Alzheimer's Disease, Huntington's Disease
Conditions
Keywords
oral single-dose 6-way crossover recreational drug users abuse potential pharmacodynamics safety
Brief summary
Dimebon will not exhibit abuse potential when compared to placebo or a positive control (alprazolam).
Detailed description
The main purpose for this study is to determine whether dimebon exhibits abuse potential.
Interventions
DRUGdimebon
Oral tablet; 20 mg dimebon, single dose
DRUGplacebo
Oral tablet or capsule; placebo, single dose
DRUGalprazolam
Oral capsule; 1 mg alprazolam, single dose
Sponsors
Medivation, Inc.
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Healthy male and/or female subjects between the ages of 18 and 55 years. * Recreational polydrug user with a history of CNS depressant use.
Exclusion criteria
* History of clinically significant neurologic condition(s), such as seizures, convulsions, epilepsy, or significant head injury, as judged by the investigator or designee. * A known history of hypersensitivity or previous intolerance to dimebon or other antihistamines. * Self-reported history of drug or alcohol dependence (except nicotine or caffeine) in the 2 years prior to screening, or drug or alcohol dependence as defined by the (DSM-IV-TR) in 12 months prior to screening, including subjects who have ever been in a substance rehabilitation program (other than treatment for smoking cessation). * History of clinically significant psychiatric disorder(s), as judged by the investigator or qualified designee.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes participants randomized to receive placebo first, alprazolam 1 mg first, alprazolam 3 mg first, dimebon 20 mg first, dimebon 40 mg first and dimebon 60 mg first. | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Fifth Intervention Period | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 |
| Fourth Intervention Period | Withdrawal by Subject | 0 | 0 | 1 | 1 | 0 | 0 |
| Second Intervention Period | Adverse Event | 2 | 1 | 0 | 0 | 0 | 0 |
| Second Intervention Period | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age Continuous | 35.4 Years STANDARD_DEVIATION 9.7 |
| Body Mass Index | 24.6 kilogram/square meter (kg/m^2) STANDARD_DEVIATION 3.4 |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 32 | 30 / 33 | 34 / 34 | 18 / 33 | 20 / 32 | 17 / 31 |
| serious Total, serious adverse events | 0 / 32 | 0 / 33 | 0 / 34 | 0 / 33 | 0 / 32 | 0 / 31 |
Outcome results
Primary
Balance of Effects- Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin)
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.
Time frame: 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose
Population: The pharmacodynamic analysis population included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Balance of Effects- Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emax | 57.8 mm | Standard Deviation 10.03 |
| Placebo | Balance of Effects- Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emin | 47.0 mm | Standard Deviation 9.38 |
| Alprazolam 1 mg | Balance of Effects- Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emax | 78.6 mm | Standard Deviation 17.53 |
| Alprazolam 1 mg | Balance of Effects- Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emin | 45.4 mm | Standard Deviation 11.21 |
| Alprazolam 3 mg | Balance of Effects- Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emax | 82.2 mm | Standard Deviation 14.55 |
| Alprazolam 3 mg | Balance of Effects- Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emin | 37.4 mm | Standard Deviation 17.32 |
| Dimebon 20 mg | Balance of Effects- Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emax | 57.2 mm | Standard Deviation 11.76 |
| Dimebon 20 mg | Balance of Effects- Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emin | 48.4 mm | Standard Deviation 8.89 |
| Dimebon 40 mg | Balance of Effects- Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emax | 55.8 mm | Standard Deviation 9.41 |
| Dimebon 40 mg | Balance of Effects- Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emin | 49.0 mm | Standard Deviation 3.59 |
| Dimebon 60 mg | Balance of Effects- Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emax | 58.5 mm | Standard Deviation 12.54 |
| Dimebon 60 mg | Balance of Effects- Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emin | 46.5 mm | Standard Deviation 10.44 |
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95 percent (%) Confidence Interval (CI) were obtained from the model.p-value: <0.000195% CI: [15.0866, 26.5327]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [18.7321, 30.1929]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.842895% CI: [-6.3385, 5.18]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.495795% CI: [-7.7832, 3.7845]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.743195% CI: [-4.8567, 6.7932]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-27.1044, -15.6734]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-28.5584, -17.0596]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-25.6435, -14.0393]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-30.6705, -19.413]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-32.1455, -20.7782]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-29.244, -17.7445]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.57295% CI: [-6.5274, 3.6198]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.000695% CI: [-14.0695, -3.918]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.470495% CI: [-3.2342, 6.9713]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.425595% CI: [-3.0533, 7.1984]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.895995% CI: [-5.5053, 4.8204]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.196795% CI: [-1.7402, 8.385]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.173395% CI: [-1.5676, 8.6203]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.669795% CI: [-4.0285, 6.2512]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [5.8712, 15.8535]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [6.0281, 16.1045]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.00195% CI: [3.5552, 13.7474]Mixed Models Analysis
Primary
Balance of Effects- Good and Bad Effects VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin)
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.
