Oral Superabsorbent Hydrogel (Plenity) for Weight Management

2020 ◽  
pp. 106002802098304
Author(s):  
Alexa Pass ◽  
Damian Bialonczyk ◽  
Elaine Chiquette ◽  
Jennifer D. Goldman
Keyword(s):  
Weight Management ◽  
Safety Profile ◽  
Data Extraction ◽  
Safety Data ◽  
Clinical Trial Data ◽  
Superabsorbent Hydrogel ◽  
Study Selection ◽  
Significant Difference ◽  
Favorable Safety ◽  
Comorbidity Status

Objective To describe the mechanism, clinical trial data, adverse effects, and potential role in therapy of an oral superabsorbent hydrogel (OSH) for weight management. Data Sources A literature search was completed using MEDLINE and Google Scholar using the following search terms: oral superabsorbent hydrogel, Plenity, and Gelesis100 (September 1999 to July 2020). Abstracts and posters were identified from relevant scientific congress archives and published supplements. Study Selection and Data Extraction All available studies were considered. Only human studies were used for drug interaction, efficacy, and safety data. Data Synthesis OSH is a first-in-class, nonsystemic agent for weight management. It is indicated for use in patients with a body mass index (BMI) of 25 to 40 kg/m2 regardless of comorbidity status. OSH functions primarily through space occupancy in the stomach and small intestine. Studies have demonstrated that OSH has modest weight loss efficacy and a favorable safety profile, with no significant difference in overall adverse events compared with placebo. Relevance to Patient Care and Clinical Practice OSH is one of the only prescription antiobesity therapeutics (AOTs) that can be utilized in overweight patients with BMI equal to 25 to 30 kg/m2, regardless of comorbidity status. Given its nonsystemic mechanism of action and safety profile, OSH may help shift the focus of weight management toward patients with a lower BMI. Conclusions OSH offers a nonsystemic approach to weight management for patients who are diagnosed with overweight or obesity. As an alternative option to current pharmacological AOTs, OSH may address an existing clinical gap in weight management.

Insulin Detemir—A New Basal Insulin Analog

2005 ◽  
Vol 39 (3) ◽  
pp. 502-507 ◽  
Author(s):  
Jennifer D Goldman-Levine ◽  
Karen W Lee
Keyword(s):  
Type 2 Diabetes ◽  
Basal Insulin ◽  
Insulin Detemir ◽  
Data Extraction ◽  
Safety Data ◽  
Clinical Trial Data ◽  
Insulin Analog ◽  
Study Selection

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical trial data, adverse effects, and role in therapy of insulin detemir. DATA SOURCES: Articles and meeting abstracts were identified through searches of MEDLINE (1996–June 2004), EMBASE (1980–June 2004), and International Pharmaceutical Abstracts (1970–June 2004) databases, and unpublished information was provided by the manufacturer. STUDY SELECTION AND DATA EXTRACTION: All available studies relating to insulin detemir's pharmacology were selected. Only human studies were used for pharmacokinetic, drug interaction, efficacy, and safety data. DATA SYNTHESIS: Insulin detemir is a basal insulin analog that has been shown to improve glycemic control in patients with type 1 and type 2 diabetes. CONCLUSIONS: Insulin detemir offers some benefits over NPH for use as basal insulin in patients with type 1 and type 2 diabetes.

Brexpiprazole

2016 ◽  
Vol 51 (4) ◽  
pp. 315-322 ◽  
Author(s):  
Marija Markovic ◽  
Alyssa Gallipani ◽  
Krina H. Patel ◽  
Megan Maroney
Keyword(s):  
English Language ◽  
Data Extraction ◽  
Safety Data ◽  
Clinical Trial Data ◽  
Primary Therapy ◽  
Phase 3 ◽  
Good Tolerability ◽  
Study Selection ◽  
Animal Data

