Inherited Erythromelalgia
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of single doses of PF-05089771 against placebo in treatment of pain in patients with primary, inherited erythromelalgia.
Interventions
DRUGPF-05089771
A single oral dose of PF-05089771 1600 mg solution to be administered on Day 1 of each treatment session. There are 2 treatment sessions, therefore 2 single oral doses of PF-05089771 will be adminstered.
DRUGPlacebo
Placebo for PF-05089771 1600 mg solution administered in each treatment session. There are 2 treatment sessions, therefore 2 single oral doses of placebo will be administered.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 78 Years
Healthy volunteers
No
Inclusion criteria
* Male and or female subjects between the ages of 18-78 years * Subject has clinical signs of IEM * Minimum BMI 17.5kg/m2 and total body weight \>50kg
Exclusion criteria
* Other severe pain conditions, e.g. rheumatologic, that may impair subject's self-assessment of pain due to IEM. * Evidence of clinically significant hypertension, clinically significant hematological, dermatological, renal, endocrine (except diabetes mellitus), pulmonary, gastrointestinal, cardiovascular, hepatic, neurological (other than IEM), or allergic disease (including drug allergies but excluding untreated asymptomatic seasonal allergies). * Subjects with severe obesity.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Pain Intensity Numerical Rating Scale (PI-NRS) Score - From 0 to 4 Hours Post-dose | Every 15 minutes from 0 to 4 hours post-dose | Participants rated severity of their pain at 11 point PI-NRS, by choosing a number between 0 and 10, where 0= no pain and 10= worst possible pain; higher scores signify more pain. The average pain score was calculated as the mean of the pain scores recorded every 15 minutes from 0 to 4 hours post-dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average PI-NRS Scores - From Post Evoked Pain Time Point 3 (EP3) to 10 Hours Post-dose | Post EP3, every 5 minutes for the first hour, then every 15 minutes up to 10 hours post-dose | Participants rated severity of their pain at 11 point PI-NRS, by choosing a number between 0 and 10. Where 0= no pain and 10= worst possible pain; higher scores signify more pain. Evoked pain time point 3= second time point post-dose when pain was evoked using the participant specific heat pain stimulus. EP3 is approximately a time point 8-9 hours post-dose. The average pain score was calculated as the mean of the pain scores recorded from EP3 to 10 hours post-dose. |
| Average PI-NRS Scores - From Post Evoked Pain Time Point 4 (EP4) to 28 Hours Post-dose | Post EP4, every 5 minutes for the first hour, then every 15 minutes up to 28 hours post-dose | Participants rated severity of their pain at 11 point PI-NRS, by choosing a number between 0 and 10. Where 0= no pain and 10= worst possible pain; higher scores signify more pain. Evoked pain time point 4= third time point post-dose when pain was evoked using the participant specific heat pain stimulus. EP4 is approximately a time point 24-25 hours post-dose. The average pain score was calculated as the mean of the pain scores recorded from EP4 to 28 hours post-dose. |
| Maximum PI-NRS Scores - From 0 Hour to 4 Hours Post-dose | From 0 hour to 4 hours post-dose | Participants rated severity of their pain at 11 point PI-NRS, by choosing a number between 0 and 10. Where 0= no pain and 10= worst possible pain; higher scores signify more pain. Maximum pain score in 4 hours period post-dosing is reported. |
| Maximum PI-NRS Scores - From Post EP2 to 8 Hours Post-dose | From post EP2 to 8 hours post-dose | Participants rated severity of their pain at 11 point PI-NRS, by choosing a number between 0 and 10. Where 0= no pain and 10= worst possible pain; higher scores signify more pain. Evoked pain time point 2= first time point post-dose when pain was evoked using the participant specific heat pain stimulus. EP2 is approximately a time point 4-5 hours post-dose. Maximum pain score in period from post EP2 to 8 hours post-dose is reported. |
| Maximum PI-NRS Scores - From Post EP3 to 10 Hours Post-dose | From the end of EP3 to 10 hours post dose | Participants rated severity of their pain at 11 point PI-NRS, by choosing a number between 0 and 10. Where 0= no pain and 10= worst possible pain; higher scores signify more pain. Evoked pain time point 3= second time point post-dose when pain was evoked using the participant specific heat pain stimulus. EP3 is approximately a time point 8-9 hours post-dose. Maximum pain score in period from post EP3 to 10 hours post-dose is reported. |
| Maximum PI-NRS Scores - From Post EP4 to 28 Hours Post-dose | Post EP4, every 5 minutes for the first hour, then every 15 minutes up to 28 hours post-dose | Participants rated severity of their pain at 11 point PI-NRS, by choosing a number between 0 and 10. Where 0= no pain and 10= worst possible pain; higher scores signify more pain. Evoked pain time point 4= third time point post-dose when pain was evoked using the participant specific heat pain stimulus. EP4 is approximately a time point 24-25 hours post-dose. Maximum pain score in period from post EP4 to 28 hours post-dose is reported. |
