 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 1, +2hr | 0.9 MSEC | Standard Deviation 12.17 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 4, Pre-Dose | -0.7 MSEC | Standard Deviation 20.35 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 36 | 0.9 MSEC | Standard Deviation 19.37 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 0, +4hr | 0.5 MSEC | Standard Deviation 7.95 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 4, +1hr | 2.7 MSEC | Standard Deviation 22.14 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 16 | 0.1 MSEC | Standard Deviation 16.2 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 4, +3hr | 0.7 MSEC | Standard Deviation 7.48 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 4, +2hr | 4.2 MSEC | Standard Deviation 24.09 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 4, +2hr | 2.8 MSEC | Standard Deviation 16.73 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 1, +3hr | 1.4 MSEC | Standard Deviation 13.81 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 4, +3hr | 3.6 MSEC | Standard Deviation 25.24 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 54 | -0.6 MSEC | Standard Deviation 13.47 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 24 | 1.9 MSEC | Standard Deviation 16 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 4, +4hr | 0.8 MSEC | Standard Deviation 22.66 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 48 | 3.1 MSEC | Standard Deviation 18.34 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 24 | 1.3 MSEC | Standard Deviation 8.02 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 8 | 0.5 MSEC | Standard Deviation 21.6 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 36 | 0.6 MSEC | Standard Deviation 16.22 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 1, +4hr | 1.1 MSEC | Standard Deviation 15.56 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 16 | -0.3 MSEC | Standard Deviation 24.52 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 0, +4hr | 1.2 MSEC | Standard Deviation 19.5 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 4, Pre-Dose | 0.2 MSEC | Standard Deviation 7.91 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 24 | 2.4 MSEC | Standard Deviation 25.99 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 48 | 1.8 MSEC | Standard Deviation 16.49 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 36 | -2.3 MSEC | Standard Deviation 12.25 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 36 | 0.0 MSEC | Standard Deviation 23.58 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 54 | 1.4 MSEC | Standard Deviation 18.74 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 8 | 0.7 MSEC | Standard Deviation 11.94 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 48 | -0.7 MSEC | Standard Deviation 26.19 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 54 | 1.7 MSEC | Standard Deviation 15.93 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 4, +3hr | 2.1 MSEC | Standard Deviation 17.72 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 54 | 2.4 MSEC | Standard Deviation 23.41 |
| RSG XR 2mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 4, +4hr | 0.8 MSEC | Standard Deviation 9.1 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 54 | -1.2 MSEC | Standard Deviation 25.41 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB interval, Week 0, +1hr | -0.7 MSEC | Standard Deviation 14.02 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 0, +2hr | 1.5 MSEC | Standard Deviation 15.68 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 16 | 0.1 MSEC | Standard Deviation 15.06 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 0, +3hr | 2.0 MSEC | Standard Deviation 14.6 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 4, +4hr | 1.4 MSEC | Standard Deviation 9.12 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 0, +4hr | 3.2 MSEC | Standard Deviation 14.99 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 4, Pre-Dose | 1.5 MSEC | Standard Deviation 18.5 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 24 | -0.5 MSEC | Standard Deviation 13.38 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 4, +1hr | 1.0 MSEC | Standard Deviation 16.88 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 4, +2hr | 2.9 MSEC | Standard Deviation 17.74 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 4, +3hr | 1.6 MSEC | Standard Deviation 17.87 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 36 | -0.9 MSEC | Standard Deviation 13.7 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 4, +4hr | 3.6 MSEC | Standard Deviation 15.95 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 8 | 3.2 MSEC | Standard Deviation 18.09 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 16 | 3.6 MSEC | Standard Deviation 16.81 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 48 | -0.8 MSEC | Standard Deviation 12.99 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 24 | 5.2 MSEC | Standard Deviation 17.97 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 8 | 0.5 MSEC | Standard Deviation 8.26 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 36 | 4.3 MSEC | Standard Deviation 19.16 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 48 | 5.0 MSEC | Standard Deviation 18.39 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 54 | 0.0 MSEC | Standard Deviation 11.99 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcB Interval, Week 54 | 4.5 MSEC | Standard Deviation 18.67 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF interval, Week 0, +1hr | 1.3 MSEC | Standard Deviation 11.99 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 0, +2hr | 2.6 MSEC | Standard Deviation 13.08 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 0, +1hr | 0.4 MSEC | Standard Deviation 5.64 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 0, +3hr | 1.9 MSEC | Standard Deviation 13.44 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 0, +4hr | 2.8 MSEC | Standard Deviation 12.93 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 4, Pre-Dose | 0.4 MSEC | Standard Deviation 17.02 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 0, +2hr | 0.4 MSEC | Standard Deviation 5.61 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 4, +1hr | 1.1 MSEC | Standard Deviation 15.15 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 16 | 0.1 MSEC | Standard Deviation 6.96 