| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT00829374 | Safety and Efficacy Study Evaluating Dimebon in Patients With Mild to Moderate Alzheimer's Disease on Donepezil | PHASE3 | COMPLETED | 1,003 | — | — | Mar 1, 2009 | Dec 1, 2011 | Sep 26, 2016 | - | — |
| NCT00675623 | A Safety and Efficacy Study of Oral Dimebon in Patients With Mild-To-Moderate Alzheimer's Disease | PHASE3 | COMPLETED | 598 | — | — | May 30, 2008 | - | Sep 26, 2016 | - | — |
| NCT00838110 | A Phase 3 Study To Evaluate The Safety And Tolerability Of Dimebon Patients With Mild To Moderate Alzheimer's Disease | PHASE3 | COMPLETED | 742 | — | — | Feb 1, 2009 | Jan 1, 2010 | Dec 6, 2018 | 118 | United States, Canada +1 |
| NCT00377715 | Double-blind, Placebo-controlled Study of Oral Dimebon in Subjects With Mild to Moderate Alzheimer's Disease | PHASE2 | COMPLETED | 183 | — | — | Sep 29, 2005 | - | Nov 10, 2015 | - | — |
| NCT00829816 | Safety and Tolerability of Dimebon in Patients on Memantine, and Memantine Plus Donepezil | PHASE1 | COMPLETED | 46 | — | — | Dec 1, 2008 | Aug 1, 2010 | Nov 9, 2015 | - | — |
| NCT00975481 | A Study To Evaluate The Abuse Potential Of Single Oral Doses Of Dimebon (Latrepirdine) In Healthy Recreational Polydrug Users | PHASE1 | COMPLETED | 36 | — | — | Oct 1, 2009 | Feb 1, 2010 | Apr 2, 2013 | - | — |
| NCT00824590 | A Phase 1, Non-Randomized, Open-Label, Single-Dose Study To Evaluate The Pharmacokinetics, Safety, And Tolerability Of Dimebon [PF 01913539] In Subjects With Severely-Impaired And Normal Renal Function | PHASE1 | COMPLETED | 20 | — | — | Feb 1, 2009 | Oct 1, 2009 | Dec 30, 2009 | 2 | United States |
| NCT00825084 | A Phase 1 Study To Evaluate The Pharmacokinetics, Safety, And Tolerability Of Dimebon [PF-01913539] In Japanese And Western Healthy Subjects | PHASE1 | COMPLETED | 45 | — | — | Feb 1, 2009 | May 1, 2009 | Apr 26, 2011 | 1 | United States |
| NCT00827034 | A Phase 1, Randomized, Open-Label, Two-Way Crossover Study To Evaluate The Steady-State Effect Of Dimebon (PF 01913539) On The Single-Dose Pharmacokinetics And Pharmacodynamics Of Warfarin In Healthy Subjects | PHASE1 | COMPLETED | 14 | — | — | Feb 1, 2009 | Apr 1, 2009 | Oct 16, 2018 | 1 | United States |
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).
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.
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).
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).
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.
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.
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Drug liking VAS is one of the measures of balance of effects that assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 millimeter (mm) bipolar visual analogue scale (VAS) anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the left with "strong disliking" (score of 0 mm) and on the right with "strong liking" (score of 100 mm). Emax is largest effect score between 0.5 to 24 hours post-dose. Emin is smallest effect score between 0.5 to 24 hours post-dose.
Overall drug liking VAS is one of the measures of balance of effects that assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carryover effects). A 100 mm bipolar VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = "strong disliking", 50 mm= "neither like nor dislike", and 100 mm= "strong liking"). Emax is the largest effect score between 6 to 24 hours post-dose. Emin is the smallest effect score between 6 to 24 hours post-dose.
Take drug again VAS is one of the measures of balance of effects. It is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm bipolar VAS with score ranging from 0 mm to 100 mm (score of 0 mm = "definitely not", 50 mm = "do not care", and 100 mm = "definitely so"). Emax is largest effect score between 6 hours to 24 hours.
Good and Bad effects VAS is one of the measures of balance of effects that assesses the effect experienced by the participant on a 100 mm bipolar VAS, anchored in the center with a neutral anchor of neither good nor bad effects (score of 50 mm), on the left with bad effects(score of 0 mm) and on the right with good effects (score of 100 mm). Emax is largest effect score between 0.5 to 24 hours post-dose. Emin is smallest effect score between 0.5 to 24 hours post-dose.
SDV is one of measures of balance of effects. It is a proxy measure of reinforcing efficacy that involves a series of independent, theoretical forced choices between drug administered and different monetary values. Participants were asked to choose between receiving another dose of same drug or an envelope containing specified amount of money, but they did not receive drug or money as described. Possible score range from 0.25 to 50. Higher score range indicates higher SDV. Emax: largest effect score between 6-24 hours post-dose.
