Efficacy Of PF-05089771 In Treating Postoperative Dental Pain

TOTPAR(6) was defined as the total area under pain relief (PR) curve through first 6 hours after dosing, calculated using trapezoidal rule. PR was assumed to be 0 at 0 hour. PR assessed on a 5-point categorical scale: 0(none), 1 (a little), 2 (some), 3 (a lot) and 4 (complete), at different time points during study up to 6 hours. Total score range for TOTPAR(6): 0 (worst) to 24 (best), higher value indicated greater degree of PR. Posterior mean, standard deviation were estimated based on analysis of covariance (ANCOVA) model with non-informative priors within outlier robust Bayesian framework.

Time frame: 0 to 6 hours

Population: Full Analysis Set (FAS): all randomized participants who received at least (\>=) 1 dose of study treatment and had \>=1 evaluable (more than or equal to \[\>=\] 90 minutes post-dose) PR score. Participants who received rescue medication prior to 90 minutes were not included in FAS. Missing data were imputed using Last Observation Carried Forward (LOCF).

Clinically significant ECG abnormalities: PR interval \>=300 milliseconds (msec); 25% increase from baseline in PR interval when baseline PR was \>200 msec; an increase from baseline of \>=50% in PR interval when baseline PR was \<=200 msec; QRS interval \>=140 msec; an increase from baseline of \>=50% in QRS interval; corrected QT interval (QTc) \>=500 msec.

Time frame: Baseline up to Day 7 to 10 (follow-up)

Population: Safety analysis set included all randomized participants who received at least 1 dose of study treatment.

Hematology (hemoglobin, hematocrit, red blood cell count, platelets, leukocytes, total neutrophils, eosinophils, basophils, lymphocytes, monocytes), blood chemistry (total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine, blood urea nitrogen, fasting glucose, uric acid, sodium, potassium, chloride, bicarbonate, calcium, albumin, total protein, creatine kinase), and urinalysis (urine white blood cells, urine red blood cells) were performed.

Time frame: Baseline up to Day 7 to 10 (follow-up)

Population: Safety analysis set included all randomized participants who received at least 1 dose of study treatment.

Clinically significant vital signs: supine/sitting pulse rate (PR) less than (\<) 40 or more than (\>) 120 beats per minute (bpm), standing PR \<40 or \>140 bpm; systolic blood pressure (BP) \>=30 millimeters of mercury (mmHg) change from baseline; absolute systolic BP \<90 mmHg; diastolic BP \>=20 mmHg change from baseline; absolute systolic BP \<50 mmHg.

Time frame: Baseline up to Day 7 to 10 (follow-up)

Population: Safety analysis set included all randomized participants who received at least 1 dose of study treatment.

Participant rated the study medication at 6 hours, 24 hours and immediately prior to rescue medication intake (only for participants who took rescue medication\[RM\]), on 5-point categorical scale: 1=poor, 2=fair, 3=good, 4=very good, and 5=excellent.

Time frame: 6, 24 hours, prior to rescue medication (assessed up to 24 hours)

Population: FAS: all randomized participants who received \>=1 dose of study treatment, had \>=1 evaluable (\>=90 minutes post-dose) PR score. Participants who received RM prior to 90 minutes were not included in FAS. N(number of participants analyzed): participants evaluable for this measure.

PPR was defined as the highest PR score achieved at any time point during the evaluation period, prior to rescue medication. PR was assessed on a 5-point categorical scale: 0 (none), 1 (a little), 2 (some), 3 (a lot) and 4 (complete).

Time frame: 0 to 24 hours

Population: FAS included all randomized participants who received \>=1 dose of study treatment and had \>=1 evaluable (\>=90 minutes post-dose) pain relief score. Participants who received rescue medication prior to 90 minutes were not included in FAS.

Participants provided assessment regarding satisfaction with study medication (SM) for pain relief (PR) and overall performance (OP) on a 5-point categorical scale, 1=very dissatisfied (VD), 2=somewhat dissatisfied (SD), 3=neither satisfied nor dissatisfied (NSND), 4=somewhat satisfied (SS) and 5=very satisfied (VS).

Time frame: 6, 24 hours, prior to rescue medication (assessed up to 24 hours)

Population: FAS: all randomized participants who received \>=1 dose of study treatment, had \>=1 evaluable (\>=90 minutes post-dose) PR score. Participants who received RM prior to 90 minutes were not included in FAS. N(number of participants analyzed): participants evaluable for this measure.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An 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/incapacity; congenital anomaly. Treatment-emergent are events between administration of study drug and up to 28 days that were absent before treatment or that worsened relative to pretreatment state.