Objective: To review the pharmacology and clinical data for brexpiprazole in schizophrenia and major depressive disorder (MDD). Data Sources: An English-language literature search using PubMed and MEDLINE was performed using the term brexpiprazole. All articles containing human clinical trial data published up to September 2016 were evaluated for inclusion as well as information from the manufacturer’s product labeling. Study Selection/Data Extraction: Phase 3 trials for brexpiprazole were evaluated. Key in vitro and animal data were incorporated into the pharmacology and pharmacokinetic sections where appropriate. Data Synthesis: Four phase 3 trials have evaluated the use of brexpiprazole as a primary therapy for schizophrenia or as an antidepressant adjunct for MDD. For its schizophrenia indication, brexpiprazole was studied in 2 placebo-controlled trials of approximately 1300 patients, with 4 mg of brexpiprazole consistently showing superiority over placebo. For MDD, brexpiprazole was compared with placebo as an adjunct to antidepressants in approximately 1000 patients who had failed trials of 1 to 3 prior antidepressants. The 2-mg and 3-mg dosages of brexpiprazole showed consistent superiority over placebo in the MDD trials. Common treatment emergent adverse effects included akathisia and weight gain. Conclusions: Brexpiprazole showed efficacy for the treatment of schizophrenia in the range of 2 to 4 mg/d and as an adjunct to antidepressant therapy in MDD when dosed at 2 to 3 mg/d. Advantages of this drug include once-daily dosing, good tolerability, and lack of effect on sexual function. Disadvantages include the lack of long-term safety data and potentially high cost.

Safety of darolutamide (DARO) for nonmetastatic castration-resistant prostate cancer (nmCRPC) from extended follow-up in the phase III ARAMIS trial.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 239-239
Author(s):  
Matthew Raymond Smith ◽  
Karim Fizazi ◽  
Teuvo L. J. Tammela ◽  
Felipe Melo Cruz ◽  
Luke T. Nordquist ◽  
...  
Keyword(s):  
Safety Profile ◽  
Safety Data ◽  
Final Analysis ◽  
Phase Iii ◽  
Prolonged Treatment ◽  
Fracture Rate ◽  
Castration Resistant Prostate Cancer ◽  
Favorable Safety Profile ◽  
Risk Of Death ◽  
Favorable Safety

239 Background: DARO is a structurally distinct androgen receptor inhibitor (ARI) approved for treating nmCRPC. In ARAMIS, DARO significantly reduced the risk of death by 31% (HR = 0.69; 95% CI: 0.53-0.88; p = 0.003) and prolonged median metastasis-free survival vs placebo (PBO; 40.4 months vs 18.4 months; HR = 0.41; 95% CI: 0.34-0.50; p < 0.001). Adverse events (AEs) of interest commonly associated with ARI therapy, such as fatigue, falls, fractures, rash, mental impairment, and hypertension, as well as interactions between ARIs and concomitantly administered drugs, can impact patient daily life. In the final analysis of the double-blind (DB) period of the ARAMIS trial, DARO had a favorable safety profile, showing ≤2% difference vs PBO for most AEs of interest. Fatigue was the only AE with > 10% incidence with DARO. The incidence of permanent discontinuation due to AEs was also similar between DARO and PBO (8.9% vs 8.7%). Here we present safety data for prolonged treatment with DARO from the final analysis of the DB + open-label (OL) period of ARAMIS. Methods: Patients (pts) with nmCRPC (N = 1509) were randomized 2:1 to DARO or matched PBO while continuing androgen deprivation therapy. The data cut-off for the primary analysis of the DB period was September 3, 2018. Study unblinding occurred on November 30, 2018, after which pts in the DARO arm still receiving study treatment continued with OL DARO. The data cut-off for final analysis of the DB+OL period was November 15, 2019. Results: At the final analysis, the median treatment duration for pts randomized to DARO was 18.5 months for the DB period and 25.8 months for the DB+OL period. At the final cut-off date, 48.8% of patients in the DARO DB+OL group were still receiving DARO treatment. The increase in the incidence of any-grade AEs (85.7% vs 89.8%) and serious AEs (26.1% vs 32.1%) between the DB and DB+OL period was small. Between the DB and DB+OL periods, only minor numerical changes for ARI-associated AEs were observed. When the incidences were corrected for exposure, there were minimal differences between the DB and DB+OL period, e.g., the fracture rate was 3.4 vs 4.0 per 100 patient-years for the DB vs DB+OL periods, respectively. Fatigue was the only ARI-associated AE of interest that exhibited > 10% incidence in the DARO arm during the DB+OL period. The incidence of permanent discontinuation of DARO due to AEs increased slightly from 8.9% during the DB period to 10.5% during the DB+OL period; the incidence of discontinuation of PBO due to AEs during the DB period was 8.7%. Conclusions: With longer treatment exposure, DARO remained well-tolerated. In the DB+OL period, no new safety signals were observed. The expected increases in incidence of AEs between the DB and DB+OL periods largely disappeared when adjusted for the longer exposure, confirming the favorable safety profile of DARO with prolonged treatment. Clinical trial information: NCT02200614.

