Poster Number-74 - CELECOXIB-TRAMADOL HYDROCHLORIDE CO-CRYSTAL IN PATIENTS WITH MODERATE-TO-SEVERE PAIN FOLLOWING BUNIONECTOMY WITH OSTEOTOMY: SECONDARY ANALYSES OF A PHASE 3, RANDOMIZED, DOUBLE-BLIND, FACTORIAL, ACTIVE- AND PLACEBO-CONTROLLED TRIAL

Poster Abstracts

Author(s)

EV

Eugene R. Viscusi, MD

Professor of Anesthesiology, Chief of Pain Medicine, and Director, Acute Pain Management
Sidney Kimmel Medical College of Thomas Jefferson University
Philadelphia, Pennsylvania
Od

Oscar de Leon-Casasola, MD

Senior VC/Prof. of Anesthesiology and Medicine/Chief, Div of Pain Medicine and Prof. of Oncology
University of Buffalo/Roswell Park Cancer Institute
Buffalo, New York
CS

Craig Sponseller, MD

Chief Medical Officer
Kowa Pharmaceuticals America, Inc.
Montgomery, Alabama
JC

Jesús Cebrecos, MD

Clinical Investigation Physician
ESTEVE Pharmaceuticals S.A.
Barcelona, Catalonia, Spain
AJ

Adam Jacobs, PhD

Senior Director, Biostatistics
Premier Research
Reading, England, United Kingdom
AM

Adelaida Morte, MD

Clinical Investigation Physician
ESTEVE Pharmaceuticals S.A.
Barcelona, Catalonia, Spain
EO

Esther Ortiz, RN

Clinical Trial Coordinator & Monitor
ESTEVE Pharmaceuticals S.A.
Barcelona, Catalonia, Spain
MS

Mariano Sust, MD

Clinical Biostatistician
ESTEVE Pharmaceuticals S.A.
Barcelona, Catalonia, Spain
AV

Anna Vaqué, MD

Medical Drug Safety Officer & back up EUQPPV
ESTEVE Pharmaceuticals S.A.
Barcelona, Catalonia, Spain
IG

Ira Gottlieb, DPM

Principal Investigator and Medical Director
Chesapeake Research Group LLC
Pasadena, Maryland
SD

Stephen Daniels, DO

Director of Medical Operations (retired)
Optimal Research LLC
Austin, Texas
DM

Derek Muse, MD

Doctor of Medicine
JBR Clinical Research
Salt Lake City, Utah
MK

Michael E. Kuss, BS MT(ASCP)

Vice President: Analgesia
Premier Research
Austin, Texas
SV

Sebastián Videla, MD

Clinical Research Physician
ESTEVE Pharmaceuticals S.A.
Barcelona, Catalonia, Spain
NG

Neus Gascón, MD

Global Drug Safety & PV Head EU QPPV
ESTEVE Pharmaceuticals S.A.
Barcelona, Catalonia, Spain
CP

Carlos Plata-Salamán, MD

External Advisor
ESTEVE Pharmaceuticals S.A.
Barcelona, Catalonia, Spain

CELECOXIB-TRAMADOL HYDROCHLORIDE CO-CRYSTAL IN PATIENTS WITH MODERATE-TO-SEVERE PAIN FOLLOWING BUNIONECTOMY WITH OSTEOTOMY: SECONDARY ANALYSES OF A PHASE 3, RANDOMIZED, DOUBLE-BLIND, FACTORIAL, ACTIVE- AND PLACEBO-CONTROLLED TRIAL

Purpose: Celecoxib and tramadol hydrochloride (Seglentis^®; CTC) is the first co‑crystal analgesic for acute pain and received US Food and Drug Administration approval in October 2021.¹ CTC provided greater analgesia than comparable doses of tramadol hydrochloride or celecoxib in the Phase 3 SUSA-301 trial (NCT03108482).² Here, we present post hoc secondary analyses.

