American College of Clinical Pharmacology

American College of Clinical Pharmacology (ACCP) is a non-profit membership association with a 40+ year history of providing exceptional interdisciplinary,

Founded in 1969 by a group of eminent physicians, the College today consists of a full spectrum of healthcare professionals who remain dedicated to advancing clinical pharmacology with the goal of providing exceptional patient care. As an organization whose primary role is education, the College does not concentrate on any one aspect of the discipline. Rather, the College seeks to address the educational needs of its diverse membership and all healthcare professionals, covering a range of topics that span the entire area of the interaction between drugs and humans. These areas include, but are not limited to, pharmaceutical chemistry, biochemistry, drug metabolism, pharmacokinetics, pharmacodynamics, pharmacometrics, pharmacogenomics, clinical pharmacology practice in the outpatient and inpatient settings, human toxicology, drug interactions, and clinical drug trials. The diversity of the College is expressed not only in the composition of its membership, but also in its leadership. Maintaining a balance of elected Regents and Officers from all pertinent professional backgrounds ensures that the College remains attuned to the needs of all professionals engaged in the practice of or with a strong interest in clinical pharmacology, from the research laboratory (academic and industrial) to the classroom, and from the clinical trial to improved patient care.

American College of Clinical Pharmacology (ACCP) is a non-profit membership association with a 40+ year history of providing exceptional interdisciplinary, accredited Continuing Education programs, publications, networking and other career-enhancing opportunities to a wide spectrum of health care professionals using clinical pharmacology in disciplines from research to patient care.

Mission: Vision & Mission To improve health by optimizing therapeutics. Provide innovative leadership and interdisciplinary education that will enable the generation, integration and translation of scientific knowledge to optimize research, development and utilization of medication for the benefit of all.

Stack the odds in your favor in finding a new job by checking out the #ACCPJOBCTR. New opportunities posted daily and are available for every career level. http://bit.ly/2J0TTKj
#pharmacology #jobsearch

June #ACCPVJC Webinar: Evaluation of the Effect of 5 QT-Positive Drugs on the JTpeak Interval - An Analysis of ECGs From the IQ-CSRC Study

Date: Wednesday, June 17, 2020
Time: 2:00 - 3:00 PM ET
Faculty: Borje Darpo, MD, PhD, Chief Scientific Officer, Cardiac Safety, ERT-Consultant
Register: http://bit.ly/ACCPVJC

Why is this webinar important to you?
The JTpeak interval of the surface ECG has been proposed as a new biomarker to demonstrate mixed-ion channel effects. It has been argued that drugs with equipotent inhibition of late sodium or calcium currents vs hERG may be safer than pure hERG blockers and that the lack of JTpeak prolongation can be used to identify mildly QT prolonging drugs that are safe enough to avoid ECG monitoring in late-stage clinical trials. Attendees that complete this course will gain clinical pearls and a comprehensive understanding and insight into proarrhythmic risk of drugs and use of a novel clinical marker, JTpeak interval and its electrophysiological meaning.
#pharmacology #CME #CPE

ACCP "Excellence in Achievement" – Barbara Ameer, PharmD, MBA

ACCP is pleased to recognize Barbara Ameer, PharmD, MBA, Adjunct Associate Professor, Medicine, Rutgers-Robert Wood Johnson Medical School in New Brunswick, NJ. Dr. Ameer joined ACCP in 1979 and her engagement with ACCP has been steadfast. She is a Fellow of the College and became an Honorary Regent in 2011. She is a member of The Journal of Clinical Pharmacology Editorial Board and serves on the ACCP Publications Committee and the 2020 Annual Meeting Program Committee. Her support of ACCP governance is extensive with a few highlights that include serving on the Executive Committee (Treasurer: 2004–2010) and Board of Regents (1999–2004), a member of the Annual Meeting Program Committee (2010 & 2018), a member of the Finance Committee (2004–2010), the Nominating Committee (2010–2012) and Chair of both the ACCP Membership Committee (2010–2014) and the International Development Committee (2002–2010). In addition to contributing to ACCP governance and strategic planning, Dr. Ameer served in the roles of Symposia Chair for Frontiers and Annual Meetings, Faculty Speaker and Abstract Reviewer. She spearheaded an ACCP position paper on availability of genetic testing. In 2010, she was the recipient of the Nathaniel T. Kwit Memorial Distinguished Service Award.