| Duration When PI-NRS Scores Were Greater Than (>) 5 - From 0 Hour to 4 Hours Post-dose | From 0 hour to 4 hours post-dose | Participants rated severity of their pain at 11 point PI-NRS, by choosing a number between 0 and 10. Where 0= no pain and 10= worst possible pain; higher scores signify more pain. The duration of time that participants experienced PI-NRS score greater than 5 from the 0 hours to 4 hours post-dose. |
| Duration When PI-NRS Scores Were >5 - From Post EP2 to 8 Hours Post-dose | Post EP2, every 5 minutes for the first hour, then every 15 minutes up to 8 hours post-dose | Participants rated severity of their pain at 11 point PI-NRS, by choosing a number between 0 and 10. Where 0= no pain and 10= worst possible pain; higher scores signify more pain. Evoked pain time point 2= first time point post-dose when pain was evoked using the participant specific heat pain stimulus. EP2 is approximately a time point 4-5 hours post-dose. The duration of time that participants experienced PI-NRS score \>5 from in period from post EP2 to 8 hours post-dose is reported. |
| Duration When PI-NRS Scores Were >5 - From Post EP3 to 10 Hours Post-dose | Post EP3, every 5 minutes for the first hour, then every 15 minutes up to 10 hours post-dose | Participants rated severity of their pain at 11 point PI-NRS, by choosing a number between 0 and 10. Where 0= no pain and 10= worst possible pain; higher scores signify more pain. Evoked pain time point 3= second time point post-dose when pain was evoked using the participant specific heat pain stimulus. EP3 is approximately a time point 8-9 hours post-dose. The duration of time that participants experienced PI-NRS score \>5 from the post EP3 to 10 hours post dose. |
| Duration When PI-NRS Scores Were >5 - From Post EP4 to 28 Hours Post-dose | After EP4, every 5 minutes for the first hour, then every 15 minutes up to 28 hours post-dose | Participants rated severity of their pain at 11 point PI-NRS, by choosing a number between 0 and 10. Where 0= no pain and 10= worst possible pain; higher scores signify more pain. Evoked pain time point 4= third time point post-dose when pain was evoked using the participant specific heat pain stimulus. EP4 is approximately a time point 24-25 hours post-dose. The duration of time that participants experienced PI-NRS score \>5 from post EP4 to 28 hours post-dose. |
| Average PI-NRS Score - From Post Evoked Pain Time Point 2 (EP2) to 8 Hours Post-dose | Post EP2, every 5 minutes for the first hour, then every 15 minutes up to 8 hours post-dose | Participants rated severity of their pain at 11 point PI-NRS, by choosing a number between 0 and 10. Where 0= no pain and 10= worst possible pain; higher scores signify more pain. Evoked pain time point 2= first time point post-dose when pain was evoked using the participant specific heat pain stimulus. EP2 is approximately a time point 4-5 hours post-dose. The average pain score was calculated as the mean of the pain scores recorded from EP2 to 8 hours post-dose. |
| Time to First Use of Rescue Therapy or Medication | Up to maximum of 24 hours post-dose | Time to rescue medication (hour) was calculated as: date/time of rescue medication minus date/time of first dose for each period. If participant who did not receive rescue medication, the time of censoring was cut off at 24 hours or the time of withdrawal, whichever was earlier. Kaplan-Meier method was used for estimation. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to the 24 Hour Post-dose (AUC24) of PF-05089771 | Predose, 0.5, 2, 4, 6, and 24 hours post-dose | — |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05089771 | Predose and 0.5, 2, 4, 6, and 24 hours post dose | — |
| Maximum Observed Plasma Concentration (Cmax) of PF-05089771 | Predose and 0.5, 2, 4, 6, and 24 hours post dose | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05089771 | Predose and 0.5, 2, 4, 6, and 24 hours post dose | — |
| Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to a maximum of Day 83 | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. |
| Number of Participants With Laboratory Abnormalities | Baseline up to a maximum of Day 73 | Laboratory abnormalities: Hemoglobin (Hgb), hematocrit, red blood cell count: less than(\<)0.8\*lower limit of normal(LLN), platelet: \<0.5\*LLN/greater than (\>)1.75\*upper limit of normal (ULN), white blood cell: \<0.6\*LLN/\>1.5\*ULN, lymphocyte, neutrophil (absolute, %):\<0.8\*LLN/\>1.2\*ULN, total neutrophil \<0.8\*LLN;basophil, eosinophil, monocyte (absolute, %):\>1.2\*ULN; mean corpuscular (MC) volume, mean cell hemoglobin, MC hemoglobin concentration, mean platelet volume: \<0.9\*LLN/\>1.1\*ULN; total bilirubin \>1.5\*ULN, aspartate aminotransferase (AT), alanine AT, gammaglutamyl transferase, alkaline phosphatase:\> 3.0\*ULN, total protein, albumin: \<0.8\*LLN/\>1.2\*ULN; blood urea nitrogen, creatinine:\>1.3\*ULN, uric acid \>1.2\*ULN; sodium \<0.95\*LLN/\>1.05\*ULN, potassium, chloride, calcium, magnesium, bicarbonate: \<0.9\*LLN/\>1.1\*ULN; glucose \<0.6\*LLN/\>1.5\*ULN; urine (specific gravity \<1.003/\>1.030, pH \<4.5/\>8, glucose, ketone, protein, blood/Hgb, urobilinogen, bilirubin, nitrite, leukocyte esterase \>=1). |
| Number of Participants With Clinically Significant Changes From Baseline in Core Body Temperature | Baseline up to a maximum of Day 83 | The minimum starting temperature to measure core body temperature used was 33 degree Celsius. Clinically significant changes from baseline in core body temperature was judged by investigator. |
