Dataset Information

Driving Ability in Patients with Severe Chronic Low Back or Osteoarthritis Knee Pain on Stable Treatment with Tapentadol Prolonged Release: A Multicenter, Open-label, Phase 3b Trial.

ABSTRACT:

Introduction

Strong centrally acting analgesics, including tapentadol prolonged release (PR), have demonstrated efficacy for the management of non-malignant, chronic pain. Maintaining patient independence, including the ability to drive safely, is a key goal of long-term analgesic therapy. This multicenter, open-label, phase 3b trial evaluated the effects of tapentadol PR on driving ability.

Methods

This study included patients who had completed previous tapentadol PR trials for severe low back or osteoarthritis pain. After at least 6 weeks of dose stability, patients continued taking tapentadol PR (50-250 mg twice daily) and could take supplemental immediate-release tapentadol 50 mg, except on the day before or day of the driving test (before the test). Pain intensity was assessed using an 11-point numerical rating scale. The Vienna Test System-Traffic Plus was used to assess cognitive and psychomotor function. The key surrogate parameter for driving ability was a global judgment based on 6 battery tests.

Results

Thirty-eight patients enrolled and completed the trial, and 35 patients completed all 6 tests. Pain scores remained unchanged from enrollment to final visit [mean (standard deviation) change, -0.2 (1.0)]. Approximately two-thirds [65.7% (23/35)] of patients were classified as fit to drive based on the global judgment of driving-specific ability [34.3% (12/35) not fit to drive]. Total daily tapentadol PR dose (>200 vs. ≤200 mg/day) did not affect global judgment of driving ability (P = 0.4885). Two adverse events (considered unrelated to study drug) were reported.

Conclusion

Results suggest that most patients receiving a stable dose of tapentadol PR for severe, chronic pain would be able to drive, consistent with earlier studies evaluating stable treatment with strong opioids. Study design limitations and needs for individual patient assessment must be considered in clinical practice.

SUBMITTER: Sabatowski R

PROVIDER: S-EPMC4108021 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:This open-label, phase 3b study (ClinicalTrials.gov Identifier: NCT00983073) evaluated the effectiveness, and tolerability of tapentadol for severe, chronic osteoarthritis knee pain that was inadequately managed with World Health Organization (WHO) Step I or II analgesics or co-analgesics, or that was not treated with regular analgesics. Prior to starting study treatment, patients discontinued any WHO Step II analgesics, while Step I analgesics and/or co-analgesics were continued at the same dose. Patients received tapentadol prolonged release (50-250 mg bid) during a 5-week titration period and a 7-week maintenance period. Doses of tapentadol immediate release 50 mg (≤twice/day; ≥4 hours apart) were permitted throughout the study (total daily dose of tapentadol prolonged and immediate release, ≤250 mg bid). The primary endpoint was the change in pain intensity on an 11-point numerical rating scale-3 (NRS-3; recalled average pain intensity [11-point NRS] during the last 3 days) from baseline to Week 6, using the last observation carried forward (LOCF) to impute missing pain intensity scores. The mean (standard deviation) change from baseline to Week 6 (LOCF) in pain intensity was -3.4 (2.10; P < 0.0001) for all patients evaluated for effectiveness (n = 195). Significant decreases in pain intensity were also observed at Weeks 6, 8, and 12 (all P < 0.0001) using observed-case analysis. Corresponding significant improvements from baseline to Weeks 6 and 12 were observed in the Western Ontario and McMaster Universities osteoarthritis index, the EuroQol-5 Dimension health status questionnaire, the Short Form-36 health survey, and the Hospital Anxiety and Depression Scale (all P ≤ 0.0103). Treatment-emergent adverse events were in line with those observed in previous studies of tapentadol prolonged release. Overall, the results of this study indicate that tapentadol treatment results in significant improvements in pain intensity, health-related quality of life, and function in patients with inadequately managed, severe, chronic osteoarthritis knee pain.

