Product-related Adverse Events Research Articles

Poly-d,l-Lactic Acid Via Transdermal Microjet Drug Delivery for Treating Rosacea in Asian Patients.

Rosacea, a chronic inflammatory skin condition, is marked by enduring redness, visible blood vessels, and inflammatory eruptions in facial areas. Managing rosacea remains a persistent challenge for dermatologists, especially in cases unresponsive to conventional treatments. Injectable poly-d,l-lactic acid (PDLLA) has shown promise in treating erythema and telangiectasia associated with rosacea in addition to age-related concerns. Employing Mirajet, a laser-induced microjet system, for administering PDLLA is a novel and promising treatment for rosacea. We aimed to evaluate the efficacy and safety of injectable PDLLA delivered via a needle-free microjet system for managing rosacea. Four Korean women with persistent and refractory rosacea received five monthly sessions of PDLLA needle-free injections. Clinical assessments were conducted using the Clinician's Erythema Assessment and Patient's Self-Assessment (PSA) at baseline, 4 weeks post-treatment, and 22 weeks post-final treatment. Adverse events were monitored throughout the study period. At 4 weeks post-treatment, both Clinician's Erythema Assessment and PSA scores indicated significant improvements in erythema that were sustained up to the 22-week follow-up. Patients reported high satisfaction with resolution of redness and improved skin texture. Mild swelling, redness, and petechiae were observed post-treatment but resolved spontaneously. No product-related adverse events were noted during the study period. Injectable PDLLA delivered via laser-induced microjet injection demonstrated promising efficacy in improving rosacea symptoms and skin quality for up to 22 weeks without significant adverse effects. Larger randomized controlled trials are needed to confirm these findings and evaluate long-term safety and sustainability of outcomes.

Supplementation of Spermidine at 40 mg/day has Minimal Effects on Circulating Polyamines: An Exploratory Double-blind Randomized Controlled Trial in Older Men

This study represents the first investigation into the safety of a novel, high-purity spermidine-trihydrochloride supplement (hpSPD) in humans. Spermidine, a natural compound found in various foods, has demonstrated potential health benefits in animal and epidemiological studies. However, evidence from clinical trials and safety evaluations of spermidine supplements is limited as pure spermidine for human administration has not been available. In this randomized, double-blind, within subject and placebo-controlled trial, 37 healthy men (50-70 years old, BMI 18.5-28 kg/m2) were administered either hpSPD or a placebo. We hypothesized that 7-day and 28-day dosing of 40 mg/day of hsSPD would have minimal effects on safety, although metabolic and polyamine homeostasis has not previously been examined at this dosage level. Consistent with our hypothesis, 40 mg/day hpSPD did not result in any significant changes in clinical, lipids, chemistry, or hematological parameters compared to placebo. Compliance was high, and no study product-related adverse events were reported. Substantial changes in serum and urine polyamine concentrations were not observed following hpSPD supplementation, suggesting effective homeostatic control of full dose highly purified spermidine supplements with no evidence of adaptation of spermidine metabolism at 40 mg/day. These findings suggest that hpSPD at 40 mg/day for up to 28 days is safe and well-tolerated in healthy older men. The study is consistent with preclinical results and provides important evidence supporting the safety of high-purity spermidine supplementation, enabling further research with single molecule spermidine to investigate its potential biology for improving human health. This trial was registered at clinicaltrials.gov (NCT05459961).

Intracerebral transplantation of MRI-trackable autologous bone marrow stromal cells for patients with subacute ischemic stroke

Ischemic stroke is one of the leading causes of death and neurological disability worldwide, and stem cell therapy is highly expected to reverse the sequelae. This phase 1/2, first-in-human study evaluated the safety, feasibility, and monitoring of an intracerebral-transplanted magnetic resonance imaging (MRI)-trackable autologous bone marrow stromal cell (HUNS001-01) for patients with subacute ischemic stroke. The study included adults with severe disability due to ischemic stroke. HUNS001-01 cultured with human platelet lysates and labeled with superparamagnetic iron oxide was stereotactically transplanted into the peri-infarct area 47-64days after ischemic stroke onset (dose: 2 or 5×107 cells). Neurological and radiographic evaluations were performed throughout 1 year after cell transplantation. The trial was registered at UMIN Clinical Trial Registry (number UMIN000026130). All seven patients who met the inclusion criteria successfully achieved cell expansion, underwent intracerebral transplantation, and completed 1 year of follow-up. No product-related adverse events were observed. The median National Institutes of Health Stroke Scale and modified Rankin scale scores before transplantation were 13 and 4, which showed improvements of 1-8 and 0-2, respectively. Cell tracking proved that the engrafted cells migrated toward the infarction border area 1-6months after transplantation, and the quantitative susceptibility mapping revealed that cell signals at the migrated area constantly increased throughout the follow-up period up to 34% of that of the initial transplanted site. Intracerebral transplantation of HUNS001-01 was safe and well tolerated. Cell tracking shed light on the therapeutic mechanisms of intracerebral transplantation. This work was supported by the Japan Agency for Medical Research and Development (AMED; JP17bk0104045 and JP20bk0104011).