Intravenous Zanamivir: A Viable Option for Critically Ill Patients With Influenza

2020 ◽  
pp. 106002802096361
Author(s):  
Douglas Slain
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Data Extraction ◽  
Clinical Trial Data ◽  
Neuraminidase Inhibitor ◽  
European Medicines Agency ◽  
Oseltamivir Resistance ◽  
Study Selection ◽  
Available Information ◽  
Intravenous Formulation

Objective: To review the pharmacology, clinical trial data, and clinical implications for the intravenous formulation of zanamivir. Data Sources: MEDLINE, PubMed, EMBASE, and Google Scholar were searched during November 2019 to July 2020. Search terms zanamivir and neuraminidase inhibitor were used. Study Selection and Data Extraction: All human trials and major reports from compassionate use programs with the intravenous zanamivir (IVZ) formulation were assessed and reviewed here. Data Synthesis: IVZ was found to be similar but not superior to oral oseltamivir in hospitalized patients when studied in populations with very low baseline oseltamivir resistance. IVZ provides an effective alternative for critically ill patients when oral antiviral therapy is not preferred or when oseltamivir resistance is increased. Relevance to Patient Care and Clinical Practice: IVZ was recently authorized for use by the European Medicines Agency, and it is eligible for consideration in emergency use protocols and US stockpile inclusion. It will be of particular interest in critically ill patients especially during influenza seasons with appreciable oseltamivir and peramivir resistance. Conclusions: The available information suggests that the intravenous formulation of zanamivir offers a viable alternative treatment for critically ill patients with influenza, especially when resistance to other agents is present.

Respiratory Syncytial Virus Immune Globulin Intravenous

1997 ◽  
Vol 31 (1) ◽  
pp. 83-88 ◽  
Author(s):  
Todd L Wandstrat
Keyword(s):  
Clinical Trials ◽  
Respiratory Syncytial Virus ◽  
Immune Globulin ◽  
Data Extraction ◽  
Safety Data ◽  
Infants And Children ◽  
Medline Search ◽  
Study Selection ◽  
Syncytial Virus ◽  
In Infants And Children

OBJECTIVE: To review the clinical data detailing the use of respiratory syncytial virus immune globulin intravenous (RSV—IGIV) in infants and children. DATA SOURCES: A MEDLINE search (1990–1996) was used to identify all publications that dealt with RSV—IGIV clinical trials, pharmacology, and pharmacokinetics in infants and children. Bibliographies of articles were also used. STUDY SELECTION: All abstracts and clinical trials were reviewed. DATA EXTRACTION: Study design, population, efficacy, and safety data were retained. DATA SYNTHESIS: RSV—IGIV is an immunoglobulin product with serum neutralizing titers against RSV. It has been shown to reduce hospital stay, admissions, intensive care unit admissions, and mechanical ventilation days in infants and children with RSV pneumonia or bronchiolitis who are younger than 24 months of age and were born prematurely, or have bronchopulmonary dysplasia. RSV—IGIV is well tolerated by infants and children. CONCLUSIONS: RSV—IGIV is an effective prophylactic agent against serious RSV disease in select groups of infants and children.

