Safety and Efficacy of Low Dose MM120 for ADHD Proof of Concept Trial

The Adult ADHD investigator symptom rating scale (AISRS) total score consists of 18 items from the original Attention-deficit/hyperactivity Disorder Rating Scale (ADHD-RS). The ADHD-RS includes 9 items that address symptoms of inattention, and 9 items that address symptoms of impulsivity and hyperactivity. Each item is rated from 0 to 3. The AISRS total score can range from 0 to 54. A higher score corresponds to a worse severity of ADHD.

Time frame: 6 weeks

Population: Full Analysis Set (FAS): All subjects in the randomized set (RAN) who were not mis-randomized

The 5 dimensions of altered states of consciousness (5D-ASC) scale is a visual analog scale (VAS) consisting of 94 items each scored on a 0-100mm VAS extrapolated to 100% scale for quantitative evaluation. These 94 items are categorized into five dimensions: oceanic boundlessness (min:0, max:2700), anxious ego dissolution (min:0, max:2100), visionary destructuralization (min:0, max:1800), auditory alterations (min:0, max:1600), and vigilance reduction (min:0, max:1200). The total score is the sum of all questions and can range from 0 to 9400. Higher scores = more alteration in state of consciousness.

Time frame: 6 weeks

Population: Full Analysis Set (FAS): All subjects in the randomized set (RAN) who were not mis-randomized.

The Adult Attention-Deficit/Hyperactivity Disorder Self-Reporting Rating Scale (ASRS) is composed of 18 questions, and uses a scale that ranges from 0-4 based on the individuals mark in either the never, rarely, sometimes, often, very often column for a possible total score of 72. A higher score corresponds to a worse severity of ADHD.

Time frame: 6 weeks

Population: Full Analysis Set (FAS): All subjects in the randomized set (RAN) who were not mis-randomized

The Connors' Adult ADHD Rating Scale (CAARS) Self-Report Long Form is a 66-item measure of ADHD symptom. Responses are scored on a 4-point scale, where 0 = not at all, 1 = just a little, 2 = pretty much, and 3 = very much. Item scores are summed to three main scores which are then transformed using population-derived age- and sex-adjusted norm values to a T-score. A T-score \< 60 indicates no ADHD. A T-score of 60-64 indicates borderline ADHD. A T-score of \> 64 indicates ADHD.

Time frame: 6 weeks

Population: Full Analysis Set (FAS): All subjects in the randomized set (RAN) who were not mis-randomized

The Clinical Global Impression - Severity (CGI-S) was used to assess the subject's current severity of illness at the time of the assessment relative to the clinician's past experience with patients who have the same diagnosis. The CGI-S comprises 1 Investigator-completed (or trained rater-completed) item with 7 possible ratings (1-7 points), where a higher score indicates more severe illness.

Time frame: Baseline, Week 2, Week 6

Population: Full Analysis Set (FAS): All subjects in the randomized set (RAN) who were not mis-randomized

The Adult ADHD investigator symptom rating scale (AISRS) total score consists of 18 items from the original Attention-deficit/hyperactivity Disorder Rating Scale (ADHD-RS). The ADHD-RS includes 9 items that address symptoms of inattention, and 9 items that address symptoms of impulsivity and hyperactivity. Each item is rated from 0 to 3. The AISRS total score can range from 0 to 54. A higher score corresponds to a worse severity of ADHD.

Time frame: Week 2

Population: Full Analysis Set (FAS): All subjects in the randomized set (RAN) who were not mis-randomized

The Mystical Experience Questionnaire 30 item (MEQ30) is a 30-item questionnaire rated on a six-point scale. The scale has been used to assess mystical experiences in studies using psilocybin and LSD. Higher scores = greater mystical experiences. The total score is expressed as a percentage of the maximum possible score (0 to 100%).

Time frame: 6 weeks

Population: Full Analysis Set (FAS): All subjects in the randomized set (RAN) who were not mis-randomized.

The Clinical Global Impression - Severity (CGI-S) was used to assess the subject's current severity of illness at the time of the assessment relative to the clinician's past experience with patients who have the same diagnosis. The CGI-S comprises 1 Investigator-completed (or trained rater-completed) item with 7 possible ratings (1-7 points), where a higher score indicates more severe illness.

Time frame: Baseline, Week 2, Week 6, Week 10

Population: Full Analysis Set (FAS): All subjects in the randomized set (RAN) who were not mis-randomized

A series of single item visual Analog Scales (VAS) are used repeatedly 0 -6 hours after drug administration: The following 9 items were used in VAS (0-100 mm): any drug effect, good drug effect, bad drug effect, drug liking, fear, nausea, alteration of vision, alteration of sense of time, and the boundaries between myself and my surroundings seem to blur. VAS scores range from 0 = no effect to 100 = strong effect. The scores for each item are extrapolated to a 100% scale and presented for each time point of assessment.

Time frame: 6 hours

Population: Full Analysis Set (FAS): All subjects in the randomized set (RAN) who were not mis-randomized.

Maximum Plasma Concentration \[Cmax\] of MM-120 in the blood at Week 1 Day 1

Time frame: 0.5, 1, 2, 3, 4, 6 hours post-dose

Population: Pharmacokinetic Set (PKS): All subjects in the randomized set (RAN) who received a dose of MM120 and had at least 1 postdose PK measurement without important protocol deviations thought to significantly affect the PK of the drug. A strategy for dealing with data affected by protocol violations and deviations was to be agreed to by the Sponsor, monitor, and pharmacokineticist, prior to clean file and code break. Subjects were analyzed according to the treatment they actually received.

Area under the concentration curve from time 0 to infinity (AUC0-inf), Area under the concentration curve from time 0 to 6 hour (AUC0-6h)

Time frame: 0.5, 1, 2, 3, 4, 6 hours post-dose

Population: Pharmacokinetic Set (PKS): All subjects in the randomized set (RAN) who received a dose of MM120 and had at least 1 postdose PK measurement without important protocol deviations thought to significantly affect the PK of the drug. A strategy for dealing with data affected by protocol violations and deviations was to be agreed to by the Sponsor, monitor, and pharmacokineticist, prior to clean file and code break. Subjects were analyzed according to the treatment they actually received.

Maximum concentration (Cmax)

Time frame: 0.5, 1, 2, 3, 4, 6 hours post-dose

Population: Pharmacokinetic Set (PKS): All subjects in the randomized set (RAN) who received a dose of MM120 and had at least 1 postdose PK measurement without important protocol deviations thought to significantly affect the PK of the drug. A strategy for dealing with data affected by protocol violations and deviations was to be agreed to by the Sponsor, monitor, and pharmacokineticist, prior to clean file and code break. Subjects were analyzed according to the treatment they actually received.

Time to maximum concentration (Tmax), half life (t1/2)

Time frame: 0.5, 1, 2, 3, 4, 6 hours post-dose

Population: Pharmacokinetic Set (PKS): All subjects in the randomized set (RAN) who received a dose of MM120 and had at least 1 postdose PK measurement without important protocol deviations thought to significantly affect the PK of the drug. A strategy for dealing with data affected by protocol violations and deviations was to be agreed to by the Sponsor, monitor, and pharmacokineticist, prior to clean file and code break. Subjects were analyzed according to the treatment they actually received.