Clinical Trials Logo

Clinical Trial Summary

To assess the safety, efficacy, and pharmacokinetics of oral SafeTynadol, Naldebain and Naldebain combine with SafeTynadol in the treatment of moderate to severe pain following knee replacement.


Clinical Trial Description

Randomized, double-blind, parallel-group, 3-arm, oral Placebo A 650 mg + Naldebain 37.5 mg (0.5 mL oil solution) + Tween 20 and PEG 400 (1 capsule), oral SafeTynadol 650 mg + Placebo B (0.5 mL oil solution) + Tween 20 and PEG 400 (1 capsule), oral Naldebain 37.5 mg (0.5 mL oil solution) + SafeTynadol 650 mg + Tween 20 and PEG 400 (1 capsule), multiple doses for 3 days. Dosing at 0(2 ± 2 hour after surgery), 6 ± 2, 14 ± 2, 22 ± 2, 34 ± 2, 46 ± 2, 58 ± 2 and 70 ± 2 hours after the first dose. The complete evaluable 36 subjects (12 subjects in each group) will be analysis in this study. The experiment is divided into three groups of 12 people each. All subjects will be evaluated pharmacokinetics by drawing blood single point at 70.75 ± 2 hours after the first dose.. The population for this study in patients scheduled for knee replacement. Each group of 12 subjects are administered group 1-3 from day 1-4 after surgery. Dosing at 0(2 ± 2 hour after surgery), 6 ± 2, 14 ± 2, 22 ± 2, 34 ± 2, 46 ± 2, 58 ± 2 and 70 ± 2 hours after the first dose. Mode of administration of oral Naldebain 37.5 mg (0.5 mL oil solution) or Placebo B (0.5 mL oil solution) is withdrawing 0.5 mL of Naldebain 37.5 mg (0.5 mL oil solution) or Placebo B (0.5 mL oil solution) from the vial by a syringe, then is injected into the empty capsule and dispense within 10 minutes prior to dosing. Screening (Days -30 to -1) (All Study Subjects) The nature of the study as well as the potential risks and benefits associated with study participation will be fully explained to all potential subjects. The following will then be obtained: 1. Informed consent. 2. Demographic information, including height and weight. 3. Vital signs (temperature, respiratory rate, blood pressure and heart rate). 4. Medical history, including medication use. 5. Complete physical examination including 12-lead ECG. 6. Laboratory testing (blood 50 ± 5 mL) to include the following: 1. CBC with differential, platelets, White blood cell count (WBC), Red blood cell count (RBC), Hemoglobin, Hematocrit, Mean cell volume (MCV), Mean cell hemoglobin (MCH), Mean cell hemoglobin concentration (MCHC), Platelet count, Differential white cell count. 2. Blood chemistry screen (Glucose, AST, ALT, BUN, creatinine, K, Na, Antibody screening, ABO Grouping & RH Type, Activated partial thromboplastin time, Prothrombin time). 3. Galactose single-point (GSP) test. 4. Urine pregnancy test (female only) (not applicable to female who has stopped menstruating for at least five years). 7. CHEST PA VIEW Study Day -1 Subjects will be required to check into the clinical site before surgery (Day -1). The following procedures will be performed: 1. Physical examination.* 2. Vital signs.* 3. Urine pregnancy test (female only) (not applicable to female who has stopped menstruating for at least five years).* 4. Review of concomitant medications.* 5. Blood (8 ± 3 mL) will be obtained to assess SDE, nalbuphine, AAP and metabolites (AAP-Sul, AAP-Glc, AAP-Cys, AAP-Nac and APAP-protein adducts) concentrations. - If the screening test items are performed in Day -1, the repeat test items only need to be tested once. Study Day 1-4 All subjects will be given regional anesthesia and be preferentially randomized into one of group 1-3. The study drug will be administered 1-4 days after surgery. First dose of study medication is given 2 ± 2 hours after surgery. Total trial drug will be giving eight times. Each group of 12 subjects are administered group 1-3 from day 1-4 after surgery. Group 1: Oral Placebo A 650 mg + Naldebain 37.5 mg (0.5 mL oil solution) + Tween 20 and PEG 400 (1 capsule), multiple doses for 3 days. Dosing at 0(2 ± 2 hour after surgery), 6 ± 2, 14 ± 2, 22 ± 2, 34 ± 2, 46 ± 2, 58 ± 2 and 70 ± 2 hours after the first dose. Group 2: Oral SafeTynadol 650 mg + Placebo B (0.5 mL oil solution) +Tween 20 and PEG 400 (1 capsule), multiple doses for 3 days. Dosing at 0(2 ± 2 hour after surgery), 6 ± 2, 14 ± 2, 22 ± 2, 34 ± 2, 46 ± 25, 58 ± 2 and 70 ± 2 hours after the first dose. Group 3: Oral Naldebain 37.5 mg (0.5 mL oil solution) + SafeTynadol 650 mg + Tween 20 and PEG 400 (1 capsule), multiple doses for 3 days. Dosing at 0(2 ± 2 hour after surgery), 6 ± 2, 14 ± 2, 22 ± 2, 34 ± 2, 46 ± 2, 58 ± 2 and 70 ± 2 hours after the first dose. After surgery, the following evaluations will be performed. 