CompletedNCT03657810Updated Mar 22, 2023Results posted

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

A Phase 3 interventional study of CL-108 5 mg and Norco in Pain, Nausea and Vomiting, sponsored by Charleston Laboratories, Inc. Completed at 5 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-03-22.

Sponsored by Charleston Laboratories, Inc · Phase 3, Interventional, and Treatment

From the registry’s dates

Registered 4 months after the study started (first participant enrolled Aug 2017, registered Dec 2017).

Phase: Phase 3
Study type: Interventional
Enrollment: 349
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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.

Read the 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.

Conditions studied

Pain
Nausea
Vomiting

Browse trials for

Keywords

Pain
Nausea
Vomiting

In context

Nausea

822 studies on the registry are indexed under Nausea; 104 are open to participants now.

This study's enrollment of 349 is above the median of 115 across 703 interventional studies indexed under Nausea.

Browse Nausea studies →

Lead sponsor

Charleston Laboratories, Inc is the lead sponsor of 6 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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

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

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 349 participants (actual)

Study arms

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

Interventions

DrugCL-108 5 mg
hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg
Also known as: hydrocodone bitartrate/ acetaminophen/ promethazine hydrochloride
DrugNorco
hydrocodone 5 mg/APAP 325 mg
Also known as: hydrocodone bitartrate/ acetaminophen
DrugPlacebo
Placebo matching CL-108
Also known as: Matching Placebo

What researchers measure

Primary outcomes

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
Time frame: 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".
Time frame: Up to 48 hours

Secondary outcomes

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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Day3 to Day7

Results

Posted Mar 22, 2023

Participant flow

This was a Phase 3, double-blind, randomized, placebo- and active-controlled, multiple-dose study conducted at different research centers in the United States

Participant flow — Overall Study
Milestone	CL-108	Norco	Placebo
Started	87	90	44
Completed	82	86	41
Not completed	5	4	3
Withdrew: Adverse event	0	1	0
Withdrew: Lack of efficacy	4	1	3
Withdrew: Protocol violation	1	0	0
Withdrew: Lost to follow-up	0	1	0
Withdrew: Not provided	0	1	0

Outcome measures

PrimaryPercentage 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

Time frame:: Up to 48 hours
Reported as:: Count of participants · Participants

Percentage of Participants With OINV Over 48 Hours
Participants	CL-108	Norco	Placebo
Percentage of Participants With OINV Over 48 Hours	8	31	4

Statistical analysis

CL-108 vs Norco · Regression, Logistic · p = <0.001 (Type III P-Value are from the likelihood ration test from the logistic regression model with factors of treatment, gender, and investigator.)

PrimaryThe 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".

Time frame:: Up to 48 hours
Reported as:: Mean · score on a scale

The Sum of Pain Intensity Differences (on PI-NRS) Over 48 Hours (SPID48)
score on a scale	CL-108	Norco	Placebo
The Sum of Pain Intensity Differences (on PI-NRS) Over 48 Hours (SPID48)	108.5 ± 80.66	94.8 ± 69.53	78.7 ± 62.66

Statistical analysis

CL-108 vs Norco · Regression, Logistic · p = 0.052 (Type III P-Value are from the likelihood ration test from the logistic regression model with factors of treatment, gender, and investigator)

SecondaryPercentage 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)

Time frame:: Up to 48 hours
Reported as:: Count of participants · Participants

Percentage of Patients With Complete Absence of OINV (no Nausea, no Vomiting, and no Use of Anti-emetic Medication) Over 48 Hours
Participants	CL-108	Norco	Placebo
Percentage of Patients With Complete Absence of OINV (no Nausea, no Vomiting, and no Use of Anti-emetic Medication) Over 48 Hours	50	34	27

SecondaryPercentage 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

Time frame:: Up to 48 hours
Reported as:: Count of participants · Participants

Percentage of Patients With Any Vomiting Over 48 Hours
Participants	CL-108	Norco	Placebo
Percentage of Patients With Any Vomiting Over 48 Hours	3	19	2

SecondaryPercentage 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

Time frame:: Up to 48 hours
Reported as:: Count of participants · Participants

Percentage of Patients With Any Nausea Over 48 Hours
Participants	CL-108	Norco	Placebo
Percentage of Patients With Any Nausea Over 48 Hours	36	55	15

SecondaryPercentage 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

Time frame:: Up to 48 hours
Reported as:: Count of participants · Participants

Percentage of Patients With Any Nausea or Vomiting Over 48 Hours
Participants	CL-108	Norco	Placebo
Percentage of Patients With Any Nausea or Vomiting Over 48 Hours	37	55	16

SecondaryPercentage 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

Time frame:: Day 3 to 7
Reported as:: Count of participants · Participants

Percentage of Patients With Any Post-discharge Nausea and Vomiting (PDNV)
Participants	CL-108	Norco	Placebo
Percentage of Patients With Any Post-discharge Nausea and Vomiting (PDNV)	9	12	6