Safety and efficacy of REGENDIL™ infused hair growth promoting product in adult human subject having hair fall complaints (alopecia).

Hair serum is recommended therapy for the management of hair fall problems. People of all ages suffer from hair fall. To evaluate safety and efficacy of hair growth promoting product in healthy adult subjects with hair fall complaints (Alopecia). In this safety and efficacy clinical study, 32 healthy individuals (aged 18-45 years) experiencing hair loss were enrolled. Participants applied 0.5 mL of the product to the affected scalp area daily for 60 days. The study evaluated various factors, including hair growth rate, thickness, density, scalp condition using CASLite-Nova, anagen-to-telogen ratio, hair fall reduction, overall hair and scalp appearance, hair strength, and participants' subjective perceptions of the product. Highly statistically significant improvement was observed in hair growth rate, thickness, and density at Day 30 and Day 60. Hair growth rate increased (p-value <0.01) by 10.52% in 30 days and 31.62% in 60 days after test product application. Average hair growth increased by 424.21 μm/day and 487.31 μm/day at Day 30 and 60 respectively. The hair growth improved by up to 1.5 times after 60 days of usage in healthy subjects with hair fall complaints. No adverse events or product-related adverse events were reported. Hair serum containing REGENDIL™ (Redensyl, AnaGain, Procapil, Capilia longa), and 5 kDa hyaluronic acid was efficacious and well tolerable in reducing hair fall (Alopecia). Hair serum significantly improved hair growth, hair density, hair thickness, and hair strength within 60 days of usage, thereby demonstrating it worth as a beneficial inclusion as a daily haircare product.

Adherence, safety, and choice of the monthly dapivirine vaginal ring or oral emtricitabine plus tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis among African adolescent girls and young women: a randomised, open-label, crossover trial

Half of new HIV acquisitions in Africa occur in adolescent girls and young women. Pre-exposure prophylaxis (PrEP) with oral tenofovir disoproxil fumarate plus emtricitabine or the monthly dapivirine vaginal ring is efficacious but has lower adherence and effectiveness among adolescent girls and young women. We aimed to assess product adherence, safety, and choice of oral PrEP compared with the dapivirine ring among African adolescent girls and young women. MTN-034/REACH was a randomised, open-label, phase 2a crossover trial among HIV-seronegative, non-pregnant adolescent girls and young women aged 16-21 years at four clinical research sites in South Africa, Uganda, and Zimbabwe. Participants were randomly assigned (1:1) to either the dapivirine ring or daily oral PrEP (200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate) for 6 months, then switched to the other product option for 6 months, followed by a third 6-month period in which participants were given a choice of oral PrEP, the dapivirine ring, or neither. Fixed block randomisation was used, stratified by site. The primary adherence endpoint was use of each product during the randomised periods, with high use defined as tenofovir-diphosphate concentrations greater than or equal to 700 fmol/punch (associated with taking an average of four or more tablets per week in the previous month) and greater than or equal to 4 mg dapivirine released from the returned ring (continuous use for 28 days in the previous month) based on residual drug concentrations. The primary safety endpoint was grade 2 or higher adverse events during each randomised period of 24 weeks of ring and oral PrEP. This trial is registered at ClinicalTrials.gov, NCT03593655. From Feb 6, 2019 to Sept 9, 2021, 396 adolescent girls and young women were screened, 247 of whom were enrolled and randomly assigned (6 months of the ring followed by 6 months of oral PrEP n=124; 6 months of oral PrEP followed by 6 months of the ring n=123). Median age was 18 years (IQR 17-19). 54 grade 2 or higher product-related adverse events were reported during oral PrEP and five during dapivirine ring use, with no product-related serious adverse events. High adherence was observed in 753 (57%) of the 1316 oral PrEP visits and 806 (57%) of the 1407 dapivirine ring visits. Four women acquired HIV during follow-up. Adherence was moderately high and similar between oral PrEP and the dapivirine ring with favourable safety and tolerability. Oral PrEP and the dapivirine ring are effective, safe, and well tolerated HIV prevention options for adolescent girls and young women who would benefit from a choice of PrEP formulations to meet their needs and preferences. National Institutes of Health.

Efficacy and In-Use Tolerance of Venusia Baby Moisturizer for Skin Hydration in Babies With Dry and/or Normal Skin.