Time frame: 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose
Population: The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Balance of Effects- Good and Bad Effects VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emax | 56.2 mm | Standard Deviation 7.15 |
| Placebo | Balance of Effects- Good and Bad Effects VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emin | 48.0 mm | Standard Deviation 8.83 |
| Alprazolam 1 mg | Balance of Effects- Good and Bad Effects VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emax | 80.9 mm | Standard Deviation 15.93 |
| Alprazolam 1 mg | Balance of Effects- Good and Bad Effects VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emin | 46.7 mm | Standard Deviation 10.7 |
| Alprazolam 3 mg | Balance of Effects- Good and Bad Effects VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emax | 81.9 mm | Standard Deviation 14.4 |
| Alprazolam 3 mg | Balance of Effects- Good and Bad Effects VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emin | 38.6 mm | Standard Deviation 15.76 |
| Dimebon 20 mg | Balance of Effects- Good and Bad Effects VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emax | 57.9 mm | Standard Deviation 13.53 |
| Dimebon 20 mg | Balance of Effects- Good and Bad Effects VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emin | 49.3 mm | Standard Deviation 2.79 |
| Dimebon 40 mg | Balance of Effects- Good and Bad Effects VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emin | 48.3 mm | Standard Deviation 8.82 |
| Dimebon 40 mg | Balance of Effects- Good and Bad Effects VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emax | 56.6 mm | Standard Deviation 11.21 |
| Dimebon 60 mg | Balance of Effects- Good and Bad Effects VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emin | 48.9 mm | Standard Deviation 3.03 |
| Dimebon 60 mg | Balance of Effects- Good and Bad Effects VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emax | 57.6 mm | Standard Deviation 8.92 |
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [19.5658, 30.1899]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [20.667, 31.3043]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.448995% CI: [-3.2911, 7.3998]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.832995% CI: [-4.7941, 5.9427]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.538795% CI: [-3.7203, 7.0929]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-28.1283, -17.5187]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-29.64, -18.9672]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-28.5768, -17.8064]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-29.1559, -18.7066]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-30.6869, -20.1358]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-29.6361, -18.9626]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.534995% CI: [-5.9725, 3.1123]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.000195% CI: [-13.6684, -4.605]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.563795% CI: [-3.2244, 5.8958]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.861295% CI: [-4.1779, 4.9909]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.695495% CI: [-3.7022, 5.5373]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.228795% CI: [-1.7552, 7.2868]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.426795% CI: [-2.7158, 6.389]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.31495% CI: [-2.2429, 6.9381]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [5.9992, 14.9456]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [5.032, 14.0544]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [5.494, 14.6144]Mixed Models Analysis
Primary
Balance of Effects- Overall Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin)
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.
Time frame: 6, 12, 24 hours post-dose
Population: The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Balance of Effects- Overall Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emax | 57.8 mm | Standard Deviation 14.31 |
| Placebo | Balance of Effects- Overall Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emin | 52.5 mm | Standard Deviation 9.13 |
| Alprazolam 1 mg | Balance of Effects- Overall Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emax | 74.6 mm | Standard Deviation 18.99 |
| Alprazolam 1 mg | Balance of Effects- Overall Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emin | 64.5 mm | Standard Deviation 20.17 |
| Alprazolam 3 mg | Balance of Effects- Overall Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emax | 78.0 mm | Standard Deviation 15.5 |
| Alprazolam 3 mg | Balance of Effects- Overall Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emin | 62.6 mm | Standard Deviation 18.13 |
| Dimebon 20 mg | Balance of Effects- Overall Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emax | 56.5 mm | Standard Deviation 11.44 |
| Dimebon 20 mg | Balance of Effects- Overall Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emin | 48.2 mm | Standard Deviation 15.96 |
| Dimebon 40 mg | Balance of Effects- Overall Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emax | 55.4 mm | Standard Deviation 11.29 |
| Dimebon 40 mg | Balance of Effects- Overall Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emin | 52.0 mm | Standard Deviation 8.75 |
| Dimebon 60 mg | Balance of Effects- Overall Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emax | 58.1 mm | Standard Deviation 12.52 |
| Dimebon 60 mg | Balance of Effects- Overall Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Emin | 51.1 mm | Standard Deviation 8.94 |
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-22.7036, -10.3923]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [10.5727, 22.7049]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [13.7627, 25.9238]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.602995% CI: [-7.7209, 4.4967]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.347795% CI: [-9.0571, 3.2089]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.976995% CI: [-6.085, 6.2667]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-24.3155, -12.1864]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-25.6616, -13.4642]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-27.4199, -15.4908]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-28.7925, -16.7422]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-25.8485, -13.6563]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.000695% CI: [5.3225, 18.8551]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.003895% CI: [3.3132, 16.8403]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.225795% CI: [-10.989, 2.6139]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.804295% CI: [-7.6927, 5.975]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.639995% CI: [-8.5177, 5.2506]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-23.0228, -9.5229]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.000295% CI: [-19.7374, -6.158]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.000195% CI: [-20.572, -6.8727]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-20.9226, -7.606]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.001695% CI: [-17.6548, -4.2165]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.000895% CI: [-18.5055, -4.9151]Mixed Models Analysis
Primary
Balance of Effects- Subjective Drug Value (SDV): Maximum Effect (Emax)
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.
