Fixed-dose Combination of Etoricoxib + Cyclobenzaprine for Pain Relief After Third Molar Extraction in Brazil

NCT05683574 | Withdrawn Phase 3

• 1 other identifier: EF 181
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Etoricoxib and cyclobenzaprine hydrochloride are active pharmaceutical ingredients (APIs) already registered in the country as mono-drugs. These products are widely used for the proposed indications, and their safety and efficacy profiles are known in daily clinical practice. Once the absence of a pharmacokinetic interaction between etoricoxib and cyclobenzaprine hydrochloride has been confirmed in relative bioavailability studies, this phase 3 study will be conducted for demonstrating the superiority of the new FDC over etoricoxib 90 mg (Arcoxia®) and cyclobenzaprine hydrochloride 15 mg (XL - Mitrul®) in the treatment of moderate to serious pain associated with muscle spasm. The purpose is to provide a new, effective, and safe therapeutic option to address these cases. Etoricoxib and cyclobenzaprine hydrochloride are active pharmaceutical ingredients (APIs) already registered in the country as mono-drugs. These products are widely used for the proposed indications, and their safety and efficacy profiles are known in daily clinical practice. Once the absence of a pharmacokinetic interaction between etoricoxib and cyclobenzaprine hydrochloride has been confirmed in relative bioavailability studies, this phase 3 study will be conducted for demonstrating the superiority of the new FDC over etoricoxib 90 mg (Arcoxia®) and cyclobenzaprine hydrochloride 15 mg (XL - Mitrul®) in the treatment of moderate to serious pain associated with muscle spasm. The purpose is to provide a new, effective, and safe therapeutic option to address these cases.

Conditions

Third Molar Extraction

Outcome Measures

Primary Outcomes (2)

• Primary efficacy variable is composed of the sum of the scores for pain relief within 6 h

  The primary efficacy variable is composed of the sum of the scores for pain relief within 6 hours and the percentage of postoperative mouth opening. After administration of the first dose, participants will rate pain relief on a 5-point categorical scale at hourly intervals (1 hour, 2 hours, 3 hours, 4 hours, 5 hours and 6 hours). Clinical success is defined as very relief (scale 3) or complete relief (scale 4) within 6 hours after treatment administration.

  The primary efficacy variable is an endpoint composed of the sum of pain relief scores within 6 hours and the percentage of postoperative mouth opening.

• Primary Efficacy Endpoint - Mouth opening will be calculated from the average of three measurements

  Mouth opening will be calculated from the average of three measurements that will be taken twice at the randomization visit and at visit 1, the evaluation visit, after three days. The measurement will be made using a calibrated digital caliper, considering the distance between upper and lower central incisors. The percentage of mouth opening at the evaluation visit will be calculated in reference to the baseline opening observed at the randomization visit. Clinical success in this variable is defined as a mouth opening ≥ 80% compared to the preoperative period.

  Clinical success in this variable is defined as a mouth opening ≥ 80% in relation to the preoperative period.

Secondary Outcomes (2)

• Secondary Efficacy Endpoints - Proportion of patients reporting much relief or complete relief in TOTPAR question items within 6 hours

  Proportion of patients reporting much relief or complete relief in TOTPAR question items within 6 hours.

• Secondary Efficacy Endpoints - Proportion of patients who maintained at least 80% of full mouth opening three days after the procedure

  Proportion of patients who maintained at least 80% of full mouth opening three days after the procedure.

Study Arms (3)

etoricoxib 90 mg + cyclobenzaprine 15 mg

EXPERIMENTAL

Investigational group: FDC of etoricoxib 90 mg + cyclobenzaprine 15 mg from Eurofarma Laboratórios SA

Drug: FDC of etoricoxib + cyclobenzaprine + etoricoxib placebo

etoricoxib 90 mg

ACTIVE COMPARATOR

Comparator group: etoricoxib 90 mg (Arcoxia®)

Drug: etoricoxib 90 mg (Arcoxia®) +FDC placebo

cyclobenzaprine hydrochloride 15 mg

ACTIVE COMPARATOR

Comparator group: cyclobenzaprine hydrochloride 15 mg (XL - Mitrul®)

Drug: cyclobenzaprine hydrochloride + etoricoxib placebo

Interventions

FDC of etoricoxib + cyclobenzaprine + etoricoxib placebo DRUG

Participants randomized to this group will receive one (01) capsule of the investigational drug and one (01) etoricoxib placebo tablet, respecting a minimum interval of twenty-four (24) hours between doses for 3 days.

