Efficacy and Safety of TRD205 Tablets for Postoperative Analgesia in Unilateral Total Hip Arthroplasty (Phase IIb)

This study used Active and placebo as a control to explore the efficacy, safety and pharmacokinetic characteristics of multiple administration of different doses of TRD205 tablets for postoperative analgesia after unilateral total hip replacement surgery

• TRD205 Tablets, oral; 400 mg initial dose, then 200 mg q12h for 3 doses; total 4 doses (Drug): First dose 2-4 hours before anesthesia induction; subsequent doses q12h (±4 hours window if nighttime)
• TRD205 Tablets, oral; 800 mg initial dose, then 400 mg q12h; total 4 doses (Drug): First dose 2-4 hours before anesthesia induction; subsequent doses q12h (±4 hours window if nighttime)
• TRD205 Tablets, oral; 1200 mg initial dose, then 600 mg q12h; total 4 doses (Drug): First dose 2-4 hours before anesthesia induction; subsequent doses q12h (±4 hours window if nighttime)
• Celecoxib, oral; 400 mg initial dose, then 200 mg q12h; total 4 doses (Drug): First dose 2-4 hours before anesthesia induction; subsequent doses q12h (±4 hours window if nighttime)
• Matching placebo tablets and capsules, same dosing schedule (Drug): First dose 2-4 hours before anesthesia induction; subsequent doses q12h (±4 hours window if nighttime)

Primary outcomes

• Area under the pain intensity-time curve (AUC0-48h) of resting pain NRS from 0 to 48 hours after surgery [0 to 48 hours after surgery]

Secondary outcomes

• AUC of resting pain NRS at 0-4, 0-6, 0-12, 0-24, 24-48 hours postoperatively [0-4, 0-6, 0-12, 0-24, 24-48 hours postoperatively]
• AUC of movement pain NRS at 0-4, 0-6, 0-12, 0-24, 24-48 hours postoperatively [0-4, 0-6, 0-12, 0-24, 24-48 hours postoperatively]
• Cumulative morphine-equivalent rescue analgesic dose at 0-4, 0-6, 0-12, 0-24, 0-48 hours [0-4, 0-6, 0-12, 0-24, 0-48 hours after surgery]
• Time to first rescue analgesia [Within 48 hours after the surgery, the period from the end of the surgery to the first administration of analgesic medication for relief purposes]
• Number and proportion of participants using rescue analgesia [0-48 hours postoperatively]
• Participant and investigator satisfaction with analgesia with the 5-point scale,the score range from 0 to 4, where 0 indicates poor, 1 indicates average, 2 indicates good, 3 indicates very good, and 4 indicates excellent. [48 hours postoperatively]: At 48 hours after the surgery, the participants and the research doctors respectively evaluated the overall pain relief satisfaction of the test drug used on a 5-point scale, with the score range from 0 to 4, where 0 indicates poor, 1 indicates average, 2 indicates good, 3 indicates very good, and 4 indicates excellent.
• By evaluating security metrics such as AEs, SAEs and TEAEs to evaluate the safety of multiple administration of TRD205 tablets in patients with postoperative analgesia after unilateral hip arthroplasty. [5 days]

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

* Able to provide written informed consent
* Age 18 to 80 years, inclusive
* BMI 18-32 kg/m²
* ASA physical status I-II
* Scheduled for elective unilateral total hip arthroplasty under general anesthesia
* Able to understand study procedures and pain rating scales

Exclusion Criteria:

* Hypersensitivity to TRD205, celecoxib, or study-related medications
* Use of prohibited analgesics, sedatives, CYP3A4 inhibitors/inducers, or analgesic herbs within specified washout periods
* Inability to take oral medications postoperatively
* Ipsilateral hip surgery within 1 year; contralateral hip surgery within 1 month
* Hip revision surgery, developmental dysplasia Crowe type IV, or tumor involving hip
* Clinically significant hemodynamic instability or cardiac arrhythmia
* Severe hepatic, renal, cardiovascular, or metabolic disease
* History of NSAID-induced asthma, active peptic ulcer disease
* Drug or alcohol abuse within 1 year
* Pregnancy, breastfeeding, or lack of effective contraception
* Participation in another interventional clinical trial within 3 months