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 4, +2hr | 2.9 MSEC | Standard Deviation 16.01 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 4, +3hr | 1.3 MSEC | Standard Deviation 16.97 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 0, +3hr | 0.5 MSEC | Standard Deviation 6.2 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 4, +4hr | 1.9 MSEC | Standard Deviation 15.19 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 48 | 1.0 MSEC | Standard Deviation 7.19 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 8 | 0.7 MSEC | Standard Deviation 16.39 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 16 | 1.9 MSEC | Standard Deviation 15.77 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 0, +4hr | -0.2 MSEC | Standard Deviation 6.15 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 24 | 2.6 MSEC | Standard Deviation 15.84 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 36 | 1.3 MSEC | Standard Deviation 19.3 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 48 | 2.4 MSEC | Standard Deviation 18.86 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 4, Pre-Dose | 0.8 MSEC | Standard Deviation 7.38 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QTcF Interval, Week 54 | 2.6 MSEC | Standard Deviation 16.74 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 24 | 1.1 MSEC | Standard Deviation 6.71 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 0, +1hr | 30.4 MSEC | Standard Deviation 92.97 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 0, +2hr | 17.7 MSEC | Standard Deviation 109.4 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 0, +1hr | 0.4 MSEC | Standard Deviation 10 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 0, +3hr | 0.6 MSEC | Standard Deviation 108.88 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 0, +4hr | -5.7 MSEC | Standard Deviation 108.33 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 4, Pre-Dose | -14.0 MSEC | Standard Deviation 107.71 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 0, +2hr | -0.8 MSEC | Standard Deviation 10.97 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 4, +1hr | 4.3 MSEC | Standard Deviation 118.85 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 4, +1hr | 1.0 MSEC | Standard Deviation 7.51 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 4, +2hr | 2.5 MSEC | Standard Deviation 122.39 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 4, +3hr | -3.0 MSEC | Standard Deviation 125.89 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 0, +3hr | -0.8 MSEC | Standard Deviation 11.78 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 4, +4hr | -20.6 MSEC | Standard Deviation 124.14 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 54 | 1.1 MSEC | Standard Deviation 8.28 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 8 | -32.6 MSEC | Standard Deviation 118.98 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 16 | -20.8 MSEC | Standard Deviation 123.59 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 0, +4hr | 0.0 MSEC | Standard Deviation 11.04 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 24 | -31.3 MSEC | Standard Deviation 126.48 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 36 | -43.4 MSEC | Standard Deviation 107.83 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 48 | -32.7 MSEC | Standard Deviation 121.98 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 1, Pre-dose | 0.7 MSEC | Standard Deviation 11.51 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | RR Interval, Week 54 | -26.0 MSEC | Standard Deviation 125.53 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 4, +2hr | 1.5 MSEC | Standard Deviation 7.71 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT interval, Week 0, +1hr | 5.4 MSEC | Standard Deviation 17.07 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 0, +2hr | 5.0 MSEC | Standard Deviation 19.62 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 1, +1hr | 1.3 MSEC | Standard Deviation 11.73 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 0, +3hr | 1.9 MSEC | Standard Deviation 21.79 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 0, +4hr | 1.8 MSEC | Standard Deviation 20.67 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 4, Pre-Dose | -1.7 MSEC | Standard Deviation 23.63 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 1, +2hr | 1.5 MSEC | Standard Deviation 11.98 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 4, +1hr | 1.4 MSEC | Standard Deviation 23.26 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 4, +2hr | 3.2 MSEC | Standard Deviation 24.54 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 4, +3hr | 0.6 MSEC | Standard Deviation 26.7 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 1, +3hr | 2.6 MSEC | Standard Deviation 12.96 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 4, +4hr | -1.4 MSEC | Standard Deviation 25.73 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 4, +3hr | 1.5 MSEC | Standard Deviation 8.08 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 8 | -4.1 MSEC | Standard Deviation 24.46 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 16 | -1.3 MSEC | Standard Deviation 25.71 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 1, +4hr | 0.8 MSEC | Standard Deviation 11.62 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 24 | -2.2 MSEC | Standard Deviation 25.06 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QRS Interval, Week 36 | 0.4 MSEC | Standard Deviation 6.66 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 36 | -4.7 MSEC | Standard Deviation 27.25 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | QT Interval, Week 48 | -2.7 MSEC | Standard Deviation 29.56 |
| RSG XR 8mg | Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration | PR Interval, Week 8 | 0.8 MSEC | Standard Deviation 12.52 |
Secondary
Changes From Baseline in Electrocardiogram (ECG) Parameters- HR
Triplicate 12-lead ECG measures was obtained digitally, approximately one minute apart after the participant had rested in the supine position in a quiet room (no TV, minimal talking) for atleast 10 minutes. The ECG parameters includes HR. The assessments were performed at Baseline and up to Week 54. Change from Baseline was calculated as value at scheduled time point minus Baseline value . Baseline was defined as value at Week 0. Full population data was presented.