Time frame: 6, 12, 24 hrs post-dose
Population: The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Balance of Effects- Subjective Drug Value (SDV): Maximum Effect (Emax) | 4.805 Dollar | Standard Deviation 9.7833 |
| Alprazolam 1 mg | Balance of Effects- Subjective Drug Value (SDV): Maximum Effect (Emax) | 19.621 Dollar | Standard Deviation 16.2519 |
| Alprazolam 3 mg | Balance of Effects- Subjective Drug Value (SDV): Maximum Effect (Emax) | 25.551 Dollar | Standard Deviation 17.0192 |
| Dimebon 20 mg | Balance of Effects- Subjective Drug Value (SDV): Maximum Effect (Emax) | 6.098 Dollar | Standard Deviation 12.3269 |
| Dimebon 40 mg | Balance of Effects- Subjective Drug Value (SDV): Maximum Effect (Emax) | 3.836 Dollar | Standard Deviation 6.5345 |
| Dimebon 60 mg | Balance of Effects- Subjective Drug Value (SDV): Maximum Effect (Emax) | 4.573 Dollar | Standard Deviation 9.8211 |
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [9.4718, 19.4737]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [14.7131, 24.7437]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.934895% CI: [-4.8289, 5.2466]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.500995% CI: [-6.7841, 3.3299]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.897595% CI: [-5.4245, 4.7595]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-19.266, -9.2619]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-21.2294, -11.1704]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-19.8822, -9.7283]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-24.4361, -14.603]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-26.423, -16.488]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-25.0872, -15.0345]Mixed Models Analysis
Primary
Balance of Effects- Take Drug Again VAS: Peak Effect (Maximum Effect [Emax])
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.
Time frame: 6, 12, 24 hours post-dose
Population: The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Balance of Effects- Take Drug Again VAS: Peak Effect (Maximum Effect [Emax]) | 53.9 mm | Standard Deviation 22.3 |
| Alprazolam 1 mg | Balance of Effects- Take Drug Again VAS: Peak Effect (Maximum Effect [Emax]) | 77.5 mm | Standard Deviation 22.26 |
| Alprazolam 3 mg | Balance of Effects- Take Drug Again VAS: Peak Effect (Maximum Effect [Emax]) | 83.2 mm | Standard Deviation 15.99 |
| Dimebon 20 mg | Balance of Effects- Take Drug Again VAS: Peak Effect (Maximum Effect [Emax]) | 47.6 mm | Standard Deviation 28.66 |
| Dimebon 40 mg | Balance of Effects- Take Drug Again VAS: Peak Effect (Maximum Effect [Emax]) | 50.4 mm | Standard Deviation 26.23 |
| Dimebon 60 mg | Balance of Effects- Take Drug Again VAS: Peak Effect (Maximum Effect [Emax]) | 52.5 mm | Standard Deviation 25.66 |
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [13.7265, 34.2916]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [19.116, 39.7151]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.223995% CI: [-16.7479, 3.9521]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.432695% CI: [-14.5328, 6.2526]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.744795% CI: [-12.195, 8.7383]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-40.6795, -20.1343]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-38.4812, -17.8161]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-36.1651, -15.3096]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-45.9257, -25.7012]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-43.7675, -23.3429]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-41.4754, -20.8124]Mixed Models Analysis
Primary
Negative Effects- Addiction Research Center Inventory (ARCI) Lysergic Acid Diethylamide (LSD): Maximum Effect (Emax)
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.
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose
Population: The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Negative Effects- Addiction Research Center Inventory (ARCI) Lysergic Acid Diethylamide (LSD): Maximum Effect (Emax) | 3.8 Units on Scale | Standard Deviation 1.83 |
| Alprazolam 1 mg | Negative Effects- Addiction Research Center Inventory (ARCI) Lysergic Acid Diethylamide (LSD): Maximum Effect (Emax) | 4.9 Units on Scale | Standard Deviation 1.76 |
| Alprazolam 3 mg | Negative Effects- Addiction Research Center Inventory (ARCI) Lysergic Acid Diethylamide (LSD): Maximum Effect (Emax) | 7.0 Units on Scale | Standard Deviation 2.57 |
| Dimebon 20 mg | Negative Effects- Addiction Research Center Inventory (ARCI) Lysergic Acid Diethylamide (LSD): Maximum Effect (Emax) | 3.8 Units on Scale | Standard Deviation 1.42 |
| Dimebon 40 mg | Negative Effects- Addiction Research Center Inventory (ARCI) Lysergic Acid Diethylamide (LSD): Maximum Effect (Emax) | 3.8 Units on Scale | Standard Deviation 1.5 |
| Dimebon 60 mg | Negative Effects- Addiction Research Center Inventory (ARCI) Lysergic Acid Diethylamide (LSD): Maximum Effect (Emax) | 3.6 Units on Scale | Standard Deviation 1.58 |
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.000595% CI: [0.5623, 1.9446]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [2.8073, 4.1948]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.334795% CI: [-0.3559, 1.0396]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.367895% CI: [-0.3808, 1.0225]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.919795% CI: [-0.6686, 0.7406]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.009995% CI: [-1.6013, -0.222]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.008895% CI: [-1.6269, -0.2384]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.000895% CI: [-1.9171, -0.5178]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-3.838, -2.4804]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-3.8656, -2.4947]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-4.1583, -2.7717]Mixed Models Analysis
Primary
Negative Effects- Bad Drug Effects: Peak Effect (Maximum Effect [Emax])
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.