Project description:INTRODUCTION:The aim of this work is to assess the safety and efficacy of repeat administration of triamcinolone acetonide extended-release (TA-ER) in patients with symptomatic knee osteoarthritis (OA), including those with advanced radiographic severity. METHODS:In this phase 3b, single-arm, open-label study, patients aged ≥ 40 years received the first intra-articular TA-ER injection on day 1. Patients received the second injection timed to the response to the first injection (at either week 12, 16, 20, or 24). Patients who received two injections were evaluated every 4 weeks for 52 weeks. Safety was evaluated via treatment-emergent adverse events and any change at 52 weeks in index-knee radiographs (chondrolysis, osteonecrosis, insufficiency fractures, subchondral bone changes). Exploratory efficacy endpoints included Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)-A (pain), -B (stiffness), -C (function), and Knee Injury and Osteoarthritis Outcome Score-Quality of Life (KOOS-QoL) after each injection. Initiative in Methods, Measurements and Pain Assessment in Clinical Trials (IMMPACT) criteria were used to determine moderate and substantial treatment response. RESULTS:A total of 208 patients were enrolled and received the first injection of TA-ER; 179 (86.1%) received the second injection (median time to second injection: 16.6 weeks). Both injections were well tolerated, with no unexpected adverse events or significant radiographic changes at week 52. The magnitude and duration of clinical benefit after the first and second injections were similar, and most patients reported a substantial (≥ 50%) analgesic response after both doses. CONCLUSIONS:Repeat administration of TA-ER using a flexible dosing schedule timed to patient response was well tolerated, with no radiographic evidence of cartilage impact. Both injections resulted in similar improvements in OA symptoms across a broad spectrum of disease severity reflective of that seen in clinical practice. TRIAL REGISTRATION INFORMATION:ClinicalTrials.gov identifier: NCT03046446. FUNDING:Flexion Therapeutics, Inc. Plain language summary available for this article.

Project description:BackgroundTapentadol prolonged release (PR; 100-250 mg twice daily) has been efficacious and well tolerated for managing moderate-to-severe, chronic osteoarthritis hip or knee pain in phase 3 studies with washout of previous analgesic treatment.ObjectiveThe objective of this study was to evaluate the effectiveness and tolerability of tapentadol PR (50-250 mg twice daily) after direct rotation from World Health Organization (WHO) step III opioids in patients with severe osteoarthritis knee pain who previously responded to WHO step III therapy but showed poor tolerability.MethodsThis open-label, phase 3b study (NCT00982280) was conducted from October 2009 through June 2010 (prematurely terminated due to slow recruitment and study drug shortages) in clinical care settings in Europe and Australia. The study population included patients with severe, chronic osteoarthritis knee pain who had taken WHO step III opioids daily for ?2 weeks before screening, responded to therapy (average pain intensity [11-point numerical rating scale-3 (NRS-3)] ?5 at screening), and reported opioid-related adverse effects as their reason for changing analgesics. Patients switched directly from WHO step III therapy to tapentadol. Patients received oral tapentadol PR (50-250 mg twice daily) during 5-week titration and 7-week maintenance periods. Oral tapentadol immediate release (IR) was permitted (?twice/day, ?4 h apart) for acute pain episodes due to index pain or withdrawal symptoms following discontinuation of previous opioids (combined dose of tapentadol [PR and IR] ?500 mg/day). This study was planned to evaluate conversion to tapentadol PR, based on responder rate 1 (percentage of patients with same/less pain [NRS-3] versus Week -1) at Week 6 (primary endpoint), adverse events (AEs), and discontinuation rates. Equianalgesic ratios were calculated for tapentadol prior to WHO step III opioids (PR and PR plus IR formulations).ResultsOf 82 patients enrolled, 63 received study medication. In the per-protocol population, responder rate 1 at Week 6 (last observation carried forward) was 94.3 % (50/53; P < 0.0001 vs. the null hypothesis rate [<60 %]). Mean (standard deviation) pain intensity scores were 4.7 (0.66) at baseline, 2.5 (1.46) at Week 6, and 1.8 (1.41) at Week 12 in the main analysis population (change from baseline at Weeks 6 and 12, P < 0.0001). Tapentadol to transdermal buprenorphine equianalgesic ratios (PR [n = 48], 262.9:1; PR plus IR [n = 48], 281.1:1) and tapentadol to oral oxycodone equianalgesic ratios (PR [n = 4], 4.3:1; PR plus IR [n = 6], 4.6:1) were calculated for the main analysis population. In the safety population, prevalence of AEs reported as associated with prior opioids at Week -1 (reasons for rotation) and related to tapentadol treatment at Week 12 decreased over time; the most common were nausea (46.0 vs. 24.1 %) and constipation (31.7 vs. 7.4 %). Overall, 14.3 % of patients discontinued the study early; reasons included AEs (9.5 %), lack of efficacy (3.2 %), and withdrawal of consent (1.6 %).ConclusionsSignificant improvements in effectiveness were observed for tapentadol PR (50-250 mg twice daily) versus WHO step III opioids in patients with severe, chronic osteoarthritis knee pain who previously responded to WHO step III therapy. Equianalgesic ratios were calculated for tapentadol to transdermal buprenorphine and oral oxycodone and were in line with observations from previous phase 3 studies.