Methods: SUSA-301 was a randomized, double-blind, factorial trial conducted at six US clinical research centers. Adults with acute moderate-to-severe pain following bunionectomy with osteotomy were randomized to oral CTC (200 mg [88 mg tramadol hydrochloride/112 mg celecoxib] every 12 hours [q12h]; n=184), tramadol hydrochloride (50 mg every 6 hours; n=183), celecoxib (100 mg q12h; n=181), or placebo (n=89) for 48 hours. Rescue medication use was permitted. First-line rescue medication was 1 g of intravenous acetaminophen every 4–6 hours as needed, up to 4 g in 24 hours. Second-line rescue medication was 5 mg of immediate-release oral oxycodone every 4–6 hours as needed, up to 30 mg in 24 hours. Rescue medication use was analyzed via two-sided Pearson chi-square test.

Results: Significantly lower proportions of patients in the CTC group, versus other groups, used rescue pain medication within 4 hours post-dose (CTC: 91 [49.5%]; tramadol hydrochloride: 113 [61.7%]; celecoxib: 118 [65.2%]; placebo: 67 [75.3%]; P=0.0178, P=0.0024, and P=0.0001 vs tramadol hydrochloride, celecoxib, and placebo, respectively), including oxycodone (CTC: 27 [14.7%]; tramadol hydrochloride: 48 [26.2%]; celecoxib: 61 [33.7%]; placebo: 31 [34.8%]; P=0.0061, P< 0.0001, and P=0.0001 vs tramadol hydrochloride, celecoxib, and placebo, respectively). A similar pattern occurred within 48 hours, irrespective of baseline pain intensity.
Among patients who used rescue medication, fewer in the CTC group required ≥3 doses, irrespective of baseline pain intensity. For patients with moderate baseline pain, 29.2%, 51.1%, 54.6%, and 57.2% of those in the CTC, tramadol hydrochloride, celecoxib, and placebo groups, respectively, required ≥3 doses of rescue medication. For patients with severe baseline pain, this was 40.0%, 60.3%, 66.3%, and 70.2%, respectively.
Adverse event (AE) incidence by age (< 65 vs ≥ 65 years) differed between groups. In those aged < 65 years, treatment-emergent AEs (TEAEs) occurred in 63.4%, 62.9%, 53.6%, and 57.3% of those taking CTC, tramadol hydrochloride, celecoxib, and placebo, respectively. For those aged ≥65 years, TEAE incidence was 63.6%, 66.7%, 37.5%, and 57.1%, for CTC, tramadol hydrochloride, celecoxib, and placebo, respectively. The incidence of TEAEs related to study drug was highest for tramadol hydrochloride in both age groups. TEAEs of special interest (confusion, constipation, difficulty with urination, dizziness, dry mouth, fatigue, headache, inability to concentrate, itching, nausea, somnolence, vertigo, and vomiting) were also highest for tramadol hydrochloride in both age groups. AE incidence was generally unaffected by the use of rescue or antiemetic medication.

Conclusion: CTC is associated with less rescue medication use than tramadol hydrochloride or celecoxib alone in acute moderate-to-severe pain, and is well tolerated by adults under 65 years and those 65 years and older.

References: 1. Seglentis® (celecoxib and tramadol hydrochloride) US prescribing information (last updated Oct 2021).
2. Viscusi ER et al. Pain Pract 2022 Jun 10. Epub ahead of print. doi: 10.1111/papr.13136.

Learning Objectives:

Describe the differences in rescue medication requirements for patients with acute moderate-to-severe pain following bunionectomy with osteotomy receiving celecoxib tramadol hydrochloride co-crystal versus those receiving reference products alone
Outline the differential adverse event profile of celecoxib-tramadol hydrochloride co-crystal versus that of tramadol hydrochloride or celecoxib
Understand the benefit/risk profile of celecoxib-tramadol hydrochloride co-crystal versus reference products alone in acute pain management, both in patients under 65 years and in those 65 years and older