| Number of Participants With Clinically Significant Changes From Baseline in Blood Pressure | Baseline up to a maximum of Day 83 | Criteria for clinically significant blood pressure abnormalities: systolic blood pressure \>=30 millimetre of Mercury (mmHg) change from baseline in same posture, systolic blood pressure \<90 mmHg, diastolic blood pressure \>=20 mmHg change from baseline in same posture, diastolic blood pressure \<50 mmHg. |
| Number of Participants With Clinically Significant Changes From Baseline in Electrocardiogram (ECG) | Baseline up to a maximum of Day 83 | Criteria for clinically significant abnormalities in ECG : PR interval \>=300 millisecond (msec) and 25 percent (%) increase when baseline \>200 msec, 50% increase when baseline less than or equal to (\<=) 200 msec; QRS interval \>=140 msec, \>=50% increase from baseline; QT interval \>=500 msec; QT interval corrected using the Fridericia formula (QTcF) 450 msec to \<480 msec, \>=480 msec, 30 to \<60 msec increase from baseline, \>=60 msec increase from baseline. |
| Number of Participants With Participant's Global Satisfaction Score | At 4 hour post-dose or at time of first rescue therapy, whichever occurred first | Participant was asked How would you rate the study medication you received for pain?. The participant was provided the following choices as an answer: excellent=4; good=3; fair=2; poor=1. Response to this question, was participant's overall impression (global evaluation) of the study medication at 4 hour post-dose or at time of first rescue treatment or medication, which ever occurred first. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants who were enrolled in the study. | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 40.2 years STANDARD_DEVIATION 18.7 |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 5 | 5 / 5 | 5 / 5 | 4 / 5 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 |
Outcome results
Primary
Average Pain Intensity Numerical Rating Scale (PI-NRS) Score - From 0 to 4 Hours Post-dose
Participants rated severity of their pain at 11 point PI-NRS, by choosing a number between 0 and 10, where 0= no pain and 10= worst possible pain; higher scores signify more pain. The average pain score was calculated as the mean of the pain scores recorded every 15 minutes from 0 to 4 hours post-dose.
Time frame: Every 15 minutes from 0 to 4 hours post-dose
Population: Full analysis set included all participants who successfully completed Part A, were randomized in Part B, and who received at least 1 dose of randomized study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Session 1: PF-05089771 1600 mg | Average Pain Intensity Numerical Rating Scale (PI-NRS) Score - From 0 to 4 Hours Post-dose | 2.08 Units on a scale | Standard Deviation 2.2 |
| Treatment Session 1: Placebo | Average Pain Intensity Numerical Rating Scale (PI-NRS) Score - From 0 to 4 Hours Post-dose | 2.73 Units on a scale | Standard Deviation 2.68 |
| Treatment Session 2: PF-05089771 1600 mg | Average Pain Intensity Numerical Rating Scale (PI-NRS) Score - From 0 to 4 Hours Post-dose | 1.95 Units on a scale | Standard Deviation 2.29 |
| Treatment Session 2: Placebo | Average Pain Intensity Numerical Rating Scale (PI-NRS) Score - From 0 to 4 Hours Post-dose | 2.04 Units on a scale | Standard Deviation 1.81 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05089771
Time frame: Predose and 0.5, 2, 4, 6, and 24 hours post dose
Population: PK parameter analysis set included all participants who were randomized, received study medication, and had at least 1 of the PK parameters of interest in at least 1 treatment session.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Session 1: PF-05089771 1600 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05089771 | 652400 Nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 19 |
| Treatment Session 1: Placebo | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05089771 | 658000 Nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 26 |
Secondary
Area Under the Plasma Concentration-Time Curve From Time Zero to the 24 Hour Post-dose (AUC24) of PF-05089771
Time frame: Predose, 0.5, 2, 4, 6, and 24 hours post-dose
Population: Pharmacokinetic (PK) parameter analysis set included all participants who were randomized, received study medication, and had at least 1 of the PK parameters of interest in at least 1 treatment session.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Session 1: PF-05089771 1600 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to the 24 Hour Post-dose (AUC24) of PF-05089771 | 652100 Nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 19 |
| Treatment Session 1: Placebo | Area Under the Plasma Concentration-Time Curve From Time Zero to the 24 Hour Post-dose (AUC24) of PF-05089771 | 657500 Nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 26 |
Secondary
Average PI-NRS Score - From Post Evoked Pain Time Point 2 (EP2) to 8 Hours Post-dose
Participants rated severity of their pain at 11 point PI-NRS, by choosing a number between 0 and 10. Where 0= no pain and 10= worst possible pain; higher scores signify more pain. Evoked pain time point 2= first time point post-dose when pain was evoked using the participant specific heat pain stimulus. EP2 is approximately a time point 4-5 hours post-dose. The average pain score was calculated as the mean of the pain scores recorded from EP2 to 8 hours post-dose.
