Safety and Efficacy Study of XPF-001 to Treat Pain Following Wisdom Tooth Extraction

Study Overview
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Brief Summary
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The purpose of this trial is to determine if XPF-001 is effective for the treatment of pain following third-molar/wisdom tooth extraction.

Official Title
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Single-Center, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Proof-of-Concept Study to Evaluate the Safety, PK, & Efficacy of a Single Oral Dose of XPF-001 in the Treatment of Pain Related to Third Molar/Wisdom Tooth Extraction.

Conditions
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Dental Pain

Intervention / Treatment
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* Drug: XPF-001
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males (aged 18-60) and females of non-childbearing potential (aged 18-60; BMI between 19.5 to 32.0 kg/m2; Outpatient, scheduled to undergo surgical extraction of 2 or more impacted 3rd molars (with at least 1 partial bony mandibular extraction); use of only the following preoperative medications 2% lidocaine with epinephrine and nitrous oxide; Able to complete the requested information on analgesic questionnaires and able to comply with study procedures and restrictions; Able to read, comprehend and sign the consent form; Deemed medically healthy to participate in the study, with normal or clinically insignificant medical history, physical examination, lab tests and ECG results; No contraindications to the study drug, it excipients or any of the study medications including rescue medications. Exclusion Criteria: Presence of a clinically significant medical condition; Positive test for HIV, Hepatitis B or Hepatitis C; Use of any prescription or over the counter medication or supplement in the 48 hours before dose of study drug until discharge; Acute local infection at the time of dental surgery; Females who are pregnant, lactating or of child-bearing potential, or who provide a positive pregnancy test result at screening or check-in; Males not undertaking adequate measures to prevent their partner becoming pregnant throughout the study; Clinically significant laboratory values; Clinically significant abnormal ECG; History or presence of alcoholism, or alcohol or substance abuse (within previous 2 years), or routine consumption of 3 or more alcoholic drinks per day; A positive urine drug test; Routine use of analgesics 5 or more times per week; Presence or history (within 2 years of enrolment) of bleeding disorder(s) or peptic ulcer disease; History of allergic reaction to any drug, including penicillin; Ingestion of caffeine containing foods or drinks in the 24 hours before dose of study drug; Consumption of alcohol in the 48 hours before dose of study drug, or a positive alcohol breath test at check-in; Consumption of grapefruit or grapefruit containing products in the 7 days before dose of study drug; Use of tobacco or nicotine substitutes within 1 month of dose of study drug, or inability to refrain from use of nicotine between check-in and follow up; Treatment for depression in the 6 months prior to enrolment; Use of another investigational drug in the 60 days before enrolment; Donation or loss of 50-500 mL of blood in the 30 days prior to enrolment, or more than 500 mL of blood in the 56 days before enrolment; Previously entered into this study; Study site or Sponsor employees or relatives of employees directly involved in the study; Any other condition that (in the opinion of the Investigator or sponsor) makes the subject unsuitable for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XPF-001<br> | Drug: XPF-001<br>* Single oral administration of 500 mg XPF-001 capsules (5 x 100 mg capsules)<br>|
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* Single oral administration of 5 x 100 mg Placebo capsules.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Pain Relief at 6 Hours Post Dose (TOTPAR 6) | The primary efficacy variable was total pain relief at the 6-hour observation (TOTPAR 6); TOTPAR 6 is an area calculation incorporating time and relief scores over the 6 hours following dosing and was calculated using Simpson's trapezoidal rule. The higher the LS Means scores, the more pain relief was obtained. Relief (REL) scores were measured at multiple timepoints after dosing, using a 5 point categorical pain relief rating scale. (None = 0, A Little Relief = 1, Some = 2, A Lot = 3, Complete Relief = 4). The minimum possible TOTPAR 6 score = 0, maximum possible score = 24 | 6 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Pain Relief (TOTPAR) at 4 Hours Post Dose | A secondary efficacy variable was total pain relief at the 4-hour observation (TOTPAR 4); TOTPAR 4 is an area calculation incorporating time and relief scores over the 4 hours following dosing and was calculated using Simpson's trapezoidal rule. The higher the LS Means scores, the more pain relief was obtained. Relief (REL) scores were measured at multiple timepoints after dosing, using a 5 point categorical pain relief rating scale. (None = 0, A Little Relief = 1, Some = 2, A Lot = 3, Complete Relief = 4). The minimum possible TOTPAR 4 score = 0, maximum possible score = 16). | 4 hours | 
