Multimodal Analgesia Approach in Acute Low Back Pain Management: A Phase III Study of a Novel Analgesic Combination of Etoricoxib/Tramadol.

INTRODUCTION: Pain and disability management are crucial for a speedy recovery. Combining analgesics with different mechanisms of action provides greater pain relief with lower doses, promoting efficient multimodal analgesia. This study evaluated the efficacy and safety between two fixed-dose combinations (FDC): etoricoxib/tramadol compared to paracetamol/tramadol for the management of acute low back pain (LBP) in a 7-day treatment. METHODS: We conducted a phase IIIb, prospective, randomized, and multicenter study in patients with acute LBP treated with etoricoxib 90 mg/tramadol 50 mg (one packet of granules diluted in 100 ml of water, once a day [QD], for 7 days) or paracetamol 975 mg/tramadol 112.5 mg (one tablet of 325 mg/37.5 mg, three times a day [TID], for 7 days) to assess the efficacy (in terms of pain and disability improvement) and safety. RESULTS: One hundred and twenty-four patients were randomized to receive either etoricoxib/tramadol QD (n = 61) or paracetamol/tramadol TID (n = 63). From the magnitude of change in pain evaluations, differences were observed between the treatment groups at 3 [p = 0.054, CI 95% - 0.648 (- 0.010 to 1.306)] and 5 days (p = 0.041). The proportion of patients with a 30% reduction in Visual Analogue Scale (VAS) score was statistically significant when comparing the treatment groups on the third day of follow-up [p = 0.008, CI 95% 0.241 (0.061-0.421)]. An improvement in LBP's disability to perform activities of daily routine (Oswestry and Roland-Morris questionnaires) was observed in both treatment groups. A total of 79 adverse events (AEs) (38 [48.1%] with etoricoxib/tramadol and 41 [51.9%] with paracetamol/tramadol) were reported. The most frequent AEs were nausea (17.7%) and dizziness (16.4%). CONCLUSIONS: The results show the clinical benefits of etoricoxib/tramadol FDC, such as the sparing effect of tramadol dose per day, early therapeutic response rate compared with paracetamol/tramadol; which translates into faster pain relief, better adherence, less tramadol drug dependency, and a reduction of related AEs incidence. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04968158.

Comparative Bioavailability of a Novel Fixed-dose Combination Etoricoxib and Tramadol.

Multimodal analgesia is defined as using several drugs or techniques simultaneously to target different pain pathways or receptors to avoid pain propagation. This study evaluated the pharmacokinetic profile and comparative bioavailability of etoricoxib 90 mg and tramadol 50 mg dosing alone (reference drugs) or in a novel fixed-dose combination (test drug) under fasting conditions in Mexican healthy volunteers. This was a randomized, open-label, 3-way, crossover, single-dose, prospective, and longitudinal study with a 14-day washout period. Eligible subjects were healthy Mexican adult volunteers. The drugs were dosing orally, according to the randomization sequence, after 10 hours of fasting and 4 hours before breakfast with 250 mL of water at room temperature. Serial blood samples were collected before and after dosing, both drugs were quantified using high-performance liquid chromatography coupled with tandem mass spectrometry. Forty-two subjects were enrolled and 38 completed the study (28 men and 14 women, mean age 25.2 years, mean weight 66.6 kg). Test products were considered to have comparative bioavailability if confidence intervals of natural log-transformed for (maximum plasma drug concentration (Cmax), (area under the plasma drug concentration-time curve form 0 up to last sampling time (AUC0-t), and (area under the plasma drug concentration-time curve from 0 up to infinity (AUC0-∞) data were within the range of 80%-125%. Non-serious adverse events were observed. The results demonstrate that the pharmacokinetic profile and bioavailability of the etoricoxib/tramadol fixed-dose combination are comparable to those of the reference products.

A Randomized Control Trial of Dexketoprofen/Vitamin B (Thiamine, Pyridoxine and Cyanocobalamin) Fixed-Dose Combination in Post-Traumatic Grade I-II Cervical Sprains.