Introduction Skin hydration is important for maintaining adequate skin barrier function. After delivery, the baby's skin faces the most difficult challenge as they are exposed to the exterior world's environmental changes, friction, and microorganisms. The management is further complicated by the availability of a large range of infant skin-care products with varying claims. The first-ever Indian study on babies was done to analyze the test product (Venusia baby moisturizer; Dr.Reddy's Laboratories Ltd., Hyderabad, India) in order to bring scientific clarity to consumers. This product is devoid of parabens, alcohol, and animal origin (Dr.Reddy's Laboratories Ltd., Hyderabad, India) and is designed for skin hydration and in-use tolerance in babies with dry and/or normal skin. The endpoints were hydration and clinical evaluation of the skin, evaluated using a moisture meter scale (MMSC; Delfin Technologies Ltd., Kuopio, Finland) and parent self-assessment questionnaire, respectively. Material and methods A total of 136 healthy babies aged between six months to two years were enrolled in a four-group, monocentric, non-randomized, evaluator-blinded study: Group 1 (Venusia baby cream for dry skin), Group 2 (Venusia baby lotion for Dry Skin), Group 3 (Venusia baby cream for normal skin), and Group 4 (Venusia baby lotion for normal skin). The endpoints were hydration and clinical evaluation of the skin, evaluated using an MMSC and parent self-assessment questionnaire, respectively. Results In babies with dry skin, skin hydration was improved with Venusia baby cream (37.50%) and Venusia baby lotion (66.40%). Additionally, 66.66% of participants strongly agreed that the baby's skin became softer and smoother after the application of Venusia baby cream; 76.47% of participants strongly agreed that the baby's skin became softer and smoother after the application of Venusia baby lotion. In babies with normal skin, skin hydration was improved with Venusia baby cream (12.20%) and Venusia baby lotion (7.20%); 59.37% of participants strongly agreed that the baby's skin became softer and smoother after the application of Venusia baby cream; and 84.84% of participants strongly agreed that the baby's skin became softer and smoother after the application of Venusia baby lotion. Conclusion Significant improvement was seen in skin hydration using Venusia baby cream and Venusia baby lotion in babies with dry skin and normal skin. No skin intolerances and product-related adverse or serious adverse events were clinically observed or reported during the study duration. Venusia baby lotion had the highest effect (66.4%) on skin hydration in babies with dry skin, where there was a significant shift from dry skin to normal skin range.

Effect of a Multi-Ingredient Coriolus-versicolor-Based Vaginal Gel in Women with HPV-Dependent Cervical Lesions: The Papilobs Real-Life Prospective Study.

Human papillomavirus (HPV) is responsible for virtually all cervical cancers in women. HPV infection and persistency may lead to different-grade squamous intraepithelial lesions that can result in high-grade lesions and cancer. The objective was to prospectively evaluate the results of using a Coriolus-versicolor-based vaginal gel (Papilocare®) on HPV-dependent low-grade cervical lesion repair in a real-life scenario. HPV-positive women ≥ 25 years with ASCUS/LSIL cervical cytology results and concordant colposcopy images were included, receiving the vaginal gel one cannula/day for 21 days (first month) + one cannula/alternate days (five months). A 6-month second treatment cycle was prescribed when needed. Repair of the cervical low-grade lesions through cytology and colposcopy, HPV clearance, and level of satisfaction, and tolerability were evaluated. In total, 192 and 201 patients accounted for the total and safety analyses, respectively, and 77.1% repaired cervical lesions at 6 or 12 months (76.0% for high-risk HPV). Additionally, 71.6% achieved HPV clearance throughout the study's duration (70.6% for high-risk HPV). Satisfaction level was rated 7.9 and 7.5 out of 10 at 6 and 12 months, respectively. Only three mild-moderate product-related adverse events were reported, and all of them were resolved by the end of the study. In our study, we observed higher regression rates of low-grade cervical lesions in women treated with Papilocare® vaginal gel than spontaneous regression rates reported in the literature.

A Topical Combination Regimen of Benzoyl Peroxide and Retinol Moisturizer for Mild to Moderate Acne

Topical therapies, in many cases over-the-counter (OTC) formulations, are available for the treatment of acne, including benzoyl peroxide (BPO), salicylic acid, and retinoids. While these agents provide therapeutic efficacy, combination regimens can offer improved outcomes due to their ability to address multiple pathways involved in acne formation, making them better suited to address the multiple factors involved in acne pathogenesis and the breadth of complexion issues associated with the condition. The present study assessed the efficacy and tolerability of a daily regimen comprised of topical low-dose (2.5%) BPO applied in the morning and topical retinol applied in the evening in 33 subjects with mild to moderate acne who completed the study. A significant reduction in global total acne count from baseline to week 12 (primary endpoint) was achieved, in addition to significant improvements in Investigator Global Assessment (IGA) of acne severity and reductions in inflammatory and non-inflammatory lesions. Treatment also significantly improved acne-complexion graded efficacy parameters (tactile surface roughness, uneven skin tone, skin blotchiness, and lack of skin clarity), and was well-tolerated, with no statistically significant (P&lt;0.05) increases in objective or subjective facial irritation. Significant improvements from baseline to week 12 were observed for both self-assessment of facial skin conditions and quality of life (QoL) scores. No product-related adverse events (AEs) were observed in the study subjects. J Drugs Dermatol. 2022;21(12):1340-1346. doi:10.36849/JDD.6845.

Exploratory evaluation of tolerability, performance, and cosmetic acceptance of dexpanthenol-containing dermo-cosmetic wash and sun-care products for tattoo aftercare.

