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

A Randomized, Double-Blind, Placebo- and Active-Controlled Study to Determine the Efficacy and Safety of CL-108 5 mg (Hydrocodone 5 mg/Acetaminophen 325 mg/Promethazine 12.5 mg) as a Treatment for Moderate-to-Severe Acute Pain and the Prevention of Opioid-Induced Nausea and Vomiting (OINV) Following Orthopedic Surgery

To determine the analgesic efficacy of CL-108 5 mg by comparison with placebo and the anti-emetic efficacy of CL-108 5 mg by comparison with hydrocodone 5 mg/acetaminophen 325 mg.

Study Overview

• Status: Completed
• Conditions: Pain; Nausea; Vomiting
• Intervention / Treatment: Drug: CL-108 5 mg; Drug: Norco; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 349
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85023
      • Arizona Research Center
  • Maryland
    • Pasadena, Maryland, United States, 21122
      • Chesapeake
  • Texas
    • Austin, Texas, United States, 78705
      • Optimal Research
    • San Antonio, Texas, United States, 78240
      • Endeavor Clinical Research
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Jean Brown Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CL-108 5 mg; Hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg (CL-108 5 mg) bi-layered tablet	Drug: CL-108 5 mg; hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg; Other Names: hydrocodone bitartrate/ acetaminophen/ promethazine hydrochloride
Active Comparator: Norco; hydrocodone 5 mg/APAP 325 mg	Drug: Norco; hydrocodone 5 mg/APAP 325 mg; Other Names: hydrocodone bitartrate/ acetaminophen
Placebo Comparator: Placebo; Placebo 0 mg matching CL-108	Drug: Placebo; Placebo matching CL-108; Other Names: Matching Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With OINV Over 48 Hours	Number and Percentage of participants With opioid-induced nausea and vomiting (OINV) who experienced any Vomiting / use of Anti-Emetic Medication Over 48 Hours	Up to 48 hours
The Sum of Pain Intensity Differences (on PI-NRS) Over 48 Hours (SPID48)	The SPID48 endpoint is calculated from the PI-NRS values at baseline, every 30 minutes until hour 12, then every hour (when awake) until hour 48 as follows: Each subsequent PI-NRS value is subtracted from the baseline PI-NRS value.; Each difference is weighted by the elapsed time from the previous PI-NRS value to the current one.; The weighed differences are summed to yield the SPID48. Summed pain intensity differences over 48 hours (SPID48) will be compared for patients treated with CL-108 5 mg and those treated with placebo. Pain intensity will be measured on a 0-10 Pain Intensity Numerical Rating Scale (PI-NRS), where 0 is "no pain" and 10 is "severe pain".	Up to 48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With Complete Absence of OINV (no Nausea, no Vomiting, and no Use of Anti-emetic Medication) Over 48 Hours	Percentage of patients with complete absence of OINV (no nausea, no vomiting, and no use of anti-emetic medication) over 48 hours comparing CL-108 5 mg to hydrocodone 5 mg/APAP 325 mg)	Up to 48 hours
Percentage of Patients With Any Vomiting Over 48 Hours	Percentage of patients with any vomiting over 48 hours, comparing CL-108 5 mg to hydrocodone 5 mg/APAP 325 mg	Up to 48 hours
Percentage of Patients With Any Nausea Over 48 Hours	Percentage of patients with any nausea over 48 hours, comparing CL-108 5 mg to hydrocodone 5 mg/APAP 325 mg	Up to 48 hours
Percentage of Patients With Any Nausea or Vomiting Over 48 Hours	Percentage of patients with any nausea or vomiting over 48 hours, comparing CL-108 5 mg to hydrocodone 5 mg/APAP 325 mg	Up to 48 hours
Percentage of Patients With Any Post-discharge Nausea and Vomiting (PDNV)	Percentage of patients with any Post-discharge Nausea and Vomiting (PDNV) over Days 3 to 7	Day 3 to 7
Number of Doses of Study Medication Taken Over Days 3to7	Number of doses of study medication taken over Days 3 to 7	Day3 to Day7
Number of Doses of Study Medication Taken Per Day Over Days 3to7	Number of doses of study medication taken per day over Days 3 to 7	Day3 to Day7

Collaborators and Investigators

• Sponsor: Charleston Laboratories, Inc

Publications and helpful links

Helpful Links

• Charleston Website

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2017
• Primary Completion (Actual): April 16, 2018
• Study Completion (Actual): November 30, 2018

Study Registration Dates

• First Submitted: December 5, 2017
• First Submitted That Met QC Criteria: August 31, 2018
• First Posted (Actual): September 5, 2018

Study Record Updates

• Last Update Posted (Actual): March 22, 2023
• Last Update Submitted That Met QC Criteria: February 24, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Pain; Nausea; Vomiting
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Signs and Symptoms, Digestive; Nausea; Vomiting; Acute Pain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antipyretics; Dermatologic Agents; Analgesics, Opioid; Narcotics; Respiratory System Agents; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Antitussive Agents; Acetaminophen; Promethazine; Oxycodone; Hydrocodone; Acetaminophen, hydrocodone drug combination
• Other Study ID Numbers: CLCT-018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No