Pharmacokinetics, Pharmacodynamics, Bioavailability, and Immunogenicity of Obexelimab Following Subcutaneous Administration in Healthy Japanese and Non-Japanese Volunteers.

Introduction: Obexelimab is an investigational, bifunctional, non-depleting, humanized monoclonal antibody that binds CD19 and FcγRIIb to inhibit B cells, plasmablasts, and CD19-expressing plasma cells. In clinical trials, intravenous (IV) administration of obexelimab has been well-tolerated, and demonstrated clinical activity in patients with rheumatoid arthritis, systemic lupus erythematosus, and immunoglobulin G4-related disease. This study was performed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of obexelimab following subcutaneous (SC) administration, and compare PK/PD profiles between healthy Japanese and non-Japanese volunteers.

Obexelimab in Systemic Lupus Erythematosus With Exploration of Response Based on Gene Pathway Co-Expression Patterns: A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial.

Objective: Obexelimab is an investigational, bifunctional, noncytolytic monoclonal antibody that binds CD19 and FcyRIIb to inhibit B cells, plasmablasts, and plasma cells. This trial evaluated the efficacy and safety of obexelimab in the treatment of patients with systemic lupus erythematosus (SLE).

Methods: During screening, patients with active, non-organ-threatening SLE received corticosteroid injections to ameliorate symptoms while immunosuppressants were withdrawn (≤10 mg/day prednisone equivalent and ≤400 mg/day hydroxychloroquine allowed).

Single-Arm Phases 1 and 2 Trial of Niraparib in Combination With Pembrolizumab in Patients With Recurrent Platinum-Resistant Ovarian Carcinoma.

Importance: Patients with recurrent ovarian carcinoma frequently develop resistance to platinum-based chemotherapy, at which time treatment options become limited.

Objective: To evaluate the poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor niraparib combined with pembrolizumab in patients with recurrent ovarian carcinoma.

Design, Setting, And Participants: The TOPACIO/KEYNOTE-162 (Niraparib in Combination With Pembrolizumab in Patients With Triple-Negative Breast Cancer or Ovarian Cancer) trial, an open-label, single-arm phases 1 and 2 study enrolled women with advanced or metastatic triple-negative breast cancer (TNBC) or recurrent ovarian carcinoma, irrespective of BRCA mutation status.

Open-label Clinical Trial of Niraparib Combined With Pembrolizumab for Treatment of Advanced or Metastatic Triple-Negative Breast Cancer.

Importance: Poly(adenosine diphosphate-ribose) polymerase inhibitor and anti-programmed death receptor-1 inhibitor monotherapy have shown limited clinical activity in patients with advanced triple-negative breast cancer (TNBC).

Objective: To evaluate the clinical activity (primary) and safety (secondary) of combination treatment with niraparib and pembrolizumab in patients with advanced or metastatic TNBC.

Design, Setting, And Participants: This open-label, single-arm, phase 2 study enrolled 55 eligible patients with advanced or metastatic TNBC irrespective of BRCA mutation status or programmed death-ligand 1 (PD-L1) expression at 34 US sites.

Niraparib Maintenance Therapy in Patients With Recurrent Ovarian Cancer After a Partial Response to the Last Platinum-Based Chemotherapy in the ENGOT-OV16/NOVA Trial.

Purpose: In the ENGOT-OV16/NOVA trial (ClinicalTrials.gov identifier: NCT01847274), maintenance therapy with niraparib, a poly(ADP-ribose) polymerase inhibitor, prolonged progression-free survival in patients with platinum-sensitive, recurrent ovarian cancer who had a response to their last platinum-based chemotherapy. The objective of the study was to assess the clinical benefit and patient-reported outcomes in patients who had a partial response (PR) and complete response (CR) to their last platinum-based therapy.

Pharmacokinetic Interactions of Rolapitant With Cytochrome P450 3A Substrates in Healthy Subjects.

Rolapitant (Varubi) is a neurokinin-1 receptor antagonist approved for the prevention of chemotherapy-induced nausea and vomiting. Rolapitant is primarily metabolized by the cytochrome P450 3A4 (CYP3A4) enzyme. Unlike other neurokinin-1 receptor antagonists, rolapitant is neither an inhibitor nor an inducer of CYP3A4 in vitro.

Pharmacokinetics, Safety, and Tolerability of Rolapitant Administered Intravenously Following Single Ascending and Multiple Ascending Doses in Healthy Subjects.

Rolapitant is a selective and long-acting neurokinin-1 receptor antagonist approved in an oral formulation in combination with dexamethasone and a 5-hydroxytryptamine type 3 receptor antagonist for the prevention of delayed chemotherapy-induced nausea and vomiting in adults. The pharmacokinetic and safety profiles of intravenous (IV) rolapitant were evaluated in two open-label, phase 1 trials in healthy subjects. Single ascending dose (SAD) and multiple ascending dose studies were conducted in one trial (PR-11-5012-C), and a supratherapeutic SAD study was conducted in a separate trial (PR-11-5022-C).