Prior to her medical school faculty appointment, Dr. Ameer was an Associate Research Professor at Rutgers in the Dept of Chemistry & Chemical Biology. She earned a doctorate degree in pharmacy at Virginia Commonwealth Univ and an MBA at Rutgers. She has peer-reviewed publications in journals of clinical therapeutics and drug development and has presented nationally and internationally. She serves on the journal editorial board of Endocrinology, Diabetes & Metabolism. She is a Diplomate of the American Board of Clinical Pharmacology and is certified in Pharmacotherapy by the Board of Pharmacy Specialties.

Dr. Ameer shared her thoughts on what ACCP membership means to her:

"One of the blessings of my four decades of involvement with ACCP has been the remarkable professional insight I garnered over the course of “doing business” in a variety of roles within our College. These interactions guided some of my most gratifying professional career decisions.

A recent example was accepting an amazing opportunity to participate in an international panel for development of a clinical practice guideline, developed using the rigorous GRADE process. It was a past President of ACCP who shared his vision at one of our Board of Regents meetings that practice guidelines would become game-changers, impacting medicine, policy makers and insurers. The past two decades have proven that correct.

Perhaps the most enduring influence was by Wayne Colburn, who was a biopharmaceutical researcher and newly minted grandfather when his life was tragically cut short, just as he proudly accepted the mantle of ACCP President. We honor his dedication to science with the ACCP’s Wayne A. Colburn Memorial Award for Students & Trainees. What our junior Members of ACCP should appreciate is an important personal lesson from Dr. Colburn’s life – Don’t wait until retirement to volunteer for the organization! Find time early and throughout your career to contribute. You won’t regret it."

Congratulations, Dr. Ameer, on being recognized for your outstanding achievements and contributions to ACCP!
#ACCPExcellenceAchievement #pharmacology

www.accessdata.fda.gov

FDA Burst: FDA Approves QINLOCK (Ripretinib) for the Treatment of Adult Patients with Advanced Gastrointestinal Stromal Tumor who Have Received Prior Treatment with 3 or More Kinase Inhibitors, Including Imatinib

On May 15, 2020, the U.S. Food and Drug Administration (FDA) approved QINLOCK (ripretinib) for the treatment of adult patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with 3 or more kinase inhibitors, including imatinib. The approved recommended dosage of QINLOCK is 150 mg orally once daily with or without food until disease progression or unacceptable toxicity. Additional information regarding dosage and administration, including dosage modifications for adverse reactions, as well as important warnings and precautions about palmar-plantar erythrodysesthesia syndrome, new primary cutaneous malignancies, hypertension, cardiac dysfunction, risk of impaired wound healing, or embryo-fetal toxicity can be found in the full prescribing information linked below.

Mechanism of Action (MOA) and Pharmacokinetics (PK)

MOA: Ripretinib is a tyrosine kinase inhibitor that inhibits KIT proto-oncogene receptor tyrosine kinase (KIT) and platelet derived growth factor receptor A (PDGFRA) kinase, including wild type, primary, and secondary mutations.

General PK: The general pharmacokinetics of ripretinib and its active metabolite, DP-5439, are presented below.

• Ripretinib: The mean (CV%) steady state Cmax and AUC0-12h was 761 ng/mL (32%) and 5678 ng•h/mL (32%), respectively. Ripretinib AUC0-24h increased proportionally over a dose range of 20 mg to 250 mg (0.13 to 1.67 times the recommended dose), but Cmax was less than dose proportional. The time to steady state of ripretinib was 14 days with a mean accumulation ratio (AUC0-12h) of 1.7 (55%).

