A Controlled Study to Determine the Efficacy and Safety of CL-108 5 mg as a Treatment for Acute Pain and the Prevention of OINV

Adult patients with moderate or severe pain after bunionectomy will be randomized to CL-108 5
mg (hydrocodone 5 mg/acetaminophen 325 mg/ promethazine 12.5 mg), hydrocodone 5 mg/
acetaminophen 325 mg, or placebo under double-blind conditions. Over 48 hours they will use
the assigned study medication and assess pain intensity, nausea, and vomiting. Uses of
supplementary analgesic and antiemetic medications will be documented. Patient responses and
adverse effects will also be documented during the 5-day outpatient period, too.

Inclusion Criteria:

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

- Gender: Male or non-pregnant and non-lactating female.

- Age: 18 years or older at time of consent.

- Foot condition: Primary unilateral first metatarsal bunionectomy (osteotomy and
internal fixation) with no additional collateral procedures.

- Pain Severity: Presence of moderate or severe pain on a categorical pain intensity
scale at Baseline

- Pain Confirmation: On the 0-10 numerical pain intensity scale at Baseline.

- Diary Completion: Be willing and able to record safety and efficacy ratings in the
Diaries.

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

Exclusion Criteria:

- Medical condition: Presence of a serious medical condition, intolerance to NSAIDs, or
any other medical condition which, in the opinion of the Investigator, makes the
patient unsuitable for participation.

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

- Drug Allergy: History of hypersensitivity to an opioid drug (such as hydrocodone),
promethazine, acetaminophen, NSAID (such as ibuprofen or aspirin), midazolam,
propofol, mepivacaine, ropivacaine or ketorolac.

- Confounding and Contraindicated Drugs: Other than protocol-permitted medications
administered pre-operatively or during surgery: use within 14 days before or during
the surgical procedure of any systemic corticosteroid or use within 24 hours or during
the surgical procedure of any confounding prescription or non-prescription drug or any
drug contraindicated with hydrocodone, acetaminophen, or promethazine. [Note:
Antibiotic for endocarditis prophylaxis (except if known to cause nausea) and aspirin
(ASA) ≤ 325 mg for cardiovascular prophylaxis are permitted during the study.] History
of consuming more than 2 alcoholic drinks per day every day for the last month or a
positive urine test for opiates, benzodiazepines, barbiturates, tetrahydrocannabinol,
methamphetamines, cocaine, oxycodone, cotinine at screening or the morning of surgery
will exclude the patient from the trial.

- Investigational 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.

- Compliance: Inability to swallow capsules whole.

- Participant relationship: Employee at the research center, employee of the Principal
Investigator, Sub-Investigators, or sponsor or relative of the Investigator,
Sub-Investigators or research staff who is involved in this study.