Project description:PurposeInvestigation of the efficacy and safety of tapentadol prolonged release (PR) compared with morphine PR for long-term treatment of pain in children.Patients and methodsChildren aged 6 to <18 years requiring long-term treatment with opioids were studied in a 12-month, 2-part, multi-center trial: Part 1, 14-day open-label, randomized, active-controlled, parallel group non-inferiority trial comparing twice daily tapentadol PR with morphine PR; Part 2, open-label treatment with tapentadol PR for up to 12 months or no treatment "safety observation period". Pain intensity was rated with visual analogue scale or Faces Pain Scale-Revised, and non-inferiority was assessed by comparison of "treatment responders" (those completing the 14-day treatment period and showing pre-defined changes in pain rating) in each group.ResultsTwenty-three of 48 centers enrolled 73 patients. In Part 1, 45 and 24 patients received tapentadol or morphine, respectively, of which 40 and 22 completed 14-day treatment. In Part 2, thirty-six and 58 patients entered the tapentadol PR or observation periods, respectively, with 20/36 completing at least 12 weeks of treatment; 10 of the 36 had received morphine in Part 1. Forty-four of the 58 patients in the safety observation period had received tapentadol. Tapentadol PR was non-inferior to morphine PR (lower limit of confidence interval above negative non-inferiority margin of -0.2) in Part 1. Rates of adverse events were as expected with nausea (22.2%) and constipation (15.6%) in the tapentadol PR group, and with vomiting (33.3%), nausea and constipation (each 16.7%) in the morphine PR group. No new safety issues were identified; the safety profile of tapentadol over the 12 months treatment and observation periods was comparable to that established in subjects >18 years old.ConclusionTapentadol PR was well tolerated and equivalent to morphine PR for both efficacy and safety in children (6 to <18 years old) requiring long-term treatment with opioids.

Project description:BackgroundOsteoarthritis (OA) and lower back pain (LBP) are most common health problems which lead to pain and disability. This study aimed to systematically review the evidence to find any relationship between knee osteoarthritis (KOA) and LBP or any potential causation.MethodsThe databases of Scopus, MEDLINE, and Embase were searched from inception to 01 October 2022. Any study published in English assessing live humans over 18 years with KOA and LBP was eligible to be included. Studies were independently screened by two researchers. Data of the included studies were extracted based on the participants, outcomes related to knee and lumbar spine, reported association or causation between LBP and KOA, and study design. Data were narratively analyzed and presented as graphs and table. Methodology quality was assessed.ResultsOf 9953 titles and abstracts, duplicates were removed, and 7552 were screened. Altogether, 88 full texts were screened, and 13 were eligible for the final inclusion. There were some biomechanical and clinical causations were observed for the concurrent presence of LBP and KOA. Biomechanically, high pelvic incidence is a risk factor for development of spondylolisthesis and KOA. Clinically, knee pain intensity was higher in KOA when presents with LBP. Less than 20% of studies have justified their sample size during the quality assessment.DiscussionDevelopment and progression of KOA in patients with degenerative spondylolisthesis may be induced by significantly greater mismatches of lumbo-pelvic sagittal alignment. Elderly patients with degenerative lumbar spondylolisthesis and severe KOA reported a different pelvic morphology, increased sagittal malalignment with a lack of lumbar lordosis due to double-level listhesis, and greater knee flexion contracture than in patients with no to mild and moderate KOA. People with concurrent LBP and KOA have reported poor function with more disability. Both LBP and lumbar kyphosis indicate functional disability and knee symptoms in patients with KOA.ConclusionsDifferent biomechanical and clinical causations were revealed for the concurrent existence of KOA and LBP. Therefore, careful assessment of both back and knee joints should be considered when treating KOA and vice versa.Systematic review registrationPROSPERO CRD42022238571.

