Alzheimer's Disease
Conditions
Keywords
Alzheimer's Disease, Dimebon, Safety, Tolerability
Brief summary
This is a multi-center, randomized, double-blind placebo-controlled safety study conducted in 2 study cohorts. In Cohort 1, subjects with Alzheimer's disease (n=250) will receive Dimebon 20 mg or placebo TID for 26 weeks. In Cohort 2 AD subjects (n=500) will be treated with Dimebon 20 mg or placebo TID for 12 weeks After completion of the randomized portion of the study, subjects in both Cohorts will have the opportunity to enroll in a Dimebon open label extension study.
Interventions
DRUGDimebon
10 mg TID for week 1 followed by 20 mg TID through Week 26
DRUGPlacebo
10 mg TID for week 1 followed by 20 mg TID through Week 26
Sponsors
Medivation, Inc.
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Alzheimer's Disease. * MMSE 12-26 inclusive. * If on existing anti-dementia therapy, have been on a stable dose of anti-dementia therapy (cholinesterase inhibitors and/or memantine) for at least 60 days prior to dosing in study. * If not taking existing anti-dementia therapy, have not received therapy with cholinesterase inhibitors and/or memantine within 60 days prior to dosing in this study.
Exclusion criteria
* Have major structural brain disease (e.g., ischemic infarcts, subdural hematoma, hemorrhage, hydrocephalus, brain tumors, multiple subcortical ischemic lesions, or a single lesion in a critical region \[e.g., thalamus, hippocampus\]). * Have any major medical illness or unstable medical condition within six months of screening that may interfere with the patient's ability to comply with study procedures and abide by study restrictions. * Have not been on a stable dose of anti-dementia therapy for at least 60 days prior to dosing or intend to start anti-dementia therapy during the double blind portion of the study. * Reside in a nursing home or assisted care facility with need for 24-hour care and supervision.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 1 | Baseline up to Week 30 (follow-up) | Abnormal clinically significant vital signs included absolute systolic blood pressure (BP) values: less than (\<) 90 millimeter of mercury (mmHg), maximum increase or decrease of greater than or equal to (\>=) 30 mmHg from baseline; absolute diastolic BP value: \<50 mmHg, maximum increase or decrease of \>=20 mmHg from baseline; absolute heart rate values: \>120 beats per minute (bpm). |
| Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 2 | Baseline up to Week 16 (follow-up) | Abnormal clinically significant vital signs included absolute systolic BP values: \<90 mmHg, maximum increase or decrease of \>=30 mmHg from baseline; absolute diastolic BP values: \<50 mmHg, maximum increase or decrease of \>=20 mmHg from baseline; absolute heart rate values: \>120 bpm. |
| Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 1 | Baseline up to Week 30 (follow-up) | Abnormal ECG findings included maximum value of \>=300 millisecond (msec), maximum increase of \>=25% for baseline value of \>200 msec and maximum increase of \>=50% for baseline value of \<=200 msec for PR interval (int); maximum value of \>=200 msec, maximum increase of \>=25% for baseline value of \>100 msec and maximum increase of \>=50% for baseline value of \<=100 msec for QRS interval; maximum value of \>=500 msec for QT interval; maximum value of 450 to \<480, 480 to \<500 and \>=500 msec, increase of \>=30 to \<60 and \>=60 msec for QT interval corrected using Fridericia's formula (QTcF interval). |
| Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 2 | Baseline up to Week 16 (follow-up) | Abnormal ECG findings included maximum value of \>=300 msec, maximum increase of \>=25% for baseline value of \>200 msec and maximum increase of \>=50% for baseline value of \<=200 msec for PR interval; maximum value of \>=200 msec, maximum increase of \>=25% for baseline value of \>100 msec and maximum increase of \>=50% for baseline value of \<=100 msec for QRS interval; maximum value of \>=500 msec for QT interval; maximum value of 450 to \<480, 480 to \<500 and \>=500 msec, increase of \>=30 to \<60 and \>=60 msec for QT interval corrected using Fridericia's formula (QTcF interval). |
| Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Baseline up to Week 30 (follow-up) | For hematology, liver function, renal function, electrolytes, clinical chemistry, abnormality was reported if the observed value was more than or less than X times the upper limit of normal (ULN) or lower limit of normal (LLN) respectively; X=specified in categories of each parameter in the measured values section. For urinalysis of glucose, ketones, protein, blood, abnormality was reported if result was \>=1 in qualitative test of respective parameters, indicating levels in urine were abnormal. Urine pH and specific gravity abnormality reported if pH \>8 and specific gravity \<1.003 or \>1.030. |
| Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Baseline up to Week 16 (follow-up) | For hematology, liver function, renal function, electrolytes, clinical chemistry, abnormality was reported if the observed value was more than or less than X times the ULN or LLN respectively; X=specified in categories of each parameter in the measured values section. For urinalysis of glucose, ketones, protein, blood, abnormality was reported if result was \>=1 in qualitative test of respective parameters, indicating levels in urine were abnormal. Urine pH and specific gravity abnormality reported if pH \>8 and specific gravity \<1.003 or \>1.030. |
| Percentage of Participants With Adverse Events (AEs) in Cohort 1 | Baseline up to Week 30 (follow-up) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. |
| Percentage of Participants With Adverse Events (AEs) in Cohort 2 | Baseline up to Week 16 (follow-up) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. |
Countries
Canada, Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dimebon Dimebon (latrepirdine) 10 milligram (mg) tablet orally three times a day for 1 week (titration period), followed by dimebon (latrepirdine) 20 mg tablet orally three times a day up to Week 26 for cohort 1 and up to Week 12 for cohort 2. | 370 |
| Placebo Placebo tablet matched to 10 mg of dimebon (latrepirdine) tablet orally three times a day for 1 week (titration period), followed by placebo tablet matched to 20 mg dimebon (latrepirdine) tablet orally three times a day up to Week 26 for cohort 1 and up to Week 12 for cohort 2. | 371 |
| Total | 741 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 11 | 10 | 8 | 7 |
| Overall Study | Death | 0 | 0 | 1 | 2 |
| Overall Study | Did not meet eligibility criteria | 0 | 0 | 1 | 2 |
| Overall Study | Lost to Follow-up | 3 | 0 | 0 | 0 |
| Overall Study | Other | 3 | 3 | 3 | 2 |
| Overall Study | Protocol Violation | 0 | 2 | 1 | 1 |
| Overall Study | Randomized but not treated | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 6 | 3 | 4 |
Baseline characteristics
| Characteristic | Dimebon | Placebo | Total |
|---|---|---|---|
| Age, Customized 50 to 59 years | 24 Participants | 13 Participants | 37 Participants |
| Age, Customized 60 to 69 years | 50 Participants | 63 Participants | 113 Participants |
| Age, Customized 70 to 79 years | 155 Participants | 154 Participants | 309 Participants |
| Age, Customized 80 to 85 years | 109 Participants | 103 Participants | 212 Participants |
| Age, Customized Greater than 85 years | 32 Participants | 38 Participants | 70 Participants |
| Sex: Female, Male Female | 192 Participants | 198 Participants | 390 Participants |
| Sex: Female, Male Male | 178 Participants | 173 Participants | 351 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 107 / 370 | 110 / 371 |
| serious Total, serious adverse events | 26 / 370 | 28 / 371 |
Outcome results
Primary
Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 1
Abnormal ECG findings included maximum value of \>=300 millisecond (msec), maximum increase of \>=25% for baseline value of \>200 msec and maximum increase of \>=50% for baseline value of \<=200 msec for PR interval (int); maximum value of \>=200 msec, maximum increase of \>=25% for baseline value of \>100 msec and maximum increase of \>=50% for baseline value of \<=100 msec for QRS interval; maximum value of \>=500 msec for QT interval; maximum value of 450 to \<480, 480 to \<500 and \>=500 msec, increase of \>=30 to \<60 and \>=60 msec for QT interval corrected using Fridericia's formula (QTcF interval).