Time frame: Baseline (Week 0) and Weeks 4, 8, 16, 24, 36, 48, 54
Population: Safety population. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 4, +1hr | -1.4 Beats per minute (BPM) | Standard Deviation 7.98 |
| Placebo | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 0, +3hr | 0.0 Beats per minute (BPM) | Standard Deviation 6.84 |
| Placebo | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 16 | -0.1 Beats per minute (BPM) | Standard Deviation 8.06 |
| Placebo | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 4, +2hr | -1.4 Beats per minute (BPM) | Standard Deviation 8.57 |
| Placebo | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 0, +2hr | -1.4 Beats per minute (BPM) | Standard Deviation 7.05 |
| Placebo | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 8 | 0.2 Beats per minute (BPM) | Standard Deviation 8.15 |
| Placebo | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 4, +3hr | -0.4 Beats per minute (BPM) | Standard Deviation 8.02 |
| Placebo | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 36 | 0.7 Beats per minute (BPM) | Standard Deviation 8.27 |
| Placebo | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 4, +4hr | 0.2 Beats per minute (BPM) | Standard Deviation 8.79 |
| Placebo | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 0, +4hr | 0.6 Beats per minute (BPM) | Standard Deviation 6.64 |
| Placebo | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 54 | -0.5 Beats per minute (BPM) | Standard Deviation 9.33 |
| Placebo | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 0, +1hr | -1.6 Beats per minute (BPM) | Standard Deviation 6.2 |
| Placebo | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 4, Pre-dose | 0.2 Beats per minute (BPM) | Standard Deviation 7.01 |
| Placebo | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 48 | 0.9 Beats per minute (BPM) | Standard Deviation 9.01 |
| Placebo | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 24 | 0.2 Beats per minute (BPM) | Standard Deviation 7.91 |
| RSG XR 2mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 24 | -0.3 Beats per minute (BPM) | Standard Deviation 9.85 |
| RSG XR 2mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 0, +1hr | -1.1 Beats per minute (BPM) | Standard Deviation 5.8 |
| RSG XR 2mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 0, +2hr | -0.5 Beats per minute (BPM) | Standard Deviation 6.88 |
| RSG XR 2mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 0, +3hr | -0.1 Beats per minute (BPM) | Standard Deviation 7.02 |
| RSG XR 2mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 0, +4hr | 1.0 Beats per minute (BPM) | Standard Deviation 6.29 |
| RSG XR 2mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 4, Pre-dose | 0.7 Beats per minute (BPM) | Standard Deviation 7.73 |
| RSG XR 2mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 4, +1hr | -0.4 Beats per minute (BPM) | Standard Deviation 8.14 |
| RSG XR 2mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 4, +2hr | -0.3 Beats per minute (BPM) | Standard Deviation 8.57 |
| RSG XR 2mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 4, +3hr | -0.2 Beats per minute (BPM) | Standard Deviation 8.25 |
| RSG XR 2mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 4, +4hr | 0.7 Beats per minute (BPM) | Standard Deviation 6.92 |
| RSG XR 2mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 8 | 0.2 Beats per minute (BPM) | Standard Deviation 8.27 |
| RSG XR 2mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 16 | 0.3 Beats per minute (BPM) | Standard Deviation 9.17 |
| RSG XR 2mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 36 | 0.5 Beats per minute (BPM) | Standard Deviation 8.74 |
| RSG XR 2mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 48 | 1.2 Beats per minute (BPM) | Standard Deviation 9.11 |
| RSG XR 2mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 54 | -0.2 Beats per minute (BPM) | Standard Deviation 8.89 |
| RSG XR 8mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 4, +1hr | -0.1 Beats per minute (BPM) | Standard Deviation 7.92 |
| RSG XR 8mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 48 | 2.4 Beats per minute (BPM) | Standard Deviation 8.94 |
