A Study of ARRY-371797 in Subjects Undergoing Third Molar Extraction

Study Overview
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Brief Summary
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This is a Phase 2 study designed to test the ability of investigational study drug ARRY-371797 to reduce pain in a postoperative pain model (third molar extraction), and to further evaluate the drug's safety. Approximately 250 subjects from the US will be enrolled in this study.

Official Title
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A Randomized, Double-blind, Placebo- and Active-controlled, Parallel-group Analgesic Efficacy Trial of Oral ARRY-371797 in Subjects Undergoing Third Molar Extraction

Conditions
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Dental Pain

Intervention / Treatment
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* Drug: Placebo; oral
* Drug: Placebo; oral
* Drug: ARRY-371797, p38 inhibitor; oral
* Drug: ARRY-371797, p38 inhibitor; oral
* Drug: Celecoxib, COX-2 inhibitor; oral
* Drug: Placebo; oral
* Drug: ARRY-371797, p38 inhibitor; oral


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Scheduled for outpatient oral surgical procedure to remove 3 or more third molars, at least 1 of which is mandibular and fully or partially impacted by bone. Females of childbearing potential must be willing to use an acceptable method of contraception within 14 days prior to first dose of study drug until the completion of the follow-up procedures. Body weight >50 kg (110 lbs). Good health determined by medical history, physical examination, vital signs and clinical laboratory results of non-clinical significance. Additional criteria exist. Key Exclusion Criteria: Evidence or history of clinically significant dermatologic, hematological, renal, endocrine (e.g. poorly controlled diabetes), pulmonary, gastrointestinal, cardiovascular, hepatic, neurologic, ophthalmologic, or allergic disease (including clinically significant drug allergies that could impact the conduct of this study, but excluding untreated, asymptomatic, seasonal allergies at time of study drug dosing). Positive urine drug screen within 28 days prior to first dose of study drug. Use of prohibited prescription drugs, or grapefruit juice within 7 days of first dose of study drug; prohibited medications are defined as nonsteroidal and steroidal antiinflammatory drugs, analgesics including opioids (except low dose aspirin for myocardial infarction prophylaxis), P450 CYP3A substrates or inhibitors (strong or moderate). Additional criteria exist.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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 |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo; oral<br>* dose 1, dose 2<br>|
| Experimental: Placebo, ARRY-371797<br> | Drug: Placebo; oral<br>* dose 1<br>Drug: ARRY-371797, p38 inhibitor; oral<br>* dose 2<br>|
| Experimental: ARRY-371797, Placebo<br> | Drug: ARRY-371797, p38 inhibitor; oral<br>* dose 1: multiple dose levels<br>Drug: Placebo; oral<br>* dose 2<br>|
| Experimental: ARRY-371797<br> | Drug: ARRY-371797, p38 inhibitor; oral<br>* dose 1: multiple dose levels; dose 2<br>|
| Active Comparator: Celecoxib, Placebo<br> | Drug: Celecoxib, COX-2 inhibitor; oral<br>* dose 1<br>Drug: Placebo; oral<br>* dose 2<br>|
| Experimental: Celecoxib, ARRY-371797<br> | Drug: Celecoxib, COX-2 inhibitor; oral<br>* dose 1<br>Drug: ARRY-371797, p38 inhibitor; oral<br>* dose 2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the efficacy of the study drug dosed postoperatively in terms of total pain relief (TOTPAR). |  | 6 hours post-dose | 
| Characterize the safety profile of the study drug in terms of adverse events, clinical laboratory tests, electrocardiograms and vital signs. |  | Duration of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the efficacy of the study drug (versus placebo and celecoxib) in terms of pain relief measurements [including TOTPAR, total pain intensity (TPI) and time to rescue medication]. |  | Duration of study |