1. Pain assessment: All subjects will assess their average pain intensity using a VAS pain scale. The VAS pain scale assessment will start at 0 ± 0.5, 2 ± 0.5, 4 ± 0.5, 6 ± 2, 10 ± 25, 14 ± 2, 22 ± 2, 28 ± 2, 34 ± 2, 46 ± 2, 52 ± 2, 58 ± 2 and 70 ± 2 hours after the first dose. 2. Blood draw (5 ± 3 mL) for assessment of liver chemistry tests (ALT and AST) at 1 ± 0.5 hours after the first oral administration. If significant hepatotoxicity occurs (ALT or AST level more than 5 folds of ULN (upper limit of normal); or ALT or AST level more than 3 folds of ULN with signs of hepatitis, such as jaundice; or ALT or AST > 1000IU), subject needs to withdraw. 3. VAS score assessed for three times in 5-minut e intervals before giving rescue medication. The VAS score is greater than 7 at least two times. VAS score assessed before giving rescue medication as VAS score for the remaining assessments. 4. When the subject takes the study medication or rescue medication, and request further rescue medication. VAS score assessed for three times in 5-minute intervals before giving rescue medication. The VAS score has to greater than 7 at least two times. Rescue medication will be given in the order of (1) to (2). The interval between rescue medications should be at least 1 hour. 5. If the subject requests rescue medicine, the group 1-3 will receive sequence of rescue medications follow the (1) IV Parecoxib 40 mg Q12H and (2) IV morphine 4 mg Q4H PRN.The above method of administration shall be carried out according to the procedure of administration in the hospital ward. 6. Recorded the first time to IV Parecoxib 40 mg and IV morphine 4 mg, and then the amount and frequency of the medications' use within 72 hours will be recorded. 7. Blood draw (8 ± 3 mL) for assessment of SDE, nalbuphine, acetaminophen and metabolites (AAP-Sul, AAP-Glc, AAP-Cys, AAP-Nac and APAP-protein adducts) concentrations before giving the first time's rescue medicationor termination or withdrawals. 8. Vital signs (temperature, respiratory rate, blood pressure and heart rate) will be checked at 0 ± 0.5, 2 ± 0.5, 4 ± 0.5, 6 ± 2, 10 ± 2, 14 ± 2, 22 ± 2, 28 ± 2, 34 ± 25, 46 ± 2, 52 ± 2, 58 ± 2 and 70 ± 2 hours after the first dose. 9. The evaluation of adverse events will continue until the end of the trial 120 hours after the first dose. 10. Review of concomitant medications. 11. Using Brief Pain Inventory short form (BPIsf) to assess pain intensity and pain interference at 22 ± 2, 46 ± 2 and 70 ± 2 hours after the first dose. On Day 4, following evaluations will be performed: 1. Review of adverse events. 2. Review of concomitant medications. 3. Blood draw (8 ± 3 mL) for assessment of SDE, nalbuphine, acetaminophen and metabolites (AAP-Sul, AAP-Glc, AAP-Cys, AAP-Nac and APAP-protein adducts) concentrations at 70.75 ± 2 hours after the first dose in all subjects and Blood draw (20 ± 3 mL) for CBC with differential, platelets and blood chemistry screen (Not include Antibody screening and ABO Grouping & RH Type determination). The blood collection time is carried out according to the routine blood drawing procedure in the hospital ward. 4. Physical examination, including vital signs and 12-lead ECG. 5. Patient satisfaction. 6. Galactose single-point (GSP) test. Follow-up visit: 24 and 48 hours after the subject took the last medication then researchers conduct telephone interviews to track the overall condition of the subject. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT05842733
Study type Interventional
Source Sinew Pharma Inc.
Contact
Status Enrolling by invitation
Phase Phase 2
Start date July 25, 2023
Completion date December 31, 2024