A Blast From the Past: Revival of Angiotensin II for Vasodilatory Shock

2018 ◽  
Vol 52 (9) ◽  
pp. 920-927 ◽  
Author(s):  
Brittany D. Bissell ◽  
Kelsey Browder ◽  
Matt McKenzie ◽  
Alexander H. Flannery
Keyword(s):  
Angiotensin Ii ◽  
Data Extraction ◽  
Peptide Hormone ◽  
Vasodilatory Shock ◽  
Vasoactive Agent ◽  
Data Synthesis ◽  
Medline Search ◽  
Study Selection ◽  
Significant Difference ◽  
Distributive Shock

Objective: To review and summarize data on angiotensin II (AT-II), approved by the Food and Drug Administration (FDA) in December 2017 to increase blood pressure in adults with septic or other distributive shock. Data Sources: A PubMed/MEDLINE search was conducted using the following terms: (angiotensin ii OR angiotensin 2) AND (shock) from 1966 to February 2018. Study Selection and Data Extraction: A total of 691 citations were reviewed with only relevant clinical data extracted. Data Synthesis: AT-II is a peptide hormone with a multitude of physiological effects—namely, vasoconstriction of venous and arterial smooth muscle. The priority approval granted by the FDA was secondary to a phase 3 study of patients receiving at least 0.2 µg/kg/min of norepinephrine or equivalent for vasodilatory shock. Compared with placebo, AT-II had a significantly higher rate of response, defined as a mean arterial pressure of 75 mm Hg or an increase of 10 mm Hg. No significant difference was found in death by day 28. Conclusions: AT-II is a newly available vasoactive agent with a novel mechanism for the treatment of distributive shock. Further research is needed to define its exact role in therapy of shock states, identify patients most likely to benefit, and further study its safety profile in critical illness.

Final results: A dose escalation phase I study of ARQ 197, a selective c-Met inhibitor, in patients with metastatic solid tumors

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3548-3548 ◽  
Author(s):  
T. Mekhail ◽  
T. Rich ◽  
L. Rosen ◽  
F. Chai ◽  
Z. Semic-Suka ◽  
...  
Keyword(s):  
Phase I ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Safety Profile ◽  
Safety Data ◽  
Dose Escalation Study ◽  
Tumor Cell Migration ◽  
Drug Concentrations ◽  
Arq 197 ◽  
Favorable Safety

3548 Background: ARQ 197 is a selective, non-ATP competitive inhibitor of c-Met, a receptor tyrosine kinase implicated in tumor cell migration, invasion, and proliferation. Methods: This phase I dose escalation study enrolled patients (pts) with metastatic solid tumors to determine the drug's safety profile, maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), pharmacokinetics (PK), and preliminary antitumor activity. Dose escalation followed an accelerated titration design and was modified to the traditional escalation design (3+3 pts) once grade 2 toxicity was observed. ARQ 197 was initially administered orally twice daily (BID) for 2 weeks followed by 1 week off and then modified to evaluate continuous BID dosing based on favorable safety data. Intra-patient dose-escalation was allowed in this study. Additional pts were enrolled and treated at the 360 mg bid continuous dose, which was determined to be the RP2D in another phase I clinical trial. Results: To date, 65 pts (38 male/27 female; median age 61; 9 colon/colorectal, 8 renal cell carcinoma/kidney, 6 ovarian, 6 sarcoma, 5 lung cancer and 31 others) have been treated at 11 dose levels (10 mg bid to 360 mg bid). All treated pts achieved plasma drug concentrations significantly above in vitro IC50 values. The most common drug-related adverse events (AEs) were fatigue (18.5%) and nausea (12.3%). One case each of the following drug-related serious AEs were reported in 4 pts: anemia, leukopenia, neutropenia, thrombocytopenia, dehydration, liver failure, abdominal pain, nausea, and vomiting. Three pts with neuroendocrine, prostate, or testicular cancer achieved a partial response (PR), 32 demonstrated stable disease (SD) and 13 progressed. The 3 PR pts were initially treated at 10, 40 or 90 mg BID respectively. Their doses were escalated to 50, 70, or 120 mg BID respectively after 18 to 33 weeks on treatment. An overall response rate of 6.3% and a disease control rate (CR+PR+SD) of 72.9% were demonstrated among 48 pts who are evaluable for efficacy. Conclusions: ARQ 197 has demonstrated a favorable safety profile up to the dose of 360 mg bid. Preliminary evidence of anti-cancer activity was observed. Final study data on drug safety, PK and efficacy will be presented. [Table: see text]

