Thorough QT/QTc Study Evaluating the Effect of Macimorelin on Cardiac Safety Parameters in Healthy Participants
AbstractMacimorelin is an orally active growth hormone secretagogue indicated for the diagnosis of adult growth hormone deficiency. The primary objective of this study was to evaluate the effect of macimorelin on the baseline and placebo ‐corrected mean QT interval using Fridericia's formula (ΔΔQTcF). Secondary objectives were to determine QTcF for moxifloxacin; evaluate the effects of macimorelin on other cardiac intervals (PR, QRS, RR), heart rate, and electrocardiogram morphology parameters; characterize pharmacokinetics; and assess safety of macimorelin. The phase 1 thorough QT/QTc study, designed accordi...
Source: Clinical Pharmacology in Drug Development - September 22, 2020 Category: Drugs & Pharmacology Authors: Michael Lissy, Valentin Demmel, Richard Sachse, Nicola Ammer, Nicky Kelepouris, Vlady Ostrow Tags: Original Manuscript Source Type: research

Pharmacokinetics, Safety, and Tolerability of Single ‐ and Multiple‐Dose Once‐Daily Baricitinib in Healthy Chinese Subjects: A Randomized Placebo‐Controlled Study
The objective of this phase 1 study was to evaluate the pharmacokinetics, safety, and tolerability of baricitinib after single and multiple doses in healthy Chinese adults. Eligible subjects received a once ‐daily dose of baricitinib 2, 4, or 10 mg or placebo on day 1 (single dose) and days 4 through 10 for 7 consecutive days (multiple doses). Plasma pharmacokinetic samples were collected up to 48 hours after dosing on days 1 and 10, with predose samples collected before dosing on day 1 and days 4 th rough 10. Safety and tolerability were also assessed. Baricitinib was rapidly absorbed, reaching peak plasma concentration...
Source: Clinical Pharmacology in Drug Development - September 17, 2020 Category: Drugs & Pharmacology Authors: Xia Zhao, Xiao Yan Sheng, Christopher D. Payne, Xin Zhang, Feng Wang, Yi Min Cui Tags: Original Manuscript Source Type: research

Bioequivalence and Pharmacokinetic Evaluation of Two Metformin Hydrochloride Tablets Under Fasting and Fed Conditions in Healthy Chinese Volunteers
This article aims to assess the bioequivalence of the test and the reference metformin hydrochloride tablets in healthy Chinese volunteers under fasting and fed conditions and to explore the effect of food on the pharmacokinetic (PK) profiles of both formulations. In total, 56 healthy Chinese subjects (28 in each group) were enrolled in this randomized, open, single ‐center, single‐dose, 2‐treatment, 2‐sequence, 2‐cycle cross clinical trial. The subjects were administrated a single dose of the test and the reference tablets at 0.25 g with a 7‐day washout. Venous blood samples of all subjects were taken from pre...
Source: Clinical Pharmacology in Drug Development - September 16, 2020 Category: Drugs & Pharmacology Authors: Xiao ‐mei Huang, Gong‐zhu Wang, Bin‐bin He, Ting Gao, Ping Long, Bi‐kui Zhang Tags: Original Manuscript Source Type: research

A Randomized, Double ‐Blind, Placebo‐ and Positive‐Controlled, 4‐Period Crossover Study of the Effects of Solriamfetol on QTcF Intervals in Healthy Participants
AbstractSolriamfetol, a dopamine and norepinephrine reuptake inhibitor, is approved (United States and European Union; Sunosi) to treat excessive daytime sleepiness associated with narcolepsy (75 ‐150 mg/day) or obstructive sleep apnea (37.5‐150 mg/day). A thorough QT/QTc study assessed solriamfetol effects on QT interval (Fridericia correction for heart rate; QTcF). This randomized, double‐blind, placebo‐ and positive‐controlled, 4‐period crossover study compared single doses of 300 and 900 mg solriamfetol, 400 mg moxifloxacin, and placebo in healthy adults. Placebo‐ and predose‐adjuste...
Source: Clinical Pharmacology in Drug Development - September 15, 2020 Category: Drugs & Pharmacology Authors: Katie Zomorodi, Dan Chen, Lawrence Lee, Dennis Swearingen, Lawrence P. Carter Tags: Original Manuscript Source Type: research

