Long-Term Efficacy and Safety of Paliperidone 6-Month Formulation: An Open-Label 2-Year Extension of a 1-Year Double-Blind Study in Adult Participants With Schizophrenia.

BACKGROUND: Paliperidone palmitate 6-month (PP6M) demonstrated noninferiority to paliperidone palmitate 3-month in preventing relapse in patients with schizophrenia in a phase 3 double-blind (DB) study (NCT03345342). Here, we report long-term efficacy and safety results from a 2-year single-arm, open-label extension (OLE; NCT04072575) of this DB study. METHODS: Participants who completed the DB study without relapse were enrolled and followed-up every 3 months up to 2 years. Participants received 4 PP6M gluteal injections (700/1000 mg eq.) at baseline, 6-month, 12-month, and 18-month visits. Efficacy endpoints included assessment of relapse, Positive and Negative Syndrome Scale total score, Personal and Social Performance score, and Clinical Global Impression-Severity scale change from baseline. Safety was assessed by treatment-emergent adverse events (TEAEs), physical examinations, and laboratory tests. RESULTS: Of 178 participants enrolled, 154 (86.5%) completed the OLE (mean age: 40.4 years, men: 70.8%; mean duration of PP6M exposure during OLE: 682.1 days). Overall, 7/178 (3.9%) participants relapsed between 20 and 703 days after enrolment. Mean (SD) changes from baseline to endpoint were as follows: Positive and Negative Syndrome Scale total score, 0.7 (8.22); Clinical Global Impression-Severity, 0.0 (0.51); and Personal and Social Performance Scale, 0.5 (7.47). Overall, 111/178 participants (62.4%) reported ≥1 TEAE; most common (>5%) TEAEs were headache (13.5%) and increased blood prolactin/hyperprolactinemia (18.0%); 8/178 (4.5%) participants experienced serious TEAEs, and 6/178 (3.4%) participants withdrew due to TEAEs. No deaths were reported. CONCLUSIONS: The relapse rate observed with PP6M during the 2-year OLE was low (3.9%). Clinical and functional improvements demonstrated in the DB study were maintained during OLE, and no new safety concerns were identified. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04072575; EudraCT number: 2018-004532-30.

Alginate-based drug carrier systems to target inflammatory bowel disease: A review.

Inflammatory bowel disease (IBD) is an inflammatory disorder that affects the gastrointestinal tract. IBD has become an increasingly common condition in both developed and developing nations over the last few decades, owing to a variety of factors like a rising population and diets packed with processed and junk foods. While the root pathophysiology of IBD is unknown, treatments are focused on medications aimed to mitigate symptoms. Alginate (AG), a marine-derived polysaccharide, is extensively studied for its biocompatibility, pH sensitivity, and crosslinking nature. This polymer is thoroughly researched in drug delivery systems for IBD treatment, as it is naturally available, non-toxic, cost effective, and can be easily and safely cross-linked with other polymers to form an interconnected network, which helps in controlling the release of drugs over an extended period. There are various types of drug delivery systems developed from AG to deliver therapeutic agents; among them, nanotechnology-based systems and hydrogels are popular due to their ability to facilitate targeted drug delivery, reduce dosage, and increase the therapeutic efficiency. AG-based carrier systems are not only used for the sustained release of drug, but also used in the delivery of siRNA, interleukins, and stem cells for site directed drug delivery and tissue regenerating ability respectively. This review is focussed on pathogenesis and currently studied medications for IBD, AG-based drug delivery systems and their properties for the alleviation of IBD. Moreover, future challenges are also be discoursed to improve the research of AG in the field of biopharmaceuticals and drug delivery.

Impact of illegal trade on the quality of epoetin alfa in Thailand.