| RSG XR 8mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 16 | 1.5 Beats per minute (BPM) | Standard Deviation 9.05 |
| RSG XR 8mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 4, Pre-dose | 1.0 Beats per minute (BPM) | Standard Deviation 7.56 |
| RSG XR 8mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 0, +4hr | 0.4 Beats per minute (BPM) | Standard Deviation 7.84 |
| RSG XR 8mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 24 | 2.3 Beats per minute (BPM) | Standard Deviation 8.86 |
| RSG XR 8mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 0, +3hr | 0.1 Beats per minute (BPM) | Standard Deviation 7.49 |
| RSG XR 8mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 0, +1hr | -1.8 Beats per minute (BPM) | Standard Deviation 6.05 |
| RSG XR 8mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 36 | 2.9 Beats per minute (BPM) | Standard Deviation 8.09 |
| RSG XR 8mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 4, +3hr | 0.2 Beats per minute (BPM) | Standard Deviation 8.32 |
| RSG XR 8mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 0, +2hr | -1.0 Beats per minute (BPM) | Standard Deviation 7.33 |
| RSG XR 8mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 4, +4hr | 1.4 Beats per minute (BPM) | Standard Deviation 8.31 |
| RSG XR 8mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 4, +2hr | -0.2 Beats per minute (BPM) | Standard Deviation 8.01 |
| RSG XR 8mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 54 | 1.7 Beats per minute (BPM) | Standard Deviation 8.87 |
| RSG XR 8mg | Changes From Baseline in Electrocardiogram (ECG) Parameters- HR | Week 8 | 2.4 Beats per minute (BPM) | Standard Deviation 8.5 |
Secondary
Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Heart Rate (HR)
HR of participants were recorded in sitting posture as vital sign at each visit. The HR values were identified as of potential clinical concern if the values were out of the reference range (50 to 100 beats per minute) or meet a change from baseline criterion. The change from baseline criterion for HR, was increase from Baseline (high) if increased by more than or equal to (\>=) 30 from Baseline; decrease from Baseline (low) if decreased by \>= 30 from Baseline. Baseline was defined as value at Week 0. Full population data was presented.
Time frame: Upto Week 54
Population: Safety population. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Heart Rate (HR) | Increase from Baseline >=30 | 0 Participants |
| Placebo | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Heart Rate (HR) | >100 or <50 | 12 Participants |
| Placebo | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Heart Rate (HR) | Decrease from Baseline >=30 | 2 Participants |
| RSG XR 2mg | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Heart Rate (HR) | Increase from Baseline >=30 | 0 Participants |
| RSG XR 2mg | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Heart Rate (HR) | >100 or <50 | 5 Participants |
| RSG XR 2mg | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Heart Rate (HR) | Decrease from Baseline >=30 | 0 Participants |
| RSG XR 8mg | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Heart Rate (HR) | >100 or <50 | 5 Participants |
| RSG XR 8mg | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Heart Rate (HR) | Decrease from Baseline >=30 | 1 Participants |
| RSG XR 8mg | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Heart Rate (HR) | Increase from Baseline >=30 | 4 Participants |
Secondary
Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP and DBP of participants were recorded in sitting posture as vital sign at each visit. The blood pressure (BP) values were identified as of potential clinical concern if the values were out of the reference range (for SBP, 90 to 140 mmHg and DBP, 50 to 90 mmHg) or meet a change from baseline criterion. The change from baseline criterion for SBP, was increase from Baseline (high) if increased by more than or equal to (\>=) 40 mm Hg from Baseline; decrease from Baseline (low) if decreased by \>= 30 mmHg from Baseline. For DBP, increase from baseline (high) if increased by \>=30 mmHg from baseline; decrease from Baseline (low) if decreased by \>= 20 mmHg from Baseline. Baseline was defined as value at Week 0.