Time frame: Post EP2, every 5 minutes for the first hour, then every 15 minutes up to 8 hours post-dose
Population: Full analysis set included all participants who successfully completed Part A, were randomized in Part B, and who received at least 1 dose of randomized study medication. Overall Number of Participants Analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Session 1: PF-05089771 1600 mg | Average PI-NRS Score - From Post Evoked Pain Time Point 2 (EP2) to 8 Hours Post-dose | 0.70 Units on a scale | Standard Deviation 0.64 |
| Treatment Session 1: Placebo | Average PI-NRS Score - From Post Evoked Pain Time Point 2 (EP2) to 8 Hours Post-dose | 0.61 Units on a scale | Standard Deviation 0.46 |
| Treatment Session 2: PF-05089771 1600 mg | Average PI-NRS Score - From Post Evoked Pain Time Point 2 (EP2) to 8 Hours Post-dose | 0.55 Units on a scale | Standard Deviation 0.51 |
| Treatment Session 2: Placebo | Average PI-NRS Score - From Post Evoked Pain Time Point 2 (EP2) to 8 Hours Post-dose | 1.08 Units on a scale | Standard Deviation 0.63 |
Secondary
Average PI-NRS Scores - From Post Evoked Pain Time Point 3 (EP3) to 10 Hours Post-dose
Participants rated severity of their pain at 11 point PI-NRS, by choosing a number between 0 and 10. Where 0= no pain and 10= worst possible pain; higher scores signify more pain. Evoked pain time point 3= second time point post-dose when pain was evoked using the participant specific heat pain stimulus. EP3 is approximately a time point 8-9 hours post-dose. The average pain score was calculated as the mean of the pain scores recorded from EP3 to 10 hours post-dose.
Time frame: Post EP3, every 5 minutes for the first hour, then every 15 minutes up to 10 hours post-dose
Population: Full analysis set included all participants who successfully completed Part A, were randomized in Part B, and who received at least 1 dose of randomized study medication. Overall Number of Participants Analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Session 1: PF-05089771 1600 mg | Average PI-NRS Scores - From Post Evoked Pain Time Point 3 (EP3) to 10 Hours Post-dose | 1.19 Units on a scale | Standard Deviation 1.22 |
| Treatment Session 1: Placebo | Average PI-NRS Scores - From Post Evoked Pain Time Point 3 (EP3) to 10 Hours Post-dose | 1.55 Units on a scale | Standard Deviation 1.15 |
| Treatment Session 2: PF-05089771 1600 mg | Average PI-NRS Scores - From Post Evoked Pain Time Point 3 (EP3) to 10 Hours Post-dose | 0.82 Units on a scale | Standard Deviation 0.52 |
| Treatment Session 2: Placebo | Average PI-NRS Scores - From Post Evoked Pain Time Point 3 (EP3) to 10 Hours Post-dose | 1.39 Units on a scale | Standard Deviation 0.58 |
Secondary
Average PI-NRS Scores - From Post Evoked Pain Time Point 4 (EP4) to 28 Hours Post-dose
Participants rated severity of their pain at 11 point PI-NRS, by choosing a number between 0 and 10. Where 0= no pain and 10= worst possible pain; higher scores signify more pain. Evoked pain time point 4= third time point post-dose when pain was evoked using the participant specific heat pain stimulus. EP4 is approximately a time point 24-25 hours post-dose. The average pain score was calculated as the mean of the pain scores recorded from EP4 to 28 hours post-dose.
Time frame: Post EP4, every 5 minutes for the first hour, then every 15 minutes up to 28 hours post-dose
Population: Full analysis set included all participants who successfully completed Part A, were randomized in Part B, and who received at least 1 dose of randomized study medication. Overall Number of Participants Analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Session 1: PF-05089771 1600 mg | Average PI-NRS Scores - From Post Evoked Pain Time Point 4 (EP4) to 28 Hours Post-dose | 0.99 Units on a scale | Standard Deviation 0.52 |
| Treatment Session 1: Placebo | Average PI-NRS Scores - From Post Evoked Pain Time Point 4 (EP4) to 28 Hours Post-dose | 0.91 Units on a scale | Standard Deviation 0.53 |
| Treatment Session 2: PF-05089771 1600 mg | Average PI-NRS Scores - From Post Evoked Pain Time Point 4 (EP4) to 28 Hours Post-dose | 0.36 Units on a scale | Standard Deviation 0.08 |
| Treatment Session 2: Placebo | Average PI-NRS Scores - From Post Evoked Pain Time Point 4 (EP4) to 28 Hours Post-dose | 0.77 Units on a scale | Standard Deviation 0.38 |
Secondary
Duration When PI-NRS Scores Were >5 - From Post EP2 to 8 Hours Post-dose
Participants rated severity of their pain at 11 point PI-NRS, by choosing a number between 0 and 10. Where 0= no pain and 10= worst possible pain; higher scores signify more pain. Evoked pain time point 2= first time point post-dose when pain was evoked using the participant specific heat pain stimulus. EP2 is approximately a time point 4-5 hours post-dose. The duration of time that participants experienced PI-NRS score \>5 from in period from post EP2 to 8 hours post-dose is reported.