• DP-5439: The mean (CV%) steady state Cmax and AUC0-12h was 804 ng/mL (46%) and 7138 ng•h/mL (44%), respectively. DP-5439 Cmax and AUC0-24h were less than dose proportional within the dose range of 50 mg to 250 mg (0.33 to 1.67 times the recommended dose). The time to steady state of DP-5439 was 14 days with a mean accumulation ratio (AUC0-12h) of 5.3 (49%).

Absorption: The median Tmax of ripretinib and DP-5439 was 4 hours and 15.6 hours, respectively.

Distribution: The mean (CV%) apparent volume of distribution ripretinib and DP-5439 at steady-state was 307 L (39%) and 507 L (51%), respectively. The plasma protein binding of ripretinib and DP-5439 was 99.8% and 99.7% to human serum albumin and 99.4% and > 99.8% to α-1 acid glycoprotein, respectively.

Elimination: The mean (CV%) half-life of ripretinib and DP-5439 was 14.8 hours (30%) and 17.8 hours (23%), respectively. The mean apparent clearance of ripretinib and DP-5439 was 15.3 L/hr (45%) and 17.5 L/hr (63%), respectively.

Metabolism: Ripretinib is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C8 and CYP2D6. DP-5439 is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C8, CYP2E1, and CYP2D6.

Excretion: After a single oral ripretinib 150 mg dose, 34% of the dose was excreted in feces as ripretinib and 6% as DP-5439, whereas 0.02% was excreted in urine as ripretinib and 0.1% as DP-5439.

Drug Interactions

Strong CYP3A Inhibitors: Monitor patients more frequently for adverse reactions. Coadministration of QINLOCK with a strong CYP3A inhibitor increased the exposure of ripretinib and its active metabolite (DP-5439), which may increase the risk of adverse reactions.

Strong CYP3A Inducers: Avoid concomitant use of QINLOCK with strong CYP3A inducers. Coadministration of QINLOCK with a strong CYP3A inducer may decrease the exposure of ripretinib and its active metabolite (DP-5439), which may decrease QINLOCK anti-tumor activity.

Use in Specific Populations

No clinically significant differences in the pharmacokinetics of ripretinib were observed based on age (19 to 87 years), sex, race (White, Black, and Asian), body weight (39 to 138 kg), tumor (GIST or other solid tumors), prior gastrectomy, mild to moderate renal impairment (CLcr 30 to ULN or total bilirubin 1 to 1.5 × ULN and AST any). The effects of severe renal impairment (CLcr 15 to 29 mL/min) or moderate to severe hepatic impairment (total bilirubin >1.5 × ULN, AST any) on the pharmacokinetics of ripretinib have not been studied.

Lactation: Advise women not to breastfeed during treatment with QINLOCK and for at least 1 week after the final dose because of the potential for serious adverse reactions in the breastfed child. There are no data regarding the presence of ripretinib or its metabolites in either human milk or its effects on a breastfed child or on milk production.

Efficacy and Safety

Efficacy of QINLOCK was demonstrated in an international, multi-center, randomized (2:1), double-blind, placebo-controlled trial that enrolled patients with unresectable, locally advanced or metastatic gastrointestinal stromal tumor (GIST) and had received prior treatment with imatinib, sunitinib, and regorafenib. The major efficacy outcome measure was progression-free survival (PFS) based on disease assessment by blinded independent central review (BICR) using modified RECIST 1.1 criteria, in which lymph nodes and bone lesions were not target lesions and a progressively growing new tumor nodule within a pre-existing tumor mass must meet specific criteria to be considered unequivocal evidence of progression. Additional information regarding the efficacy trial can be found in the full prescribing information linked below.