Time frame: 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose
Population: The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Negative Effects- Bad Drug Effects: Peak Effect (Maximum Effect [Emax]) | 17.2 mm | Standard Deviation 24.38 |
| Alprazolam 1 mg | Negative Effects- Bad Drug Effects: Peak Effect (Maximum Effect [Emax]) | 33.9 mm | Standard Deviation 29.88 |
| Alprazolam 3 mg | Negative Effects- Bad Drug Effects: Peak Effect (Maximum Effect [Emax]) | 44.6 mm | Standard Deviation 23.58 |
| Dimebon 20 mg | Negative Effects- Bad Drug Effects: Peak Effect (Maximum Effect [Emax]) | 15.9 mm | Standard Deviation 25.38 |
| Dimebon 40 mg | Negative Effects- Bad Drug Effects: Peak Effect (Maximum Effect [Emax]) | 16.8 mm | Standard Deviation 24.27 |
| Dimebon 60 mg | Negative Effects- Bad Drug Effects: Peak Effect (Maximum Effect [Emax]) | 19.7 mm | Standard Deviation 25.47 |
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.001695% CI: [6.321, 26.5998]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [17.8247, 38.1696]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.825495% CI: [-11.3591, 9.0742]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.885895% CI: [-9.5075, 11.0015]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.512895% CI: [-6.8972, 13.7529]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.000895% CI: [-27.7485, -7.4572]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.002895% CI: [-25.9136, -5.5132]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.013595% CI: [-23.3295, -2.7355]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-39.1071, -19.1721]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-37.3224, -17.178]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-34.7614, -14.3772]Mixed Models Analysis
Primary
Other Subjective Effects- Addiction Research Center Inventory (ARCI) Benzedrine Group (BG): Maximum Effect (Emax) and Minimum Effect (Emin)
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.
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose
Population: The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Other Subjective Effects- Addiction Research Center Inventory (ARCI) Benzedrine Group (BG): Maximum Effect (Emax) and Minimum Effect (Emin) | Emax | 6.3 Units on Scale | Standard Deviation 1.14 |
| Placebo | Other Subjective Effects- Addiction Research Center Inventory (ARCI) Benzedrine Group (BG): Maximum Effect (Emax) and Minimum Effect (Emin) | Emin | 4.8 Units on Scale | Standard Deviation 1.9 |
| Alprazolam 1 mg | Other Subjective Effects- Addiction Research Center Inventory (ARCI) Benzedrine Group (BG): Maximum Effect (Emax) and Minimum Effect (Emin) | Emax | 6.6 Units on Scale | Standard Deviation 1.34 |
| Alprazolam 1 mg | Other Subjective Effects- Addiction Research Center Inventory (ARCI) Benzedrine Group (BG): Maximum Effect (Emax) and Minimum Effect (Emin) | Emin | 2.5 Units on Scale | Standard Deviation 2.05 |
| Alprazolam 3 mg | Other Subjective Effects- Addiction Research Center Inventory (ARCI) Benzedrine Group (BG): Maximum Effect (Emax) and Minimum Effect (Emin) | Emax | 7.2 Units on Scale | Standard Deviation 2.01 |
| Alprazolam 3 mg | Other Subjective Effects- Addiction Research Center Inventory (ARCI) Benzedrine Group (BG): Maximum Effect (Emax) and Minimum Effect (Emin) | Emin | 1.7 Units on Scale | Standard Deviation 1.31 |
| Dimebon 20 mg | Other Subjective Effects- Addiction Research Center Inventory (ARCI) Benzedrine Group (BG): Maximum Effect (Emax) and Minimum Effect (Emin) | Emax | 6.5 Units on Scale | Standard Deviation 1.72 |
| Dimebon 20 mg | Other Subjective Effects- Addiction Research Center Inventory (ARCI) Benzedrine Group (BG): Maximum Effect (Emax) and Minimum Effect (Emin) | Emin | 4.4 Units on Scale | Standard Deviation 2.08 |
| Dimebon 40 mg | Other Subjective Effects- Addiction Research Center Inventory (ARCI) Benzedrine Group (BG): Maximum Effect (Emax) and Minimum Effect (Emin) | Emax | 6.3 Units on Scale | Standard Deviation 1.66 |
| Dimebon 40 mg | Other Subjective Effects- Addiction Research Center Inventory (ARCI) Benzedrine Group (BG): Maximum Effect (Emax) and Minimum Effect (Emin) | Emin | 4.7 Units on Scale | Standard Deviation 1.72 |
| Dimebon 60 mg | Other Subjective Effects- Addiction Research Center Inventory (ARCI) Benzedrine Group (BG): Maximum Effect (Emax) and Minimum Effect (Emin) | Emax | 6.4 Units on Scale | Standard Deviation 1.38 |
| Dimebon 60 mg | Other Subjective Effects- Addiction Research Center Inventory (ARCI) Benzedrine Group (BG): Maximum Effect (Emax) and Minimum Effect (Emin) | Emin | 4.3 Units on Scale | Standard Deviation 1.85 |
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.169195% CI: [-0.1566, 0.884]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.001795% CI: [0.3238, 1.365]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.430595% CI: [-0.3141, 0.7327]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.651795% CI: [-0.4064, 0.6476]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.889295% CI: [-0.5666, 0.4919]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.557695% CI: [-0.6737, 0.3649]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.359495% CI: [-0.7658, 0.2796]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.135595% CI: [-0.9291, 0.127]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.015395% CI: [-1.1466, -0.1236]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.006595% CI: [-1.2418, -0.2059]Mixed Models Analysis
Comparison: For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.001195% CI: [-1.4042, -0.3594]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-2.9373, -1.3856]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-3.8085, -2.2587]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.480495% CI: [-1.0586, 0.5004]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.951995% CI: [-0.7608, 0.8087]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.215295% CI: [-1.286, 0.2921]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [1.1094, 2.6553]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [1.407, 2.9638]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [0.8786, 2.4503]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [1.9912, 3.5179]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [2.2858, 3.8294]Mixed Models Analysis
Comparison: For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [1.7578, 3.3155]Mixed Models Analysis
Primary
Other Subjective Effects- Any Drug Effects: Peak Effect (Maximum Effect [Emax])
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.
