Tramadol/Diclofenac Fixed-dose Combination Phase III Trial in Acute Pain After Third Molar Extraction

NCT03714672 | Completed Phase 3 Results

• 2 other identifiers: KF8001-01U1111-1179-2333
• Study Type: interventional
• Target: 1,151
• Locations: 1 country
• Sites: 8

Brief Summary

This study evaluated a new drug fixed-dose combination tablet (FDC) called tramadol/diclofenac at two different strengths (fixed doses of 25 milligrams \[mg\] of tramadol and of diclofenac or of 50 mg each). Tramadol and diclofenac each relieve pain, but they do so by different mechanisms. They were used alone as comparator drug in this study. Both are marketed drugs and are standard treatment for acute pain, including wisdom tooth removal.

Conditions

Acute Pain

Keywords

Wisdom tooth removal; Dental pain

Outcome Measures

Primary Outcomes (1)

• Pain Relief Expressed as Total Pain Relief (TOTPAR) Over the 4 Hours Post-dose Period (TOTPAR4)

  Pain relief was assessed by the participant at defined time points after the first IMP dose using a 5-point verbal rating scale (VRS) with categories 0 (none), 1 (a little), 2 (some), 3 (a lot), or 4 (complete). Total Pain Relief (TOTPAR4) is a time-weighted summary measure of the total area under the pain relief curve that integrates serial assessments of a participant's pain over the duration of 4 hours after IMP intake. Minimum and maximum values for TOTPAR4 were 0=worst score and 16=best score, a higher score indicates more pain relief.

  Up to 4 hours after first dose

Secondary Outcomes (9)

• Total Pain Relief at 6 Hours Post-dose (TOTPAR6)

  Up to 6 hours after first dose

• Total Pain Relief at 8 Hours Post-dose (TOTPAR8)

  Up to 8 hours after first dose

• Summed Pain Intensity Difference (SPID) at 4, 6, 8, and 24 Hours Post-dose

  Baseline; up to 24 hours after first dose

• Time to Achieve a 50 Percent Reduction in Baseline Pain (Pain at Least Half Gone)

  Up to 24 hours after first dose

• Time to Onset of First Perceptible Pain Relief

  Up to 8 hours after first dose

Study Arms (4)

Tramadol/Diclofenac 50/50

EXPERIMENTAL

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 50 mg/50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Drug: Tramadol/Diclofenac 50/50

Tramadol/Diclofenac 25/25

EXPERIMENTAL

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 25 mg/25 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Drug: Tramadol/Diclofenac 25/25

Tramadol 50

ACTIVE COMPARATOR

Participants received 3 doses of tramadol hydrochloride 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Drug: Tramadol 50

Diclofenac 50

ACTIVE COMPARATOR

Participants received 3 doses of diclofenac sodium 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction

Drug: Diclofenac 50

Interventions

Tramadol/Diclofenac 50/50 DRUG

Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Also known as: Adorlan Forte (Registered Trademark)

Tramadol/Diclofenac 50/50

Tramadol/Diclofenac 25/25 DRUG

Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Also known as: Adorlan (Registered Trademark)

Tramadol/Diclofenac 25/25

Tramadol 50 DRUG

Each dose comprised 1 capsule containing 50 mg tramadol hydrochloride and 3 placebo tablets matching the other active treatment groups. Doses were taken 8 hours apart.

Also known as: Tramadol immediate-release capsule, Tradol (Registered Trademark)

Tramadol 50

Diclofenac 50 DRUG

Each dose comprised 1 tablet containing 50 mg diclofenac sodium and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Also known as: Voltaren (Registered Trademark) (diclofenac enteric-coated tablet)

Diclofenac 50

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female participants above 18 years up to 60 years.
• Female participants of childbearing potential must be practicing an acceptable method of birth control and must have a negative urine pregnancy test at enrollment with confirmation at the Allocation Visit.
• Participants are in good health, i.e., the medical record, vital signs, physical examination, and laboratory parameter assessments do not show any abnormal deviations impeding the participation in the clinical study.
• Participants requiring extraction of 3 or more third molars with 2 mandibular impacted third molars.
• Clinical and radiological diagnosis of impacted lower third molars.
• Class I and Class II molars according to Pell and Gregory's classification (Gay Escoda et al. 2004).
• Participants must be able to swallow the IMPs.