Rolapitant for the prevention of nausea in patients receiving highly or moderately emetogenic chemotherapy.

Most patients receiving highly or moderately emetogenic chemotherapy experience chemotherapy-induced nausea and vomiting without antiemetic prophylaxis. While neurokinin-1 receptor antagonists (NK-1RAs) effectively prevent emesis, their ability to prevent nausea has not been established. We evaluated the efficacy of the long-acting NK-1RA rolapitant in preventing chemotherapy-induced nausea using post hoc analyses of data from 3 phase 3 trials.

Pharmacokinetics of Rolapitant in Patients With Mild to Moderate Hepatic Impairment.

Rolapitant is a selective and long-acting neurokinin-1 receptor antagonist approved in an oral formulation in combination with other antiemetic agents for the prevention of delayed chemotherapy-induced nausea and vomiting in adults. This was a phase 1 open-label, parallel-group pharmacokinetic and safety study of a single oral dose of 180 mg of rolapitant and its major active metabolite, M19, in subjects with mild and moderate hepatic impairment compared with healthy matched controls. Pharmacokinetics were assessed by a mixed-model analysis of variance of log-transformed values for maximum observed plasma concentration (C ), observed time at C (t ), area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUC ), and AUC from time 0 to 120 hours (AUC ), with hepatic group as a fixed effect.

Bioequivalence of Intravenous and Oral Rolapitant: Results From a Randomized, Open-Label Pivotal Study.

Rolapitant, a selective and long-acting neurokinin-1 receptor antagonist, is approved in an oral formulation for the prevention of delayed chemotherapy-induced nausea and vomiting in adults. The objective of this pivotal study was to assess the bioequivalence of a single intravenous infusion of rolapitant versus a single oral dose of rolapitant. In this randomized, open-label phase 1 study, healthy volunteers were administered rolapitant as a 180-mg oral dose or a 30-minute 166.

Effects of Rolapitant Administered Intravenously or Orally on the Pharmacokinetics of Digoxin (P-glycoprotein Substrate) and Sulfasalazine (Breast Cancer Resistance Protein Substrate) in Healthy Volunteers.

Rolapitant is a selective and long-acting neurokinin-1 receptor antagonist approved in an oral formulation in combination with other antiemetic agents for the prevention of delayed chemotherapy-induced nausea and vomiting in adults. Four open-label phase 1 studies evaluated the safety and drug-drug interactions of a single dose of rolapitant given intravenously (166.5 mg) or orally (180 mg) with oral digoxin (0.

Rolapitant improves quality of life of patients receiving highly or moderately emetogenic chemotherapy.

Purpose: Addition of rolapitant to standard antiemetic therapy improved protection against chemotherapy-induced nausea and vomiting (CINV) in phase 3 trials of patients receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Here, we assessed the impact of CINV on the daily lives of patients receiving HEC or MEC using the Functional Living Index-Emesis (FLIE).

Methods: In three double-blind phase 3 studies, patients receiving HEC or MEC were randomized 1:1 to receive oral rolapitant 180 mg or placebo prior to chemotherapy plus 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone therapy.

Efficacy of the neurokinin-1 receptor antagonist rolapitant in preventing nausea and vomiting in patients receiving carboplatin-based chemotherapy.

Background: Rolapitant, a novel neurokinin-1 receptor antagonist, provided effective protection against chemotherapy-induced nausea and vomiting (CINV) in a randomized, double-blind phase 3 trial of patients receiving moderately emetogenic chemotherapy or an anthracycline and cyclophosphamide regimen. The current analysis explored the efficacy and safety of rolapitant in preventing CINV in a subgroup of patients receiving carboplatin.

Methods: Patients were randomized 1:1 to receive oral rolapitant (180 mg) or a placebo 1 to 2 hours before chemotherapy administration; all patients received oral granisetron (2 mg) on days 1 to 3 and oral dexamethasone (20 mg) on day 1.

Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting over multiple cycles of moderately or highly emetogenic chemotherapy.

Objective: Rolapitant, a novel neurokinin-1 receptor antagonist (RA), was shown to protect against delayed chemotherapy-induced nausea and vomiting (CINV) during the first cycle of moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) in randomized, double-blind trials. This analysis explored the efficacy and safety of rolapitant in preventing CINV over multiple cycles of MEC or HEC.

Patients And Methods: Patients in one phase III MEC, one phase II HEC, and two phase III HEC clinical trials were randomized to receive oral rolapitant (180 mg) or placebo in combination with a 5-hydroxytryptamine type 3 RA and dexamethasone.

Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of cisplatin-based highly emetogenic chemotherapy in patients with cancer: two randomised, active-controlled, double-blind, phase 3 trials.