Larotrectinib efficacy and safety in adult TRK fusion cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3122-3122 ◽  
Author(s):  
David S. Hong ◽  
Shivaani Kummar ◽  
Anna F. Farago ◽  
Ulrik Niels Lassen ◽  
Jordan Berlin ◽  
...  
Keyword(s):  
Disease Progression ◽  
Safety Profile ◽  
Safety Data ◽  
Disease Status ◽  
Bone Sarcoma ◽  
Primary Diagnosis ◽  
Efficacy And Safety ◽  
Favorable Safety Profile ◽  
Duration Of Response ◽  
Favorable Safety

3122 Background: A broad range of pediatric and adult malignancies harbor TRK fusions involving the NTRK1, NTRK2, and NTRK3 genes. The highly-selective TRK inhibitor, larotrectinib, has previously shown a high overall response rate (ORR) and a favorable safety profile in patients (pts) with TRK fusion cancer. To better delineate efficacy in adults, as pediatric pts have a particularly high ORR, here we report updated efficacy and safety data from the adult subset of pts with TRK fusion cancer treated with larotrectinib. Methods: Adult pts (aged 18 or older) with TRK fusion cancer detected by local testing in 2 larotrectinib clinical trials (NCT02122913 and NCT02576431) were analyzed. Larotrectinib was administered 100 mg PO BID until disease progression, withdrawal, or unacceptable toxicity. Disease status was assessed by both investigator (INV) and independent assessment (IRC) using RECIST v1.1. Results: As of July 30, 2018, 83 adults (median age: 57 y, range 20–80 y) with TRK fusion cancer had been treated. Cancer types included salivary gland (23%) and thyroid cancer (19%), soft tissue sarcoma (14%), lung cancer (13%), colon cancer and melanoma (7% each), GIST (5%), and bone sarcoma, cholangiocarcinoma, and appendiceal, breast, and pancreas cancer (≤2% each). TRK fusions involved NTRK1 (40%), NTRK2 (2%), and NTRK3 (57%). 77% of pts had received prior systemic therapy (median lines: 2, range 0–10). In 74 pts evaluable per INV, the ORR was 76% with 9% CR, 57% confirmed PR, 9% PR pending confirmation, 12% SD, 11% PD, and 1% not determined; 9 pts were non-evaluable (NE) due to lack of post-baseline assessment. In 65 pts evaluable per IRC, the ORR was 68% with 17% CR, 51% PR, 15% SD, 12% PD, and 5% NE. With a median follow up of 17.2 and 17.5 mo per INV and IRC, respectively, the median duration of response had not been reached (ranges identical: 1.9+ to 38.7+ months). At data cutoff, 63% remained on treatment; 30% had discontinued due to disease progression. Adverse events were mostly grade 1–2. Conclusions: Larotrectinib demonstrated robust tumor-agnostic efficacy and a favorable safety profile in adult pts with TRK fusion cancer. These results support testing for TRK fusion cancer in pts with advanced solid tumors, regardless of site of primary diagnosis. Clinical trial information: NCT02122913 and NCT02576431.

IMpower110: Clinical safety in a phase III study of atezolizumab (atezo) monotherapy (mono) vs platinum-based chemotherapy (chemo) in first-line non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21623-e21623 ◽  
Author(s):  
Jacek Jassem ◽  
Roy S. Herbst ◽  
Filippo de Marinis ◽  
Jacques Cadranel ◽  
Tibor Csőszi ◽  
...  
Keyword(s):  
Safety Profile ◽  
Safety Data ◽  
Stage Iv ◽  
Phase Iii ◽  
Low Grade ◽  
Clinical Safety ◽  
Meaningful Improvement ◽  
Platinum Based Chemotherapy ◽  
Ecog Ps ◽  
Favorable Safety