You may not qualify if:

• Findings in the medical record, vital signs, and/or physical examination demonstrating abnormal conditions of participant's general state of health preventing his/her participation in the clinical study according to the investigator's opinion.
• Participant unable to speak, read, or write in Spanish language.
• Clinical laboratory parameters exceed the pre-defined alert ranges (i.e., 1 standard deviation above or below the upper/lower limit of the normal ranges).
• Known hypersensitivity to the IMPs, the anesthetic to be used during surgery, or to the rescue medication (ibuprofen, ketorolac).
• Known alcohol or drug abuse in the last 6 months or any history of seizures. Alcohol abuse is defined as the consumption of more than 3 ounces (about 90 milliliters) of liquor or spirits or 18 ounces (about 530 milliliters) of beer per day, for 5 consecutive days during the 6-month period. Drug abuse is defined as the use of any recreational drug for 5 consecutive days during the 6 month period.
• Participants who take analgesic medication for chronic pain, monoamine oxidase inhibitors, tricyclic antidepressants, neuroleptics, or other drugs that reduce the seizure threshold within 4 weeks of enrollment.
• Pregnant or lactating women.
• Participants who received systemic corticosteroids or opioid analgesics less than 2 weeks before surgery.
• Participants with molars linked to the mandibular canal.
• Participants requiring immediate dental procedures other than third and fourth molars extraction,
• Participant received a long-acting non-steroidal anti-inflammatory drug within 24 hours or 5 times the elimination half-life of that drug prior to surgery, whatever the longer.
• Participant received any analgesic medication other than short-acting pre-operative or intra-operative anesthetic agents within 24 hours before taking IMPs.
• Participant received more than 300 mg of lidocaine in total.
• Participant received any analgesic medication other than the IMPs immediately after the oral surgical procedure was completed.
• Baseline pain intensity of the participant after oral surgical procedure remains below 5 points on the 11-point NRS.

Sponsors & Collaborators

• Grünenthal GmbH: lead
• Grünenthal, S.A.: collaborator

Study Sites (8)

Private Clinic

Zapopan, Jalisco, CP 45030, Mexico

Location

Private Clinic

Monterrey, Nuevo León, CP 64000, Mexico

Location

Private Clinic

Monterrey, Nuevo León, CP 64718, Mexico

Location

Private Clinic

Aguascalientes, CP 20230, Mexico

Location

Private Clinic

Chihuahua City, CP 31203, Mexico

Location

Private Clinic

León, CP 37160, Mexico

Location

Private Clinic

Puebla City, CP 72160, Mexico

Location

University

San Luis Potosí City, CP 78290, Mexico

Location

Related Publications (1)

• Gay Escoda C, Piñera Penalva M, Velasco Vivancos V, Berini Aytés L. Cordales incluidos. Patología, clínica y tratamiento del tercer molar incluído. In: Gay Escoda C, Berini Aytés L. (eds.). Tratado de Cirugía Bucal. Tomo I. Madrid: Ergón; 2004. p. 355-85

  BACKGROUND

MeSH Terms

Conditions

Acute Pain; Toothache

Interventions

Tramadol; Diclofenac

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Tooth Diseases; Stomatognathic Diseases; Facial Pain

Intervention Hierarchy (Ancestors)

Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Dimethylamines; Methylamines; Amines; Lipids; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids

Results Point of Contact

• Title: Clinical Trial Helpdesk
• Organization: Grünenthal GmbH

clinical-trials@grunenthal.com

+49 241 569

Study Officials

• Grünenthal Study Director

  Grünenthal GmbH

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This study used double-blind and double-dummy methods to guarantee the blinding of all personnel involved in the study. Participants, investigators, and all persons involved in the conduct, data management, and analysis of the study were fully blinded to the participant's treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2018
• First Posted: October 22, 2018
• Study Start: August 26, 2017
• Primary Completion: March 9, 2018
• Study Completion: March 22, 2018
• Last Updated: July 24, 2019
• Results First Posted: July 24, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR

Locations

ME (8)