Purdue Pharma (United States)

In today's world, with an increasing patient population, the need for medications is increasing rapidly. However, the current practice of drug development is time-consuming and requires a lot of investment by the pharmaceutical industries. Currently, it takes around 8-10years and $3 billion of investment to develop a medication. Pharmaceutical industries and regulatory authorities are continuing to adopt new technologies to improve the efficiency of the drug development process. However, over the decades the pharmaceutical industries were not able to accelerate the drug development process. The pandemic (COVID-19) has taught the pharmaceutical industries and regulatory agencies an expensive lesson showing the need for emergency preparedness by accelerating the drug development process. Over the last few years, the pharmaceutical industries have been collaborating with artificial intelligence (AI) companies to develop algorithms and models that can be implemented at various stages of the drug development process to improve efficiency and reduce the developmental timelines significantly. In recent years, AI-screened drug candidates have entered clinical testing in human subjects which shows the interest of pharmaceutical companies and regulatory agencies. End-end integration of AI within the drug development process will benefit the industries for predicting the pharmacokinetic and pharmacodynamic profiles, toxicity, acceleration of clinical trials, study design, virtual monitoring of subjects, optimization of manufacturing process, analyzing and real-time monitoring of product quality, and regulatory preparedness. This review article discusses in detail the role of AI in various avenues of the pharmaceutical drug development process, its limitations, regulatory and future perspectives.

Potent synthetic opioids such as fentanyl and its analogues now account for most opioid overdose deaths in the United Stated (US). To help combat this development, Food and Drug Administration (FDA)-approved doses of the opioid overdose reversal agent naloxone and use of multiple naloxone administrations by emergency medical services (EMS) have increased. To determine whether use of multiple naloxone administrations was similarly increasing in emergency departments (EDs) by investigating recent trends in ED naloxone use. A retrospective claims-based cohort study using data from the Merative MarketScan® and the National Emergency Department Sample (NEDS) databases was conducted. The percentage of patients who received multiple naloxone administrations during their first ED visit in the analysis period (MarketScan) and percentage of ED visits with multiple naloxone administrations (NEDS) were calculated with 95% confidence intervals. Time trends were analyzed by 2-sided Cochran-Armitage trend tests. Among MarketScan patients who received naloxone in the ED, the percentage who received multiple naloxone administrations was 14.7% across the years 2016 to 2022 and increased 72.8% from 10.1% to 17.4%. (p < 0.01). Similarly, the percentage of NEDS ED visits with multiple naloxone administrations among visits where naloxone was administered was 6.3% in 2016 to 2021 and increased 146.7% from 3.0% to 7.3% (p < 0.01). A small but growing percentage of ED patients require multiple naloxone administrations, highlighting the need to monitor this trend and the ongoing adequacy of current treatment options for managing opioid intoxication.

People living with chronic pain may use wearable health technology (WHT) in conjunction with an expert-directed pain management program for up to 1 year. WHT use may be associated with improvements in key patient outcomes. A 12-month study of WHT use among people with chronic pain was conducted, consisting of iPhone and Apple Watch applications to measure movement, sleep, and self-reported pain. Clinical outcomes among 105 patients enrolled in a multidisciplinary pain program that included WHT use were compared with 146 patients in the same program but without WHT, and to 161 patients receiving medical pain management without WHT. Participants used the WHT on average 143.0 (SD: 117.6) out of 365 days. Mixed-effects models revealed participants who used WHT had decreases in depression scores (-7.83, P <0.01) and prescribed morphine milligram equivalents (-21.55, P =0.04) over 1 year. Control groups also showed decreases in depression scores (-5.08, P =0.01; -5.68, P <0.01) and morphine milligram equivalents (-18.67, P =0.01; -10.99, ns). The estimated slope of change among the WHT was not statistically different than control groups. Patients who used WHT as part of their pain management program demonstrated a willingness to do so for extended periods of time despite living with chronic pain and other comorbidities. Data trends suggest that WHT use may positively impact depression and prescribed medication. Additional research is warranted to investigate the potential of WHT to improve the negative consequences of chronic pain.