ACCP Abstract Booklet
Clinical Pharmacology in Drug Development, Volume 9, Issue S2, Page 1-75, September 2020. (Source: Clinical Pharmacology in Drug Development)
Source: Clinical Pharmacology in Drug Development - September 8, 2020 Category: Drugs & Pharmacology Tags: Abstracts Source Type: research

Issue Information
AbstractAbstracts: 2020 Annual Meeting American College of Clinical Pharmacology ® September 21–23, 2020 Virtual (Source: Clinical Pharmacology in Drug Development)
Source: Clinical Pharmacology in Drug Development - September 8, 2020 Category: Drugs & Pharmacology Tags: Issue Information Source Type: research

Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Oral Venglustat in Healthy Volunteers
AbstractVenglustat is a small ‐molecule glucosylceramide synthase (GCS) inhibitor designed to reduce the production of glucosylceramide (GL‐1) and thus is expected to substantially reduce formation of glucosylceramide‐based glycosphingolipids. Because of its effect on glycosphingolipid formation, GCS inhibition has therape utic potential across many disorders affecting glycosphingolipid metabolism. Therefore, venglustat is under development for substrate reduction therapy in multiple diseases, including Gaucher disease type 3, Parkinson's disease associated withGBA mutations, Fabry disease, GM2 gangliosidosis, and au...
Source: Clinical Pharmacology in Drug Development - August 26, 2020 Category: Drugs & Pharmacology Authors: M. Judith Peterschmitt, Nigel P. S. Crawford, Sebastiaan J. M. Gaemers, Allena J. Ji, Jyoti Sharma, Theresa T. Pham Tags: Original Manuscript Source Type: research

Biosimilarity Assessment of 2 Filgrastim Therapeutics in Healthy Volunteers
This study aimed to compare the pharmacokinetic, pharmacodynamic, and safety profiles of a proposed biosimilar and innovator filgrastim therapeutics in healthy volunteers. In a crossover design, 23 subjects received a single subcutaneous injection of 300 ‐µg filgrastim, followed by a 7‐day washout period. Assessed pharmacokinetic parameters were the maximum observed filgrastim serum concentration (Cmax), time to reach Cmax (tmax), the area under the concentration ‐time curve (AUC), and elimination half‐life. Pharmacodynamics were assessed by the maximum observed absolute neutrophil count effect (Emax), tmax,E...
Source: Clinical Pharmacology in Drug Development - August 21, 2020 Category: Drugs & Pharmacology Authors: Seyed Reza Khandoozi, Majid Shahbazi, Hossein Amini Tags: Original Manuscript Source Type: research

Phase 1 Studies to Define the Safety, Tolerability, and Pharmacokinetic and Pharmacodynamic Profiles of the Nonsteroidal Mineralocorticoid Receptor Antagonist Apararenone in Healthy Volunteers
AbstractApararenone is a long ‐acting, nonsteroidal mineralocorticoid receptor antagonist (MRA). The safety, tolerability, and pharmacokinetic (PK) and pharmacodynamic (PD) profiles of single‐ and multiple‐dose apararenone were assessed in 3 phase 1 randomized, double‐blind studies in 223 healthy adults. Study 1 assessed the PK, safety/tolerability, and PD of single‐dose apararenone (3.75–640 mg) and multiple‐dose apararenone (10–40 mg/day on days 1–14, 320 mg loading dose on day 1 + 10 mg/day on days 2–14, or 40–320 mg loading dose on day 1 + 2.5–20 mg/day on days 2–14...
Source: Clinical Pharmacology in Drug Development - August 20, 2020 Category: Drugs & Pharmacology Authors: Tadakatsu Nakamura, Atsuhiro Kawaguchi Tags: Original Manuscript Source Type: research