Background and AimsTattoo prevalence has significantly increased over the last decades. Proper tattoo aftercare, such as cleansing, moisturizing, and protection against sunlight, is essential to prevent complications and to keep the beauty of the tattoo. The tolerability, performance, and cosmetic acceptability of two dexpanthenol‐containing dermo‐cosmetic products, a wash and a sun‐care, were investigated on tattooed skin in two separate trials.MethodsTwo single‐center, exploratory, open‐label cosmetic studies were conducted between August and November 2020 to evaluate the dexpanthenol‐containing dermo‐cosmetic products. In the first study, healthy adults applied the 2.5% dexpanthenol‐containing wash right after their tattoo session daily for 14 consecutive days. In the second study, healthy adults applied the 2.5% dexpanthenol‐containing sun‐care sun protection factor 50+ cream on existing tattoos that were daily exposed to sunlight for 28 consecutive days. Clinical examination by a dermatologist and self‐assessment through subject questionnaires were used to assess the tolerability, acceptance, ease of use, and cosmetic outcomes of both products. Additionally, transepidermal water loss and moisturization assessments were performed to evaluate skin hydration after use of the sun‐care product.ResultsBoth study products were well tolerated, and no product related adverse events were reported during the studies. At least 90% of the study participants appreciated the performance of the dexpanthenol‐containing wash and sun‐care product, including moisturizing properties, relief of unpleasant sensations, and preservation of the cosmetic appearance of the tattoo. For the sun‐care, it was shown that its application supported maintaining the skin barrier of tattooed skin, while keeping it hydrated.ConclusionThe 2.5% dexpanthenol‐containing wash and sun‐care products are well tolerated and appreciated by tattooed subjects. Hence, they represent valid options for tattoo aftercare in line with current recommendations and practice.

Pediatric Melatonin Ingestions - United States, 2012-2021.

Melatonin is an endogenous neurohormone that regulates the sleep-wake cycle (1). It is used therapeutically for insomnia in adults and for primary sleep disorders in children (2). Melatonin is regulated by the Food and Drug Administration (FDA) as a dietary supplement. Various synthetic melatonin preparations are widely available over the counter (OTC) in the United States with sales increasing from $285 million in 2016 to $821 million in 2020 (3). Children are at increased risk for melatonin exposure because of the supplement's widespread use and growing popularity as a sleep aid. In 2020, melatonin became the most frequently ingested substance among children reported to national poison control centers (4); however, more research is needed to describe the toxicity and outcomes associated with melatonin ingestions in children. This study assessed isolated melatonin ingestions among the pediatric population (defined here as children, adolescents, and young adults aged ≤19 years) during January 1, 2012-December 31, 2021, using the American Association of Poison Control Centers' National Poison Data System (NPDS). During the 10-year study period, 260,435 pediatric melatonin ingestions were reported to NPDS, and the annual number of ingestions increased 530%. In addition, pediatric melatonin ingestions accounted for 4.9% of all pediatric ingestions reported to poison control centers in 2021 compared with 0.6% in 2012. Pediatric hospitalizations and more serious outcomes due to melatonin ingestions increased during the study period, primarily related to an increase in unintentional ingestions among children aged ≤5 years. Five children required mechanical ventilation, and two died. Consumers and health care professionals should be encouraged to report any melatonin product-related adverse events to MedWatch, the FDA's medical product safety reporting program. Public health initiatives should focus on raising awareness of increasing numbers of melatonin ingestions among children and on the development of preventive measures to eliminate this risk.

A Prospective Multicenter Study to Evaluate the Safety and Efficacy of the Topical Application of MYOWNN™, an Autologous Growth Factor Concentrate (AGFC) Serum, in Anti-Aging.

BackgroundGrowth factors from platelets have been emerging as a revolutionary treatment with the ability to induce cell growth in the skin, which results in retarding and reversing the aging process. Platelet-rich plasma (PRP) allows for greater release of growth factors and biologically active proteins, which in turn activates the cascade of stimulation of neoangiogenesis and collagen production. PRP is used in anti-aging and facial skin rejuvenation in the form of dermal injections and topical application during micro-needling. This study was conducted to assess the safety and efficacy of a topically applied face serum, MYOWNN™ (Wockhardt Ltd., Mumbai, India). MYOWNN™ is an autologous growth factor concentrate that has been made into a topical face serum.MethodsMale and female subjects in the age group between 30 and 55 years (both inclusive) with Fitzpatrick skin type III-V who had not taken any oral or topical treatments for at least four weeks before and any platelet-rich plasma (PRP) based facial treatment (injections) at least six months before the study entry were included. MYOWNN™ serum was applied on the face once daily at night, approximately 30 minutes before sleeping preferably, for a total duration of five months. Six parameters, i.e. spots, pores, wrinkles, texture, moisture, and pigmentation, were evaluated at regular intervals with Visage-LS (dermaindia®, Tamil Nadu, India), a face analysis system that gives the live status of these six parameters and is an advanced live status skin detection equipment together with shooting, analyzing, and displaying functions, as well as the subjective analysis, was performed by subjects and physicians using different globally accepted scales like physician’s global aesthetic improvement scale (PGAIS), subject’s global aesthetic improvement scale (SGAIS), subject satisfaction score (SSS), and wrinkle severity rating scale (WSRS). For analysis, a mixed model for repeated measures was used. The model had change from baseline as the dependent variable visit as a factor and baseline assessment result as a covariate. All primary and secondary efficacy endpoints were analyzed using Modified Intent-to-Treat (mITT) populations.ResultsImprovement in an average of six anti-aging parameters was observed as early as three months while statistically significant improvement was observed by the end of five months of application. A statistically significant improvement in wrinkles was observed by the end of three months of the application itself. There were no product-related adverse events reported.ConclusionsFive months of application of MYOWNN™ serum showed a statistically significant improvement in an average of six parameters of anti-aging and face rejuvenation with a p-value of 0.0150 (<5% level of significance (i.e. 0.05) and was also well-tolerated.

