PF-06372865

The SPR was defined as the number of frequency steps between and including the lower and upper bound at which a generalized electroencephalogram (EEG) epileptiform activity had occurred, whereby subjects were exposed to 14 different frequencies ranging from 2 to 60 flashes per second. The SPR is then an integer score that ranges from 0 to 14 with lower scores representing better outcomes. The primary outcome measure was based on the average Least Squares Mean (LSmean) effect over the first 6 hours postdose.

Daily average low back pain was assessed on an 11-point numeric rating scale (NRS). Participants described their average low back pain during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicate higher pain. Baseline value was calculated as the mean of the scores over the last 7 days in the placebo run-in period, prior to randomization. Post-baseline weekly scores were calculated based on the mean of the scores over the 7 days prior to and including the day at the end of the corresponding week.

An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. The SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events.

Abnormality criteria included: hemoglobin, hematocrit and red blood cells (RBCs) (less than \[\<\] 0.8\*lower limit of normal \[LLN\]); white blood cells (WBC) (\<0.6\*LLN, greater than \[\>\] 1.5\*upper limit of normal \[ULN\]); MCV, MCH, MCHC (\<0.9\*LLN, \>1.1\*ULN); platelets (\<0.5\*LLN\>, \>1.75\*ULN); neutrophils, lymphocytes(\<0.8\*LLN, \>1.2\*ULN); eosinophils, basophils, monocytes (\>1.2\*ULN); total bilirubin (\>1.5\*ULN); aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (\>3\*ULN); total protein, albumin (\<0.8\*LLN, \>1.2\*ULN); creatinine, blood urea nitrogen (\>1.3\*ULN); glucose (\<0.6\*LLN, \>1.5\*ULN); uric acid (\>1.2\*ULN); sodium, potassium, chloride, calcium, bicarbonate (\<0.9\*LLN, \>1.1\*ULN); urine pH (\<4.5, \>8); qualitative urine glucose, ketones, protein, blood values (greater than or equal to \[\>=\] 1) in urine dipstick test; urine RBC, WBC (\>=20); hyaline casts (\>1), bacteria (\>20).

Participants who met the criteria for abnormal findings in vital signs data were reported. Criteria for abnormalities in vital signs: supine systolic blood pressure (SBP) \<90 millimeter of mercury (mmHg), supine diastolic BP (DBP) \<50 mmHg, supine pulse rate \<40 beats per minute (bpm) or \>120 bpm. Maximum increase or decrease from baseline in supine SBP \>=30 mmHg and maximum increase or decrease from baseline in supine DBP \>=20 mmHg.

Participants with abnormal ECG findings were reported. Criteria for potential clinical concern in ECG parameters: maximum (max.) PR interval of \>=300 milliseconds (msec), maximum QRS interval \>=140 msec, maximum QTCF interval (Fridericia's Correction) of 450 to \<480 msec, 480 to \<500 msec and \>=500 msec, maximum of \>=25 percent (%) increase from baseline (IFB) value of \>200 msec and \>=50% for baseline value of less than or equal to (\<=) 200 msec for PR interval, maximum increase from baseline of \>=50% for QRS interval, maximum increase from baseline of \>=30 msec to \<60 msec and maximum increase from baseline of \>60 msec in QTCF interval (Fridericia's Correction).

The C-SSRS (mapped to Columbia Classification Algorithm of Suicide Assessment \[C-CASA\]) is an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced following: completed suicide =1, suicide attempt =2 (response of "Yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior =3 ("Yes" on "preparatory acts or behavior"), suicidal ideation =4 ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent), any suicidal behavior or ideation, self-injurious behavior =7 ("Yes" on "Has participant engaged in non-suicidal self-injurious behavior").

PWC is a 20 item physician rated interview to measure anxiolytic drug withdrawal-related signs and symptoms. Each individual item score ranges from 0 (not present) to 3 (severe), where higher scores = more affected condition. PWC total score range from 0 (not present) to 60 (severe), where higher score = more affected condition. Change: score at follow-up visit minus score at the end of treatment visit.

Treatment-related AEs are any untoward medical occurrences attributed to study drug in a participant who received study drug. A serious adverse events (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28-35 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to study drug is assessed by the investigator. Participants with multiple occurrences of an AE within a category are counted once within the category.

Measurement of systolic and diastolic blood pressure and pulse rate

Measurement of the following ECG parameters: QT interval, QTcF, PR interval, RR interval, QRS interval, and heart rate.

Lab tests include: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid albumin, total protein, folate); urinalysis (decimal logarithm of reciprocal of hydrogen ion activity \[pH\], glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy); other (follicle stimulating hormone, urine drug screening, hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, human immunodeficiency virus).

Maximum observed plasma concentration

Time to reach maximum observed plasma concentration

Area under the concentration curve from time 0 to end of the dosing interval. The dosing interval is 12 hours.

Maximum observed plasma concentration

Time to reach maximum observed plasma concentration

Area under the concentration curve from time 0 to end of the dosing interval. The dosing interval is 12 hours.

Time for the plasma concentration to decrease by one half.

AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8).

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.