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

Phase 3
Completed
Conditions
Vomiting
Nausea
Pain
Interventions
Drug: CL-108 5 mg
Drug: Placebo
Registration Number
NCT03657810
Lead Sponsor
Charleston Laboratories, Inc
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
349
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CL-108 5 mgCL-108 5 mgHydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg (CL-108 5 mg) bi-layered tablet
PlaceboPlaceboPlacebo 0 mg matching CL-108
NorcoNorcohydrocodone 5 mg/APAP 325 mg
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With OINV Over 48 HoursUp to 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

The Sum of Pain Intensity Differences (on PI-NRS) Over 48 Hours (SPID48)Up to 48 hours

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".

Secondary Outcome Measures
NameTimeMethod
Number of Doses of Study Medication Taken Over Days 3to7Day3 to Day7

Number of doses of study medication taken over Days 3 to 7

Percentage of Patients With Complete Absence of OINV (no Nausea, no Vomiting, and no Use of Anti-emetic Medication) Over 48 HoursUp to 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)

Percentage of Patients With Any Nausea Over 48 HoursUp to 48 hours

Percentage of patients with any nausea over 48 hours, comparing CL-108 5 mg to hydrocodone 5 mg/APAP 325 mg

Percentage of Patients With Any Nausea or Vomiting Over 48 HoursUp to 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

Percentage of Patients With Any Vomiting Over 48 HoursUp to 48 hours

Percentage of patients with any vomiting over 48 hours, comparing CL-108 5 mg to hydrocodone 5 mg/APAP 325 mg

Number of Doses of Study Medication Taken Per Day Over Days 3to7Day3 to Day7

Number of doses of study medication taken per day over Days 3 to 7

Percentage of Patients With Any Post-discharge Nausea and Vomiting (PDNV)Day 3 to 7

Percentage of patients with any Post-discharge Nausea and Vomiting (PDNV) over Days 3 to 7

Trial Locations

Locations (5)

Arizona Research Center

🇺🇸

Phoenix, Arizona, United States

Chesapeake

🇺🇸

Pasadena, Maryland, United States

Optimal Research

🇺🇸

Austin, Texas, United States

Endeavor Clinical Research

🇺🇸

San Antonio, Texas, United States

Jean Brown Research

🇺🇸

Salt Lake City, Utah, United States

Arizona Research Center
🇺🇸Phoenix, Arizona, United States
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