Background: Highly emetogenic chemotherapy induces emesis in almost all patients in the absence of prophylaxis. Guidelines recommend use of a neurokinin-1 (NK-1) receptor antagonist in conjunction with a 5-HT3 receptor antagonist and corticosteroid in patients receiving highly emetogenic chemotherapy. We aimed to assess rolapitant, an NK-1 receptor antagonist, for prevention of chemotherapy-induced nausea and vomiting in patients with cancer after administration of cisplatin-based highly emetogenic chemotherapy.

Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of moderately emetogenic chemotherapy or anthracycline and cyclophosphamide regimens in patients with cancer: a randomised, active-controlled, double-blind, phase 3 trial.

Background: Chemotherapy-induced nausea and vomiting is a common side-effect of many antineoplastic regimens and can occur for several days after treatment. We aimed to assess the neurokinin-1 receptor antagonist rolapitant, in combination with a serotonin (5-HT3) receptor antagonist and dexamethasone, for the prevention of chemotherapy-induced nausea and vomiting in patients with cancer after administration of moderately emetogenic chemotherapy or regimens containing an anthracycline and cyclophosphamide.

Methods: We conducted a global, randomised, double-blind, active-controlled, phase 3 study at 170 cancer centres in 23 countries.

Study of rolapitant, a novel, long-acting, NK-1 receptor antagonist, for the prevention of chemotherapy-induced nausea and vomiting (CINV) due to highly emetogenic chemotherapy (HEC).

Purpose: Rolapitant is a novel, long-acting neurokinin-1 (NK-1) receptor antagonist. This study evaluated the safety and efficacy of four different doses of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) due to highly emetogenic chemotherapy (HEC).

Methods: This randomized, double-blind, active-controlled, global study was conducted in patients receiving cisplatin-based chemotherapy ≥70 mg/m(2).

Multicenter study of decitabine administered daily for 5 days every 4 weeks to adults with myelodysplastic syndromes: the alternative dosing for outpatient treatment (ADOPT) trial.

Purpose: Decitabine, a DNA-targeted hypomethylating agent, is approved by the United States Food and Drug Administration for treatment of patients with myelodysplastic syndromes (MDS) on a schedule of 15 mg/m(2) administered via intravenous (IV) infusion every 8 hours for 3 days. This study assessed the efficacy and safety of an alternative dosing regimen administered on an outpatient basis in academic and community-based practices.

Patients And Methods: Patients were treated with decitabine 20 mg/m(2) by IV infusion daily for 5 consecutive days every 4 weeks.

Evaluation of imiquimod 5% cream to modify the natural history of herpes labialis: a pilot study.

Background: Imiquimod is currently approved for the treatment of genital warts and has been shown to decrease recurrences of genital herpes in the guinea pig model of genital herpes. Therefore, we evaluated the safety and potential of topical imiquimod to decrease the rate of recurrence in humans with a history of recurrent herpes labialis.

Methods: Forty-seven subjects with recurrent herpes labialis applied imiquimod 5% (n=30) or vehicle cream (n=17) to recurrent lesion(s) on days 1, 3, and 5 of the study (day 1 of observation occurred within 48 h after recurrence of lesion).

Switching from conventional to extrafine aerosol beclomethasone dipropionate therapy in children: a 6-month, open- label, randomized trial.

Background: In adults with asthma, hydrofluoralkane-134a beclomethasone dipropionate (HFA-BDP) extrafine aerosol provides equivalent asthma control at half the daily dose of conventional chlorofluorocarbon (CFC)-BDP.

Objective: We sought to compare the efficacy and tolerability of switching from CFC-BDP to HFA-BDP at half the daily dose in children with stable asthma.

Methods: This 6-month, open-label, randomized, multicenter study enrolled 520 children aged 5 to 11 years with well-controlled asthma receiving inhaled CFC-BDP or budesonide 200 to 800 microg/d x.

Growth, systemic safety, and efficacy during 1 year of asthma treatment with different beclomethasone dipropionate formulations: an open-label, randomized comparison of extrafine and conventional aerosols in children.

Objective: To assess the long-term safety of hydrofluoroalkane 134a (HFA)-beclomethasone dipropionate (BDP) extrafine aerosol administered by the Autohaler compared with chlorofluorocarbon (CFC)-BDP administered by a press-and-breathe metered-dose inhaler (pMDI) and spacer (+S) in the treatment of children with asthma.

Methods: This 12-month, open-label, randomized, multicenter study enrolled 300 children who were aged 5 to 11 years and had well-controlled asthma on inhaled CFC-BDP or budesonide; 256 patients were using doses within the recommended range (200-400 microg) and were analyzed separately. Patients were randomized in a 1:3 ratio to continue on CFC-BDP+S at approximately the same dose as they were using before study entry or switch to HFA-BDP at half the daily dose.