The most common adverse reactions (≥20%) were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia, and vomiting. The most common Grade 3 or 4 laboratory abnormalities (≥4%) were increased lipase and decreased phosphate.
________________________________________
Full prescribing information is available at https://bit.ly/3cWSZu8.

accessdata.fda.gov

It's not too late to register for the May #ACCPVJC Webinar: Concept of Pharmacologic Target-Mediated Drug Disposition in Large-Molecule and Small-Molecule Compounds presented today @ 2:00 PM ET! We hope to see you there.

Reserve your spot now! http://bit.ly/ACCPVJC
#CE #CME #CPE #pharmacology #webinar

The May #ACCPVJC Webinar: Concept of Pharmacologic Target-Mediated Drug Disposition in Large-Molecule and Small-Molecule Compounds is tomorrow, May 20th @ 2:00 PM ET. We hope you can join us!

Faculty: Guohua An, MD, PhD, Assistant Professor, Div of Pharmaceutics & Translational Therapeutics, University of Iowa College of Pharmacy
Save your spot today! http://bit.ly/ACCPVJC
#CE #CME #CPE #pharmacology #webinar

{Reminder} Call for 2021 Proposals Workshops & Symposia | #2021ACCP Annual Meeting | Sept 12 – 14, 2021 | Renaissance Phoenix Downtown Hotel, Phoenix, AZ

ACCP is accepting Proposals for the 2021 ACCP Annual Meeting, "Spearheading Innovations in Clinical Pharmacology"!

Areas of submission will be categorized into the following tracks: Basic Research & Drug Development, Patient Centric & Both: Basic Research/Drug Development & Patient Centric. Learn more: https://bit.ly/2V5VgMZ
#callforproposals #annualmeeting #pharmacology

fda.gov

List of Cleared or Approved Companion Diagnostic Devices

FDA Approves TABRECTA (Capmatinib) for Treatment of Adult Patients with Metastatic Non-small Cell Lung Cancer

On May 6, 2020, the U.S. Food and Drug Administration (FDA) approved TABRECTA (capmatinib) for treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test. Information on FDA-approved tests is available at: https://bit.ly/2ImsVuj. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

The approved recommended dosage of TABRECTA is 400 mg orally twice daily with or without food. Additional information regarding dosage and administration, including dosage modifications for adverse reactions, as well as important warnings and precautions about interstitial lung disease/pneumonitis, hepatotoxicity, risk of photosensitivity, or embryo-fetal toxicity can be found in the full prescribing information linked below.

Mechanism of Action (MOA) and Pharmacokinetics (PK)

• MOA: Capmatinib is a kinase inhibitor that targets MET, including the mutant variant produced by exon 14 skipping.

• General PK: Capmatinib exposure (AUC0-12h and Cmax) increased approximately proportionally over a dose range of 200 mg (0.5 times the recommended dosage) to 400 mg. Capmatinib reached steady-state by day 3 following twice daily dosing, with a mean (% coefficient of variation [%CV]) accumulation ratio of 1.5 (41%).

• Absorption: After administration of TABRECTA 400 mg orally in patients with cancer, capmatinib peak plasma concentrations (Cmax) were reached in approximately 1 to 2 hours (Tmax). The absorption of capmatinib after oral administration is estimated to be greater than 70%.

• Distribution: The apparent mean volume of distribution at steady-state is 164 L. Capmatinib plasma protein binding is 96%, independent of capmatinib concentration. The blood-to-plasma ratio was 1.5, but decreased at higher concentrations to 0.9.

• Elimination: The effective elimination half-life of capmatinib is 6.5 hours. The mean (%CV) steady-state apparent clearance of capmatinib is 24 L/hr (82%).

• Metabolism: Capmatinib is primarily metabolized by CYP3A4 and aldehyde oxidase.

• Excretion: Following a single oral administration of radiolabeled-capmatinib to healthy subjects, 78% of the total radioactivity was recovered in feces with 42% as unchanged and 22% was recovered in urine with negligible as unchanged.