27891 Safety and efficacy of an Avena sativa (oat) skin care regimen for therapy-related xerosis and pruritus in adult oncology patients undergoing systemic cancer treatments

Dermatologic adverse events, including xerosis and pruritus, are frequent in patients receiving systemic anticancer agents. There are few studies evaluating tolerance and efficacy of topical regimens to alleviate these untoward events. A 5-week (±1 week) clinical study was performed to determine the safety and efficacy of an Avena sativa (oat) skin care regimen (body wash, cream, and 0.5% pramoxine balm) in improving skin dryness and itch of adult patients undergoing systemic oncology treatments. Patients enrolled (n = 52) exhibited CTCAE Grade 1 or 2 (mild to moderate) xerosis (μ = 1.5), and/or pruritus (μ = 0.9) as a side effect of their cancer treatment. Baseline patient skin characteristics including skin hydration and barrier properties were evaluated revealing a dry skin state with an impaired moisture barrier. After 5 weeks, significant improvements (P ˂ .05) in xerosis (μ = 0.5) and pruritus (μ = 0.4) were observed by the dermatologist according to CTCAE Version 5.0 and noted by patients in the PRO-CTCAE. The regimen was well tolerated with no serious product-related adverse events. Significant improvements (P ˂ .05) in skin moisture were also measured following regimen usage. Patients perceived significant improvements, as demonstrated by the QOL scores (Skindex-16), in all subgroups: symptoms, emotional, and functional scales. Improvements in skin moisture, itch and comfort were also perceived by patients at 2 weeks. The Avena sativa (oat) daily skin care regimen not only demonstrated significant dry skin and itch reduction, but also improved patient QOL, suggesting that this regimen is effective for management of mild to moderate dermatologic side effects faced by adults undergoing systemic oncology treatments.

Gene Therapy for Beta Thalassemia: Preliminary Results from the PHASE I/II Tiget-Bthal Trial of Autologous Hematopoietic Stem Cells Genetically Modified with GLOBE Lentiviral Vector

Gene Therapy for Beta Thalassemia: Preliminary Results from the PHASE I/II Tiget-Bthal Trial of Autologous Hematopoietic Stem Cells Genetically Modified with GLOBE Lentiviral Vector

Autologous EBV-Specific T Cells (CMD-003): Early Results from a Multicenter, Multinational Phase 2 Trial for Treatment of EBV-Associated NK/T-Cell Lymphoma

Autologous EBV-Specific T Cells (CMD-003): Early Results from a Multicenter, Multinational Phase 2 Trial for Treatment of EBV-Associated NK/T-Cell Lymphoma

Acute Myeloid Leukemia/Myelodysplastic Syndrome (AML/MDS) Associated with PARP Inhibitors: A Real-World Analysis