Time frame: Baseline up to Day 28 (follow-up)

Population: Safety analysis set included all randomized participants who received at least 1 dose of study treatment.

PID was calculated as pain intensity at baseline (baseline pain severity score range 2 \[moderate\] to 3 \[severe\]) minus pain intensity at the respective post-baseline visit (pain severity score range 0 \[none\] to 3 \[severe\]). Total possible score range for PID: -1 (worst) to 3 (best).

Time frame: 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 24 hours

Population: FAS included all randomized participants who received \>=1 dose of study treatment and had \>=1 evaluable (\>=90 minutes post-dose) pain relief score. Analysis excluded influential outliers. Participants who received rescue medication prior to 90 minutes were not included in FAS.

PR was assessed on a 5-point categorical scale; 0 (none), 1 (a little), 2 (some), 3 (a lot) and 4 (complete).

Time frame: 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 24 hours

Population: FAS included all randomized participants who received \>=1 dose of study treatment and had \>=1 evaluable (\>=90 minutes post-dose) pain relief score. Analysis excluded influential outliers. Participants who received rescue medication prior to 90 minutes were not included in FAS.

Ibuprofen concentration was reported separately for 2 isomers of ibuprofen: (S)-Ibuprofen, and (R)-Ibuprofen, where S implied sinister (clockwise configuration) and R implied rectus (anti-clockwise configuration).

Time frame: 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 24 hours post-dose

Population: Pharmacokinetic analysis set included all randomized participants who received study treatment and had a pharmacokinetic sample analyzed within the treatment period.

Time frame: 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 24 hours post-dose

Population: Pharmacokinetic analysis set included all randomized participants who received study treatment and had a pharmacokinetic sample analyzed within the treatment period.

SPID: area under the PID effect curve from 0 to 6 hours (SPID\[6\]) and 0 to 24 hours (SPID\[24\]). AUC was calculated using the trapezoidal rule. Total score range: -6 (worst) to 18 (best) for SPID(6), and -24 (worst) to 72 (best) for SPID(24). Higher value of SPID indicated greater degree of pain relief. PID was calculated as pain intensity at baseline minus pain intensity at the respective post-baseline visit. Pain intensity was assessed on a categorical scale ranging from 0 (none), 1 (mild), 2 (moderate) and 3 (severe).

Time frame: 0 to 6 hours; 0 to 24 hours

Population: FAS included all randomized participants who received \>=1 dose of study treatment and had \>=1 evaluable (\>=90 minutes post-dose) pain relief score. Analysis excluded influential outliers. Participants who received rescue medication prior to 90 minutes were not included in FAS. Missing data were imputed using LOCF.

Time to first use of rescue medication (acetaminophen 500 mg or hydrocodone 5 mg) was calculated by subtracting time of first administration of study medication from the rescue medication administration time.

Time frame: 0 to 24 hours

Population: FAS included all randomized participants who received \>=1 dose of study treatment and had \>=1 evaluable (\>=90 minutes post-dose) pain relief score. Participants who received rescue medication prior to 90 minutes were not included in FAS.

Participants evaluated the time to first perceptible pain relief by stopping a stopwatch labeled 'first perceptible pain relief' at the moment they first began to experience any relief.

Time frame: 0 to 24 hours

Population: FAS included all randomized participants who received \>=1 dose of study treatment and had \>=1 evaluable (\>=90 minutes post-dose) pain relief score. Participants who received rescue medication prior to 90 minutes were not included in FAS.

Participants evaluated the time to first meaningful relief by stopping a stopwatch labeled 'meaningful pain relief' at the moment they first began to experience meaningful relief.

Time frame: 0 to 24 hours

Population: FAS included all randomized participants who received \>=1 dose of study treatment and had \>=1 evaluable (\>=90 minutes post-dose) pain relief score. Participants who received rescue medication prior to 90 minutes were not included in FAS.

TOTPAR(24) was defined as the total area under the PR curve through the first 24 hours after dosing, calculated using trapezoidal rule. PR was assumed to be 0 at 0 hour. PR assessed on a 5-point categorical scale: 0 (none), 1 (a little), 2 (some), 3 (a lot) and 4 (complete), at different time points during the study up to 6 hours. Total score range for TOTPAR (24): 0 (worst) to 96 (best), higher value indicated greater degree of PR. The least square mean and standard error are based on ANCOVA model with treatment as a fixed effect and baseline pain intensity as a covariate

Time frame: 0 to 24 hours

Population: FAS included all randomized participants who received \>=1 dose of study treatment and had \>=1 evaluable (\>=90 minutes post-dose) pain relief score. Analysis excluded influential outliers. Participants who received rescue medication prior to 90 minutes were not included in FAS. Missing data were imputed using LOCF.