| Total Pain Relief (TOTPAR) at 8 Hours Post Dose | A secondary efficacy variable was total pain relief at the 8-hour observation (TOTPAR 8); TOTPAR 8 is an area calculation incorporating time and relief scores over the 8 hours following dosing and was calculated using Simpson's trapezoidal rule. The higher the LS Means scores, the more pain relief was obtained. Relief (REL) scores were measured at multiple timepoints after dosing, using a 5 point categorical pain relief rating scale. (None = 0, A Little Relief = 1, Some = 2, A Lot = 3, Complete Relief = 4). The minimum possible TOTPAR 8 score = 0, maximum possible score = 32 | 8 hours | 
| Total Pain Relief (TOTPAR) at 12 Hours Post Dose | A secondary efficacy variable was total pain relief at the 12-hour observation (TOTPAR 12); TOTPAR 12 is an area calculation incorporating time and relief scores over the 12 hours following dosing and was calculated using Simpson's trapezoidal rule. The higher the LS Means scores, the more pain relief was obtained. Relief (REL) scores were measured at multiple timepoints after dosing, using a 5 point categorical pain relief rating scale. (None = 0, A Little Relief = 1, Some = 2, A Lot = 3, Complete Relief = 4). The minimum possible TOTPAR 12 score = 0, maximum possible score = 48. | 12 hours | 
| Summed Pain Intensity Difference (SPID) at 4 Hours Post Dose | Pain intensity was scored on an 11-point scale (PINRS), (0=no pain - 10=pain as bad as you can imagine). Scores were measured at baseline (after surgery but before dosing) and at multiple timepoints after dosing. At each timepoint, pain intensity difference (PID) was calculated (ie, baseline score minus timepoint score). SPID4 is an area calculation encompassing time and the PID scores over the 4 hours following dosing. The minimum possible SPID4 value = -40, the maximum possible = 40. A positive SPID LS Means score implies reduced pain intensity over the corresponding time period. | Baseline to 4 hours post dose | 
| Summed Pain Intensity Difference (SPID) at 6 Hours Post Dose | Pain intensity was scored on an 11-point scale (PINRS), (0=no pain - 10=pain as bad as you can imagine). Scores were measured at baseline (after surgery but before dosing) and at multiple timepoints after dosing. At each timepoint, pain intensity difference (PID) was calculated (ie, baseline score minus timepoint score). SPID6 is an area calculation encompassing time and the PID scores over the 6 hours following dosing. The minimum possible SPID6 value = -60, the maximum possible = 60. A positive SPID LS Means score implies reduced pain intensity over the corresponding time period. | Baseline to 6 hours post dose | 
| Summed Pain Intensity Difference (SPID) at 8 Hours Post Dose | Pain intensity was scored on an 11-point scale (PINRS), (0=no pain - 10=pain as bad as you can imagine). Scores were measured at baseline (after surgery but before dosing) and at multiple timepoints after dosing. At each timepoint, pain intensity difference (PID) was calculated (ie, baseline score minus timepoint score). SPID8 is an area calculation encompassing time and the PID scores over the 8 hours following dosing. The minimum possible SPID8 value = -80, the maximum possible = 80. A positive SPID LS Means score implies reduced pain intensity over the corresponding time period. | Baseline to 8 hours post dose | 
| Summed Pain Intensity Difference (SPID) at 12 Hours Post Dose | Pain intensity was scored on an 11-point scale (PINRS), (0=no pain - 10=pain as bad as you can imagine). Scores were measured at baseline (after surgery but before dosing) and at multiple timepoints after dosing. At each timepoint, pain intensity difference (PID) was calculated (ie, baseline score minus timepoint score). SPID12 is an area calculation encompassing time and the PID scores over the 12 hours following dosing. The minimum possible SPID12 value = -120, the maximum possible = 120. A positive SPID LS Means score implies reduced pain intensity over the corresponding time period. | Baseline to 12 hours post dose | 
| Time to First Perceptible Relief | Onset of analgesia was measured using 2 stopwatches. Both stopwatches were started at the time of dose administration. Stopwatch 1 was pressed by the subject when any pain relief was first perceived (Time to First Perceptible Relief) and stopwatch 2 was pressed by the subject when pain relief became meaningful (Time to Meaningful Relief). | 24 hours | 
| Time to Meaningful Relief | Onset of analgesia was measured using 2 stopwatches. Both stopwatches were started at the time of dose administration. Stopwatch 1 was pressed by the subject when any pain relief was first perceived (Time to First Perceptible Relief) and stopwatch 2 was pressed by the subject when pain relief became meaningful (Time to Meaningful Relief). 'Meaningful Relief' was defined as when the relief became 'meaningful' to each individual subject, and was not necessarily a complete absence of pain. 'Meaningful Relief' could not occur before 'First Perceptible Relief'. | 24 hours | 
| Time to Rescue Medication | The time of administration of rescue medication (if any) was recorded for each subject and the duration since dosing was calculated. | 24 hours | 
| Treatment Emergent Adverse Events | Adverse Events were recorded at the time of occurence. Clinically significant findings (if any) in ECG and vital signs assessments and laboratory samples were recorded as adverse events. Treatment Emergent Adverse Events (TEAEs) are those which either started or worsened following administration of study drug (XPF-001 or placebo). | 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain following 3rd molar/wisdom tooth extraction