Time frame: Baseline up to Week 30 (follow-up)
Population: Cohort 1 analysis set included all those participants in the SAS (all participants who received at least one dose of study medication, including partial doses) who were randomized into cohort 1 of the study. Here, 'n' signifies those participants who were evaluable for particular category for each group respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 1 | Increase in QRS int (>=25/50%) (n=126,126) | 1.6 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 1 | QT int (>=500 msec) (n=127,127) | 0.0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 1 | QTcF int (450 to <480 msec) (n=127,127) | 15.7 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 1 | QTcF int (480 to <500 msec) (n=127,127) | 1.6 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 1 | QTcF int (>=500 msec) (n=127,127) | 0.0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 1 | Increase in QTcF int (>=30 to <60msec )(n=126,126) | 9.5 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 1 | Increase in QTcF int (>=60 msec) (n=126,126) | 0.8 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 1 | PR int (>=300 msec) (n=123,113) | 0.0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 1 | Increase in PR int (>=25/50%) (n=122,112) | 0.0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 1 | QRS int (>=200 msec) (n=127,127) | 0.0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 1 | PR int (>=300 msec) (n=123,113) | 0.0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 1 | Increase in QRS int (>=25/50%) (n=126,126) | 0.0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 1 | Increase in QTcF int (>=30 to <60msec )(n=126,126) | 7.1 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 1 | QT int (>=500 msec) (n=127,127) | 2.4 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 1 | QRS int (>=200 msec) (n=127,127) | 0.0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 1 | QTcF int (450 to <480 msec) (n=127,127) | 13.4 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 1 | Increase in QTcF int (>=60 msec) (n=126,126) | 0.0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 1 | QTcF int (480 to <500 msec) (n=127,127) | 4.7 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 1 | Increase in PR int (>=25/50%) (n=122,112) | 0.0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 1 | QTcF int (>=500 msec) (n=127,127) | 0.8 percentage of participants |
Primary
Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 2
Abnormal ECG findings included maximum value of \>=300 msec, maximum increase of \>=25% for baseline value of \>200 msec and maximum increase of \>=50% for baseline value of \<=200 msec for PR interval; maximum value of \>=200 msec, maximum increase of \>=25% for baseline value of \>100 msec and maximum increase of \>=50% for baseline value of \<=100 msec for QRS interval; maximum value of \>=500 msec for QT interval; maximum value of 450 to \<480, 480 to \<500 and \>=500 msec, increase of \>=30 to \<60 and \>=60 msec for QT interval corrected using Fridericia's formula (QTcF interval).
Time frame: Baseline up to Week 16 (follow-up)
Population: Cohort 2 analysis set included all those participants in the SAS (all participants who received at least one dose of study medication, including partial doses) who were randomized into cohort 2 of the study. Here, 'n' signifies those participants who were evaluable for particular category for each group respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 2 | PR int (>=300 msec) (n=232,232) | 0.9 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 2 | Increase in PR int (>=25/50%) (n=231,229) | 0.0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 2 | QRS int (>=200 msec) (n=243,244) | 0.0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 2 | Increase in QRS int (>=25/50%) (n=242,243) | 0.8 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 2 | QT int (>=500 msec) (n=243,244) | 0.8 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 2 | QTcF int (450 to <480 msec) (n=243,244) | 15.6 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 2 | QTcF int (480 to <500 msec) (n=243,244) | 2.1 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 2 | QTcF int (>=500 msec) (n=243,244) | 1.2 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 2 | Increase in QTcF int (>=30 to <60 msec)(n=242,243) | 6.6 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 2 | Increase in QTcF int (>=60 msec) (n=242,243) | 0.4 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 2 | QTcF int (>=500 msec) (n=243,244) | 0.0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 2 | PR int (>=300 msec) (n=232,232) | 0.0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 2 | QTcF int (450 to <480 msec) (n=243,244) | 19.3 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 2 | Increase in PR int (>=25/50%) (n=231,229) | 0.0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 2 | Increase in QTcF int (>=60 msec) (n=242,243) | 0.0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 2 | QRS int (>=200 msec) (n=243,244) | 0.0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 2 | QTcF int (480 to <500 msec) (n=243,244) | 0.8 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 2 | Increase in QRS int (>=25/50%) (n=242,243) | 0.4 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 2 | Increase in QTcF int (>=30 to <60 msec)(n=242,243) | 5.8 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 2 | QT int (>=500 msec) (n=243,244) | 0.8 percentage of participants |
Primary
Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1
For hematology, liver function, renal function, electrolytes, clinical chemistry, abnormality was reported if the observed value was more than or less than X times the upper limit of normal (ULN) or lower limit of normal (LLN) respectively; X=specified in categories of each parameter in the measured values section. For urinalysis of glucose, ketones, protein, blood, abnormality was reported if result was \>=1 in qualitative test of respective parameters, indicating levels in urine were abnormal. Urine pH and specific gravity abnormality reported if pH \>8 and specific gravity \<1.003 or \>1.030.