Time frame: Post EP2, every 5 minutes for the first hour, then every 15 minutes up to 8 hours post-dose
Population: Full analysis set included all participants who successfully completed Part A, were randomized in Part B, and who received at least 1 dose of randomized study medication. Overall Number of Participants Analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Session 1: PF-05089771 1600 mg | Duration When PI-NRS Scores Were >5 - From Post EP2 to 8 Hours Post-dose | 0.0 Minutes | Standard Deviation 0 |
| Treatment Session 1: Placebo | Duration When PI-NRS Scores Were >5 - From Post EP2 to 8 Hours Post-dose | 0.0 Minutes | Standard Deviation 0 |
| Treatment Session 2: PF-05089771 1600 mg | Duration When PI-NRS Scores Were >5 - From Post EP2 to 8 Hours Post-dose | 0.0 Minutes | Standard Deviation 0 |
| Treatment Session 2: Placebo | Duration When PI-NRS Scores Were >5 - From Post EP2 to 8 Hours Post-dose | 0.0 Minutes | Standard Deviation 0 |
Secondary
Duration When PI-NRS Scores Were >5 - From Post EP3 to 10 Hours Post-dose
Participants rated severity of their pain at 11 point PI-NRS, by choosing a number between 0 and 10. Where 0= no pain and 10= worst possible pain; higher scores signify more pain. Evoked pain time point 3= second time point post-dose when pain was evoked using the participant specific heat pain stimulus. EP3 is approximately a time point 8-9 hours post-dose. The duration of time that participants experienced PI-NRS score \>5 from the post EP3 to 10 hours post dose.
Time frame: Post EP3, every 5 minutes for the first hour, then every 15 minutes up to 10 hours post-dose
Population: Full analysis set included all participants who successfully completed Part A, were randomized in Part B, and who received at least 1 dose of randomized study medication. Overall Number of Participants Analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Session 1: PF-05089771 1600 mg | Duration When PI-NRS Scores Were >5 - From Post EP3 to 10 Hours Post-dose | 0.0 Minutes | Standard Deviation 0 |
| Treatment Session 1: Placebo | Duration When PI-NRS Scores Were >5 - From Post EP3 to 10 Hours Post-dose | 0.0 Minutes | Standard Deviation 10.4 |
| Treatment Session 2: PF-05089771 1600 mg | Duration When PI-NRS Scores Were >5 - From Post EP3 to 10 Hours Post-dose | 0.0 Minutes | Standard Deviation 0 |
| Treatment Session 2: Placebo | Duration When PI-NRS Scores Were >5 - From Post EP3 to 10 Hours Post-dose | 0.0 Minutes | Standard Deviation 0 |
Secondary
Duration When PI-NRS Scores Were >5 - From Post EP4 to 28 Hours Post-dose
Participants rated severity of their pain at 11 point PI-NRS, by choosing a number between 0 and 10. Where 0= no pain and 10= worst possible pain; higher scores signify more pain. Evoked pain time point 4= third time point post-dose when pain was evoked using the participant specific heat pain stimulus. EP4 is approximately a time point 24-25 hours post-dose. The duration of time that participants experienced PI-NRS score \>5 from post EP4 to 28 hours post-dose.
Time frame: After EP4, every 5 minutes for the first hour, then every 15 minutes up to 28 hours post-dose
Population: Full analysis set included all participants who successfully completed Part A, were randomized in Part B, and who received at least 1 dose of randomized study medication. Overall Number of Participants Analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Session 1: PF-05089771 1600 mg | Duration When PI-NRS Scores Were >5 - From Post EP4 to 28 Hours Post-dose | 0.0 Minutes | Standard Deviation 0 |
| Treatment Session 1: Placebo | Duration When PI-NRS Scores Were >5 - From Post EP4 to 28 Hours Post-dose | 0.0 Minutes | Standard Deviation 0 |
| Treatment Session 2: PF-05089771 1600 mg | Duration When PI-NRS Scores Were >5 - From Post EP4 to 28 Hours Post-dose | 0.0 Minutes | Standard Deviation 0 |
| Treatment Session 2: Placebo | Duration When PI-NRS Scores Were >5 - From Post EP4 to 28 Hours Post-dose | 0.0 Minutes | Standard Deviation 0 |
Secondary
Duration When PI-NRS Scores Were Greater Than (>) 5 - From 0 Hour to 4 Hours Post-dose
Participants rated severity of their pain at 11 point PI-NRS, by choosing a number between 0 and 10. Where 0= no pain and 10= worst possible pain; higher scores signify more pain. The duration of time that participants experienced PI-NRS score greater than 5 from the 0 hours to 4 hours post-dose.
Time frame: From 0 hour to 4 hours post-dose
Population: Full analysis set included all participants who successfully completed Part A, were randomized in Part B, and who received at least 1 dose of randomized study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Session 1: PF-05089771 1600 mg | Duration When PI-NRS Scores Were Greater Than (>) 5 - From 0 Hour to 4 Hours Post-dose | 20.0 Minutes | Standard Deviation 42 |
| Treatment Session 1: Placebo | Duration When PI-NRS Scores Were Greater Than (>) 5 - From 0 Hour to 4 Hours Post-dose | 29.4 Minutes | Standard Deviation 63 |
| Treatment Session 2: PF-05089771 1600 mg | Duration When PI-NRS Scores Were Greater Than (>) 5 - From 0 Hour to 4 Hours Post-dose | 10.4 Minutes | Standard Deviation 23.3 |
| Treatment Session 2: Placebo | Duration When PI-NRS Scores Were Greater Than (>) 5 - From 0 Hour to 4 Hours Post-dose | 8.2 Minutes | Standard Deviation 12.1 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of PF-05089771
Time frame: Predose and 0.5, 2, 4, 6, and 24 hours post dose
Population: PK parameter analysis set included all participants who were randomized, received study medication, and had at least 1 of the PK parameters of interest in at least 1 treatment session.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Session 1: PF-05089771 1600 mg | Maximum Observed Plasma Concentration (Cmax) of PF-05089771 | 66760 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 22 |
| Treatment Session 1: Placebo | Maximum Observed Plasma Concentration (Cmax) of PF-05089771 | 59080 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 21 |
Secondary
Maximum PI-NRS Scores - From 0 Hour to 4 Hours Post-dose
Participants rated severity of their pain at 11 point PI-NRS, by choosing a number between 0 and 10. Where 0= no pain and 10= worst possible pain; higher scores signify more pain. Maximum pain score in 4 hours period post-dosing is reported.
