Oral appliance therapy (OAT) for treating obstructive sleep apnea (OSA) is one of the cornerstones of OSA management and requires multidisciplinary care management. When complete, the study will provide data on the use of the Panthera D-SAD, a CAD/CAM, 3D printed biocompatible nylon oral appliance. The primary endpoint of at least a ≥50% reduction in baseline apnea-hypopnea index (AHI) will be evaluated at five years, with interim sleep data at 3-6 months. The study fulfills French reimbursement requirements. OAT naïve individuals with an AHI of 15-30 or those with severe OSA (AHI > 30) who decline CPAP and meet all other criteria will be included. Sites will follow the standard of care in France. Fifteen centers will enroll 217 participants via consecutive sampling. Participants will be medically and dentally evaluated. Evaluation time points are three to six months (sleep testing/medical), annual check-in, and five years (both). Secondary endpoints include side effects, oxygenation metrics, quality of life, self-reported adherence, and subjective symptoms. Ethics approval obtained. Enrollment is complete (N=257). Baseline demographics n=239 (mean/SD): Age 50.7 (12.8), BMI 26.6 (4.7), M 51%, AHI 22.7 (9.0), ODI 17.0 (11.4), lowest SpO2 84.6% (6.8), ESS >10, 42.4% (n=198). Change from baseline sleep respiratory variables at 3-6 Mos (n=179): a mean decrease in AHI of 10.5 (8.1) and an AHI reduction ≥ 50% in 60.3%. Additionally, 87.8% of moderate and 83.4% of severe transitioned to a lower AHI classification. ODI decreased to 9.7 (8.4). Subjective usage was sustained >4 hrs./night at six months in 94.8% of participants and 91.9% at one year (n=76), averaging 6.4 nights per week, demonstrating sustained adherence. Treatment satisfaction was 85.8% at three months. The mean ESS decreased from 9.1 (5.3) to 7.4 (4.8). The ≥50% AHI reduction was not influenced by BMI categories or gender, (p= 0.813 and 0.694, respectively). These data demonstrate a reduction in total mean AHI with a substantial transition migration to a less severe AHI category. High OAT acceptance and adherence were found. In this sample, the percentage of patients whose AHI decreased by at least 50% does not differ between the subgroups. Panthera Dental Inc.
TPS7097 Background: Relapsed/refractory (R/R) aggressive B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), remain challenging to treat, particularly in patients who have exhausted approved therapies. BTM-3566, a novel compound demonstrated efficacy against diverse B-cell malignancies, with the most pronounced impact observed in DLBCL and MCL. BTM-3566 initiates the mitochondrial ATF-4-mediated integrated stress response (ISR) pathway via a unique mechanism governed by the mitochondrial protein FAM210B. In vitro, BTM-3566 induces apoptosis across multiple hematological and solid tumor cell lines with several in vivo models demonstrating tumor regression or significant tumor growth inhibition. This includes complete tumor regressions in DLBCL and MCL patient-derived xenograft (PDX) mouse models carrying genetic alterations linked to unfavorable prognosis such as double hit (DH) and triple hit lymphoma (TH) and MCL PDX models from patients previously treated with CAR T, rituximab, venetoclax and/or BTK inhibitors. Methods: This ongoing Phase 1, single-arm, open-label, multi-center trial is evaluating the safety, tolerability, and preliminary efficacy of BTM-3566 in adult patients with mature B-cell lymphomas. Eligible participants must have histologically confirmed mature B cell lymphoma that has progressed after at least two prior lines of systemic therapy. BTM-3566 is administered orally in two weeks cycles (7 days on, 7 days off). Primary endpoints include incidence of dose-limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs). Secondary and exploratory endpoints include objective response rate (ORR), duration of response (DoR), progression-free survival (PFS) pharmacokinetics and pharmacodynamic assessments. Enrollment is scheduled to start in Q1 2025 in US and Canada. Clinical trial information: NCT06792734 .