Time frame: Baseline up to Week 30 (follow-up)
Population: Cohort 1 analysis set. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure for each group respectively. Here, 'n' signifies those participants who were evaluable for particular category for each group respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Potassium (<0.9*LLN) (n=125,123) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | White blood cell count (>1.5*ULN) (n=126,123) | 1 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Potassium (>1.1*ULN) (n=125,123) | 2 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Monocytes (>1.2*ULN) (n=126,123) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Calcium (>1.1*ULN) (n=125,123) | 1 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Mean corpuscular volume (>1.1*ULN) (n=126,123) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Magnesium (<0.9*LLN) (n=125,123) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Total bilirubin (>1.5*ULN) (n=125,123) | 1 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Magnesium (>1.1*ULN) (n=125,123) | 20 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Lymphocytes (<0.8*LLN) (n=126,123) | 2 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Phosphate (<0.8*LLN) (n=125,123) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Aspartate aminotransferase (>3.0*ULN) (n=125,123) | 1 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Phosphate (>1.2*ULN) (n=125,123) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Mean corpuscular volume (<0.9*LLN) (n=126,123) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Bicarbonate (<0.9*LLN) (n=125,123) | 2 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Alanine aminotransferase (>3.0*ULN) (n=125,123) | 1 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Bicarbonate (>1.1*ULN) (n=125,123) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Lymphocytes (>1.2*ULN) (n=126,123) | 1 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Glucose (>1.5*ULN) (n=125,123) | 9 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Blood urea nitrogen (>1.3*ULN) (n=125,123) | 1 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Creatine kinase (>2.0*ULN) (n=125,123) | 3 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | White blood cell count (<0.6*LLN) (n=126,123) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Urine specific gravity (<1.003) (n=125,123) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Creatinine (>1.3*ULN) (n=125,123) | 2 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Urine specific gravity (>1.030) (n=125,123) | 2 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Total Neutrophils (<0.8*LLN) (n=126,123) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Urine pH (>8) (n=125,123) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Sodium (<0.95*LLN) (n=125,123) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Urine glucose (>=1) (n=125,123) | 4 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Red blood cell count (<0.8*LLN) (n=126,123) | 2 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Urine ketones (>=1) (n=125,123) | 1 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Sodium (>1.05*ULN) (n=125,123) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Urine blood (>=1) (n=125,123) | 32 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Total Neutrophils (>1.2*ULN) (n=126,123) | 4 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Urine protein (>=1) (n=125,123) | 4 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Hemoglobin (<0.8*LLN) (n=126,123) | 1 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Urine protein (>=1) (n=125,123) | 2 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Hemoglobin (<0.8*LLN) (n=126,123) | 1 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Red blood cell count (<0.8*LLN) (n=126,123) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Mean corpuscular volume (<0.9*LLN) (n=126,123) | 2 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Mean corpuscular volume (>1.1*ULN) (n=126,123) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | White blood cell count (<0.6*LLN) (n=126,123) | 1 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | White blood cell count (>1.5*ULN) (n=126,123) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Lymphocytes (<0.8*LLN) (n=126,123) | 1 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Lymphocytes (>1.2*ULN) (n=126,123) | 2 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Total Neutrophils (<0.8*LLN) (n=126,123) | 1 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Total Neutrophils (>1.2*ULN) (n=126,123) | 3 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Monocytes (>1.2*ULN) (n=126,123) | 1 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Total bilirubin (>1.5*ULN) (n=125,123) | 2 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Aspartate aminotransferase (>3.0*ULN) (n=125,123) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Alanine aminotransferase (>3.0*ULN) (n=125,123) | 1 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Blood urea nitrogen (>1.3*ULN) (n=125,123) | 2 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Creatinine (>1.3*ULN) (n=125,123) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Sodium (<0.95*LLN) (n=125,123) | 1 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Sodium (>1.05*ULN) (n=125,123) | 1 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Potassium (<0.9*LLN) (n=125,123) | 2 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Potassium (>1.1*ULN) (n=125,123) | 1 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Calcium (>1.1*ULN) (n=125,123) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Magnesium (<0.9*LLN) (n=125,123) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Magnesium (>1.1*ULN) (n=125,123) | 24 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Phosphate (<0.8*LLN) (n=125,123) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Phosphate (>1.2*ULN) (n=125,123) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Bicarbonate (<0.9*LLN) (n=125,123) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Bicarbonate (>1.1*ULN) (n=125,123) | 1 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Glucose (>1.5*ULN) (n=125,123) | 10 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Creatine kinase (>2.0*ULN) (n=125,123) | 2 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Urine specific gravity (<1.003) (n=125,123) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Urine specific gravity (>1.030) (n=125,123) | 2 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Urine pH (>8) (n=125,123) | 1 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Urine glucose (>=1) (n=125,123) | 3 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Urine ketones (>=1) (n=125,123) | 2 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | Urine blood (>=1) (n=125,123) | 7 percentage of participants |
Primary
Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2
For hematology, liver function, renal function, electrolytes, clinical chemistry, abnormality was reported if the observed value was more than or less than X times the ULN or LLN respectively; X=specified in categories of each parameter in the measured values section. For urinalysis of glucose, ketones, protein, blood, abnormality was reported if result was \>=1 in qualitative test of respective parameters, indicating levels in urine were abnormal. Urine pH and specific gravity abnormality reported if pH \>8 and specific gravity \<1.003 or \>1.030.
Time frame: Baseline up to Week 16 (follow-up)
Population: Cohort 2 analysis set. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure for each group respectively. Here, 'n' signifies those participants who were evaluable for particular category for each group respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Urine blood (>=1) (n=237,240) | 26 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Potassium (>1.1*ULN) (n=239,241) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Calcium (>1.1*ULN) (n=239,241) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Magnesium (<0.9*LLN) (n=239,241) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Magnesium (>1.1*ULN) (n=239,241) | 18 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Phosphate (<0.8*LLN) (n=239,241) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Phosphate (>1.2*ULN) (n=239,241) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Bicarbonate (<0.9*LLN) (n=239,241) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Bicarbonate (>1.1*ULN) (n=239,241) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Glucose (>1.5*ULN) (n=239,241) | 6 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Creatine kinase (>2.0*ULN) (n=239,241) | 3 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Urine protein (>=1) (n=237,240) | 1 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Urine specific gravity (<1.003) (n=237,240) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Urine specific gravity (>1.030) (n=237,240) | 2 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Urine pH (>8) (n=237,240) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Urine glucose (>=1) (n=237,240) | 3 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Alanine aminotransferase (>3.0*ULN) (n=239,241) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Blood urea nitrogen (>1.3*ULN) ((n=239,241) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Creatinine (>1.3*ULN) (n=239,241) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Sodium (<0.95*LLN) (n=239,241) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Sodium (>1.05*ULN) (n=239,241) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Potassium (<0.9*LLN) (n=239,241) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Urine ketones (>=1) (n=237,240) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Hemoglobin (<0.8*LLN) (n=239,241) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Red blood cell count (<0.8*LLN) (n=239,241) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Mean corpuscular volume (<0.9*LLN) (n=239,241) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Mean corpuscular volume (>1.1*ULN) (n=239,241) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | White blood cell count (<0.6*LLN) (n=239,241) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | White blood cell count (>1.5*ULN) (n=239,241) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Lymphocytes (<0.8*LLN) (n=239,241) | 1 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Lymphocytes (>1.2*ULN) (n=239,241) | 3 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Total Neutrophils (<0.8*LLN) (n=239,241) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Total Neutrophils (>1.2*ULN) (n=239,241) | 2 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Monocytes (>1.2*ULN) (n=239,241) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Total bilirubin (>1.5*ULN) (n=239,241) | 0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Aspartate aminotransferase (>3.0*ULN) (n=239,241) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Mean corpuscular volume (<0.9*LLN) (n=239,241) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Potassium (<0.9*LLN) (n=239,241) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Blood urea nitrogen (>1.3*ULN) ((n=239,241) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Potassium (>1.1*ULN) (n=239,241) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Mean corpuscular volume (>1.1*ULN) (n=239,241) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Calcium (>1.1*ULN) (n=239,241) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Creatinine (>1.3*ULN) (n=239,241) | 1 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Magnesium (<0.9*LLN) (n=239,241) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | White blood cell count (>1.5*ULN) (n=239,241) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Magnesium (>1.1*ULN) (n=239,241) | 17 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Sodium (<0.95*LLN) (n=239,241) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Phosphate (<0.8*LLN) (n=239,241) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Total bilirubin (>1.5*ULN) (n=239,241) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Phosphate (>1.2*ULN) (n=239,241) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Sodium (>1.05*ULN) (n=239,241) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Bicarbonate (<0.9*LLN) (n=239,241) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | White blood cell count (<0.6*LLN) (n=239,241) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Bicarbonate (>1.1*ULN) (n=239,241) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Total Neutrophils (<0.8*LLN) (n=239,241) | 1 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Glucose (>1.5*ULN) (n=239,241) | 4 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Urine ketones (>=1) (n=237,240) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Urine blood (>=1) (n=237,240) | 5 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Monocytes (>1.2*ULN) (n=239,241) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Creatine kinase (>2.0*ULN) (n=239,241) | 1 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Hemoglobin (<0.8*LLN) (n=239,241) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Urine specific gravity (<1.003) (n=237,240) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Lymphocytes (<0.8*LLN) (n=239,241) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Urine specific gravity (>1.030) (n=237,240) | 1 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Red blood cell count (<0.8*LLN) (n=239,241) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Urine pH (>8) (n=237,240) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Total Neutrophils (>1.2*ULN) (n=239,241) | 1 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Urine glucose (>=1) (n=237,240) | 3 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Urine protein (>=1) (n=237,240) | 3 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Aspartate aminotransferase (>3.0*ULN) (n=239,241) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Lymphocytes (>1.2*ULN) (n=239,241) | 0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | Alanine aminotransferase (>3.0*ULN) (n=239,241) | 0 percentage of participants |
Primary
Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 1
Abnormal clinically significant vital signs included absolute systolic blood pressure (BP) values: less than (\<) 90 millimeter of mercury (mmHg), maximum increase or decrease of greater than or equal to (\>=) 30 mmHg from baseline; absolute diastolic BP value: \<50 mmHg, maximum increase or decrease of \>=20 mmHg from baseline; absolute heart rate values: \>120 beats per minute (bpm).