Time frame: 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose
Population: The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Other Subjective Effects- Any Drug Effects: Peak Effect (Maximum Effect [Emax]) | 37.2 mm | Standard Deviation 35.3 |
| Alprazolam 1 mg | Other Subjective Effects- Any Drug Effects: Peak Effect (Maximum Effect [Emax]) | 84.0 mm | Standard Deviation 23.27 |
| Alprazolam 3 mg | Other Subjective Effects- Any Drug Effects: Peak Effect (Maximum Effect [Emax]) | 88.7 mm | Standard Deviation 11.12 |
| Dimebon 20 mg | Other Subjective Effects- Any Drug Effects: Peak Effect (Maximum Effect [Emax]) | 37.5 mm | Standard Deviation 35.91 |
| Dimebon 40 mg | Other Subjective Effects- Any Drug Effects: Peak Effect (Maximum Effect [Emax]) | 33.4 mm | Standard Deviation 34.54 |
| Dimebon 60 mg | Other Subjective Effects- Any Drug Effects: Peak Effect (Maximum Effect [Emax]) | 44.4 mm | Standard Deviation 34.44 |
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [33.4091, 59.7996]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [37.5038, 63.9407]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.917495% CI: [-13.9815, 12.584]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.500295% CI: [-17.9006, 8.7749]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.348295% CI: [-7.0337, 19.8301]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-60.4869, -34.1193]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-64.4276, -37.9069]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-53.589, -26.8234]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-64.3974, -38.4445]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-68.3904, -42.1798]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-57.5825, -31.0656]Mixed Models Analysis
Primary
Other Subjective Effects- Drug Similarity
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.
Time frame: 12 hours post-dose
Population: The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period. 'n' is signifying those participants who were evaluated for this measure for various drugs for similarity in each treatment group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Other Subjective Effects- Drug Similarity | Placebo (n=32, 33, 34, 33, 32, 31) | 56.3 mm | Standard Deviation 42.65 |
| Placebo | Other Subjective Effects- Drug Similarity | Codeine/Morphine (n=20, 20, 23, 22, 20, 20) | 18.5 mm | Standard Deviation 28.02 |
| Placebo | Other Subjective Effects- Drug Similarity | THC (n=32, 33, 34, 33, 32, 31) | 21.2 mm | Standard Deviation 27.97 |
| Placebo | Other Subjective Effects- Drug Similarity | Benzodiazepines (n=23, 23, 25, 24, 22, 22) | 51.0 mm | Standard Deviation 38.99 |
| Placebo | Other Subjective Effects- Drug Similarity | Pseudoephedrine (n=6, 6, 6, 6, 7, 5) | 21.8 mm | Standard Deviation 33.42 |
| Alprazolam 1 mg | Other Subjective Effects- Drug Similarity | Pseudoephedrine (n=6, 6, 6, 6, 7, 5) | 21.5 mm | Standard Deviation 27.7 |
| Alprazolam 1 mg | Other Subjective Effects- Drug Similarity | Benzodiazepines (n=23, 23, 25, 24, 22, 22) | 88.6 mm | Standard Deviation 21.87 |
| Alprazolam 1 mg | Other Subjective Effects- Drug Similarity | Codeine/Morphine (n=20, 20, 23, 22, 20, 20) | 42.7 mm | Standard Deviation 38.43 |
| Alprazolam 1 mg | Other Subjective Effects- Drug Similarity | THC (n=32, 33, 34, 33, 32, 31) | 45.6 mm | Standard Deviation 37.08 |
| Alprazolam 1 mg | Other Subjective Effects- Drug Similarity | Placebo (n=32, 33, 34, 33, 32, 31) | 10.2 mm | Standard Deviation 22.2 |
| Alprazolam 3 mg | Other Subjective Effects- Drug Similarity | Placebo (n=32, 33, 34, 33, 32, 31) | 4.0 mm | Standard Deviation 12.27 |
| Alprazolam 3 mg | Other Subjective Effects- Drug Similarity | Pseudoephedrine (n=6, 6, 6, 6, 7, 5) | 66.5 mm | Standard Deviation 12.14 |
| Alprazolam 3 mg | Other Subjective Effects- Drug Similarity | THC (n=32, 33, 34, 33, 32, 31) | 48.9 mm | Standard Deviation 32.96 |
| Alprazolam 3 mg | Other Subjective Effects- Drug Similarity | Benzodiazepines (n=23, 23, 25, 24, 22, 22) | 92.7 mm | Standard Deviation 20.66 |
| Alprazolam 3 mg | Other Subjective Effects- Drug Similarity | Codeine/Morphine (n=20, 20, 23, 22, 20, 20) | 46.3 mm | Standard Deviation 33.82 |
| Dimebon 20 mg | Other Subjective Effects- Drug Similarity | Pseudoephedrine (n=6, 6, 6, 6, 7, 5) | 31.7 mm | Standard Deviation 35.35 |
| Dimebon 20 mg | Other Subjective Effects- Drug Similarity | Placebo (n=32, 33, 34, 33, 32, 31) | 61.4 mm | Standard Deviation 36.34 |
| Dimebon 20 mg | Other Subjective Effects- Drug Similarity | Benzodiazepines (n=23, 23, 25, 24, 22, 22) | 33.0 mm | Standard Deviation 40.56 |
| Dimebon 20 mg | Other Subjective Effects- Drug Similarity | THC (n=32, 33, 34, 33, 32, 31) | 21.9 mm | Standard Deviation 30.44 |
| Dimebon 20 mg | Other Subjective Effects- Drug Similarity | Codeine/Morphine (n=20, 20, 23, 22, 20, 20) | 14.7 mm | Standard Deviation 28.49 |
| Dimebon 40 mg | Other Subjective Effects- Drug Similarity | Placebo (n=32, 33, 34, 33, 32, 31) | 57.8 mm | Standard Deviation 43.15 |
| Dimebon 40 mg | Other Subjective Effects- Drug Similarity | Benzodiazepines (n=23, 23, 25, 24, 22, 22) | 42.6 mm | Standard Deviation 40.81 |
| Dimebon 40 mg | Other Subjective Effects- Drug Similarity | Codeine/Morphine (n=20, 20, 23, 22, 20, 20) | 24.5 mm | Standard Deviation 29.55 |
| Dimebon 40 mg | Other Subjective Effects- Drug Similarity | THC (n=32, 33, 34, 33, 32, 31) | 16.2 mm | Standard Deviation 25.88 |
| Dimebon 40 mg | Other Subjective Effects- Drug Similarity | Pseudoephedrine (n=6, 6, 6, 6, 7, 5) | 30.7 mm | Standard Deviation 28.89 |