Time frame: From 0 hour to 4 hours post-dose
Population: Full analysis set included all participants who successfully completed Part A, were randomized in Part B, and who received at least 1 dose of randomized study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Session 1: PF-05089771 1600 mg | Maximum PI-NRS Scores - From 0 Hour to 4 Hours Post-dose | 7.6 Units on a scale | Standard Deviation 1.7 |
| Treatment Session 1: Placebo | Maximum PI-NRS Scores - From 0 Hour to 4 Hours Post-dose | 8.0 Units on a scale | Standard Deviation 1.4 |
| Treatment Session 2: PF-05089771 1600 mg | Maximum PI-NRS Scores - From 0 Hour to 4 Hours Post-dose | 8.2 Units on a scale | Standard Deviation 2.1 |
| Treatment Session 2: Placebo | Maximum PI-NRS Scores - From 0 Hour to 4 Hours Post-dose | 8.6 Units on a scale | Standard Deviation 1.1 |
Secondary
Maximum PI-NRS Scores - From Post EP2 to 8 Hours Post-dose
Participants rated severity of their pain at 11 point PI-NRS, by choosing a number between 0 and 10. Where 0= no pain and 10= worst possible pain; higher scores signify more pain. Evoked pain time point 2= first time point post-dose when pain was evoked using the participant specific heat pain stimulus. EP2 is approximately a time point 4-5 hours post-dose. Maximum pain score in period from post EP2 to 8 hours post-dose is reported.
Time frame: From post EP2 to 8 hours post-dose
Population: Full analysis set included all participants who successfully completed Part A, were randomized in Part B, and who received at least 1 dose of randomized study medication. Overall Number of Participants Analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Session 1: PF-05089771 1600 mg | Maximum PI-NRS Scores - From Post EP2 to 8 Hours Post-dose | 3.5 Units on a scale | Standard Deviation 1.7 |
| Treatment Session 1: Placebo | Maximum PI-NRS Scores - From Post EP2 to 8 Hours Post-dose | 5.7 Units on a scale | Standard Deviation 3.1 |
| Treatment Session 2: PF-05089771 1600 mg | Maximum PI-NRS Scores - From Post EP2 to 8 Hours Post-dose | 5.5 Units on a scale | Standard Deviation 3.3 |
| Treatment Session 2: Placebo | Maximum PI-NRS Scores - From Post EP2 to 8 Hours Post-dose | 7.8 Units on a scale | Standard Deviation 1.9 |
Secondary
Maximum PI-NRS Scores - From Post EP3 to 10 Hours Post-dose
Participants rated severity of their pain at 11 point PI-NRS, by choosing a number between 0 and 10. Where 0= no pain and 10= worst possible pain; higher scores signify more pain. Evoked pain time point 3= second time point post-dose when pain was evoked using the participant specific heat pain stimulus. EP3 is approximately a time point 8-9 hours post-dose. Maximum pain score in period from post EP3 to 10 hours post-dose is reported.
Time frame: From the end of EP3 to 10 hours post dose
Population: Full analysis set included all participants who successfully completed Part A, were randomized in Part B, and who received at least 1 dose of randomized study medication. Overall Number of Participants Analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Session 1: PF-05089771 1600 mg | Maximum PI-NRS Scores - From Post EP3 to 10 Hours Post-dose | 2.3 Units on a scale | Standard Deviation 2.6 |
| Treatment Session 1: Placebo | Maximum PI-NRS Scores - From Post EP3 to 10 Hours Post-dose | 6.0 Units on a scale | Standard Deviation 3.6 |
| Treatment Session 2: PF-05089771 1600 mg | Maximum PI-NRS Scores - From Post EP3 to 10 Hours Post-dose | 5.3 Units on a scale | Standard Deviation 2.6 |
| Treatment Session 2: Placebo | Maximum PI-NRS Scores - From Post EP3 to 10 Hours Post-dose | 8.3 Units on a scale | Standard Deviation 2.1 |
Secondary
Maximum PI-NRS Scores - From Post EP4 to 28 Hours Post-dose
Participants rated severity of their pain at 11 point PI-NRS, by choosing a number between 0 and 10. Where 0= no pain and 10= worst possible pain; higher scores signify more pain. Evoked pain time point 4= third time point post-dose when pain was evoked using the participant specific heat pain stimulus. EP4 is approximately a time point 24-25 hours post-dose. Maximum pain score in period from post EP4 to 28 hours post-dose is reported.