Time frame: Baseline up to Week 30 (follow-up)
Population: Cohort 1 analysis set included all those participants in the safety analysis set (SAS) (all participants who receive at least one dose of study medication, including partial doses) who were randomized into cohort 1 of the study. Here, 'n' signifies those participants who were evaluable for particular category for each group respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 1 | Decrease in systolic BP (>=30 mmHg) (n=126,124) | 16.7 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 1 | Increase in diastolic BP (>=20 mmHg) (n=126,124) | 7.1 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 1 | Increase in systolic BP (>=30 mmHg) (n=126,124) | 9.5 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 1 | Decrease in diastolic BP (>=20 mmHg) (n=126,124) | 15.9 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 1 | Diastolic BP (<50 mmHg) (n=127,127) | 0.8 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 1 | Heart rate (>120 bpm) (n=127,127) | 0.0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 1 | Systolic BP (<90 mmHg) (n=127,127) | 0.8 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 1 | Heart rate (>120 bpm) (n=127,127) | 0.0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 1 | Systolic BP (<90 mmHg) (n=127,127) | 1.6 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 1 | Increase in systolic BP (>=30 mmHg) (n=126,124) | 10.5 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 1 | Decrease in systolic BP (>=30 mmHg) (n=126,124) | 12.9 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 1 | Diastolic BP (<50 mmHg) (n=127,127) | 1.6 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 1 | Increase in diastolic BP (>=20 mmHg) (n=126,124) | 7.3 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 1 | Decrease in diastolic BP (>=20 mmHg) (n=126,124) | 12.9 percentage of participants |
Primary
Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 2
Abnormal clinically significant vital signs included absolute systolic BP values: \<90 mmHg, maximum increase or decrease of \>=30 mmHg from baseline; absolute diastolic BP values: \<50 mmHg, maximum increase or decrease of \>=20 mmHg from baseline; absolute heart rate values: \>120 bpm.
Time frame: Baseline up to Week 16 (follow-up)
Population: Cohort 2 analysis set included all those participants in the SAS (all participants who receive at least one dose of study medication, including partial doses) who were randomized into cohort 2 of the study. Here, 'n' signifies those participants who were evaluable for particular category for each group respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 2 | Decrease in systolic BP (>=30 mmHg) (n=240,240) | 9.6 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 2 | Increase in diastolic BP (>=20 mmHg) (n=240,240) | 6.3 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 2 | Increase in systolic BP (>=30 mmHg) (n=240,240) | 3.8 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 2 | Decrease in diastolic BP (>=20 mmHg) (n=240,240) | 6.7 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 2 | Diastolic BP (<50 mmHg) (n=243,244) | 1.2 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 2 | Heart rate (>120 bpm) (n=243,244) | 0.0 percentage of participants |
| Dimebon (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 2 | Systolic BP (<90 mmHg) (n=243,244) | 0.8 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 2 | Heart rate (>120 bpm) (n=243,244) | 0.0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 2 | Systolic BP (<90 mmHg) (n=243,244) | 0.0 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 2 | Increase in systolic BP (>=30 mmHg) (n=240,240) | 8.3 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 2 | Decrease in systolic BP (>=30 mmHg) (n=240,240) | 8.8 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 2 | Diastolic BP (<50 mmHg) (n=243,244) | 0.8 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 2 | Increase in diastolic BP (>=20 mmHg) (n=240,240) | 5.4 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 2 | Decrease in diastolic BP (>=20 mmHg) (n=240,240) | 7.5 percentage of participants |
Primary
Percentage of Participants With Adverse Events (AEs) in Cohort 1
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Time frame: Baseline up to Week 30 (follow-up)
Population: Cohort 1 analysis set included all those participants in the SAS (all participants who received at least one dose of study medication, including partial doses) who were randomized into cohort 1 of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dimebon (Cohort 1) | Percentage of Participants With Adverse Events (AEs) in Cohort 1 | 64.6 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Adverse Events (AEs) in Cohort 1 | 64.6 percentage of participants |
Primary
Percentage of Participants With Adverse Events (AEs) in Cohort 2
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Time frame: Baseline up to Week 16 (follow-up)
Population: Cohort 2 analysis set included all those participants in the SAS (all participants who received at least one dose of study medication, including partial doses) who were randomized into cohort 2 of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dimebon (Cohort 1) | Percentage of Participants With Adverse Events (AEs) in Cohort 2 | 55.1 percentage of participants |
| Placebo (Cohort 1) | Percentage of Participants With Adverse Events (AEs) in Cohort 2 | 53.3 percentage of participants |