Fixed Dose Combination of COdeine + DIpyrone to Mitigate Moderate to Intense Pain Post-impacted Third Lower Molar Extraction

NCT04972292 | Completed Phase 3

• 1 other identifier: EF174
• Study Type: interventional
• Target: 288
• Locations: 1 country
• Sites: 2

Brief Summary

A clinical, multicenter, randomized, parallel-group, double-blind, double-dummy, comparative study of non-inferiority. ⚠️Study will only be conducted in research centers in Brazil (please do not send e-mail if your center is outside brazil).

Conditions

Pain

Keywords

postoperative; third lower molar extraction

Outcome Measures

Primary Outcomes (1)

• sum of pain relief scores over 6 hours (TOTPAR6)

  After the first study treatment dose is given, subjects will evaluate the pain relief using a 5-point categorical scale (0 = no relief, 1 = little relief, 2 = some relief, 3 = a lot of relief, 4 = complete relief) in 1-hour intervals (1, 2, 3, 4, 5 and 6 hours). The sum of the relief scores over 6 hours determines the TOTPAR6, which ranges from 0 to 24, with a higher score indicating more pain relief.

  6 hours

Secondary Outcomes (1)

• Sum of pain relief scores over four (4) hours (TOTPAR4)

  4 hours

Study Arms (2)

Group 1: FDC of codeine 30 mg/dipyrone 500 mg from Eurofarma Laboratórios SA

EXPERIMENTAL

Subjects randomized to this group will receive one (1) experimental drug tablet + one (1) Tylex® placebo tablet when the postoperative pain becomes moderate to intense (≥ 40 mm at a VAS of 0-100 mm). Then, subjects will be instructed to use the study treatment whenever it is necessary for pain relief, respecting a minimal interval of six (6) hours between two administrations, for up to 3 days (72 hours after the initial dose).

Drug: FDC of codeine 30 mg/dipyrone 500 mg

Group 2: Tylex® (codeine 30 mg/paracetamol 500 mg)

ACTIVE COMPARATOR

Subjects randomized to this group will receive one (1) Tylex® tablet (codeine 30 mg/paracetamol 500 mg) + one (1) FDC placebo tablet when the postoperative pain becomes moderate to intense (≥ 40 mm at a VAS of 0-100 mm). Then, subjects will be instructed to use the study treatment whenever it is necessary for pain relief, respecting a minimal interval of six (6) hours between two administrations, for up to 3 days (72 hours after the initial dose).

Drug: Tylex

Interventions

FDC of codeine 30 mg/dipyrone 500 mg DRUG

Group 1: receive one (1) experimental drug tablet (FCD of codeine 30mg/dipyrone 500mg) + one (1) Tylex® placebo.

Group 1: FDC of codeine 30 mg/dipyrone 500 mg from Eurofarma Laboratórios SA

Tylex DRUG

Group 2: receive one (1) Tylex® tablet (codeine 30 mg/paracetamol 500 mg) + one (1) FDC placebo tablet

Group 2: Tylex® (codeine 30 mg/paracetamol 500 mg)

Eligibility Criteria

• Age: 16 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Aged between 16 and 35 years old (inclusive).
• Maximum surgery duration of 30 minutes, counted from the initial incision to the impacted third molar extraction.
• Moderate to intense postoperative pain (≥ 40 mm at a VAS of 0-100 mm) up to four (4) hours after the end of the surgery (counted from the end of the suture).
• Informed Consent Form (ICF) and Informed Assent Form (IAF) signature, when applicable, before performing any study procedure.

You may not qualify if:

• Known hypersensitivity to dipyrone or to other pirazolones or pirazolidines (e.g.: phenazone, propyphenazone, isopropylaminophenazone, phenylbutazone, oxyphenbutazone), including history of previous agranulocytosis with one of these substances;
• Known hypersensitivity to codeine or to other opioid agents;
• Known hypersensitivity to paracetamol or to any component of the Tylex® formulation;
• Bone marrow function impairment (e.g.: after cytostatic treatment) or hematopoietic system diseases;
• History of bronchospasm or other anaphylactoid reactions (e.g.: hives, rhinitis, angioedema) associated with the use of analgesics, such as salicylates, paracetamol, diclofenac, ibuprofen, indomethacin, naproxen;
• History of significant hypotensive reaction associated with the administration of dipyrone;
• Abuse of illegal drugs, including alcoholism; emotional instability and/or previous attempt of suicide;
• Pregnancy or breastfeeding.
• Women of childbearing potential who do not agree to use a known effective birth control method, unless the participants are surgically sterile or state they are expressly free of the risk of getting pregnant for not having sexual intercourse or for having sexual intercourse with no reproductive potential.
• Participation in a clinical research protocol within the past 12 months, unless the investigator considers that the participation in the study could result in a direct benefit to the subject.
• Presence of any condition that, in the investigator's opinion, would make the subject ineligible to participate in the study.

Sponsors & Collaborators

• Eurofarma Laboratorios S.A.: lead

Study Sites (2)

Eurofarma Laboratórios S.A

Brasil, São Paulo, 06696-000, Brazil

Location

Eurofarma Laboratorios S.A

São Paulo, São Paulo, 06696-000, Brazil

Location

MeSH Terms

Conditions

Pain

Interventions

Dipyrone

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aminopyrine; Pyrazolones; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2021
• First Posted: July 22, 2021
• Study Start: November 8, 2023
• Primary Completion: May 28, 2024
• Study Completion: May 30, 2024
• Last Updated: February 14, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

BR (2)