Also known as: Investigation drug 1

etoricoxib 90 mg + cyclobenzaprine 15 mg

etoricoxib 90 mg (Arcoxia®) +FDC placebo DRUG

Participants randomized to this group will receive one (01) etoricoxib 90 mg tablet (Arcoxia®) and one (01) FDC placebo capsule, respecting a minimum interval of twenty-four (24) hours between doses for 3 days.

Also known as: Comparator drug 2

etoricoxib 90 mg

cyclobenzaprine hydrochloride + etoricoxib placebo DRUG

Participants randomized to this group will receive one (01) cyclobenzaprine hydrochloride 15 mg capsule (XL - Mitrul®) and one (01) etoricoxib placebo tablet, respecting a minimum interval of twenty-four (24) hours between doses for 3 days.

Also known as: Comparator drug 3

cyclobenzaprine hydrochloride 15 mg

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients of both sexes who meet all of the following criteria will be included in the study:
• Age between 18 and 35 years (inclusive).
• Impacted lower third molar in vertical or mesioangular position: may be included, as long as it belongs to Pell \& Gregory classes Ia, Ib, IIa or IIb;
• Lower third molar impacted in a horizontal position: may be included, as long as it belongs to Pell \& Gregory classes Ia, Ib or IIa.

You may not qualify if:

• Patients who meet at least one of the following criteria will be excluded from the study:
• Presence of previous inflammatory and/or infectious oral lesion with indication for the use of anti-inflammatory agent and/or antibiotic therapy.
• Presence of any oral lesion in the region of the third molar to be extracted that may contraindicate extraction, at the discretion of the dental team (for example, pericoronitis, periodontitis, cysts, among others).
• Smoking\* \*Any use of tobacco, including e-cigarettes, is prohibited during the study. In the case of the participant who occasionally smokes, he/she must be willing not to use tobacco throughout his/her participation in the study.

Sponsors & Collaborators

• Eurofarma Laboratorios S.A.: lead

Study Sites (1)

Eurofarma Laboratorios S.A

São Paulo, São Paulo, 06696-000, Brazil

Location

MeSH Terms

Interventions

cyclobenzaprine; Etoricoxib

Intervention Hierarchy (Ancestors)

Sulfones; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Comparator Group: etoricoxib 90 mg (Arcoxia®). Participants randomized to this group will receive one (01) etoricoxib 90 mg tablet (Arcoxia®) when postoperative pain intensity reaches moderate to serious intensity (≥ 40 mm at VAS 0-100 mm) and one (01) FDC placebo capsule. The participants will be instructed, from then on, to use this same treatment, respecting a minimum interval of twenty-four (24) hours between doses for 3 days. Comparator Group: cyclobenzaprine hydrochloride 15 mg (XL - Mitrul®). Participants randomized to this group will receive one (01) cyclobenzaprine hydrochloride 15 mg capsule (XL - Mitrul®) (which will be masked inside a capsule like the FDC) when postoperative pain intensity reaches moderate to serious intensity (≥ 40 mm at VAS 0-100 mm) and one (01) etoricoxib placebo tablet. The participants will be instructed, from then on, to use this same treatment, respecting a minimum interval of twenty-four (24) hours between doses for 3 days.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants who meet all eligibility criteria will be randomized to one of the following treatment groups: Investigational group: FDC of etoricoxib 90 mg + cyclobenzaprine 15 mg from Eurofarma Laboratórios SA (investigational drug). Participants randomized to this group will receive one (01) capsule of the investigational drug when postoperative pain intensity reaches moderate to serious intensity (≥ 40 mm at VAS 0-100 mm) and one (01) etoricoxib placebo tablet. The participants will be instructed, from then on, to use this same treatment, respecting a minimum interval of twenty-four (24) hours between doses for 3 days.

Study Record Dates

• First Submitted: December 1, 2022
• First Posted: January 13, 2023
• Study Start (Estimated): May 30, 2026
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): February 28, 2028
• Last Updated: February 28, 2024

Record last verified: 2024-01

Locations

BR (1)