A Double-Blind, Randomized, Active- and Placebo-Controlled, Multiple-Dose Multi-Center Phase 3 Study of the Safety and Efficacy of CL-108 in the Treatment of Moderate to Severe Acute Pain and Opioid-Induced Nausea and Vomiting (OINV)
A Double-Blind, Randomized, Active- and Placebo-Controlled, Multiple-Dose Multi-Center Phase 3 Study of the Safety and Efficacy of CL-108 in the Treatment of Moderate to Severe Acute Pain and Opioid-Induced Nausea and Vomiting (OINV)
The objectives of this study are to compare the occurrence and severity of opioid-induced
 nausea and vomiting (OINV) associated with CL-108 to Norco®, and to demonstrate the efficacy
 of CL-108 when compared to placebo for the relief of moderate to severe pain In patients with
 moderate to severe pain following bunionectomy (osteotomy with fixation of the head of the
 first metatarsal bone).
INCLUSION CRITERIA

 -  Informed Consent: Signed consent obtained at screening prior to any procedures being
 performed.

 -  Gender: Male or non-pregnant and non-lactating female. 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 (i.e., oral,
 transdermal, or implanted contraceptives, intrauterine device, diaphragm, condom,
 abstinence, or surgical sterilization)

 -  Age: 18 years or older

 -  OINV Status: At risk of OINV on the Nausea Prone Questionnaire (NPQ)

 -  Foot Condition: Surgical extraction of a unilateral first metatarsal bunion confirmed
 by foot x-ray (assessed by surgeon prior to surgery)

 -  Pain Severity: Presence of moderate or severe pain (i.e., ≥ 4 on the baseline
 numerical pain intensity rating scale [PI-NRS])

 -  Pain Confirm: Rating ≥ 50 mm on the baseline visual analog pain intensity scale
 (PI-VAS)

 -  Diary Completion: Be willing and able to record safety and efficacy information in the
 In-patient and Outpatient Diaries

 -  Safe Transportation: Patient must have arrangements for transportation home from the
 research center accompanied by a responsible adult

 EXLUSION CRITERIA

 -  Medical Condition: Presence of a serious medical condition (e.g., poorly controlled
 hypertension or diabetes, neurological disease including Parkinson's or other
 condition associated with a movement disorder, significantly impaired cardiac, renal,
 hepatic, respiratory, or thyroid function)

 -  Infection: Acute local infection at the time of surgery that could confound
 post-surgical evaluation.

 -  Drug Allergy: History of hypersensitivity or allergy to an opioid drug such as
 hydrocodone, promethazine, acetaminophen, ondansetron, NSAID (such as ibuprofen,
 including aspirin) or ketorolac or history of a dystonic/dyskinetic reaction to prior
 anti-emetic or anti-psychotic medication

 -  Contraindicated Drugs: Use (within 24 hours of the surgical procedure) of any
 confounding prescription or non-prescription drug (e.g., analgesic, anti-emetic,
 sedating antihistamine, sedative, alcohol, CNS/psychotropic agent, including sleep
 aides, benzodiazepines, performance/attention enhancers, marijuana, anti-depressants)
 or any drug contraindicated with hydrocodone, acetaminophen, or promethazine (except
 for pre-op medications). Antibiotic prophylaxis for endocarditis (except if known to
 cause nausea) and ASA 62.5 mg for cardiovascular prophylaxis are permitted during the
 study.

 -  History of drug or alcohol abuse

 -  Caffeine Use: Ingestion of any caffeine-containing beverage or chocolate since
 mid-night before the operation

 -  Investigation Drug Use: Use of an investigational drug within the past 30 days

 -  Participated in Study:Previous participation in this study

 -  Pregnancy, Lactation: Women who are pregnant or lactating

 -  Participant Relation: Employee at the research center or of Charleston Laboratories or
 relative of the Principal Investigator, Sub-Investigators, or research staff who is
 directly involved in this study