Drug Interactions

• Strong CYP3A Inhibitors: Closely monitor patients for adverse reactions during coadministration of TABRECTA with strong CYP3A inhibitors. Coadministration of TABRECTA with a strong CYP3A inhibitor increased capmatinib exposure, which may increase the incidence and severity of adverse reactions of TABRECTA.
• Strong and Moderate CYP3A Inducers: Avoid coadministration of TABRECTA with strong or moderate CYP3A inducers. Coadministration of TABRECTA with a strong or moderate CYP3A inducer decreased capmatinib exposure, which may decrease TABRECTA anti-tumor activity.
• CYP1A2 Substrates: If coadministration is unavoidable between TABRECTA and CYP1A2 substrates where minimal concentration changes may lead to serious adverse reactions, decrease the CYP1A2 substrate dosage in accordance with the approved prescribing information. Coadministration of TABRECTA increased the exposure of a CYP1A2 substrate, which may increase the adverse reactions of these substrates.
• P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) Substrates: If coadministration is unavoidable between TABRECTA and P-gp or BCRP substrates where minimal concentration changes may lead to serious adverse reactions, decrease the P-gp or BCRP substrate dosage in accordance with the approved prescribing information. Coadministration of TABRECTA increased the exposure of a P-gp substrate and a BCRP substrate, which may increase the adverse reactions of these substrates.
• MATE1 and MATE2K Substrates: If coadministration is unavoidable between TABRECTA and MATE1 or MATE2K substrates where minimal concentration changes may lead to serious adverse reactions, decrease the MATE1 or MATE2K substrate dosage in accordance with the approved prescribing information. Coadministration of TABRECTA may increase the exposure of MATE1 and MATE2K substrates, which may increase the adverse reactions of these substrates.

Use in Specific Populations

No clinically significant effects on the pharmacokinetic parameters of capmatinib were identified for the following covariates assessed: age (26 to 90 years), sex, race (White, Asian, Native American, Black, unknown), body weight (35 to 131 kg), mild to moderate renal impairment (baseline CLcr 30 to 89 mL/min by Cockcroft-Gault) and mild, moderate or severe hepatic impairment (Child-Pugh classification).

• Renal Impairment: No dosage adjustment is recommended in patients with mild (baseline creatinine clearance [CLcr] 60 to 89 mL/min by Cockcroft-Gault) or moderate renal impairment (CLcr 30 to 59 mL/min). TABRECTA has not been studied in patients with severe renal impairment (CLcr 15 to 29 mL/min).

• Lactation: Advise women not to breastfeed during treatment with TABRECTA and for 1 week after the last dose because of the potential for serious adverse reactions in breastfed children. There are no data on the presence of capmatinib or its metabolites in either human or animal milk or its effects on the breastfed child or on milk production.

Efficacy and Safety

Efficacy of TABRECTA was demonstrated in a multicenter, non-randomized, open-label, multi-cohort study that enrolled patients with NSCLC with a mutation that leads to MET exon 14 skipping, epidermal growth factor receptor wild-type and anaplastic lymphoma kinase negative status, and at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The major efficacy outcome measure was overall response rate (ORR) as determined by a Blinded Independent Review Committee according to RECIST 1.1. Additional information regarding the efficacy trial can be found in the full prescribing information linked below.

The most common adverse reactions (≥ 20%) are peripheral edema, nausea, fatigue, vomiting, dyspnea, and decreased appetite.

________________________________________
Full prescribing information is available at https://bit.ly/2Z0v1dt.

fda.gov A companion diagnostic device provides information that is essential for the safe and effective use of a corresponding therapeutic product.

Telephone

Address


21750 Red Rum Dr, Ste 137
Ashburn, VA
20147

General information

ACCP is a member-driven/member-focused organization that provides accredited continuing education to healthcare professionals. ACCP also publishes The Journal of Clinical Pharmacology and will soon publish the eJournal Clinical Pharmacology in Drug Development.

Opening Hours

Monday 08:00 - 17:00
Tuesday 08:00 - 17:00
Wednesday 08:00 - 17:00
Thursday 08:00 - 17:00
Friday 08:00 - 17:00