Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Jan 2020
Comparative StudyA Comparison of EMA and FDA Decisions for New Drug Marketing Applications 2014-2016: Concordance, Discordance, and Why.
The Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have robust scientific and technical collaborations. As a window to the impact of these activities we compared the agencies' decisions on drug marketing applications. Decisions were compared for 107 new drug applications with a regulatory outcome at both agencies in the period 2014-2016. ⋯ The EMA and the FDA had high concordance (91-98%) in decisions on marketing approvals. Divergence in approval decisions, type of approval, and approved indication were primarily due to differences in agencies' conclusions about efficacy based on review of the same data or differing clinical data submitted to support the application. This high rate of concordance suggests that engagement and collaboration on regulatory science has a positive impact.
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Clin. Pharmacol. Ther. · Jun 2019
Genetic Variants Associated With Vincristine-Induced Peripheral Neuropathy in Two Populations of Children With Acute Lymphoblastic Leukemia.
Vincristine is one of the core chemotherapy agents used in the treatment of pediatric acute lymphoblastic leukemia (ALL). However, one of the major toxicities resulting from vincristine exposure is vincristine-induced peripheral neuropathy (VIPN). When VIPN results in significant morbidity, the vincristine dose may need to be reduced, thus potentially decreasing the effectiveness of treatment. ⋯ The current study included genomewide association study (GWAS) in two independent cohorts: Pediatric Oncology Group (POG) ALL trials and a multicenter study based at Indiana University in children with ALL. A meta-analysis of the cohorts identified two single-nucleotide polymorphisms (SNPs), rs1045644 and rs7963521, as being significantly (P value threshold 0.05/4749 = 1.05E-05) associated with neuropathy. Subsequently these SNPs may be effective biomarkers of VIPN in children with ALL.
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Clin. Pharmacol. Ther. · May 2019
ReviewPositive and Negative Effects of Cannabis and Cannabinoids on Health.
Cannabis is the most popular illicit drug in the Western world. Repeated cannabis use has been associated with short- and long-term side effects, including respiratory and cardiovascular disorders, cognitive alterations, psychosis, schizophrenia, and mood disorders. ⋯ The current article presents a contemporary review on the adverse effects, safety, and the therapeutic potential of cannabis and cannabinoid-based drugs. Given the growing popularity in the use of cannabinoid-based drugs for both recreational and medical purposes and their potential harmful effects, there is a need for further investigation in this field.
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Clin. Pharmacol. Ther. · May 2019
Randomized Controlled TrialPharmacokinetics and Pharmacodynamics of the BACE1 Inhibitor Verubecestat (MK-8931) in Healthy Japanese Adults: A Randomized, Placebo-Controlled Study.
β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is required for the production of β-amyloid (Aβ) peptides and is considered a potential treatment target for Alzheimer's disease (AD). To support Japan's participation in the global clinical development program, we characterized the safety, pharmacokinetics (PKs), and pharmacodynamics of the BACE1 inhibitor verubecestat (MK-8931) in 24 healthy Japanese adults in a two-part, single-center, randomized, placebo-controlled phase I trial (protocol MK-8931-007) and compared the results with historical data from non-Japanese subjects. ⋯ Verubecestat also reduced mean cerebrospinal fluid concentrations of the Aβ proteins Aβ40, Aβ42, and soluble β fragment of amyloid precursor protein; the level of reduction was comparable between Japanese and non-Japanese subjects. These results support the continued global development of verubecestat as a potential disease-modifying agent for Japanese and non-Japanese subjects who are at risk for developing AD.