| Dimebon 60 mg | Other Subjective Effects- Drug Similarity | Codeine/Morphine (n=20, 20, 23, 22, 20, 20) | 28.2 mm | Standard Deviation 29.66 |
| Dimebon 60 mg | Other Subjective Effects- Drug Similarity | Benzodiazepines (n=23, 23, 25, 24, 22, 22) | 53.0 mm | Standard Deviation 40.45 |
| Dimebon 60 mg | Other Subjective Effects- Drug Similarity | Placebo (n=32, 33, 34, 33, 32, 31) | 55.7 mm | Standard Deviation 42.15 |
| Dimebon 60 mg | Other Subjective Effects- Drug Similarity | Pseudoephedrine (n=6, 6, 6, 6, 7, 5) | 33.4 mm | Standard Deviation 26.32 |
| Dimebon 60 mg | Other Subjective Effects- Drug Similarity | THC (n=32, 33, 34, 33, 32, 31) | 25.3 mm | Standard Deviation 31.56 |
Comparison: For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI was obtained from the model.p-value: <0.000195% CI: [-62.1244, -30.6401]Mixed Models Analysis
Comparison: For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-67.2633, -35.7765]Mixed Models Analysis
Comparison: For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.452495% CI: [-9.7924, 21.8657]Mixed Models Analysis
Comparison: For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.76295% CI: [-13.4599, 18.3446]Mixed Models Analysis
Comparison: For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.984695% CI: [-15.8609, 16.1754]Mixed Models Analysis
Comparison: For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [36.7157, 68.1221]Mixed Models Analysis
Comparison: For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [33.0228, 64.6264]Mixed Models Analysis
Comparison: For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [30.5968, 62.4823]Mixed Models Analysis
Comparison: For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [42.0679, 73.0451]Mixed Models Analysis
Comparison: For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [38.3293, 69.5952]Mixed Models Analysis
Comparison: For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [35.866, 67.4884]Mixed Models Analysis
Comparison: For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.000395% CI: [17.7051, 57.1857]Mixed Models Analysis
Comparison: For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [22.2888, 61.054]Mixed Models Analysis
Comparison: For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.074495% CI: [-37.2956, 1.7789]Mixed Models Analysis
Comparison: For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.345895% CI: [-29.5573, 10.4471]Mixed Models Analysis
Comparison: For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.937595% CI: [-19.1777, 20.7616]Mixed Models Analysis
Comparison: For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-74.8113, -35.5961]Mixed Models Analysis
Comparison: For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-67.002, -26.9989]Mixed Models Analysis
Comparison: For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.000495% CI: [-56.7246, -16.5822]Mixed Models Analysis
Comparison: For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-78.5162, -40.3433]Mixed Models Analysis
Comparison: For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-70.8131, -31.6399]Mixed Models Analysis
Comparison: For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.000195% CI: [-60.4726, -21.2862]Mixed Models Analysis
Comparison: For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.010295% CI: [5.7096, 41.3298]Mixed Models Analysis
Comparison: For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.002195% CI: [10.3632, 45.1011]Mixed Models Analysis
Comparison: For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.593595% CI: [-22.2807, 12.814]Mixed Models Analysis
Comparison: For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.694595% CI: [-14.3397, 21.437]Mixed Models Analysis
Comparison: For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.417795% CI: [-10.4975, 25.0847]Mixed Models Analysis
Comparison: For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.001995% CI: [-45.802, -10.7042]Mixed Models Analysis
Comparison: For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.029995% CI: [-37.9541, -1.988]Mixed Models Analysis
Comparison: For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.075995% CI: [-34.1785, 1.7264]Mixed Models Analysis
Comparison: For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.000295% CI: [-49.2278, -15.7032]Mixed Models Analysis
Comparison: For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.006995% CI: [-41.5832, -6.7838]Mixed Models Analysis
Comparison: For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.022295% CI: [-37.8861, -2.991]Mixed Models Analysis
Comparison: For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.000295% CI: [12.0126, 37.1654]Mixed Models Analysis
Comparison: For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [16.4903, 41.7298]Mixed Models Analysis
Comparison: For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.680995% CI: [-10.0309, 15.3165]Mixed Models Analysis
Comparison: For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.606795% CI: [-16.0415, 9.3985]Mixed Models Analysis
Comparison: For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.399995% CI: [-7.335, 18.2795]Mixed Models Analysis
Comparison: For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.000795% CI: [-34.5327, -9.3596]Mixed Models Analysis
Comparison: For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-40.564, -15.257]Mixed Models Analysis
Comparison: For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.003695% CI: [-31.8907, -6.3428]Mixed Models Analysis
Comparison: For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-38.8298, -14.1046]Mixed Models Analysis
Comparison: For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-44.925, -19.938]Mixed Models Analysis