Introduction: Poly (ADP-ribose) polymerase inhibitors (PARPi's) represent a newer class of antineoplastic agents targeting cancers with defective DNA-damage repair. PARPi's indications include subtypes of ovarian, fallopian tube and primary peritoneal cancer as well as subsets of patients with breast pancreatic and prostate cancers. There are currently 4 PARPi approved by the Food and Drug Administration (FDA): olaparib (approved 12/19/2014), rucaparib (approved 12/19/2016), niraparib (approved 3/27/2017), and talazoparib (approved 10/16/2018). The incidence of AML/MDS is known to be increased following chemotherapy, with a standardized incidence ratio (observed number of cases of AML/MDS among those treated with chemotherapy/expected number of cases in the general population) of 5.8 among patients with ovarian cancer, and 3.8 among patients with breast cancer (Morton et al, JAMA Onc 2018). All 4 PARPi also carry the potential risk of AML/MDS as an adverse event (AE), but a causal relationship has not been established. Notably, almost all patients treated with a PARPi would have exposure to cytotoxic chemotherapy prior to or during PARPi therapy. For patients treated with PARPi's in clinical trials, the duration of therapy prior to cases of AML/MDS emerging ranged from &amp;lt;1 month to 28 months. The incidence of AML/MDS observed in clinical trials with olaparib was &amp;lt;1.5%, rucaparib 1.1%, niraparib 0.8%, and talazoparib 0.3%. Real-world data regarding this rare but life-threatening AE in PARPi-treated patients is needed. We evaluated reports of AML/MDS associated with PARPi's in the post-approval setting. Methods: The FDA Adverse Events Reporting System (FAERS) database was queried for AEs associated with any of the 4 approved PARPi's, from the date of the initial FDA approval for each agent (irrespective of the indication) through March 31, 2020. The FAERS database contains de-identified reports of product-related AEs, coded using the Medical Dictionary for Regulatory Activities (MedDRA) and classified as serious or non-serious. Cases reported outside the United States were excluded. The proportion of AML/MDS reports was analyzed overall and by PARPi. To account for the variation in length of time on the market due to the different approval dates, reports of AML/MDS for each PARPi were analyzed in the first 17 months after approval (the post-marketing period for the most recently approved agent). The indication for which the PARPi was used, the sex and age of the patient experiencing the AE, and the seriousness and outcome of the AE were assessed. Comparisons of the proportion of AML/MDS cases by agent were made using the Chi-square test; statistical significance was determined at a two-sided α=0.05. Results: A total of 12823 post-marketing AE reports were associated with PARPi's, with 88 (0.7%) reporting cases of AML/MDS (Table). The largest proportion of AML/MDS cases were associated with olaparib (54 of a total of 2121 AE reports; 2.5%, p&amp;lt;0.00001 vs. all other PARPi), followed by niraparib (23 of a total of 5879 AE reports; 0.4%) and rucaparib (11 of a total of 4707 AE reports; 0.2%). No AML/MDS cases were associated with talazoparib (0 of a total 116 AE reports). During the first 17 months following each agent's approval, 14 cases of AML/MDS were reported in association with olaparib, 10 with rucaparib, 9 with niraparib, and 0 with talazoparib. The majority of cases of AML/MDS occurred in women (73%), and the most common indication for treatment was ovarian cancer (52%). The median age of the patients in the AML/MDS reports was 66 years. Nearly all cases were classified as serious (98%), and the outcome of the AE was death for 28% of cases, hospitalization for 17% of cases. Conclusions: Our retrospective analysis found that AML/MDS associated with PARPi's was reported rarely in the post-marketing setting, and that 60% involved olaparib. This study is limited by its retrospective design, and the possibility of under-reporting of cases to the FAERS database. Additionally, the time elapsed since approval differed by agent, and lower observed incidence of AML/MDS for some agents may reflect the limited duration of surveillance. No data is available in the case reports regarding length of exposure to chemotherapy. This real-world analysis complements existing clinical trial data and provides insight into AML/MDS associated with 4 different PARPi's in clinical practice. Disclosures Gajra: Cardinal Health: Current Employment. Zettler:Cardinal Health: Current Employment. Klink:Cardinal Health: Current Employment. Feinberg:Cardinal Health: Current Employment.

A Prospective, Double-Blind, Randomized, Placebo-Controlled, Crossover Study Using an Orally Administered Oxalate Decarboxylase (OxDC).

Hyperoxaluria is typically associated with excessive oxalate intake in the diet, decreased dietary calcium, hyperabsorption of oxalate, or increased endogenous production of oxalate. The disorder spectrum extends from recurrent kidney stones to ESKD. This clinical trial sought to evaluate the effectiveness of an acid stable oxalate decarboxylase (OxDC) to reduce urinary oxalate in healthy subjects on a high-oxalate diet. In this prospective, double-blind, randomized, placebo-controlled, crossover clinical trial, 33 healthy volunteers were randomized into two crossover sequences separated by a 2-day washout period. A controlled high-oxalate diet (750-800 mg oxalate, 500-550 mg calcium daily) was utilized, and six 24-hour urine collections were measured. Subjects were given approximately 1000 U (micromoles per minute per milligram) of OxDC or placebo with meals three times daily during the 4 days of treatment. Urinary oxalate significantly decreased with OxDC treatment. The baseline corrected within-subject mean reduction in 24-hour urinary excretion (after OxDC dosing versus high-oxalate baseline preceding treatment) was 12.5 mg or 29% (P<0.001). OxDC treatment was effective (>5% reduction) in 31 of 33 subjects (94%). Compared with placebo, OxDC produced a 24% reduction (P<0.001) in 24-hour oxalate excretion. Other urinary parameters (creatinine, uric acid, citrate, magnesium, calcium) were not affected by OxDC. No serious adverse events and no product-related adverse events occurred. An orally administered OxDC is capable of significantly reducing urinary oxalate levels in healthy volunteers on a high-oxalate diet without affecting creatinine clearance, urine creatinine, or other solutes related to supersaturation of calcium oxalate. Evaluation of Nephure, and the Reduction of Dietary Oxalate, in Healthy Volunteers, NCT03661216.