See also
  Status Clinical Trial Phase
Completed NCT05480111 - The Role of Quadratus Lumborum Blocks Following Minimally Invasive Hysterectomy Phase 4
Completed NCT06129305 - Erector Spina Muscle Distance From the Skin at Different Thoracal Elevations
Completed NCT04401826 - Micro-surgical Treatment of Gummy Smile N/A
Recruiting NCT04020133 - the Role of Popliteal Plexus Block in Pain Management After Anterior Cruciate Ligament Reconstruction. N/A
Completed NCT03023462 - Efficacy of an Anterior Quadratus Lumborum Block vs. a TAP-block for Inguinal Hernia Repair N/A
Completed NCT03652103 - Efficiency of Erector Spinae Plane Block For Patients Undergoing Percutaneous Nephrolithotomy Phase 4
Completed NCT03546738 - Spinal Cord Burst Stimulation for Chronic Radicular Pain Following Lumbar Spine Surgery N/A
Withdrawn NCT03528343 - Narcotic vs. Non-narcotic Pain Regimens After Pediatric Appendectomy Phase 1/Phase 2
Terminated NCT03261193 - ITM + Bupivacaine QLB vs. ITM + Sham Saline QLB for Cesarean Delivery Pain Phase 3
Completed NCT02525133 - Phase 3 Study of Efficacy and Safety of the XaraColl® Bupivacaine Implant After Hernioplasty Phase 3
Completed NCT03244540 - Regional Analgesia After Cesarean Section Phase 4
Enrolling by invitation NCT05316168 - Post Operative Pain Management for ACL Reconstruction Phase 3
Recruiting NCT04130464 - Intraperitoneal Infusion of Analgesic for Postoperative Pain Management Phase 4
Enrolling by invitation NCT04574791 - Addition of Muscle Relaxants in a Multimodal Analgesic Regimen for Analgesia After Primary Total Knee Arthroplasty N/A
Completed NCT04073069 - Scalp Infiltration With Diprospan Plus Ropivacaine for Postoperative Pain After Craniotomy in Adults Phase 4
Completed NCT04526236 - Influence of Aging on Perioperative Methadone Dosing Phase 4
Recruiting NCT05351229 - Intrathecal Morphine for Analgesia in Video-assisted Thoracic Surgery Phase 4
Enrolling by invitation NCT05543109 - Ultrasound Guided Psoas Compartment Block vs Suprainguinal Fascia Iliaca Compartment Block N/A
Completed NCT05346588 - THRIVE Feasibility Trial Phase 3
Completed NCT04919317 - Combination Dexamethasone and Bupivacaine Pain Control in Reduction Mammaplasty Phase 2