Dose selection of indacaterol for marketing approval: a FDA story in pharmacometrics review

doi:10.12092/j.issn.1009-2501.2018.09.011

Abstract

Abstract:

The safety of long-acting β2 agonist (LABA) has always been controversial, and the dose selection of this type of drugs becomes very important issue. Pharmacometrics is a key evaluation tool for the dose selection. In the process of review of indacaterol for marketing approval by US FDA, the pharmacometric scientists from FDA and an enterprise, respectively conduct modeling & simulation based the data from the same trials, and they found different doses for marketing with refuting each other and debating in academic journals, even the journal published the commentary. Apparently, FDA's model is more persuasive. This is an excellent case of pharmacometrics in the new drug review of dose for marketing, which fully demonstrates the advantages of pharmacometrics, that is, when the head-to-head study is lacking, many trial data are integrated, and the final marketing dose is determined by modeling and simulation. At the same time, pharmacometric characteristics, such as multidisciplinary, highly professional, complex analytical process and the requirements of experience, are also showed. Be boldly hypothesized but must be carefully verified.

Key words: pharmacometrics, modeling &, simulation, dose selection, long acting beta-agonists

CLC Number:

R969.1

YIN Fang, WANG Yuzhu, ZHENG Qingshan. Dose selection of indacaterol for marketing approval: a FDA story in pharmacometrics review[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(9): 1031-1039.

References

［1］Nelson HS, Weiss ST, Bleecker ER, et al. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol［J］. Chest,2006,129:15-26.
［2］Kramer JM. Balancing the benefits and risks of inhaled long-acting beta-agonists--the influence of values［J］. N Engl J Med, 2009, 360(16):1592-1595.
［3］Chowdhury BA, Dal PG. The FDA and safe use of long-acting beta-agonists in the treatment of asthma［J］. N Engl J Med, 2010, 362(13):1169-1171.
［4］Chowdhury BA, Seymour SM, Levenson MS. Assessing the safety of adding LABAs to inhaled corticosteroids for treating asthma［J］. N Engl J Med, 2011, 364(26):2473-2475.
［5］Busse WW, Bateman ED, Caplan AL, et al. Combined analysis of asthma safety trials of long-acting β2-agonists［J］. N Engl J Med, 2018,378:2497-505.
［6］Mann M, Chowdhury B, Sullivan E, et al. Serious asthma exacerbations in asthmatics treated with high-dose formoterol［J］. Chest, 2003, 124(1):70-74.
［7］Chowdhury BA, Seymour SM, Michele TM, et al. The risks and benefits of indacaterol--the FDA's review［J］. N Engl J Med, 2011, 365(24):2247.
［8］Barnes PJ, Pocock SJ, Magnussen H, et al. Integrating indacaterol dose selection in a clinical study in COPD using an adaptive seamless design［J］. Pulm Pharmacol Ther, 2010, 23(3):165-171.
［9］Renard D, Looby M, Kramer B, et al. Characterization of the bronchodilatory dose response to indacaterol in patients with chronic obstructive pulmonary disease using model-based approaches［J］. Resp Res, 2011, 12(1):1-9.
［10］Wang Y, Lee JY, Michele T, et al. Limitations of model based dose selection for indacaterol in patients with chronic obstructive pulmonary disease［J］. Int J Clin Pharmacol Ther, 2012, 50(50):622-630.
［11］Center for Drug Evaluation and Research. Clinical pharmacology and biopharmceutics review(ApplicationNO.022383Orig1s000)［R/OL］.［2018-09-05］.https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022383Orig1s000ClinPharmR.pdf.
［12］Looby M, Renard D, Wright A, et al. Comment on the report "Limitations of model based dose selection for indacaterol in patients with chronic obstructive pulmonary disease"［J］. Int J Clin Pharmacol Ther, 2012,50(9): 631-637.
［13］Wang Y, Lee JY, Michele T, et al. Response to comment on the report "Limitations of model-based dose selection for indacaterol in patients with chronic obstructive pulmonary disease"［J］. Int J Clin Pharmacol Ther, 2012,50(9): 638.
［14］Derendorf H. Model-based drug approval-the rubber hits the road［J］. Int J Clin Pharmacol Ther, 2012, 50(9):621.
［15］Center for Drug Evaluation and Research. Summary review(Application NO.022383Orig1s000)［R/OL］.［2018-09-05］.https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022383Orig1s000SumR.pdf.
［16］王玉珠，杨进波. 定量药理学在确定非劣效试验界值中的作用［J］. 中国临床药理学杂志,2017, 33(23): 187-192.
［17］许羚, 李禄金, 王鲲,等. 新药早期临床试验中的定量药理学方法［J］. 中国新药杂志, 2015(1):52-55.