110. Use of a novel allograft in single-level posterolateral lumbar spine fusion surgery: 1-year clinical and radiographic results from a prospective multicenter study with comparison to reported results for ICBG

BACKGROUND CONTEXT Instrumented posterolateral lumbar fusion (PLF) surgery is commonly used to alleviate pain and other symptoms associated with degenerative conditions of the lumbosacral spine. Although autologous iliac crest bone graft (ICBG) remains the “gold standard” grafting material for these procedures, surgeons have sought alternatives to avoid the potential morbidity associated with ICBG harvest. OSTEOAMP is a novel allograft bone graft substitute (BGS) that has been processed to retain multiple endogenous growth factors. A prospective multicenter study was designed to enable comparison of this novel product to available data for autologous bone graft controls from large randomized controlled trials (RCTs). PURPOSE Compare 1-year outcomes from an ongoing study investigating radiographic and clinical outcomes to reported results for ICBG controls from a large RCT. STUDY DESIGN/SETTING Prospective multicenter single-arm study conducted in the United States. PATIENT SAMPLE Consenting patients, 21 to 85 years of age, scheduled for PLF surgery with a diagnosis of degenerative disc disease (DDD), degenerative spondylolisthesis, and/or mild degenerative scoliosis. OUTCOME MEASURES Bilateral radiographic fusion (blinded, multireader with adjudication) was assessed. Additional outcome measures included Oswestry Disability Index (ODI), Short Form-36 (SF-36) physical component summary (PCS) and mental component summary (MCS) scores, and improvement in leg/back pain scores. Product-related serious adverse events (SAEs) and secondary surgeries were also assessed. METHODS Forty-two patients were prospectively enrolled after obtaining IRB approval at each of 9 centers and underwent a 1-level (26 patients) or 2-level (16 patients) PLF procedure utilizing the novel BGS (67% BGS: 33% local bone graft). Clinical outcomes were measured and radiographic studies were obtained preop and postop at 1.5, 3, 6, and 12 months. Radiographic analysis included CT assessment of fusion at 12 months. One-year outcomes were available for 23 of the 26 patients who underwent a 1-level procedure and were compared to 1-year outcomes reported for ICBG controls from a large previously published RCT by estimation of novel BGS:ICBG Risk Ratios (RR) with 95% confidence intervals (CI). RESULTS One-year fusion rates and results for each of the measures (novel BGS vs ICBG) are as follows: bilateral fusion = 73.9% (17/23) vs 82.5% (151/183) with RR 0.90 (0.69, 1.15 CI); ODI (>15 improvement) = 73.9% (17/23) vs 73.9% (150/203), RR 1.00 (0.77, 1.29 CI); leg pain = 95.7% (22/23) vs 87.6% (177/202), RR 1.09 (0.99, 1.21 CI); back pain = 91.3% (21/23) vs 93.1% (180/203), RR 0.98 (0.86, 1.12 CI); SF-36 MCS = 73.9% (17/23) vs 68.7% (138/201), RR 1.08 (0.83, 1.40); SF-36 PCS = 95.7% (22/23) vs 86.6% (174/201), RR 1.10 (1.00, 1.22 CI). No statistically significant difference was found in RR between groups for all comparisons. No product-related SAEs and only one secondary surgery were observed with the novel BGS. CONCLUSIONS One-year clinical and radiographic outcomes following single-level PLF procedures with OSTEOAMP compare favorably to results reported for an ICBG control group from a large RCT. FDA DEVICE/DRUG STATUS OSTEOAMP (Approved for this indication)

A single-blind, randomised controlled trial of StrataXRT® – A silicone-based film-forming gel dressing for prophylaxis and management of radiation dermatitis in patients with head and neck cancer

AimInvestigate the effects of StrataXRT® versus 10% Glycerine (Sorbolene cream) for preventing and managing radiation dermatitis in patients with head and neck cancer receiving radical radiotherapy (≥50 Gy) with or without chemotherapy or biotherapy. MethodsA single-blind, randomised controlled, superiority trial was conducted. Patients either received StrataXRT® or Sorbolene (usual care). Skin toxicity, pain, itching and skin-related quality of life scores were collected from baseline, and up to four weeks post-treatment. ResultsA total of 197 patients were randomised into the study. Skin toxicity was dependent on the treatment group with StrataXRT® patients experiencing lower mean skin toxicity at the end of the radiation treatment (P = 0.002). At the end of treatment, the StrataXRT® arm had a lower percentage of grade 2 (80%) and grade 3 (28%) skin toxicity compared to the sorbolene arm (91% and 45% respectively). After adjustment for Cetuximab, the StrataXRT® arm had a 12% lower risk of experiencing grade 2 skin toxicity (RRR = 0.876, 95% CI: 0.778–0.987, P = 0.031); and a 36% lower risk of experiencing grade 3 skin toxicity (RRR = 0.648, 95% CI: 0.442–0.947, P = 0.025). Cox regression analysis showed that patients receiving StrataXRT® had a 41.0% and 49.4% reduced risks of developing grade 2 and 3 skin toxicity respectively throughout treatment compared to the Sorbolene arm. There were no differences between groups in patient-reported outcomes. No treatment interruptions and study product related adverse events were reported in either arm. ConclusionStrataXRT® is effective for preventing, and delaying the development of grade 2 and 3 skin toxicity.Trial registration: ACTRN12616000511437.