Project description:Purpose: High dose monotherapies or drug combinations are used to achieve sufficient analgesia for the treatment of severe chronic low back pain, before invasive therapy options are considered. In order to demonstrate an alternative for an empirical treatment approach, the authors' primary aim was to present an algorithm for the objective identification of treatment predictors. Additionally, the study identified baseline-characteristics in chronic low back pain patients prior to tapentadol PR treatment, as well as scrutinized those patients, either benefitting from a medium/high dose tapentadol PR monotherapy or a combination therapy (medium dose tapentadol PR + pregabalin). Patients and Methods: The statistical approach included data of a previously published randomized, double blind, phase 3b study which compared the effectiveness and safety of tapentadol PR vs. a combination of tapentadol PR and pregabalin. In total, 46 clinical parameters were included in the statistical prediction models which were applied separately either to 50 patients who already responded well during the titration period (i.e., medium dose tapentadol PR) or to 261 patients with in the comparative treatment period [i.e., monotherapy (high dose tapentadol PR) or combination therapy (medium dose tapentadol PR/pregabalin)]. Results: The first statistical model identified three co-variables (NRS-3, PDQ, SQ) with predictive effects on patients responding well ("optimal responders") to a medium dose tapentadol PR titration. Those patients presented low baseline pain intensity scores, good sleep quality and high painDETECT scores. The second statistical model identified eight co-variables (PDQ, numbness, SF-12 MCS, SF-12 PCS, VAS, HADS-A, HADS-D, SQ) with predictive effects on patients responding to high dose tapentadol PR monotherapy vs. a combination therapy (tapentadol PR + pregabalin). The high dose tapentadol PR responders indicated high painDETECT scores, little numbness and a good mental health status. Whereas, the combination therapy (tapentadol PR + pregabalin) responders were characterized by severe sleep disturbances and little anxiety. Conclusion: The statistical analysis characterized chronic low back pain patients and identified factors contributing to a treatment response. Thus, this retrospective statistical algorithm represents an elegant method, which may contribute to future strategies toward a more individualized and improved mechanism based pain therapy.

Project description:This study determined whether injection with hypertonic dextrose and morrhuate sodium (prolotherapy) using a pragmatic, clinically determined injection schedule for knee osteoarthritis (KOA) results in improved knee pain, function, and stiffness compared to baseline status.This was a prospective three-arm uncontrolled study with 1-year follow-up.The setting was outpatient.The participants were 38 adults who had at least 3 months of symptomatic KOA and who were in the control groups of a prior prolotherapy randomized controlled trial (RCT) (Prior-Control), were ineligible for the RCT (Prior-Ineligible), or were eligible but declined the RCT (Prior-Declined).The injection sessions at occurred at 1, 5, and 9 weeks with as-needed treatment at weeks 13 and 17. Extra-articular injections of 15% dextrose and 5% morrhuate sodium were done at peri-articular tendon and ligament insertions. A single intra-articular injection of 6?mL 25% dextrose was performed through an inferomedial approach.The primary outcome measure was the validated Western Ontario McMaster University Osteoarthritis Index (WOMAC). The secondary outcome measure was the Knee Pain Scale and postprocedure opioid medication use and participant satisfaction.The Prior-Declined group reported the most severe baseline WOMAC score (p=0.02). Compared to baseline status, participants in the Prior-Control group reported a score change of 12.4±3.5 points (19.5%, p=0.002). Prior-Decline and Prior-Ineligible groups improved by 19.4±7.0 (42.9%, p=0.05) and 17.8±3.9 (28.4%, p=0.008) points, respectively; 55.6% of Prior-Control, 75% of Prior-Decline, and 50% of Prior-Ineligible participants reported score improvement in excess of the 12-point minimal clinical important difference on the WOMAC measure. Postprocedure opioid medication resulted in rapid diminution of prolotherapy injection pain. Satisfaction was high and there were no adverse events.Prolotherapy using dextrose and morrhuate sodium injections for participants with mild-to-severe KOA resulted in safe, significant, sustained improvement of WOMAC-based knee pain, function, and stiffness scores compared to baseline status.