SecondaryNumber of Doses of Study Medication Taken Over Days 3to7

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

Time frame:: Day3 to Day7
Reported as:: Mean · doses

Number of Doses of Study Medication Taken Over Days 3to7
doses	CL-108	Norco	Placebo
Number of Doses of Study Medication Taken Over Days 3to7	10.0 ± 7.05	8.4 ± 7.30	6.2 ± 5.70

SecondaryNumber 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

Time frame:: Day3 to Day7
Reported as:: Mean · doses per day

Number of Doses of Study Medication Taken Per Day Over Days 3to7
doses per day	CL-108	Norco	Placebo
Number of Doses of Study Medication Taken over Day 3	3.0 ± 1.60	2.4 ± 1.83	2.1 ± 1.59
Number of Doses of Study Medication Taken over Day 4	2.1 ± 1.65	1.9 ± 1.70	1.4 ± 1.45
Number of Doses of Study Medication Taken over Day 5	1.9 ± 1.81	1.7 ± 1.73	1.1 ± 1.40
Number of Doses of Study Medication Taken over Day 6	1.8 ± 1.77	1.5 ± 1.72	1.0 ± 1.16
Number of Doses of Study Medication Taken over Day 7	1.1 ± 1.46	0.9 ± 1.29	0.6 ± 1.06

Adverse events

Collected over Up to Visit 3 (Approximately 8 days after surgery). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
CL-108	0/87 (0%)	1/87 (1.1%)	80/87 (92%)
Norco	0/90 (0%)	0/90 (0%)	79/90 (87.8%)
Placebo	0/44 (0%)	0/44 (0%)	37/44 (84.1%)

Most frequent serious events

Most frequent serious events
Event	CL-108	Norco	Placebo
DEEP VEIN THROMBOSIS RIGHT CALFVascular disorders	1/87	0/90	0/44

Most frequent other events

Showing 10 of 72

Most frequent other events
Event	CL-108	Norco	Placebo
NauseaGastrointestinal disorders	38/87	54/90	17/44
SomnolenceNervous system disorders	46/87	40/90	9/44
Dry mouthGastrointestinal disorders	31/87	16/90	8/44
HeadacheNervous system disorders	22/87	26/90	12/44
ConstipationGastrointestinal disorders	23/87	24/90	4/44
PruritusSkin and subcutaneous tissue disorders	23/87	21/90	8/44
DizzinessNervous system disorders	22/87	23/90	6/44
VomitingGastrointestinal disorders	3/87	20/90	3/44
Disturbance in attentionNervous system disorders	10/87	7/90	3/44
DiarrhoeaGastrointestinal disorders	2/87	1/90	5/44

Baseline characteristics

Safety Population: All randomized patients who received at least 1 dose of study medication constituted the Safety Population.

Age, Continuous
Age, Continuous(years)	CL-108	Norco	Placebo	Total
Mean	43.3 ± 12.97	43.5 ± 14.74	47.2 ± 13.40	44.2 ± 13.82

Sex: Female, Male
Sex: Female, Male(Participants)	CL-108	Norco	Placebo	Total
Female	75	77	40	192
Male	12	13	4	29

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	CL-108	Norco	Placebo	Total
Hispanic or Latino	27	22	9	58
Not Hispanic or Latino	60	68	35	163
Unknown or Not Reported	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	CL-108	Norco	Placebo	Total
American Indian or Alaska Native	0	0	2	2
Asian	1	2	1	4
Native Hawaiian or Other Pacific Islander	1	0	0	1
Black or African American	12	12	8	32
White	69	73	33	175
More than one race	2	2	0	4
Unknown or Not Reported	2	1	0	3

Region of Enrollment
Region of Enrollment(participants)	CL-108	Norco	Placebo	Total
United States	87	90	44	221

Weight
Weight(kg)	CL-108	Norco	Placebo	Total
Mean	79.19 ± 23.427	74.56 ± 18.054	81.86 ± 18.827	77.83 ± 20.592

Height
Height(cm)	CL-108	Norco	Placebo	Total
Mean	164.94 ± 9.457	165.09 ± 9.133	164.45 ± 8.256	164.90 ± 9.060

BMI
BMI(kg/m^2)	CL-108	Norco	Placebo	Total
Mean	28.88 ± 6.876	27.29 ± 5.549	30.26 ± 6.358	28.51 ± 6.333

Study locations

5 sites

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

References and documents

Study documents

Protocol and statistical analysis plan · Aug 17, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Mar 22, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03657810
Lead sponsor: Charleston Laboratories, Inc
Responsible party: Sponsor
First posted: Sep 5, 2018
Start date: Aug 2, 2017
Primary completion: Apr 16, 2018
Completion: Nov 30, 2018
Results posted: Mar 22, 2023
Last update: Mar 22, 2023

Study contacts

Bernard Schachtel, MD

study director · Charleston Laboratories, Inc

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Feb 2023. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Nausea→

Other studies from this sponsor

Charleston Laboratories, Inc

Start the discussion