Tenofovir disoproxil fumarate intravaginal ring for HIV pre-exposure prophylaxis in sexually active women: a phase 1, single-blind, randomised, controlled trial

An intravaginal ring that releases the tenofovir prodrug, tenofovir disoproxil fumarate, provided 100% protection in macaques against simian HIV and was safe in a 14-day clinical trial in sexually abstinent women. We aimed to assess the safety and pharmacokinetics of this intravaginal ring over 90 days in sexually active women. We did a phase 1, single-blind, randomised, placebo-controlled trial to assess safety, pharmacokinetics, and acceptability of a tenofovir disoproxil fumarate intravaginal ring used continuously with monthly ring changes for 3 months. Sexually active women who were HIV negative were randomly assigned (3:1) to a tenofovir disoproxil fumarate ring or placebo ring. Primary safety endpoint was the proportion of women who had grade 2 or higher genitourinary adverse events judged related to study product and any grade 2 or higher adverse event as defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. We quantified tenofovir disoproxil fumarate and tenofovir concentrations in cervicovaginal fluid, tenofovir in plasma, and tenofovir diphosphate, the active metabolite, in cervical tissue and dried blood spots 1 month after each ring insertion. We compared changes over time in cervicovaginal fluid cytokine and chemokine concentrations and vaginal microbiota. The study was electively stopped early and is registered with ClinicalTrials.gov, number NCT02762617. Between Feb 24 and July 20, 2017, 17 women were enrolled before study termination. 12 were assigned to receive the tenofovir disoproxil fumarate ring and five were assigned to receive the placebo ring. Two participants in the tenofovir disoproxil fumarate ring group completed 3 months of continuous ring use; eight were asked to discontinue ring use early because of ulcerations (grade 1) near the ring; in the remaining two women, rings were electively removed by study staff on day 20 and day 23. Ulcers were detected a mean of 32 days after ring use (range 23-56). Four of eight participants with ulcers were symptomatic with vaginal discharge; four had ulcers identified when examined; three had two ulcers; all ulcers resolved after ring removal. No participants in the placebo group developed ulcers. No grade 2 product-related adverse events were reported in either group and four non-product-related grade 2 adverse events were reported in the tenofovir disoproxil fumarate ring group. Cervicovaginal fluid tenofovir concentrations did not differ at day 14 (p=0·14) comparing the eight patients who did (median 1·0 × 105 ng/mL [IQR 9·1 × 104-1·1 × 105]) with the four who did not (6·0 × 104 ng/mL [5·6 × 104-1·1 × 105]) develop ulcers. No significant changes in vaginal microbiota were detected in either group. Concentrations of multiple inflammatory cytokines and chemokines were significantly higher at days 14 and 28 compared with baseline in the tenofovir disoproxil fumarate ring group but not the placebo group. Future studies are needed to establish whether the unanticipated finding of ulcerations is specific to this tenofovir disoproxil fumarate ring or generalisable to other sustained topical release formulations of tenofovir or its prodrugs. National Institutes of Health.

Safety and Clinical Outcomes of an Equine-derived Heptavalent Botulinum Antitoxin Treatment for Confirmed or Suspected Botulism in the United States.

Botulism is a rare, life-threatening paralytic illness. Botulism Antitoxin Heptavalent (A,B,C,D,E,F,G)-(Equine) (BAT) manufactured by Emergent BioSolutions Canada Inc is an equine-derived heptavalent botulinum antitoxin product indicated for the treatment of symptomatic botulism following documented or suspected exposure to botulinum neurotoxin serotypes A-G in adults and pediatric patients. BAT product was US-licensed in 2013. In the United States, from October 2014 through July 2017, safety and clinical outcomes data were collected under a registry for patients treated with BAT product. Registry patients had a median age of 51 years (range, 32 days to 92 years). Among 162 patients, 7 (4.3%) experienced BAT product-related serious adverse events, including 1 (0.6%) report each of pneumonia, pneumonia aspiration, ventricular tachycardia, upper gastrointestinal hemorrhage, anaphylactic reaction, acute kidney injury, and acute myocardial infarction. Thirty-one (19.1%) patients had 41 BAT product-related adverse events. Six (3.7%) deaths were reported in the registry. All deaths were attributed to the underlying illness and were assessed as unlikely related to BAT product. Among 113 (69.8%) patients with a final diagnosis of botulism, those treated early (≤2 days) spent fewer days in the hospital (5 vs 15.5 days), in the intensive care unit (ICU) (4 vs 12 days), and on mechanical ventilation (6 vs 14.5 days) than those treated late (>2 days), respectively. BAT product was well tolerated in patients. Treatment with BAT product at ≤2 days of symptom onset was associated with shorter hospital and ICU stays, and shorter duration and need for mechanical ventilation, showing clinical benefit associated with early treatment.