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

Sponsor

Charleston Laboratories, Inc (Industry)

Overall Status

Completed

CT.gov ID

NCT03657810

Collaborator

(none)

349

Enrollment

Locations

Arms

15.9

Actual Duration (Months)

69.8

Patients Per Site

4.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pain Nausea Vomiting	Drug: CL-108 5 mg Drug: Norco Drug: Placebo	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

349 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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 Acute Pain and the Prevention of Opioid-Induced Nausea and Vomiting (OINV)

Actual Study Start Date :

Aug 2, 2017

Actual Primary Completion Date :

Apr 16, 2018

Actual Study Completion Date :

Nov 30, 2018

Arms and Interventions

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
Active Comparator: Norco hydrocodone 5 mg/APAP 325 mg	Drug: Norco hydrocodone 5 mg/APAP 325 mg
Placebo Comparator: Placebo Placebo 0 mg matching CL-108	Drug: Placebo Placebo matching CL-108

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

Active Comparator: Norco

hydrocodone 5 mg/APAP 325 mg

Drug: Norco

hydrocodone 5 mg/APAP 325 mg

Placebo Comparator: Placebo

Placebo 0 mg matching CL-108

Drug: Placebo

Placebo matching CL-108

Outcome Measures

Primary Outcome Measures

OINV endpoint: Occurrence of any vomiting over 48 hours, comparing CL-108 5 mg to hydrocodone 5 mg/acetaminophen (APAP) 325 mg [Up to 48 hours]
Vomiting Frequency Scale (VFS), a 0-to-3 ordinal scale to assess the occurrence of vomiting
OINV endpoint: Use of antiemetic over 48 hours, comparing CL-108 5 mg to hydrocodone 5 mg/acetaminophen (APAP) 325 mg [Up to 48 hours]
Uses of antiemetic documented as they occur.
The sum of pain intensity differences over 48 hours (SPID48), comparing CL-108 5 mg to placebo [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 Numerical Pain Intensity Rating Scale (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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Research Center	Phoenix	Arizona	United States	85023
2	Chesapeake	Pasadena	Maryland	United States	21122
3	Optimal Research	Austin	Texas	United States	78705
4	Endeavor Clinical Research	San Antonio	Texas	United States	78240
5	Jean Brown Research	Salt Lake City	Utah	United States	84124