BACKGROUND: Reports from the World Health Organization have suggested that counterfeit medicines pose a serious problem in developing countries. An investigation of anti-erythropoietin antibody-mediated pure red cell aplasia in Thailand found evidence of drug smuggling, which may have serious safety implications. OBJECTIVE: This study assessed the authenticity and quality of epoetin alfa samples in Thailand. METHODS: Samples of epoetin alfa-prefilled syringes were collected from the pharmacies at 2 major hospitals (62 samples), 8 retail pharmacies (41 samples), and Thai authorities (30 samples confiscated from smugglers at 2 airports, and 6 samples from a condominium used by smugglers). These samples were tested against the European Union Pharmacopeia specifications for aggregate content in epoetins of <2%. The integrity of epoetin alfa distribution channels, coldchain processes (maintenance at 2 degrees C-8 degrees C), primary and secondary packaging components (eg, batch number, expiration date, appearance, letter size), and company's confidential features (eg, nature of the ink, type and quality of the paper, other covered features) were also investigated. The main outcome measures were protein aggregate content, determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blotting; and isoform distribution, assessed by isoelectric focusing and Western blotting. RESULTS: Epoetin alfa samples obtained from the company's cold-chain and authorized distribution channels met all quality standards, as did all epoetin alfa samples obtained from the hospital pharmacies. However, evidence showed that some samples were being smuggled or sold illegally through certain unauthorized retail pharmacies. The epoetin alfa samples obtained from both airports and the condominium were stored improperly at room temperature. Aggregate levels exceeded the specification of <2% in 11 samples from 2 of the retail pharmacies (range, 1.2%-3.1%), 15 samples from the Dongmuang Airport (range, 2.2%-17.0%), and all 6 samples from the condominium (range, 10.5%-19.8%). All samples from the 2 hospitals, 8 retail pharmacies, and Suvarnabhumi Airport had the authentic 6 isoform bands. Samples from Dongmuang Airport and the condominium appeared to have the 6 characteristic bands, but positive confirmation was difficult because of band smearing caused by a high level of aggregates. All features of primary and secondary packaging were found to be authentic. CONCLUSIONS: This investigation found evidence that some epoetin alfa samples were smuggled into Thailand without proper cold chain, contained high levels of protein aggregates, and were sold illegally through certain retail pharmacies. The Thai authorities have intervened to stop such unauthorized products from reaching patients. Strenuous efforts must be made to prevent illegal cross-border smuggling of biopharmaceuticals without proper cold chain because of the serious safety implications for patients in developing countries.

Anemia and thrombocytopenia in patients undergoing chemotherapy for solid tumors: a descriptive study of a large outpatient oncology practice database, 2000-2007.

OBJECTIVE: This study was conducted to evaluate data on chemotherapy-associated anemia and thrombocytopenia, and cycle delays in patients with cancer in a community oncology practice. METHODS: Data on adult patients (age > or =18 years) with cancer treated in outpatient oncology clinics throughout the United States between 2000 and 2007 were obtained from a large electronic medical records database. All types of cancer were included, although the focus was on solid cancers (ie, lung, breast, ovarian, head and neck, and colorectal cancers). Chemotherapy regimens were grouped from most to least toxic as follows: platinum-based, anthracycline-based, gemcitabine-based, taxane-based, and all other regimens. Anemia (defined as hemoglobin <11 g/dL), thrombocytopenia (defined as platelet count <150 x 10(9)/L), red blood cell (RBC) and platelet transfusions, and use of erythropoietin-stimulating agents (ESAs) were examined by tumor and regimen type. Cycle delays (>7 days) during chemotherapy were also evaluated. RESULTS: A total of 47,159 patients were included in the study (58.4% female; mean [SD] age, 60.76 [13.9] years). The most common cancer was breast cancer (19.5%), followed by non-small cell lung cancer (14.9%), colorectal cancer (11.9%), ovarian cancer (3.1%), and head and neck cancer (2.5%). At baseline, 20.9% of patients had anemia and 11.1% had thrombocytopenia. A total of 75,243 chemotherapy regimens were administered. During the course of chemotherapy, from 46.4% to 59.0% of patients developed anemia. The prevalence of thrombocytopenia ranged from 21.9% in patients treated with taxane-based regimens to 64.2% in patients treated with gemcitabine-based regimens. In patients from a single hospital-based outpatient center that had the most complete transfusion data (representing 18.3% of the population), the use of RBC transfusion ranged from 4.5% in patients treated with anthracycline-based regimens to 11.6% in patients treated with platinum-based regimens. ESAs were received at some point during chemotherapy by 49.1% of patients. For those with complete dose information, dose delay occurred in 8.2% of chemotherapy cycles; the mean delay was 17 days. CONCLUSION: In this study of anemia and thrombocytopenia in a large cohort of patients undergoing chemotherapy for solid tumors in an outpatient oncology clinic in 2000-2007, the burden of anemia and thrombocytopenia remained high.