Abstract 760: A randomized, crossover, phase 1 study to evaluate the effect of a strong CYP3A4 inhibitor on tivantinib (ARQ 197) pharmacokinetics in healthy subjects

2012 ◽  
Author(s):  
Hamim Zahir ◽  
Toshihiro Oguma ◽  
Daniel Weiss ◽  
Joseph Walker ◽  
Taro Tokui
Keyword(s):  
Healthy Subjects ◽  
Phase 1 ◽  
Cyp3a4 Inhibitor ◽  
Phase 1 Study ◽  
Arq 197 ◽  
Crossover Phase

Evaluation of the effect of food and age on the pharmacokinetics of oral netupitant and palonosetron in healthy subjects: A randomized, open-label, crossover phase 1 study

2015 ◽  
Vol 4 (5) ◽  
pp. 377-386 ◽  
Author(s):  
Selma Calcagnile ◽  
Corinna Lanzarotti ◽  
Michaela Gutacker ◽  
Verena Jakob-Rodamer ◽  
Klaus Peter Kammerer ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Phase 1 ◽  
Open Label ◽  
Phase 1 Study ◽  
Crossover Phase ◽  
Effect Of Food

A Phase 1 Study to Evaluate the Effect of Crushing, Cutting Into Half, or Grinding of Glecaprevir/Pibrentasvir Tablets on Exposures in Healthy Subjects

2018 ◽  
Vol 107 (6) ◽  
pp. 1724-1730 ◽  
Author(s):  
Rajneet K. Oberoi ◽  
Weihan Zhao ◽  
Dilraj S. Sidhu ◽  
Rolando M. Viani ◽  
Roger Trinh ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Phase 1 ◽  
Phase 1 Study

A phase 1 study to assess potential interaction between ASP8062 and alcohol in healthy adult subjects

2022 ◽  
pp. 026988112110589
Author(s):  
Mototsugu Ito ◽  
Anna Spence ◽  
Mary Beth Blauwet ◽  
Nakyo Heo ◽  
Ronald Goldwater ◽  
...  
Keyword(s):  
Phase 1 ◽  
Pharmacokinetic Interaction ◽  
Opioid Use Disorder ◽  
Potential Interaction ◽  
Analysis Of Covariance ◽  
Opioid Use ◽  
Phase 1 Study ◽  
Double Blind ◽  
Pharmacodynamic Interaction ◽  
Crossover Phase

Background: ASP8062 is a novel orally active GABAB receptor positive allosteric modulator in clinical development for the treatment of alcohol use disorder (AUD) and opioid use disorder (OUD). Aims: This study assessed the potential pharmacokinetic/pharmacodynamic interaction between ASP8062 and alcohol under single-dose conditions in healthy adults. Methods: A double-blind, placebo-controlled, crossover phase 1 study was conducted in which 20 subjects were randomly assigned to four treatment sequences (ASP8062 + alcohol; ASP8062 + placebo alcohol; placebo + alcohol; placebo + placebo alcohol) each consisting of four treatment periods, separated by washout periods of at least 14 days. An analysis of variance was used to assess pharmacokinetic interaction and a mixed-effects analysis of covariance was used to assess pharmacodynamic interaction. Results/outcomes: After administration of alcohol, a mild to minimal increase in plasma exposure (AUCinf and Cmax) of ASP8062 was observed, but tmax and t½ for ASP8062 remained unchanged after administration of alcohol. In contrast, ASP8062 did not affect the AUClast and Cmax of ethanol. No clinically relevant differences in cognition measurements were observed with ASP8062 compared with placebo, but there were expected impairments in psychomotor and executive function with alcohol alone. ASP8062 in combination with alcohol resulted in worse scores in cognition measurements than alcohol alone, but this potentiation was not consistent. ASP8062 administered alone was safe and well-tolerated and safety findings in subjects administered alcohol alone were not augmented when ASP8062 was administered in combination with alcohol. Conclusion/interpretation: The data support further clinical studies investigating ASP8062 in patients with AUD.