BACKGROUND: Musculoskeletal disorders are an important cause of work absence. Clinical practice guidelines recommend nonsteroidal anti-inflammatory drugs (NSAIDs) for grade I-II cervical sprains. The combination of thiamine + pyridoxine + cyanocobalamin vitamins has been used, alone and in combination with NSAIDs, for pain and inflammation in musculoskeletal disorders. OBJECTIVE: The objective of this study was to demonstrate the analgesic synergy of dexketoprofen, and the combination of vitamins thiamine + pyridoxine + cyanocobalamin in a fixed-dose combination (FDC) for the treatment of acute pain caused by grade I-II cervical sprains. METHODS: We conducted a multicentre, prospective, randomized, double-blind, phase IIIb clinical study comparing two treatment groups: (1) dexketoprofen 25 mg/vitamin B (thiamine 100 mg, pyridoxine 50 mg and cyanocobalamin 0.50 mg) in an FDC (two or more active ingredients combined in a single dosage form) versus (2) dexketoprofen 25 mg monotherapy (single drug to treat a particular disease), one capsule or tablet orally, every 8 h for 7 days. Final mean, average change, and percentage change in pain perception (measured using a visual analogue scale [VAS]) were compared with baseline between groups. A p value < 0.05 was considered statistically significant. Analyses were conducted using SPSS software, v.29.0. RESULTS: A statistically significant reduction in pain intensity was observed from the third day of treatment with the FDC compared with monotherapy (- 3.1 ± - 1.5 and - 2.6 ± - 1.1 cm, respectively) measured using the VAS (p = 0.011). Regarding the degree of disability, using the Northwick Park Neck Pain Questionnaire (NPQ), statistical difference was observed for the final measurement (7.5%, interquartile range [IQR] 2.5, 10.5; vs. 7.9%, IQR 5.0, 13.8; p = 0.028). A lower proportion of adverse events was reported when using the FDC. CONCLUSIONS: The FDC of dexketoprofen/thiamine + pyridoxine + cyanocobalamin vitamins demonstrated superior efficacy and a better safety profile compared with dexketoprofen monotherapy for pain treatment in patients with grade I-II cervical sprains. CLINICAL TRIALS REGISTRATION: NCT05001555, registered 29 July 2021 ( https://clinicaltrials.gov/study/NCT05001555 ).

Real-World Evidence Evaluation on the Lipid Profile, Therapeutic Goals, and Safety of the Fixed-Dose Combination of Rosuvastatin/Ezetimibe (Trezete®) in Dyslipidemia Patients.

Introduction: Cardiovascular diseases are the leading cause of death worldwide. The combination of statins and cholesterol-absorption inhibitors promotes the decrease in risk factors, such as high concentrations of LDL (low-density lipoproteins). The aim of the study was to evaluate changes in the lipid profile and the effect on therapeutic goals, as well as the safety of dyslipidemia patients treated with Rosuvastatin/Ezetimibe (Trezete®). Materials and Methods: A real-world evidence study was conducted with retrospective data collection through a review of clinical records from dyslipidemia patients treated with Trezete® in routine medical practice. Clinical records included results of biochemical markers before treatment and at least one follow up between weeks 8 and 16. Results: The study included 103 patients' clinical records (55.4% men) with a mean age of 56.0 ± 13.0 years. More than 57% of the patients had mixed dyslipidemia and a median disease progression of 3.1 (IQR, 1.5; 9.1) years. Regarding LDL concentrations, 72.8% of the patients achieved therapeutic goals according to cardiovascular risk (CVR), which was statistically significant. Similarly, 94.1% achieved goals for total cholesterol (<200 mg/dL) and 56.0% for triglycerides (<150 mg/dL), a p value <0.001. No cardiovascular events were observed. Conclusion: Trezete® shows an important clinical impact on CVR-related target markers during the treatment of dyslipidemia patients. It is relevant to mention that a significant percentage of patients achieved therapeutic goals during the first months of treatment. Fixed-dose combination therapy has shown to be as safe as monotherapy treatment. ClinicalTrials.gov Identifier: NCT04862962.

Treatment with metformin glycinate reduces SARS-CoV-2 viral load: An in vitro model and randomized, double-blind, Phase IIb clinical trial.

The health crisis caused by the new coronavirus SARS-CoV-2 highlights the need to identify new treatment strategies for this viral infection. During the past year, over 400 coronavirus disease (COVID-19) treatment patents have been registered; nevertheless, the presence of new virus variants has triggered more severe disease presentations and reduced treatment effectiveness, highlighting the need for new treatment options for the COVID-19. This study evaluates the Metformin Glycinate (MG) effect on the SARS-CoV-2 in vitro and in vivo viral load. The in vitro study was conducted in a model of Vero E6 cells, while the in vivo study was an adaptive, two-armed, randomized, prospective, longitudinal, double-blind, multicentric, and phase IIb clinical trial. Our in vitro results revealed that MG effectively inhibits viral replication after 48 h of exposure to the drug, with no cytotoxic effect in doses up to 100 µM. The effect of the MG was also tested against three variants of interest (alpha, delta, and epsilon), showing increased survival rates in cells treated with MG. These results are aligned with our clinical data, which indicates that MG treatment reduces SARS-CoV2-infected patients´ viral load in just 3.3 days and supplementary oxygen requirements compared with the control group. We expect our results can guide efforts to position MG as a therapeutic option for COVID-19 patients.