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Dimebon

Phase 3

Alzheimer Disease | Small molecule | Neurology |Pfizer, Inc.|Trials Updated: Dec 6, 2018

Dimebon development status

Highest phase Phase 3
Registered trials 18 across 2 sponsors since Jan 2009

Dimebon target and mechanism

ModalitySmall molecule

Also known as Dimebon Transdermal

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindCONTROLLEDDMC
Total Trials15
Total Enrollment3,239

FDA Designations

No designations recorded

Dimebon clinical trials

Dimebon · 15 trials · 5 indications

Phase 3 4Phase 2 2Phase 1/2 1Phase 1 8
NCT00920946A Safety and Efficacy Study of Dimebon in Patients With Huntington DiseaseHuntington Disease
COMPLETED403 Analytics
NCT00829374Safety and Efficacy Study Evaluating Dimebon in Patients With Mild to Moderate Alzheimer's Disease on DonepezilAlzheimer's Disease
COMPLETED1,003 Analytics
NCT00675623A Safety and Efficacy Study of Oral Dimebon in Patients With Mild-To-Moderate Alzheimer's DiseaseAlzheimer's Disease
COMPLETED598 Analytics
NCT00838110A Phase 3 Study To Evaluate The Safety And Tolerability Of Dimebon Patients With Mild To Moderate Alzheimer's DiseaseAlzheimer's Disease
COMPLETED742 Analytics
PHASE3COMPLETED
A Safety and Efficacy Study of Dimebon in Patients With Huntington Disease
Huntington DiseaseUnlock trial analytics
PHASE3COMPLETED
Safety and Efficacy Study Evaluating Dimebon in Patients With Mild to Moderate Alzheimer's Disease on Donepezil
Alzheimer's DiseaseUnlock trial analytics
PHASE3COMPLETED
A Safety and Efficacy Study of Oral Dimebon in Patients With Mild-To-Moderate Alzheimer's Disease
Alzheimer's DiseaseUnlock trial analytics
PHASE3COMPLETED
A Phase 3 Study To Evaluate The Safety And Tolerability Of Dimebon Patients With Mild To Moderate Alzheimer's Disease
Alzheimer's DiseaseUnlock trial analytics

Study Endpoints

Primary Endpoints

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.

Balance of Effects- Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin)
0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose

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.

Balance of Effects- Overall Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin)
6, 12, 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.

Balance of Effects- Take Drug Again VAS: Peak Effect (Maximum Effect [Emax])
6, 12, 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.

Balance of Effects- Good and Bad Effects VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin)
0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose

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.

Balance of Effects- Subjective Drug Value (SDV): Maximum Effect (Emax)
6, 12, 24 hrs 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.

Positive Effects- Addiction Research Center Inventory (ARCI) Morphine Benzedrine Group (MBG): Maximum Effect (Emax)
0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 12, 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.

Positive Effects- Good Drug Effects: Peak Effect (Maximum Effect [Emax])
0.5, 1, 2, 3, 4, 6, 8, 12, 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.

Positive Effects- High VAS: Peak Effect (Maximum Effect [Emax])
0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 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.

Negative Effects- Bad Drug Effects: Peak Effect (Maximum Effect [Emax])
0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose

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.

Negative Effects- Addiction Research Center Inventory (ARCI) Lysergic Acid Diethylamide (LSD): Maximum Effect (Emax)
0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose

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.

Sedative Effects- Addiction Research Center Inventory (ARCI) Pentobarbital Chlorpromazine Group (PCAG): Maximum Effect (Emax)
0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 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.

Sedative Effects- Alertness/Drowsiness: Minimum Effect (Emin)
0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 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.

Other Subjective Effects- Any Drug Effects: Peak Effect (Maximum Effect [Emax])
0.5, 1, 2, 3, 4, 6, 8, 12, 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.

Other Subjective Effects- Drug Similarity
12 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.

Other Subjective Effects- Addiction Research Center Inventory (ARCI) Benzedrine Group (BG): Maximum Effect (Emax) and Minimum Effect (Emin)
0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose

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.

Plasma drug concentrations
96
Single dose pharmacokinetics (Cmax, AUCinf) of warfarin 25 mg with and without co-administration of steady-state Dimebon 20 mg TID in healthy adult subjects.
7+18 days
Single dose pharmacodynamics (INRmax, AUC-INR) of warfarin 25 mg with and without co-administration of steady-state Dimebon 20 mg TID in healthy adult subjects.
7+18 days
Safety and tolerability ( adverse event monitoring, physical examinations, vital signs, ECG's and clinical laboratory tests) of multiple doses of Dimebon 20 mg TID with a single dose of warfarin 25 mg in healthy adult subjects.
7+18 days
AUC24 and Cmin of digoxin on Day 14
Day 14
Pharmacokinetics (AUC and Cmax)
1 day
Dextromethorphan exposure in combination with Dimebon 20 mg TID relative to Dextromethorphan exposure alone
Day 12