Clinical and Model ‐Based Evaluation of the Effect of Glasdegib on Cardiac Repolarization From a Randomized Thorough QT Study
AbstractGlasdegib is a potent, selective oral inhibitor of the Hedgehog signaling pathway. This phase 1 double ‐blind thorough QT study (NCT03162900) evaluated the effects of glasdegib on QTc interval. The study enrolled 36 healthy volunteers to receive a single dose of 150 mg glasdegib (representing a therapeutic dose), 300 mg glasdegib (representing a supratherapeutic dose), 400 mg moxifloxacin (positive control), or placebo under fasted conditions. The study demonstrated that therapeutic and supratherapeutic doses of glasdegib had no significant effect on QTc interval; the upper bound of the 2‐sided 90% confidence i...
Source: Clinical Pharmacology in Drug Development - August 12, 2020 Category: Drugs & Pharmacology Authors: Joanna C. Masters, Naveed Shaik, Laure Mendes da Costa, Brian Hee, Robert R. LaBadie Tags: Original Manuscript Source Type: research

Correction
Clinical Pharmacology in Drug Development, EarlyView. (Source: Clinical Pharmacology in Drug Development)
Source: Clinical Pharmacology in Drug Development - August 9, 2020 Category: Drugs & Pharmacology Tags: Correction Source Type: research

Pharmacokinetics and Bioequivalence Estimation of Two Formulations of Alfuzosin Extended ‐Release Tablets
AbstractAlfuzosin is a medication approved by the US Food and Drug Administration to treat benign prostatic hyperplasia symptoms. Bioequivalence studies are demanded by regulatory authorities to evaluate the expected in vivo biological similarity of 2 formulations of a medication. The aim of this study is to assess the bioavailability of the generic (test) and branded (reference) formulations of 10 ‐mg alfuzosin extended‐release tablets after oral administration to healthy adults under fed conditions. The study used a comparative randomized, single‐dose, 2‐way crossover open‐label study design. Thirty‐three par...
Source: Clinical Pharmacology in Drug Development - August 7, 2020 Category: Drugs & Pharmacology Authors: Abdel Qader Al Bawab, Bashar A. Alkhalidi, Esra'a Albarahmieh, Sami M.A. Qassim, Mohammad A.D. Al ‐Saifi, Bashar Al‐Saifi, Jonathan Ling, Walid Al‐Qerem Tags: Original Manuscript Source Type: research

Pharmacokinetics and Bioequivalence of 2 Immediate ‐Release Tofacitinib Tablet Formulations in Chinese Healthy Volunteers Under Fasting and Fed Conditions
AbstractThe purpose of this study was to evaluate the bioequivalence of a generic immediate ‐release tofacitinib tablet versus a brand‐named immediate‐release tofacitinib tablet under fasting and fed conditions, and the food effect on pharmacokinetic profiles of the both formulations. This randomized, open‐label, 2‐period, crossover, bioequivalence study included 52 healthy Chine se subjects (fasting cohort: n = 26; fed cohort: n = 26). The subjects were assigned to receive a single 5‐mg dose of generic or brand‐named tofacitinib. Blood samples were collected at predosing and up to 14 hours after dosing. Tofa...
Source: Clinical Pharmacology in Drug Development - August 7, 2020 Category: Drugs & Pharmacology Authors: Xin Li, Lihua Liu, Yang Deng, Yuan Li, Ping Zhang, Yangyang Wang, Bing Xu, Jie Feng, Lu Huang Tags: Original Manuscript Source Type: research

Pharmacokinetics and Bioequivalence Estimation of Two Formulations of Alfuzosin Extended ‐Release Tablets
AbstractAlfuzosin is a medication approved by the US Food and Drug Administration to treat benign prostatic hyperplasia symptoms. Bioequivalence studies are demanded by regulatory authorities to evaluate the expected in vivo biological similarity of 2 formulations of a medication. The aim of this study is to assess the bioavailability of the generic (test) and branded (reference) formulations of 10 ‐mg alfuzosin extended‐release tablets after oral administration to healthy adults under fed conditions. The study used a comparative randomized, single‐dose, 2‐way crossover open‐label study design. Thirty‐three par...
Source: Clinical Pharmacology in Drug Development - August 7, 2020 Category: Drugs & Pharmacology Authors: Abdel Qader Al Bawab, Bashar A. Alkhalidi, Esra'a Albarahmieh, Sami M.A. Qassim, Mohammad A.D. Al ‐Saifi, Bashar Al‐Saifi, Jonathan Ling, Walid Al‐Qerem Tags: Original Manuscript Source Type: research