Time frame: Post EP4, every 5 minutes for the first hour, then every 15 minutes up to 28 hours post-dose
Population: Full analysis set included all participants who successfully completed Part A, were randomized in Part B, and who received at least 1 dose of randomized study medication. Overall Number of Participants Analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Session 1: PF-05089771 1600 mg | Maximum PI-NRS Scores - From Post EP4 to 28 Hours Post-dose | 7.3 Units on a scale | Standard Deviation 1.2 |
| Treatment Session 1: Placebo | Maximum PI-NRS Scores - From Post EP4 to 28 Hours Post-dose | 7.3 Units on a scale | Standard Deviation 2.5 |
| Treatment Session 2: PF-05089771 1600 mg | Maximum PI-NRS Scores - From Post EP4 to 28 Hours Post-dose | 5.7 Units on a scale | Standard Deviation 2.1 |
| Treatment Session 2: Placebo | Maximum PI-NRS Scores - From Post EP4 to 28 Hours Post-dose | 8.0 Units on a scale | Standard Deviation 2 |
Secondary
Number of Participants With Clinically Significant Changes From Baseline in Blood Pressure
Criteria for clinically significant blood pressure abnormalities: systolic blood pressure \>=30 millimetre of Mercury (mmHg) change from baseline in same posture, systolic blood pressure \<90 mmHg, diastolic blood pressure \>=20 mmHg change from baseline in same posture, diastolic blood pressure \<50 mmHg.
Time frame: Baseline up to a maximum of Day 83
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Session 1: PF-05089771 1600 mg | Number of Participants With Clinically Significant Changes From Baseline in Blood Pressure | 0 Participants |
| Treatment Session 1: Placebo | Number of Participants With Clinically Significant Changes From Baseline in Blood Pressure | 0 Participants |
| Treatment Session 2: PF-05089771 1600 mg | Number of Participants With Clinically Significant Changes From Baseline in Blood Pressure | 0 Participants |
| Treatment Session 2: Placebo | Number of Participants With Clinically Significant Changes From Baseline in Blood Pressure | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes From Baseline in Core Body Temperature
The minimum starting temperature to measure core body temperature used was 33 degree Celsius. Clinically significant changes from baseline in core body temperature was judged by investigator.
Time frame: Baseline up to a maximum of Day 83
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Session 1: PF-05089771 1600 mg | Number of Participants With Clinically Significant Changes From Baseline in Core Body Temperature | 0 Participants |
| Treatment Session 1: Placebo | Number of Participants With Clinically Significant Changes From Baseline in Core Body Temperature | 0 Participants |
| Treatment Session 2: PF-05089771 1600 mg | Number of Participants With Clinically Significant Changes From Baseline in Core Body Temperature | 0 Participants |
| Treatment Session 2: Placebo | Number of Participants With Clinically Significant Changes From Baseline in Core Body Temperature | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes From Baseline in Electrocardiogram (ECG)
Criteria for clinically significant abnormalities in ECG : PR interval \>=300 millisecond (msec) and 25 percent (%) increase when baseline \>200 msec, 50% increase when baseline less than or equal to (\<=) 200 msec; QRS interval \>=140 msec, \>=50% increase from baseline; QT interval \>=500 msec; QT interval corrected using the Fridericia formula (QTcF) 450 msec to \<480 msec, \>=480 msec, 30 to \<60 msec increase from baseline, \>=60 msec increase from baseline.
Time frame: Baseline up to a maximum of Day 83
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Session 1: PF-05089771 1600 mg | Number of Participants With Clinically Significant Changes From Baseline in Electrocardiogram (ECG) | 0 Participants |
| Treatment Session 1: Placebo | Number of Participants With Clinically Significant Changes From Baseline in Electrocardiogram (ECG) | 0 Participants |
| Treatment Session 2: PF-05089771 1600 mg | Number of Participants With Clinically Significant Changes From Baseline in Electrocardiogram (ECG) | 0 Participants |
| Treatment Session 2: Placebo | Number of Participants With Clinically Significant Changes From Baseline in Electrocardiogram (ECG) | 0 Participants |
Secondary
Number of Participants With Laboratory Abnormalities
Laboratory abnormalities: Hemoglobin (Hgb), hematocrit, red blood cell count: less than(\<)0.8\*lower limit of normal(LLN), platelet: \<0.5\*LLN/greater than (\>)1.75\*upper limit of normal (ULN), white blood cell: \<0.6\*LLN/\>1.5\*ULN, lymphocyte, neutrophil (absolute, %):\<0.8\*LLN/\>1.2\*ULN, total neutrophil \<0.8\*LLN;basophil, eosinophil, monocyte (absolute, %):\>1.2\*ULN; mean corpuscular (MC) volume, mean cell hemoglobin, MC hemoglobin concentration, mean platelet volume: \<0.9\*LLN/\>1.1\*ULN; total bilirubin \>1.5\*ULN, aspartate aminotransferase (AT), alanine AT, gammaglutamyl transferase, alkaline phosphatase:\> 3.0\*ULN, total protein, albumin: \<0.8\*LLN/\>1.2\*ULN; blood urea nitrogen, creatinine:\>1.3\*ULN, uric acid \>1.2\*ULN; sodium \<0.95\*LLN/\>1.05\*ULN, potassium, chloride, calcium, magnesium, bicarbonate: \<0.9\*LLN/\>1.1\*ULN; glucose \<0.6\*LLN/\>1.5\*ULN; urine (specific gravity \<1.003/\>1.030, pH \<4.5/\>8, glucose, ketone, protein, blood/Hgb, urobilinogen, bilirubin, nitrite, leukocyte esterase \>=1).