Background: This study assessed the clinical effects of a ventilatory assist (VA) device in addition to supplemental O2 (VA+O2) on exercise endurance in subjects with severe to very severe COPD managed with long-term oxygen therapy (LTOT). Methods: This was a crossover clinical feasibility study of the effects of VA+O2 in subjects with severe to very severe COPD managed with LTOT (N = 15). At visit 1, physiologic measures were obtained, and subjects were tested on the cycle ergometer with VA. Peak work rate and flow for continuous supplemental O2/VA+O2 were established. At visit 2, subjects exercised at a constant work rate of 80% peak work rate to maximum endurance after allocation to VA+O2 or O2. Cardiorespiratory variables, work rate, and dyspnea were included to define potential clinical benefits of VA+O2. Data were analyzed using a linear mixed model. Results: Fifteen subjects with COPD (mean +/- SD, age 67.9 +/- 9.0 y, FEV1 0.89 +/- 0.35 observed) completed the study. Exercise duration in minutes was significantly longer with VA+O2 versus O2 (least squares mean [standard error], 12.0 [2.0] vs 6.2 [2.0], P = .01). VA+O2 versus O2 was also associated with significantly greater isotime improvements in Borg dyspnea scores (3.6 [0.5] vs 5.7 [0.5], P < .001), SpO2 (96.9 [0.9] vs 91.4 [0.9], P < .001), leg fatigue scores (3.8 [0.6] vs 5.2 [0.6], P = .008), and breathing frequency (22.8 [0.9] vs 25.8 [0.9] breaths/min, P = .01). There were no differences in heart rate. Conclusions: In symptomatic subjects with severe to very severe COPD, VA+O2 significantly increased exercise time and improved dyspnea, SpO2 , breathing frequency, and leg fatigue versus O2 alone.
What is this summary about? This is a plain language summary of an article published in the journal Clinical Pharmacology in Drug Development . It is about a study of a medicine called vibegron . Vibegron is approved by the US Food and Drug Administration (also called the FDA) to treat overactive bladder, also known as OAB. It may be easier for people with swallowing issues to take a pill by crushing it and mixing it with applesauce instead of swallowing it whole. Researchers did this study to find out if vibegron could be safely crushed and mixed with applesauce. Participants took vibegron that was either crushed or intact, and researchers compared how much vibegron made it into the bloodstream over time. The researchers asked whether people who took crushed vibegron had more unwanted medical events (called adverse events) than people who took vibegron as an intact pill. What were the results? Crushed vibegron tablets did not change in applesauce for 4 h at room temperature. Just over half of the participants (53%) said that the taste was not different than expected. The amount of vibegron in blood over time was similar between those who took crushed vibegron and those who took intact vibegron . The most common adverse events were headache, constipation, and nausea. No participant experienced a serious adverse event during the study, meaning that no adverse events required hospital care or caused permanent damage or disability. Adverse events that might be related to vibegron occurred in seven participants (23%) after they took crushed vibegron and six participants (20%) after they took the intact pill. What do the results mean? The results of this study show that vibegron can be crushed and taken with applesauce without increases in adverse events compared to taking the intact pill. Crushed vibegron did not change in applesauce and the amount of vibegron in blood over time was similar when vibegron was crushed in applesauce or taken whole. This means that people may take vibegron as a crushed or intact pill for overactive bladder. This may be particularly important for people with difficulty swallowing. Who should read this article? This article is for people with overactive bladder symptoms who have a hard time swallowing pills. It may also be helpful for their families and care partners, and for health care professionals who care for people with overactive bladder. Where can I find the original article on which this summary is based? The original article is called “Pharmacokinetics and Safety of Vibegron 75 mg Administered as an Intact or Crushed Tablet in Healthy Adults.” You can read the original article published in Clinical Pharmacology in Drug Development at this link: • https://accp1.onlinelibrary.wiley.com/doi/10.1002/cpdd.1169