Comparison: For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.000395% CI: [-36.2802, -10.9954]Mixed Models Analysis
Comparison: For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.972895% CI: [-39.708, 41.043]Mixed Models Analysis
Comparison: For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.024695% CI: [6.1059, 79.4894]Mixed Models Analysis
Comparison: For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.706895% CI: [-33.785, 48.8672]Mixed Models Analysis
Comparison: For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.549295% CI: [-26.0358, 47.4496]Mixed Models Analysis
Comparison: For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.589995% CI: [-31.3098, 53.5595]Mixed Models Analysis
Comparison: For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.699895% CI: [-29.8691, 43.6163]Mixed Models Analysis
Comparison: For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.618795% CI: [-31.4818, 51.5606]Mixed Models Analysis
Comparison: For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.586395% CI: [-29.0355, 49.9502]Mixed Models Analysis
Comparison: For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.083295% CI: [-75.608, 5.0948]Mixed Models Analysis
Comparison: For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.082795% CI: [-68.7519, 4.5704]Mixed Models Analysis
Comparison: For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.138695% CI: [-74.5352, 11.1895]Mixed Models Analysis
Primary
Positive Effects- Addiction Research Center Inventory (ARCI) Morphine Benzedrine Group (MBG): Maximum Effect (Emax)
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.
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 12, 24 hours post-dose
Population: The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Positive Effects- Addiction Research Center Inventory (ARCI) Morphine Benzedrine Group (MBG): Maximum Effect (Emax) | 3.2 Units on scale | Standard Deviation 2.51 |
| Alprazolam 1 mg | Positive Effects- Addiction Research Center Inventory (ARCI) Morphine Benzedrine Group (MBG): Maximum Effect (Emax) | 6.2 Units on scale | Standard Deviation 4.16 |
| Alprazolam 3 mg | Positive Effects- Addiction Research Center Inventory (ARCI) Morphine Benzedrine Group (MBG): Maximum Effect (Emax) | 8.1 Units on scale | Standard Deviation 4.37 |
| Dimebon 20 mg | Positive Effects- Addiction Research Center Inventory (ARCI) Morphine Benzedrine Group (MBG): Maximum Effect (Emax) | 3.5 Units on scale | Standard Deviation 3.1 |
| Dimebon 40 mg | Positive Effects- Addiction Research Center Inventory (ARCI) Morphine Benzedrine Group (MBG): Maximum Effect (Emax) | 3.6 Units on scale | Standard Deviation 3.22 |
| Dimebon 60 mg | Positive Effects- Addiction Research Center Inventory (ARCI) Morphine Benzedrine Group (MBG): Maximum Effect (Emax) | 3.5 Units on scale | Standard Deviation 2.87 |
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [1.9014, 4.4254]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [3.4066, 5.9346]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.818495% CI: [-1.1217, 1.4173]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.732495% CI: [-1.054, 1.4963]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.884495% CI: [-1.1898, 1.3791]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-4.2754, -1.7558]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-4.2101, -1.6745]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-4.3484, -1.7891]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-5.7651, -3.2805]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-5.7031, -3.1959]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-5.8438, -3.3081]Mixed Models Analysis
Primary
Positive Effects- Good Drug Effects: Peak Effect (Maximum Effect [Emax])
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.
Time frame: 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose
Population: The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Positive Effects- Good Drug Effects: Peak Effect (Maximum Effect [Emax]) | 35.2 mm | Standard Deviation 31.94 |
| Alprazolam 1 mg | Positive Effects- Good Drug Effects: Peak Effect (Maximum Effect [Emax]) | 81.2 mm | Standard Deviation 18.16 |
| Alprazolam 3 mg | Positive Effects- Good Drug Effects: Peak Effect (Maximum Effect [Emax]) | 84.7 mm | Standard Deviation 14.32 |
| Dimebon 20 mg | Positive Effects- Good Drug Effects: Peak Effect (Maximum Effect [Emax]) | 34.4 mm | Standard Deviation 32.87 |
| Dimebon 40 mg | Positive Effects- Good Drug Effects: Peak Effect (Maximum Effect [Emax]) | 32.0 mm | Standard Deviation 32.33 |
| Dimebon 60 mg | Positive Effects- Good Drug Effects: Peak Effect (Maximum Effect [Emax]) | 39.7 mm | Standard Deviation 31.34 |
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [34.0453, 58.1142]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [37.8247, 61.9295]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.924895% CI: [-12.6918, 11.5325]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.585795% CI: [-15.5264, 8.8]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.476895% CI: [-7.827, 16.6719]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-58.6804, -34.6385]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-61.5346, -37.3514]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-53.86, -29.4546]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-62.2925, -38.621]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-65.1923, -41.2882]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-57.5459, -33.3633]Mixed Models Analysis
Primary
Positive Effects- High VAS: Peak Effect (Maximum Effect [Emax])
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.