Objectives: We analyzed patient-reported sleep parameters for an extended-release methylphenidate formulation (PRC-063) in adolescents with attention-deficit/hyperactivity disorder. Methods: Clinical efficacy and long-term safety/tolerability data from a 4-week, double-blind, placebo-controlled, fixed-dose study (NCT02139111) and a subsequent 6-month, optimized-dose, open-label extension (OLE) study (NCT02168127) were used. In the double-blind study, participants were randomly assigned 1:1:1:1:1 to one of four doses of PRC-063 (25, 45, 70, or 85 mg/day) or placebo. In both the double-blind and OLE studies, sleep outcomes were assessed using the Pittsburgh Sleep Quality Index (PSQI). Results: During double-blind treatment, no statistically significant least-squares mean difference in change from baseline between PRC-063 (all doses combined; N = 293) and placebo (N = 74) was found for either global PSQI score (-0.3 vs. -0.5; p = 0.6110) or scores for any of the seven PSQI subscales. Compared with the placebo group, a marginally higher proportion of patients in the PRC-063 group (all doses combined) went from being poor to good sleepers (global PSQI score ≤5; 14.4% vs. 11.3%). In a logistic regression analysis, study treatment was not a predictor of poor sleep (p = 0.5368) at the end of the double-blind study. In the OLE study, there was a trend of improvement in sleep after 1 month of individualized dosing that was maintained through 6 months. Sleep efficiency (time asleep as a proportion of time in bed) showed improvement at the end of the OLE study. Conclusion: While individual patients may experience changes in sleep as an adverse event, group data evaluating sleep as an outcome found there were no differences between PRC-063 and placebo in self-reported sleep outcomes on the PSQI.

IntroductionPolyvinylpyrrolidone–iodine (PVP-I) demonstrates broad-spectrum anti-infective activity and is available in different formulations for oral rinse and topical use in medical and personal care settings. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has underscored the need to supplement available preventive strategies.MethodsWe assessed virucidal activity of PVP-I formulations, including 0.5% (w/v) solution, 5.0% (w/v) solution, 7.5% (w/v) scrub, and 10.0% (w/v) solution, versus placebos when challenged with coronaviruses in two in vitro studies. Murine coronavirus strain A59 (American Type Culture Collection [ATCC]® VR-764™), human coronavirus strain OC43 (ZeptoMetrix Corp. #0810024CF), human coronavirus strain NL63 (ZeptoMetrix Corp. #0810228CF), and human coronavirus strain 229E (ATCC® VR-740™) were used as surrogates for SARS-CoV-2. Both studies used the American Society for Testing and Materials in vitro time-kill method.ResultsAll active PVP-I formulations in study 1 demonstrated virucidal activity at 15 s, with mean log10 reduction of greater than 4.56 or greater than 99.99% inactivation; a cytotoxic effect against the National Collection of Type Cultures clone 1469 host cells was observed with 5.0% (w/v) solution, 7.5% (w/v) scrub, and 10.0% (w/v) solution. Active PVP-I formulations in study 2 demonstrated effective virucidal activity against coronaviruses in less than 15 s; log10 reduction in viral titer for each coronavirus strain was consistently higher for 10.0% (w/v) solution and 0.5% (w/v) solution versus 7.5% (w/v) scrub.ConclusionBoth studies demonstrated in vitro virucidal activity of PVP-I formulations when challenged with SARS-CoV-2 surrogate coronaviruses. Although promising, further investigations are needed to evaluate SARS-CoV-2 inactivation.

Objective: To determine the safety and efficacy of PRC-063, a once-daily, multilayer, extended-release (ER) formulation of methylphenidate (MPH) hydrochloride, in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children in a randomized, double-blind, parallel group, dose-optimized, placebo-controlled phase 3 study.Methods: Boys and girls aged 6–12 years diagnosed with ADHD were enrolled. During a 6-week, open-label, dose-optimization phase, subjects began treatment at 25 mg/day of PRC-063 and were titrated until an optimal dose (maximum 85 mg/day) was reached. During the double-blind period, subjects were randomized to receive treatment with their optimal dose of PRC-063 or placebo for 1 week. Efficacy was assessed in a laboratory classroom setting on the final day of the double-blind treatment using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product Measure of Performance (PERMP). Safety was assessed measuring adverse events (AEs), vital signs, and electrocardiograms.Results: The study was completed by 147 subjects. In the primary efficacy analysis, significant improvements were demonstrated with PRC-063 versus placebo (p < 0.0001) when SKAMP-Combined scores were averaged over the 13-hour full-day laboratory classroom (least squares mean difference = −8.6, 95% confidence interval = −10.6 to −6.6). Mean average PERMP-Total scores were also significantly improved with PRC-063 versus placebo at all time points postdose (p < 0.01). The onset of treatment effect was present by 1-hour postdose (the first time point measured) and duration of efficacy was up to and including 13 hours postdose. AEs reported in ≥5% of subjects during the dosing optimization period were decreased appetite, abdominal pain upper, affect lability, weight decreased, headache, irritability, and insomnia.Conclusions: PRC-063 was effective in improving attention and reducing symptoms of ADHD versus placebo and had a rapid onset and extended duration of effect. AEs were consistent to those reported with other ER MPH treatments. Clinical Trial Registry: NCT03172481.

