Phase III Study of the Safety and Efficacy of Cl-108 in the Treatment of Moderate to Severe Pain

Study Overview
=================
Brief Summary
-----------------
This is a double-blind, randomized, multiple-dose, placebo- and positive-controlled study of CL-108 (hydrocodone 7.5 mg/APAP 325 mg, promethazine 12.5 mg) in patients with moderate to severe pain following surgical removal of impacted third molar teeth. A positive control ( Norco, a commercial formulation of hydrocodone 7.5 mg/APAP 325 mg) was included to determine the anti-emetic effects of CL-108. The efficacy of CL-108 was also evaluated to placebo for the relief of pain.

Official Title
-----------------
A Double-Blind, Randomized, Placebo-Controlled, Multiple-dose Multi-Center Phase III Study of the Safety and Efficacy of Cl-108 in the Treatment of Moderate to Severe Pain

Conditions
-----------------
Pain, Nausea, Vomiting

Intervention / Treatment
-----------------
* Drug: CL-108 (hydrodocone 7.5 mg, acetaminophen 325 mg, promethazine 12.5 mg)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Determination of being likely or possibly nausea-prone. Male or non-pregnant and non-lactating female. Surgical extraction of at least 2 impacted third molar teeth A female of child-bearing potential is eligible to participate in this study if she has a negative urine pregnancy test and is using an acceptable method of birth control. Surgical extraction of at least 2 impacted third molar teeth. Presence of at least moderate post-operative pain. Exclusion Criteria: Medial Condition, presence of a serious medical condition. Active local infection. Drug Allergy history of hypersensitivity to an Opioid, Promethazine, Acetaminophen. Caffeine use since midnight before the operation. Use of an IND Drug within past 30 days. Previous participation in this study. Pregnant or lactating. Employee of the PI,sub-investigator or Charleston Labs or relative of an employee.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CL-108<br>CL-108 (hydrocodone 7.5 mg, acetaminophen 325 mg, Promethazine 12.5 mg) | Drug: CL-108 (hydrodocone 7.5 mg, acetaminophen 325 mg, promethazine 12.5 mg)<br> <br> * Other names: Placebo;|
| Active Comparator: Norco<br>Commercial product containing hydrocodone 7.5 mg. acetaminophen 325 mg | Drug: CL-108 (hydrodocone 7.5 mg, acetaminophen 325 mg, promethazine 12.5 mg)<br> <br> * Other names: Placebo;|
| Placebo Comparator: Placebo<br>CL-108 formulation without API | Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the occurrence and severity of opioid-induced nausea and vomiting (OINV) associated with CL-108 to Norco. | After data has been locked. | Over the first 24 hours | 
| To demonstrate the efficacy of CL-108 when compared to placebo for the relief of pain following surgical removal of impacted third molar teeth. | After data has been locked. | over 24 hours (SPID24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of the severity of nausea in patients treated with an opioid-containing pain reliever. | After data lock. | over 6 hours | 
| Reduction of vomiting in patients treated with an opioid-containing pain reliever. | After data lock. | over 6 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pain, Nausea, Vomiting