Secondary Endpoints

Safety assessment including physical/neurological examination findings, clinical safety laboratory assessments, 12-lead ECGs, vital sign measurements, and adverse event monitoring.
96
Safety will be including physical/neurological examination findings, clinical safety laboratory assessments, 12-lead ECGs, vital sign measurements and adverse event monitoring
72 hours post last dose
Cmax, Tmax, Ae, and renal clearance of digoxin on Day 14
Day 14
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Study Design & Arms

Treatment Arms

ArmTypeDescription
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 mgEXPERIMENTAL -
dimebon 40 mgEXPERIMENTAL -
dimebon 60 mgEXPERIMENTAL -
placeboPLACEBO_COMPARATOR -
alprazolam 1 mgACTIVE_COMPARATOR -
alprazolam 3 mgACTIVE_COMPARATOR -
Severe renal impairment groupEXPERIMENTALSubjects with severe renal impairment defined by creatinine clearance of less than 30 mL/min but not yet on dialysis
normal renal functionEXPERIMENTALSubjects 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 groupEXPERIMENTALJapanese healthy subjects
single dose cohort-Western groupEXPERIMENTALWestern healthy subjects
multiple dose cohort-Japanese groupEXPERIMENTALJapanese healthy subjects
multiple dose cohort-Western groupEXPERIMENTALWestern healthy subjects
AOTHERA: Warfarin alone
BOTHERB: Dimebon and Warfarin co-administration
NormalEXPERIMENTALHealthy Volunteers
Mild Hepatic ImpairmentEXPERIMENTALMild hepatic impairment patients
Moderate hepatic ImpairmentEXPERIMENTALModerate Hepatic Impairment Patients
Severe Hepatic ImpairmentEXPERIMENTALSevere Hepatic Impairment Patients
Regimen A (Reference)OTHER -
Regimen B (Test)EXPERIMENTAL -

Interventions

NameTypeDescription
DimebonDRUG20 mg Dimebon orally TID
PlaceboOTHEROrally TID
Placebo comparatorDRUGPlacebo orally three times daily
alprazolamDRUGOral capsule; 1 mg alprazolam, single dose
WarfarinDRUGA: a single oral dose of warfarin 25 mg administered on Day 1 of the relevant dosing period, as tablets.
digoxinDRUGdigoxin once daily (0.125 mg QD) plus placebo three times daily (TID), 8 hours apart for 14 days.
DextromethorphanDRUGDextromethorphan HCl 30 syrup single dose
Dimebon + DextromethorphanDRUGDimebon 20 mg tablets given three times daily for 14 days plus Dextromethorphan HCl 30 syrup single dose administered on Day 12
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Eligibility Criteria

Age Range50 Years to N/A
SexALL

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...

Countries:United StatesCanadaPuerto Rico
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Frequently asked questions about Dimebon

What is Dimebon?

Dimebon is an investigational small molecule developed by Pfizer, Inc. (PFE) for neurological conditions. It has been studied in Alzheimer's disease, Huntington's disease, and hepatic failure. Dimebon is also known as latrepirdine and has been tested in combination with ketoconazole and dextromethorphan, as well as in a transdermal form.

What is Dimebon used for?

Dimebon has been studied for the treatment of Alzheimer's disease and Huntington's disease, and for hepatic failure. It is not approved for any indication and remains an investigational therapy. Clinical trials have evaluated its safety, tolerability, and efficacy in these patient populations.

Who makes Dimebon?

Dimebon is developed by Pfizer, Inc., which trades on the New York Stock Exchange under the ticker symbol PFE. Pfizer conducted multiple clinical trials of Dimebon, including Phase 3 studies in Alzheimer's disease and Huntington's disease.

What phase is Dimebon in?

Dimebon has been tested in Phase 3 clinical trials. Ten trials have been completed, including Phase 3 studies in Alzheimer's disease and Huntington's disease, and Phase 1 studies in healthy volunteers and patients with hepatic impairment. No trials are currently active.

What clinical trials is Dimebon in?

Dimebon has been evaluated in completed trials including NCT00975481, a Phase 1 abuse potential study; NCT00920946, a Phase 3 safety and efficacy study in Huntington disease; NCT00838110, a Phase 3 safety and tolerability study in mild to moderate Alzheimer's disease; and NCT00831532, a Phase 1 pharmacokinetic study in hepatic impairment.

Is Dimebon the same as latrepirdine?

Yes, Dimebon is also known as latrepirdine. Other names used in research include Dimebon plus ketoconazole, Dimebon plus dextromethorphan, and Dimebon transdermal. These refer to different formulations or combination approaches studied with the same active agent.