Time frame: Baseline up to a maximum of Day 73
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Session 1: PF-05089771 1600 mg | Number of Participants With Laboratory Abnormalities | 2 Participants |
| Treatment Session 1: Placebo | Number of Participants With Laboratory Abnormalities | 2 Participants |
| Treatment Session 2: PF-05089771 1600 mg | Number of Participants With Laboratory Abnormalities | 2 Participants |
| Treatment Session 2: Placebo | Number of Participants With Laboratory Abnormalities | 2 Participants |
Secondary
Number of Participants With Participant's Global Satisfaction Score
Participant was asked How would you rate the study medication you received for pain?. The participant was provided the following choices as an answer: excellent=4; good=3; fair=2; poor=1. Response to this question, was participant's overall impression (global evaluation) of the study medication at 4 hour post-dose or at time of first rescue treatment or medication, which ever occurred first.
Time frame: At 4 hour post-dose or at time of first rescue therapy, whichever occurred first
Population: Full analysis set included all participants who successfully completed Part A, were randomized in Part B, and who received at least 1 dose of randomized study medication.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Session 1: PF-05089771 1600 mg | Number of Participants With Participant's Global Satisfaction Score | Poor Score | 1 Participants |
| Treatment Session 1: PF-05089771 1600 mg | Number of Participants With Participant's Global Satisfaction Score | Fair Score | 2 Participants |
| Treatment Session 1: PF-05089771 1600 mg | Number of Participants With Participant's Global Satisfaction Score | Good Score | 1 Participants |
| Treatment Session 1: PF-05089771 1600 mg | Number of Participants With Participant's Global Satisfaction Score | Excellent Score | 1 Participants |
| Treatment Session 1: Placebo | Number of Participants With Participant's Global Satisfaction Score | Fair Score | 1 Participants |
| Treatment Session 1: Placebo | Number of Participants With Participant's Global Satisfaction Score | Good Score | 0 Participants |
| Treatment Session 1: Placebo | Number of Participants With Participant's Global Satisfaction Score | Excellent Score | 1 Participants |
| Treatment Session 1: Placebo | Number of Participants With Participant's Global Satisfaction Score | Poor Score | 3 Participants |
| Treatment Session 2: PF-05089771 1600 mg | Number of Participants With Participant's Global Satisfaction Score | Good Score | 1 Participants |
| Treatment Session 2: PF-05089771 1600 mg | Number of Participants With Participant's Global Satisfaction Score | Fair Score | 3 Participants |
| Treatment Session 2: PF-05089771 1600 mg | Number of Participants With Participant's Global Satisfaction Score | Excellent Score | 1 Participants |
| Treatment Session 2: PF-05089771 1600 mg | Number of Participants With Participant's Global Satisfaction Score | Poor Score | 0 Participants |
| Treatment Session 2: Placebo | Number of Participants With Participant's Global Satisfaction Score | Excellent Score | 0 Participants |
| Treatment Session 2: Placebo | Number of Participants With Participant's Global Satisfaction Score | Fair Score | 1 Participants |
| Treatment Session 2: Placebo | Number of Participants With Participant's Global Satisfaction Score | Poor Score | 4 Participants |
| Treatment Session 2: Placebo | Number of Participants With Participant's Global Satisfaction Score | Good Score | 0 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state.
Time frame: Baseline up to a maximum of Day 83
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Session 1: PF-05089771 1600 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 5 Participants |
| Treatment Session 1: PF-05089771 1600 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Treatment Session 1: Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Treatment Session 1: Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 5 Participants |
| Treatment Session 2: PF-05089771 1600 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 5 Participants |
| Treatment Session 2: PF-05089771 1600 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Treatment Session 2: Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 4 Participants |
| Treatment Session 2: Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
Secondary
Time to First Use of Rescue Therapy or Medication
Time to rescue medication (hour) was calculated as: date/time of rescue medication minus date/time of first dose for each period. If participant who did not receive rescue medication, the time of censoring was cut off at 24 hours or the time of withdrawal, whichever was earlier. Kaplan-Meier method was used for estimation.
Time frame: Up to maximum of 24 hours post-dose
Population: Full analysis set included all participants who successfully completed Part A, were randomized in Part B, and who received at least 1 dose of randomized study medication. Number of Participants Analyzed = number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Session 1: PF-05089771 1600 mg | Time to First Use of Rescue Therapy or Medication | 14.9 Hours |
| Treatment Session 1: Placebo | Time to First Use of Rescue Therapy or Medication | 2.3 Hours |
| Treatment Session 2: PF-05089771 1600 mg | Time to First Use of Rescue Therapy or Medication | 15.3 Hours |
| Treatment Session 2: Placebo | Time to First Use of Rescue Therapy or Medication | 10.3 Hours |
p-value: 1Hierarchical rank test
p-value: 1Hierarchical rank test
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05089771
Time frame: Predose and 0.5, 2, 4, 6, and 24 hours post dose
Population: PK parameter analysis set included all participants who were randomized, received study medication, and had at least 1 of the PK parameters of interest in at least 1 treatment session.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Session 1: PF-05089771 1600 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05089771 | 3.95 Hours |
| Treatment Session 1: Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05089771 | 6.00 Hours |