SAT-341-MET409, an optimized sustained FXR agonist, was safe and well-tolerated in a 14-day phase 1 study in healthy subjects

2019 ◽  
Vol 70 (1) ◽  
pp. e789
Author(s):  
Hubert Chen ◽  
Karl Cremer ◽  
Eric Bischoff ◽  
Kyoung-Jin Lee ◽  
Rozalyn Littler ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Phase 1 ◽  
Phase 1 Study

scholarly journals A first-in-human phase 1 study of ACE910, a novel factor VIII–mimetic bispecific antibody, in healthy subjects

Blood ◽  
2016 ◽  
Vol 127 (13) ◽  
pp. 1633-1641 ◽  
Author(s):  
Naoki Uchida ◽  
Takehiko Sambe ◽  
Koichiro Yoneyama ◽  
Naoki Fukazawa ◽  
Takehiko Kawanishi ◽  
...  
Keyword(s):  
Factor Viii ◽  
Half Life ◽  
Healthy Subjects ◽  
Bispecific Antibody ◽  
Phase 1 ◽  
Procoagulant Activity ◽  
Phase 1 Study ◽  
Key Points ◽  
White Adults

Key Points Single subcutaneous dosing of ACE910 has a linear PK profile, a half-life of 4 to 5 weeks, and FVIII-mimetic procoagulant activity in humans. ACE910 at doses up to 1 mg/kg is well tolerated and has no notable adverse hypercoagulable effect in healthy Japanese and white adults.

scholarly journals O83 Phase 1 study of an anti-CD27 agonist as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors

2020 ◽  
Vol 8 (Suppl 1) ◽  
pp. A2.1-A2
Author(s):  
Ronnie Shapira-Frommer ◽  
Marloes GJ van Dongen ◽  
Konstantin Dobrenkov ◽  
Elliot Chartash ◽  
Fang Liu ◽  
...  
Keyword(s):  
Adverse Events ◽  
Solid Tumors ◽  
Phase 1 ◽  
Fixed Dose ◽  
Advanced Solid Tumors ◽  
Phase 1 Study ◽  
Grade 5 ◽  
Crossover Phase ◽  
Grade 3 ◽  
Ecog Ps

BackgroundMK-5890 is a humanized agonist monoclonal antibody that binds to CD27 to provide a costimulatory signal that enhances T-cell–mediated responses. This first-in-human phase 1 study of MK-5890 evaluated the safety and efficacy of escalating doses of MK-5890 as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors.MethodsKey eligibility criteria included histologically or cytologically confirmed advanced solid tumor, measurable disease by RECIST v1.1, and ECOG PS ≤1. MK-5890 was tested alone (dose range, 2-700 mg) or with pembrolizumab (fixed dose, 200 mg). Patients with disease progression following MK-5890 monotherapy were eligible to cross over to combination treatment. The primary objective was safety and tolerability. Objective response rate by investigator per RECIST v1.1 was also evaluated. The database cutoff for this analysis was May 30, 2019.ResultsOf 44 patients enrolled, 25 received MK-5890 and 19 received MK-5890 plus pembrolizumab; their median age was 59.0 years, 61.4% were female, 47.7% had ECOG PS 1, and 13.6% previously received immune checkpoint inhibitor therapy. In the initial phase, dose-limiting toxicities (DLTs) were reported in 3 patients receiving MK-5890 and 1 patient receiving MK-5890 plus pembrolizumab; all DLTs were associated with infusion-related adverse events. Maximum tolerated dose was defined. Treatment-related adverse events (TRAEs) were reported in 40 patients (90.9%): 22 patients (88.0%) receiving MK-5890 and 18 patients (94.7%) receiving MK-5890 plus pembrolizumab. The most common TRAEs were fatigue (28.0%) and infusion-related reactions (28.0%) with MK-5890 and fatigue (36.8%) and pruritus (31.6%) with MK-5809 plus pembrolizumab. Grade 3-4 TRAEs were reported in 10 patients (22.7%): 6 patients (24.0%) receiving MK-5890 and 4 patients (21.1%) receiving MK-5890 plus pembrolizumab; no grade 5 events were observed. One patient (4.0%) achieved a partial response (PR) with MK-5890 and 1 patient (5.3%) achieved a PR with MK-5890 plus pembrolizumab. Fourteen patients entered the crossover phase to receive MK-5890 plus pembrolizumab. In the crossover phase, no DLTs were reported. TRAEs were reported in 12 patients (85.7%); the most common were pruritus (21.4%), rash (21.4%), and headache (14.3%). One patient (7.1%) reported grade 3-4 TRAEs of increased amylase and increased lipase; no grade 5 events were observed. Two patients (14.3%) achieved a complete response and 2 patients (14.3%) achieved a PR.ConclusionsTreatment with MK-5890, alone and in combination with pembrolizumab, demonstrated an acceptable safety profile. Early antitumor activity was observed in patients with advanced solid tumors in both monotherapy and combination therapy arms.

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