scholarly journals Effect of Vicriviroc on the QT/Corrected QT Interval and Central Nervous System in Healthy Subjects

2010 ◽  
Vol 54 (6) ◽  
pp. 2448-2454 ◽  
Author(s):  
Edward O'Mara ◽  
Claudia Kasserra ◽  
John Robert Huddlestone ◽  
Yuntao Wan ◽  
Peter Soni ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Single Dose ◽  
Healthy Subjects ◽  
Third Party ◽  
Qtc Interval ◽  
Two Phase ◽  
Parallel Group Study ◽  
Parallel Group ◽  
The Central Nervous System

ABSTRACT Vicriviroc is a CCR5 antagonist in clinical development for the treatment of HIV-1. Two phase I studies were conducted to assess the safety of vicriviroc. One study characterized the drug's potential to prolong the QT/corrected QT (QTc) interval and to induce arrhythmia. In this partially blind, parallel-group study, 200 healthy subjects aged 18 to 50 years were randomized in equal groups to the following regimens: (i) placebo for 9 days and a single dose of moxifloxacin at 400 mg on day 10, (ii) placebo, (iii) vicriviroc-ritonavir (30 and 100 mg), (iv) vicriviroc-ritonavir (150 and 100 mg), and (v) ritonavir (100 mg). The second study characterized the effects of a range of vicriviroc doses on the central nervous system (CNS). In this third-party-blind, parallel-group study, 30 healthy subjects aged 18 to 48 years were randomized to receive a single dose of either vicriviroc at 200, 250, or 300 mg or placebo, followed by multiple (seven) once-daily doses of either vicriviroc at 150, 200, or 250 mg or placebo, respectively. In the first study, vicriviroc produced no clinically meaningful effect on the QT/QTc interval when administered at a supratherapeutic or therapeutic dose concurrently with ritonavir. In the second study, vicriviroc produced no observable seizure activity, nor was it held to be associated with any clinically relevant changes in brain waveforms in the final consensus of reviewers. These findings showed that vicriviroc produced no clinically relevant QTc prolongation cardiac or epileptogenic effects in healthy individuals at exposures as high as five times those expected for HIV-infected patients receiving therapeutic doses of vicriviroc in a ritonavir-boosted protease inhibitor-containing regimen.

scholarly journals A randomised, single-blind, single-dose, three-arm, parallel-group study in healthy subjects to demonstrate pharmacokinetic equivalence of ABP 501 and adalimumab

2016 ◽  
Vol 76 (3) ◽  
pp. 526-533 ◽  
Author(s):  
Primal Kaur ◽  
Vincent Chow ◽  
Nan Zhang ◽  
Michael Moxness ◽  
Arunan Kaliyaperumal ◽  
...  
Keyword(s):  
Single Dose ◽  
Healthy Subjects ◽  
Study Groups ◽  
Time Curve ◽  
End Points ◽  
Parallel Group Study ◽  
Parallel Group ◽  
The Usa ◽  
Abp 501 ◽  
Single Blind

ObjectiveTo demonstrate pharmacokinetic (PK) similarity of biosimilar candidate ABP 501 relative to adalimumab reference product from the USA and European Union (EU) and evaluate safety, tolerability and immunogenicity of ABP 501.MethodsRandomised, single-blind, single-dose, three-arm, parallel-group study; healthy subjects were randomised to receive ABP 501 (n=67), adalimumab (USA) (n=69) or adalimumab (EU) (n=67) 40 mg subcutaneously. Primary end points were area under the serum concentration-time curve from time 0 extrapolated to infinity (AUCinf) and the maximum observed concentration (Cmax). Secondary end points included safety and immunogenicity.ResultsAUCinf and Cmax were similar across the three groups. Geometrical mean ratio (GMR) of AUCinf was 1.11 between ABP 501 and adalimumab (USA), and 1.04 between ABP 501 and adalimumab (EU). GMR of Cmax was 1.04 between ABP 501 and adalimumab (USA) and 0.96 between ABP 501 and adalimumab (EU). The 90% CIs for the GMRs of AUCinf and Cmax were within the prespecified standard PK equivalence criteria of 0.80 to 1.25. Treatment-related adverse events were mild to moderate and were reported for 35.8%, 24.6% and 41.8% of subjects in the ABP 501, adalimumab (USA) and adalimumab (EU) groups; incidence of antidrug antibodies (ADAbs) was similar among the study groups.ConclusionsResults of this study demonstrated PK similarity of ABP 501 with adalimumab (USA) and adalimumab (EU) after a single 40-mg subcutaneous injection. No new safety signals with ABP 501 were identified. The safety and tolerability of ABP 501 was similar to the reference products, and similar ADAb rates were observed across the three groups.Trial registration numberEudraCT number 2012-000785-37; Results.

scholarly journals Proposal of open field test as a model of varenicline pharmacokinetic study in rats

2018 ◽  
Vol 11 (3) ◽  
Author(s):  
Julia Zaccarelli-Magalhães ◽  
Thaisa Meira Sandini ◽  
André Rinaldi Fukushima ◽  
Helenice De Souza Spinosa
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Single Dose ◽  
Open Field ◽  
Field Test ◽  
Open Field Test ◽  
Male Rats ◽  
Control Group ◽  
Immobility Time ◽  
The Central Nervous System

Varenicline is a medication used for smoking treatment that acts as a partial agonist for nicotinic cholinergic receptors α4β2 and α3β4 and as a total agonist of receptor α7 in the central nervous system. Pharmacokinetic is important information for medications that acts in the central nervous system. This kind of assay is commonly done by expensive and complex analytical techniques. Therefore, the aim of this study was to evaluate the possibility of using the open field test as a pharmacokinetic model for varenicline in male rats exposed to a single dose of varenicline. Male rats received a single dose orally (gavage) of three different concentrations of varenicline: 0.03 (therapeutic dose for humans), 0.1 and 0.3 mg/kg or water (control group). The open field observations were recorded 30 min, 1, 2, 4, 6, 24, 48, 72 h and 7 days after the administration of varenicline or water. The results showed alterations in locomotion and rearing frequencies, as well as in immobility time observed in open field, which is consistent with this drug’s plasma peak. Consequently, this behavioral test apparently can be considerate as a model for pharmacokinetic evaluation of varenicline.

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