Clinical pharmacology and therapeutics
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Our nation's ongoing prescription opioid abuse crisis, amounting to over 78 billion dollars in health and social costs annually,1 is a critical priority for the US Food and Drug Administration (FDA). As a part of our mission to support the safe and effective use of prescription medicines, the FDA is taking a fresh look at potential scientific and regulatory actions we can take to address this crisis.
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Clin. Pharmacol. Ther. · May 2018
Randomized Controlled TrialPhase I, Randomized, Double-blind, Placebo-controlled, Single-dose, and Multiple-dose Studies of Erenumab in Healthy Subjects and Patients With Migraine.
Monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) signaling are being explored as prophylactic treatments for migraine. Erenumab (AMG 334) is the first potent, selective, and competitive human mAb antagonist of the CGRP receptor. ⋯ Single doses of erenumab resulted in >75% inhibition of capsaicin-induced dermal blood flow, with no apparent dose-dependency for erenumab ≥21 mg. Erenumab was generally well tolerated, with an acceptable safety profile, supporting further clinical development of erenumab for migraine prevention.
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Clin. Pharmacol. Ther. · Dec 2017
Multicenter StudyMoving Beyond Maximum Tolerated Dose for Targeted Oncology Drugs: Use of Clinical Utility Index to Optimize Venetoclax Dosage in Multiple Myeloma Patients.
Exposure-response analyses of venetoclax in combination with bortezomib and dexamethasone in previously treated patients with multiple myeloma (MM) were performed on a phase Ib venetoclax dose-ranging study. Logistic regression models were utilized to determine relationships, identify subpopulations with different responses, and optimize the venetoclax dosage that balanced both efficacy and safety. ⋯ However, the probability of neutropenia (grade ≥3) was estimated to increase at doses >800 mg. Using a clinical utility index, a venetoclax dosage of 800 mg daily was selected to optimally balance the VGPR or better rates and neutropenia rates in MM patients administered 1-3 prior lines of therapy and nonrefractory to bortezomib.
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Clin. Pharmacol. Ther. · Aug 2017
ReviewChallenges in the Development of Novel Cardiovascular Therapies.
Cardiovascular disease accounts for nearly one in three deaths globally, but few novel therapies have reached patients and clinicians in recent years. This translational report reviews trends in the development and approval of cardiovascular drugs and evaluates recent innovation in the field of cardiovascular disease therapeutics. New policies are needed to better support the development of safe and effective therapies with the greatest potential to improve patient health outcomes.
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Clin. Pharmacol. Ther. · Aug 2017
ReviewOcclusion in the Flow of New Drugs for Cardiovascular Disease.
There is a large misalignment between unmet need and both private and public investment activity in cardiovascular disease. In this paper, we quantify the magnitude of the gap, analyze a range of potential root causes in two main categories (issues of feasibility and valuation), and propose steps toward solutions to close the gap.