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose
Population: The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Positive Effects- High VAS: Peak Effect (Maximum Effect [Emax]) | 30.4 mm | Standard Deviation 30.22 |
| Alprazolam 1 mg | Positive Effects- High VAS: Peak Effect (Maximum Effect [Emax]) | 77.1 mm | Standard Deviation 24.93 |
| Alprazolam 3 mg | Positive Effects- High VAS: Peak Effect (Maximum Effect [Emax]) | 88.0 mm | Standard Deviation 13.13 |
| Dimebon 20 mg | Positive Effects- High VAS: Peak Effect (Maximum Effect [Emax]) | 25.9 mm | Standard Deviation 28.39 |
| Dimebon 40 mg | Positive Effects- High VAS: Peak Effect (Maximum Effect [Emax]) | 29.9 mm | Standard Deviation 33.07 |
| Dimebon 60 mg | Positive Effects- High VAS: Peak Effect (Maximum Effect [Emax]) | 35.8 mm | Standard Deviation 32.44 |
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [34.6464, 59.0436]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [45.3036, 69.6991]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.412995% CI: [-17.3421, 7.1595]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.848895% CI: [-13.4954, 11.1168]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.408695% CI: [-7.1963, 17.5954]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-64.1108, -39.7618]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-60.2801, -35.7885]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-53.9964, -29.2946]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-74.5881, -50.5971]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-70.7965, -46.5847]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-64.5427, -40.0609]Mixed Models Analysis
Primary
Sedative Effects- Addiction Research Center Inventory (ARCI) Pentobarbital Chlorpromazine Group (PCAG): Maximum Effect (Emax)
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.
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose
Population: The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Sedative Effects- Addiction Research Center Inventory (ARCI) Pentobarbital Chlorpromazine Group (PCAG): Maximum Effect (Emax) | 4.7 Units on Scale | Standard Deviation 2.57 |
| Alprazolam 1 mg | Sedative Effects- Addiction Research Center Inventory (ARCI) Pentobarbital Chlorpromazine Group (PCAG): Maximum Effect (Emax) | 9.9 Units on Scale | Standard Deviation 3.51 |
| Alprazolam 3 mg | Sedative Effects- Addiction Research Center Inventory (ARCI) Pentobarbital Chlorpromazine Group (PCAG): Maximum Effect (Emax) | 11.5 Units on Scale | Standard Deviation 2.48 |
| Dimebon 20 mg | Sedative Effects- Addiction Research Center Inventory (ARCI) Pentobarbital Chlorpromazine Group (PCAG): Maximum Effect (Emax) | 5.3 Units on Scale | Standard Deviation 3.26 |
| Dimebon 40 mg | Sedative Effects- Addiction Research Center Inventory (ARCI) Pentobarbital Chlorpromazine Group (PCAG): Maximum Effect (Emax) | 5.5 Units on Scale | Standard Deviation 2.75 |
| Dimebon 60 mg | Sedative Effects- Addiction Research Center Inventory (ARCI) Pentobarbital Chlorpromazine Group (PCAG): Maximum Effect (Emax) | 5.5 Units on Scale | Standard Deviation 2.75 |
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [4.0783, 6.5102]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [5.6799, 8.1167]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.291795% CI: [-0.5676, 1.8767]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.173895% CI: [-0.3784, 2.0763]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.137395% CI: [-0.3024, 2.1767]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-5.8537, -3.4257]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-5.6662, -3.2244]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-5.5887, -3.1255]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-7.4397, -5.0477]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-7.2568, -4.8419]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-7.1812, -4.741]Mixed Models Analysis
Primary
Sedative Effects- Alertness/Drowsiness: Minimum Effect (Emin)
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.
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose
Population: The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Sedative Effects- Alertness/Drowsiness: Minimum Effect (Emin) | 42.1 mm | Standard Deviation 18.77 |
| Alprazolam 1 mg | Sedative Effects- Alertness/Drowsiness: Minimum Effect (Emin) | 14.4 mm | Standard Deviation 17.83 |
| Alprazolam 3 mg | Sedative Effects- Alertness/Drowsiness: Minimum Effect (Emin) | 8.6 mm | Standard Deviation 9.36 |
| Dimebon 20 mg | Sedative Effects- Alertness/Drowsiness: Minimum Effect (Emin) | 42.9 mm | Standard Deviation 21.32 |
| Dimebon 40 mg | Sedative Effects- Alertness/Drowsiness: Minimum Effect (Emin) | 37.7 mm | Standard Deviation 21.32 |
| Dimebon 60 mg | Sedative Effects- Alertness/Drowsiness: Minimum Effect (Emin) | 38.5 mm | Standard Deviation 16.1 |
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-33.1192, -20.1219]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [-39.1073, -26.0375]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.568595% CI: [-4.6607, 8.454]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.284895% CI: [-10.159, 3.0068]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: 0.34495% CI: [-9.7855, 3.4347]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [22.0454, 34.989]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [16.5383, 29.5506]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [16.8772, 30.0131]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [28.1136, 40.8244]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [22.5734, 35.4192]Mixed Models Analysis
Comparison: Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.p-value: <0.000195% CI: [22.8946, 35.8994]Mixed Models Analysis