Time frame: Upto Week 54
Population: Safety population. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP >140 or <90 | 67 Participants |
| Placebo | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP Increase from Baseline>=40 | 1 Participants |
| Placebo | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP Decrease from Baseline>=30 | 19 Participants |
| Placebo | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP >90 or <50 | 8 Participants |
| Placebo | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP Increase from Baseline>=30 | 0 Participants |
| Placebo | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP Decrease from Baseline >=20 | 12 Participants |
| RSG XR 2mg | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP Decrease from Baseline >=20 | 18 Participants |
| RSG XR 2mg | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP >140 or <90 | 72 Participants |
| RSG XR 2mg | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP >90 or <50 | 15 Participants |
| RSG XR 2mg | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP Increase from Baseline>=30 | 0 Participants |
| RSG XR 2mg | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP Increase from Baseline>=40 | 3 Participants |
| RSG XR 2mg | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP Decrease from Baseline>=30 | 19 Participants |
| RSG XR 8mg | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP Increase from Baseline>=40 | 3 Participants |
| RSG XR 8mg | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP Decrease from Baseline>=30 | 14 Participants |
| RSG XR 8mg | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP Decrease from Baseline >=20 | 13 Participants |
| RSG XR 8mg | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP >90 or <50 | 12 Participants |
| RSG XR 8mg | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP >140 or <90 | 86 Participants |
| RSG XR 8mg | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP Increase from Baseline>=30 | 1 Participants |
Secondary
Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Weight
Body weight was measured at all visits, without shoes and wearing light clothing. The assessment was performed a t Baseline and up to Week 54. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Full population data was presented.
Time frame: Upto Week 54
Population: Safety population. Only those participants available at the indicated time point were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Weight | Increase from Baseline >=7% | 33 Participants |
| Placebo | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Weight | Decrease from Baseline >=7% | 28 Participants |
| RSG XR 2mg | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Weight | Increase from Baseline >=7% | 31 Participants |
| RSG XR 2mg | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Weight | Decrease from Baseline >=7% | 32 Participants |
| RSG XR 8mg | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Weight | Increase from Baseline >=7% | 47 Participants |
| RSG XR 8mg | Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Weight | Decrease from Baseline >=7% | 23 Participants |
Secondary
Number of Participants With On-treatment Adverse Events (AEs), Serious Adverse Events (SAEs) and Severity of AEs
AE was defined as any untoward medical occurrence in a participant temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE was any untoward medical occurrence that, at any dose results in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect or was considered as medically significant.
Time frame: Upto Week 48
Population: Safety population consisted of all participants randomized to treatment who had taken at least one dose of study medication. This population was used for analysis of safety data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With On-treatment Adverse Events (AEs), Serious Adverse Events (SAEs) and Severity of AEs | Moderate AEs | 111 Participants |
| Placebo | Number of Participants With On-treatment Adverse Events (AEs), Serious Adverse Events (SAEs) and Severity of AEs | Mild AEs | 109 Participants |
| Placebo | Number of Participants With On-treatment Adverse Events (AEs), Serious Adverse Events (SAEs) and Severity of AEs | On treatment AEs | 275 Participants |
| Placebo | Number of Participants With On-treatment Adverse Events (AEs), Serious Adverse Events (SAEs) and Severity of AEs | On treatment SAEs | 60 Participants |
| Placebo | Number of Participants With On-treatment Adverse Events (AEs), Serious Adverse Events (SAEs) and Severity of AEs | Severe AEs | 55 Participants |
| RSG XR 2mg | Number of Participants With On-treatment Adverse Events (AEs), Serious Adverse Events (SAEs) and Severity of AEs | Mild AEs | 119 Participants |
| RSG XR 2mg | Number of Participants With On-treatment Adverse Events (AEs), Serious Adverse Events (SAEs) and Severity of AEs | On treatment AEs | 298 Participants |
| RSG XR 2mg | Number of Participants With On-treatment Adverse Events (AEs), Serious Adverse Events (SAEs) and Severity of AEs | On treatment SAEs | 58 Participants |
| RSG XR 2mg | Number of Participants With On-treatment Adverse Events (AEs), Serious Adverse Events (SAEs) and Severity of AEs | Moderate AEs | 128 Participants |
| RSG XR 2mg | Number of Participants With On-treatment Adverse Events (AEs), Serious Adverse Events (SAEs) and Severity of AEs | Severe AEs | 50 Participants |
| RSG XR 8mg | Number of Participants With On-treatment Adverse Events (AEs), Serious Adverse Events (SAEs) and Severity of AEs | Severe AEs | 48 Participants |
| RSG XR 8mg | Number of Participants With On-treatment Adverse Events (AEs), Serious Adverse Events (SAEs) and Severity of AEs | Moderate AEs | 158 Participants |
| RSG XR 8mg | Number of Participants With On-treatment Adverse Events (AEs), Serious Adverse Events (SAEs) and Severity of AEs | On treatment AEs | 319 Participants |
| RSG XR 8mg | Number of Participants With On-treatment Adverse Events (AEs), Serious Adverse Events (SAEs) and Severity of AEs | Mild AEs | 112 Participants |
| RSG XR 8mg | Number of Participants With On-treatment Adverse Events (AEs), Serious Adverse Events (SAEs) and Severity of AEs | On treatment SAEs | 66 Participants |