[1]	WU Yujie, ZHAO Chengcheng, XI Qing. Evaluation of tegacycline regimens in treatment of gram-negative bacterial infections with Monte Carlo simulation [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(9): 1027-1033.
[2]	MA Guangli, ZHANG Jing. Application of quantitative pharmacology in vaccine research and de-velopment: overview and prospect [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(3): 315-322.
[3]	ZHANG Jinhua, LIU Maobai, CAI Mingzhi, ZHENG Yingli, LAO Haiyan, XIANG Qian, DU Liping, ZHU Zhu, DONG Jing, ZUO Xiaocong, LI Xingang, SHANG Dewei, CHEN Bing, YE Yanrong, WANG Yuzhu, GAO Jianjun, ZHANG Jian, CHEN Wansheng, XIE Haitang, JIAO Zheng. Model informed precision dosing of warfarin: China expert consensus report (2022 version) [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(11): 1201-1212.
[4]	LIU Wei, XUE Junsheng, YU Zhiheng, WANG Ziyu, CHEN Rong, ZHOU Tianyan. Interpretation of pharmacokinetic-based criteria for supporting alternative dosing regimens of programmed cell death receptor-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) blocking antibodies for treatment of patients with cancer guidance for industry [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(1): 86-94.
[5]	GAO Lili, CHEN Rui, LI Lujin, ZHENG Qingshan . Dose selection of obeticholic acid in hepatic impairment patients and the review consideration of FDA [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2021, 26(7): 760-767.
[6]	ZHANG Ningyuan, ZHENG Xijun, XU Ling, LIU Hongxia, ZHENG Qingshan. Disease progression model for Alzheimer's disease and its research progress [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2021, 26(6): 687-694.
[7]	JIAO Zheng, LI Xingang, SHANG Dewei, DONG Jing, ZUO Xiaocong, CHEN Bing, LIU Jianmin, PAN Yan, ZHOU Tianyan, ZHANG Jing, LIU Dongyang, LI Lujin, FANG Yi, MA Guangli, DING Junjie, ZHAO Wei, CHEN Rui, XIANG Xiaoqiang, WANG Yuzhu, GAO Jianjun, XIE Haitang, HU Pei, ZHENG Qingshan. Model informed precision dosing: China expert consensus report [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2021, 26(11): 1215-1228.
[8]	LI Jian, YANG Jinbo, WANG Yuzhu. Discussion on the format and content of new drug population pharmacokinetic study report [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(5): 546-549.
[9]	XU Gaoqi, ZHANG Yiwen, ZHENG Xiaowei, LIU Yujia, LI Li, HUANG Ping. Missed and remedial dosage regimens of erlotinib by Monte Carlo simulation [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(5): 540-545.
[10]	MA Guangli, XU Ling, CHEN Rui, CHEN Yuancheng, ZHAO Wei, LIU Dongyang, JIAO Zheng, LI Jian, JI Shuangmin, LI Li, LI Liang, WANG Yuzhu, YANG Jinbo, WANG Yaning, SUN He, HU Pei, ZHENG Qingshan, LU Wei. General considerations of population pharmacokinetic/pharmacodynamic study in new drug development [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(11): 1201-1220.
[11]	ZHANG Huimin, LIU Aiming, ZHU Wenfeng, YU Lingzhi, CHEN Fangliang. Scientific decision process and regulation requirements based on the current guidelines of data extrapolation from adult to pediatric population [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(1): 49-56.
[12]	JI Shuangmin, ZHU Xiao, GAO Liucun, YANG Huan, GAO Chenyan. Research advances on target-mediated drug disposition(TMDD) models [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(5): 481-487.
[13]	SHANG Feng, YU Chengkai, YANG Peng. Bridging method of adjusted significance levels α' in the target region concerning superiority design for normal data distribution in MRCT [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(1): 59-64.
[14]	WU Yonglei, WANG Dan, ZHANG Suiyang, WANG Ying, SUN Qin. Pharmacokinetics and pharmacodynamics of meropene administered by traditional prolonged infusion or optimized prolonged infusion in different tissues of septic rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(7): 767-774.
[15]	LU Meng-Jie, ZHONG Wei-Hua, LIU Yu-Xiu, LI Yong-Chang, MIAO Hua-Zhang. Sample Size Calculations for Equivalence Clinical Trials by Decomposing β [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2015, 20(6): 647-652.