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Trial record 1 of 1 for:    NCT01769274
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Evaluation Of The Efficacy And Safety Of Single Doses Of PF-05089771 In Patients With Primary (Inherited) Erythromelalgia (IEM)

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ClinicalTrials.gov Identifier: NCT01769274
Recruitment Status : Completed
First Posted : January 16, 2013
Results First Posted : November 19, 2019
Last Update Posted : November 19, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE October 18, 2012
First Posted Date  ICMJE January 16, 2013
Results First Submitted Date  ICMJE October 25, 2019
Results First Posted Date  ICMJE November 19, 2019
Last Update Posted Date November 19, 2019
Actual Study Start Date  ICMJE October 22, 2012
Actual Primary Completion Date July 12, 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 18, 2019)
Average Pain Intensity Numerical Rating Scale (PI-NRS) Score - From 0 to 4 Hours Post-dose [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 15, 2013)
Average pain score postdose based on Pain Intensity Numerical Rating Scale (PI-NRS) scores [ Time Frame: 0-4 hr postdose ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 18, 2019)
  • Average PI-NRS Score - From Post Evoked Pain Time Point 2 (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 ]
    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.
  • Average PI-NRS Scores - From Post Evoked Pain Time Point 3 (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 ]
    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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
  • Number of Participants With Participant's Global Satisfaction Score [ Time Frame: 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.
  • Time to First Use of Rescue Therapy or Medication [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Predose and 0.5, 2, 4, 6, and 24 hours post dose ]
  • Maximum Observed Plasma Concentration (Cmax) of PF-05089771 [ Time Frame: Predose and 0.5, 2, 4, 6, and 24 hours post dose ]
  • 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 ]
  • Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 15, 2013)
  • Maximum pain score postdose based on Pain Intensity Numerical Rating Scale scores. [ Time Frame: 0-4 hr postdose ]
  • Duration of time above Pain Intensity Numerical Rating Scale score of 5. [ Time Frame: 0-4hr postdose ]
  • Average pain score post Evoked Pain (EP) timepoint 2 based on Pain Intensity Numerical Rating Scale scores. [ Time Frame: 4-8 hr postdose ]
  • Maximum pain score post Evoked Pain timepoint 2 based on maximum Pain Intensity Numerical Rating Scale scores. [ Time Frame: 4-8h hr postdose ]
  • Duration of time above Pain Intensity Numerical Rating Scale score of 5 in the period post Evoked Pain timepoint 2 [ Time Frame: 4-8 hr postdose ]
  • Average pain score post Evoked Pain timepoint 3 based on Pain Intensity Numerical Rating scale scores [ Time Frame: 8-10 hr postdose ]
  • Maximum pain score post Evoked Pain timepoint 3 based on maximum Pain Intensity Numerical Rating Scale scores [ Time Frame: 8-10 hr postdose ]
  • Duration of time above Pain Intensity Numerical Rating Scale score of 5 post Evoked Pain timepoint 3 [ Time Frame: 8-10 hr postdose ]
  • Average pain score post Evoked Pain timepoint 4 based on Pain Intensity Numerical Rating scale scores [ Time Frame: 24-28 hr postdose ]
  • Maximum pain score post Evoked Pain timepoint 4 based on maximum Pain Intensity Numerical Rating Scale scores [ Time Frame: 24-28 hr postdose ]
  • Duration of time above Pain Intensity Numerical Rating Scale score of 5 post Evoked Pain timepoint 4 [ Time Frame: 24-28 hr postdose ]
  • Patient's global satisfaction with study medication based on categorical rating scale [ Time Frame: 4 hr postdose ]
  • Time to first rescue therapy or medication post dose [ Time Frame: 0-28 hr postdose ]
  • Plasma concentrations of PF-05089771, maximum observed concentration (Cmax), time to maximum concentration (Tmax) [ Time Frame: Day 1 predose, then 0.5hr, 2hr, 4hr, 6hr and 24hr postdose ]
  • Type, incidence and severity of Laboratory test result abnormalities as a measure of safety and toleration [ Time Frame: Day 0, Day 2; 24 hr postdose ]
  • Type, incidence and severity of Adverse Events in study subjects [ Time Frame: up to 28 days post last dose ]
  • Blood pressure changes of clinical significance, as a measure of safety and toleration [ Time Frame: Day -2, Day -1, Predose and 6hr post dose ]
  • Electrocardiogram changes of clinical significance, as a measure of safety and toleration [ Time Frame: Day -2, predose, 6 hr 24 hr post dose ]
  • Pulse rate changes of clinical significance, as a measure of safety and toleration [ Time Frame: Day -2, Day -1, Predose and 6hr post dose ]
  • Reason for first rescue therapy or medication postdose [ Time Frame: 0-28 hr postdose ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation Of The Efficacy And Safety Of Single Doses Of PF-05089771 In Patients With Primary (Inherited) Erythromelalgia
Official Title  ICMJE A RANDOMIZED, DOUBLE BLIND THIRD PARTY OPEN PLACEBO-CONTROLLED EXPLORATORY STUDY TO EVALUATE THE EFFICACY AND SAFETY OF SINGLE DOSES OF PF-05089771 IN PATIENTS WITH PRIMARY (INHERITED) ERYTHROMELALGIA
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Inherited Erythromelalgia
Intervention  ICMJE
  • Drug: PF-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.
  • Drug: Placebo
    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.
Study Arms  ICMJE
  • Experimental: PF-05089771 1600 mg
    Intervention: Drug: PF-05089771
  • Placebo Comparator: Placebo comparator: matching placebo
    Single oral dose of placebo for PF-05089771 1600 mg
    Intervention: Drug: Placebo
Publications * Cao L, McDonnell A, Nitzsche A, Alexandrou A, Saintot PP, Loucif AJ, Brown AR, Young G, Mis M, Randall A, Waxman SG, Stanley P, Kirby S, Tarabar S, Gutteridge A, Butt R, McKernan RM, Whiting P, Ali Z, Bilsland J, Stevens EB. Pharmacological reversal of a pain phenotype in iPSC-derived sensory neurons and patients with inherited erythromelalgia. Sci Transl Med. 2016 Apr 20;8(335):335ra56. doi: 10.1126/scitranslmed.aad7653.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 30, 2013)
5
Original Estimated Enrollment  ICMJE
 (submitted: January 15, 2013)
20
Actual Study Completion Date  ICMJE July 12, 2013
Actual Primary Completion Date July 12, 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 78 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01769274
Other Study ID Numbers  ICMJE B3291006
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP