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)

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