e21623 Background: IMpower110 evaluated atezo mono in PD-L1–selected, chemo-naive patients (pts) with nonsquamous (nsq) or squamous (sq) NSCLC. At the interim analysis, IMpower110 met its primary OS endpoint, with a statistically significant and clinically meaningful improvement for atezo vs chemo in TC3 or IC3 wild-type ( EGFR/ALK-negative) pts. We report on the safety profile of atezo vs chemo in IMpower110. Methods: 572 pts with stage IV nsq or sq NSCLC, PD-L1 expression ≥ 1% on TC or IC and ECOG PS 0-1 were randomized 1:1 to receive atezo (1200 mg IV q3w) or chemo (4 or 6 21-day cycles). In the chemo arm, nsq pts received cisplatin (cis) 75 mg/m2 or carboplatin (carbo) AUC 6 + pemetrexed (pem) 500 mg/m2 IV q3w; sq pts received cis 75 mg/m2 + gemcitabine (gem) 1250 mg/m2 or carbo AUC 5 + gem 1000 mg/m2 IV q3w. Safety was assessed in all treated pts (safety evaluable [SE] population [pop]), regardless of PD-L1 expression or EGFR/ALK status. AEs were summarized per MedDRA v22.0 and severity graded per NCI CTCAE v4.0. Immune-mediated AEs (imAEs) were defined per a sponsor-specified list of terms, regardless of whether the events led to systemic glucocorticoid, endocrine therapy, or other immunosuppressants use. Results: At data cutoff (Sep 10, 2018) within the ITT pop, treatment (tx) was ongoing in 90 (atezo: 31.6%) and 25 (chemo: 8.7%) pts, with 13.7 mo of follow-up. Within the SE pop (atezo: n = 286, chemo: n = 263), atezo pts had longer tx exposure (5.3 mo) vs chemo pts (pem, 3.5 mo; gem, 2.6 mo; carbo, 2.3 mo; cis, 2.1 mo). Atezo had a favorable safety profile vs chemo (table); safety data were consistent with data from a pooled atezo mono pop. imAEs occurred in 40.2% (atezo) and 16.7% (chemo) of pts and were Grade (Gr) 3-4 in 6.6% and 1.5%, respectively. Conclusions: Atezo was better tolerated than chemo and imAEs were generally low grade. Overall, the safety experience with atezo mono in IMpower110 was consistent with its known safety profile; no new safety signals were identified. Clinical trial information: NCT02409342. [Table: see text]

scholarly journals Jingtong Granule: A Chinese Patent Medicine for Cervical Radiculopathy

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Liguo Zhu ◽  
Jinghua Gao ◽  
Jie Yu ◽  
Minshan Feng ◽  
Jinyu Li ◽  
...  
Keyword(s):  
Treatment Effects ◽  
Data Extraction ◽  
Meta Analysis ◽  
Neck Disability Index ◽  
Cervical Radiculopathy ◽  
Pain Scores ◽  
Study Selection ◽  
Significant Difference ◽  
Methodological Assessment ◽  
Neck Disability

Objective. This paper systematically assessed the efficacy and safety of Jingtong granule (JG) for cervical radiculopathy (CR).Methods. Randomized controlled trials comparing JG with no intervention, placebo, or conventional therapies were retrieved. The trials testing JG combined with conventional therapies versus conventional therapies were also enrolled. Study selection, methodological assessment, data extraction, and analysis were conducted in accordance with the Cochrane standards. The strength of evidence was evaluated according to GRADE approach.Results. Three trials with 400 participants were included. Methodological quality was evaluated as generally low. One study found that JG showed significant difference on decreasing pain scores compared with placebo. Meta-analysis indicated that JG plus conventional analgesic exhibited a significant immediate effect on the pain scores (WMD = 1.63; 95% CI: 1.29 to 1.98;P<0.00001). Additionally, JG combined with analgesic presented beneficial immediate effect on neck disability index. However, the treatment effects of JG demonstrated in the trials were not large, and the safety of JG was unproven. Finally the evidence level was evaluated to be low.Conclusions. Our results indicated that JG showed some potential benefits for CR. Nevertheless, treatment effects are uncertain due to both the methodological concerns and the very modest reported improvements.

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