Objective Opioid surveillance in response to the opioid epidemic will benefit from scalable, automated algorithms for identifying patients with clinically documented signs of problem prescription opioid use. Existing algorithms lack accuracy. We sought to develop a high-sensitivity, high-specificity classification algorithm based on widely available structured health data to identify patients receiving chronic extended-release/long-acting (ER/LA) therapy with evidence of problem use to support subsequent epidemiologic investigations. Methods Outpatient medical records of a probability sample of 2,000 Kaiser Permanente Washington patients receiving ≥60 days’ supply of ER/LA opioids in a 90-day period from 1 January 2006 to 30 June 2015 were manually reviewed to determine the presence of clinically documented signs of problem use and used as a reference standard for algorithm development. Using 1,400 patients as training data, we constructed candidate predictors from demographic, enrollment, encounter, diagnosis, procedure, and medication data extracted from medical claims records or the equivalent from electronic health record (EHR) systems, and we used adaptive least absolute shrinkage and selection operator (LASSO) regression to develop a model. We evaluated this model in a comparable 600-patient validation set. We compared this model to ICD-9 diagnostic codes for opioid abuse, dependence, and poisoning. This study was registered with ClinicalTrials.gov as study NCT02667262 on 28 January 2016. Results We operationalized 1,126 potential predictors characterizing patient demographics, procedures, diagnoses, timing, dose, and location of medication dispensing. The final model incorporating 53 predictors had a sensitivity of 0.582 at positive predictive value (PPV) of 0.572. ICD-9 codes for opioid abuse, dependence, and poisoning had a sensitivity of 0.390 at PPV of 0.599 in the same cohort. Conclusions Scalable methods using widely available structured EHR/claims data to accurately identify problem opioid use among patients receiving long-term ER/LA therapy were unsuccessful. This approach may be useful for identifying patients needing clinical evaluation.

BackgroundCapturing the impact of caring for patients with debilitating rare disease is important for understanding disease burden. We aimed to develop and validate an instrument to measure the impact on caregivers of caring for children with three lysosomal storage diseases (LSDs): metachromatic leukodystrophy (MLD), neuronopathic mucopolysaccharidosis type II (MPS II) and mucopolysaccharidosis type IIIA (MPS IIIA).MethodsA draft instrument was developed based on targeted literature searches and revised through sequential qualitative interviews with caregivers of patients first with MLD (n = 16), then with MPS II (n = 22), and finally with MPS IIIA (n = 8). The instrument, which covered domains of physical, emotional, social and economic burden, was refined at each stage of development based on caregiver feedback. Saturation of major concepts was reached during concept elicitation (MLD and MPS II).ResultsIt was confirmed that caring for a patient with an LSD impacts social functioning, emotional/psychological functioning, physical functioning, daily activities, and finances/work productivity. Results from cognitive debriefing of the draft questionnaires were considered during each round of interviews, resulting in a final set of items that caregivers found clear and easy to understand. The Caregiver Impact Questionnaire (CIQ) has 30 items in five domains: (1) social functioning (7 items); (2) impact on daily activities (5 items); (3) emotional/psychological functioning (10 items); (4) physical functioning (6 items); and (5) financial impact (2 items).ConclusionsThese findings demonstrate that the content of the CIQ is relevant for determining the impact of caring on caregivers of patients with MLD, MPS II and MPS IIIA.