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Dimebon

Phase 3

Alzheimer's Disease | Small molecule | Rare Disease |Pfizer, Inc.|Last Updated: Dec 6, 2018

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindCONTROLLEDDMCBiomarker
Total Trials9
Total Enrollment2,687
FDA Designations
No designations recorded
Clinical Trials (9)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT00829374Safety and Efficacy Study Evaluating Dimebon in Patients With Mild to Moderate Alzheimer's Disease on DonepezilPHASE3 COMPLETED 1,003Mar 1, 2009Dec 1, 2011Sep 26, 2016 -
NCT00675623A Safety and Efficacy Study of Oral Dimebon in Patients With Mild-To-Moderate Alzheimer's DiseasePHASE3 COMPLETED 598May 30, 2008 -Sep 26, 2016 -
NCT00838110A Phase 3 Study To Evaluate The Safety And Tolerability Of Dimebon Patients With Mild To Moderate Alzheimer's DiseasePHASE3 COMPLETED 742Feb 1, 2009Jan 1, 2010Dec 6, 2018118 United States, Canada +1
NCT00377715Double-blind, Placebo-controlled Study of Oral Dimebon in Subjects With Mild to Moderate Alzheimer's DiseasePHASE2 COMPLETED 183Sep 29, 2005 -Nov 10, 2015 -
NCT00829816Safety and Tolerability of Dimebon in Patients on Memantine, and Memantine Plus DonepezilPHASE1 COMPLETED 46Dec 1, 2008Aug 1, 2010Nov 9, 2015 -
NCT00975481A Study To Evaluate The Abuse Potential Of Single Oral Doses Of Dimebon (Latrepirdine) In Healthy Recreational Polydrug UsersPHASE1 COMPLETED 36Oct 1, 2009Feb 1, 2010Apr 2, 2013 -
NCT00824590A 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 FunctionPHASE1 COMPLETED 20Feb 1, 2009Oct 1, 2009Dec 30, 20092 United States
NCT00825084A Phase 1 Study To Evaluate The Pharmacokinetics, Safety, And Tolerability Of Dimebon [PF-01913539] In Japanese And Western Healthy SubjectsPHASE1 COMPLETED 45Feb 1, 2009May 1, 2009Apr 26, 20111 United States
NCT00827034A 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 SubjectsPHASE1 COMPLETED 14Feb 1, 2009Apr 1, 2009Oct 16, 20181 United States
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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
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
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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
Interventions
NameTypeDescription
DimebonDRUG5 mg orally three times daily
Placebo comparatorDRUGPlacebo orally three times daily
PlaceboDRUGPlacebo three times daily for six months
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.
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Eligibility Criteria
Age Range50 Years — 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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