ARCI (MBG) is one of the measures of positive effects. It is a set of 16 questions in which each question contributes to total score. Participants indicate their responses by selecting 'False' or 'True'. One point is given for each response that agrees with the scoring direction on scale i.e, true items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when the answer is opposite to the scoring direction. Score range: 0 to 16, higher score indicated positive effects. Emax: largest effect score between 0 to 24 hours post-dose.
Good drug effects VAS is one of the measures of positive effects that assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so). Emax is the largest effect score between 0.5 to 24 hours post-dose.
High VAS is one of the measures of positive effects that assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so). Emax is largest effect score between 0 to 24 hours.
Bad effects VAS is one of the measures of negative effects that assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so). Emax is largest effect score between 0.5 to 24 hrs.
ARCI (LSD) is one of the measures of negative effects. It is a set of 14 questions in which each question contributes to total score. Participants indicate their responses by selecting 'False' or 'True'. One point is given for each response that agrees with scoring direction on scale i.e, true items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when the answer is opposite to scoring direction. Score range: 0 to 14, higher score indicated higher negative effects. Emax: largest effect score between 0 to 24 hours post-dose.
ARCI (PCAG) is one of the measures of sedative effects. It is a set of 15 questions in which each question contributes to total score. Participants indicate their responses by selecting 'False' or 'True'. One point is given for each response that agrees with the scoring direction on scale i.e, true items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when answer is opposite to scoring direction. Score range: 0 to 15, higher score indicated higher sedative effects. Emax: largest effect score between 0 to 24 hours post-dose.
Alertness/Drowsiness VAS is one of the measures of sedative effects. It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of "neither drowsy nor alert" (score of 50 mm), on the left with "very drowsy" (score of 0 mm) and on the right with "very alert" (score of 100 mm). Emin is the smallest effect score between 0 to 24 hours post-dose.
Any drug effects VAS is one of the measures of other subjective effects. It assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so). Emax is the largest effect score between 0.5 to 24 hours post-dose.
Drug similarity VAS is one of the measures of other subjective effects. It assesses the similarity of the drug recently received by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= not at all similar) to 'extremely' (score of 100 mm= very similar). Recently received drugs were compared with placebo, benzodiazepines, codeine/morphine, Tetrahydrocannabinol (THC), pseudoephedrine.
ARCI (BG) is measure of other subjective effects. It is a set of 13 questions in which each question contributes to total score. Participants select 'False' / 'True' for response. One point given for each response that agrees with scoring direction, true items receive score of 1 if answer 'True', false items receive score of 1 if answer 'False'. No points if answer is opposite to scoring direction. Score range: 0 to 13, higher score indicated higher other subjective effects. Emax: largest effect score between 0 - 24 hours post-dose. Emin: smallest effect score between 0 - 24 hours post-dose.
| Arm | Type | Description |
|---|---|---|
| Dimebon 20 mg TID (Cohort 1) | EXPERIMENTAL | - |
| Placebo TID (Cohort 1) | PLACEBO_COMPARATOR | - |
| Dimebon 20 mg TID (Cohort 2) | EXPERIMENTAL | - |
| Placebo TID (Cohort 2) | PLACEBO_COMPARATOR | - |
| dimebon 20 mg | EXPERIMENTAL | - |
| dimebon 40 mg | EXPERIMENTAL | - |
| dimebon 60 mg | EXPERIMENTAL | - |
| placebo | PLACEBO_COMPARATOR | - |
| alprazolam 1 mg | ACTIVE_COMPARATOR | - |
| alprazolam 3 mg | ACTIVE_COMPARATOR | - |
| Severe renal impairment group | EXPERIMENTAL | Subjects with severe renal impairment defined by creatinine clearance of less than 30 mL/min but not yet on dialysis |
| normal renal function | EXPERIMENTAL | Subjects with normal renal function defined by creatinine clearance of greater than 80 mL/min and demographically comparable to subjects with impaired renal function |
| single dose cohort-Japanese group | EXPERIMENTAL | Japanese healthy subjects |
| single dose cohort-Western group | EXPERIMENTAL | Western healthy subjects |
| multiple dose cohort-Japanese group | EXPERIMENTAL | Japanese healthy subjects |
| multiple dose cohort-Western group | EXPERIMENTAL | Western healthy subjects |
| A | OTHER | A: Warfarin alone |
| B | OTHER | B: Dimebon and Warfarin co-administration |
| Name | Type | Description |
|---|---|---|
| Dimebon | DRUG | 5 mg orally three times daily |
| Placebo comparator | DRUG | Placebo orally three times daily |
| Placebo | DRUG | Placebo three times daily for six months |
| alprazolam | DRUG | Oral capsule; 1 mg alprazolam, single dose |
| Warfarin | DRUG | A: a single oral dose of warfarin 25 mg administered on Day 1 of the relevant dosing period, as tablets. |
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-demen...