Pharmacokinetics and Bioequivalence of 2 Immediate ‐Release Tofacitinib Tablet Formulations in Chinese Healthy Volunteers Under Fasting and Fed Conditions
AbstractThe purpose of this study was to evaluate the bioequivalence of a generic immediate ‐release tofacitinib tablet versus a brand‐named immediate‐release tofacitinib tablet under fasting and fed conditions, and the food effect on pharmacokinetic profiles of the both formulations. This randomized, open‐label, 2‐period, crossover, bioequivalence study included 52 healthy Chine se subjects (fasting cohort: n = 26; fed cohort: n = 26). The subjects were assigned to receive a single 5‐mg dose of generic or brand‐named tofacitinib. Blood samples were collected at predosing and up to 14 hours after dosing. Tofa...
Source: Clinical Pharmacology in Drug Development - August 7, 2020 Category: Drugs & Pharmacology Authors: Xin Li, Lihua Liu, Yang Deng, Yuan Li, Ping Zhang, Yangyang Wang, Bing Xu, Jie Feng, Lu Huang Tags: Original Manuscript Source Type: research

Issue Information
Clinical Pharmacology in Drug Development, Volume 9, Issue 6, Page 659-663, August/September 2020. (Source: Clinical Pharmacology in Drug Development)
Source: Clinical Pharmacology in Drug Development - August 5, 2020 Category: Drugs & Pharmacology Tags: Issue Information Source Type: research

Safety, Tolerability, and Dose Proportionality of a Novel Transdermal Fentanyl Matrix Patch and Bioequivalence With a Matrix Fentanyl Patch: Two Phase 1 Single ‐Center Open‐Label, Randomized Crossover Studies in Healthy Japanese Volunteers
AbstractTwo open ‐label, single‐dose, randomized crossover studies were conducted in healthy Japanesemen to (1) assess dose proportionality of 5 doses (1.38, 2.75, 5.5, 8.25, and 11.0 mg) of Lafenta, a novel matrix‐type transdermal fentanyl patch with a rate‐controlling membrane; and (2) compare patch bioeq uivalence (11.0 mg) with a commercially available reference patch (Durotep MT Patch [16.8 mg]). Pharmacokinetics, adhesion performance, residual fentanyl, and safety parameters were assessed. Increases in mean AUC0 ‐t and Cmax after application of the test patch were dose proportional. The test patch (11....
Source: Clinical Pharmacology in Drug Development - August 3, 2020 Category: Drugs & Pharmacology Authors: Ulrike Lorch, Tomasz Pierscionek, Anne Freier, Christopher S. Spencer, J örg Täubel Tags: Original Manuscript Source Type: research

Pharmacokinetics and Safety of the Selective Progesterone Receptor Modulator Vilaprisan in Chinese Healthy Postmenopausal Women
This study investigated the pharmacokinetics, safety, and tolerability of vilaprisan in healthy Chinese postmenopausal women. Twelve participants received multiple doses of vilaprisan once daily over 14 days as a 2‐mg tablet. Plasma vilapr isan concentrations were determined using liquid chromatography–tandem mass spectrometry. The main pharmacokinetic parameters of vilaprisan were assessed with noncompartmental analysis, including maximum observed concentration (Cmax), systemic exposure (area under the plasma concentration –time curve), time to reach Cmax and terminal half ‐life. Safety assessmen...
Source: Clinical Pharmacology in Drug Development - July 27, 2020 Category: Drugs & Pharmacology Authors: Hongzhong Liu, Ji Jiang, Zhaozhao Chen, Yunhui Zhang, Jinyi Li, Joachim Hoechel, Beate Rohde, Torsten Zimmermann, Marcus ‐Hillert Schultze‐Mosgau Tags: Original Manuscript Source Type: research

Evaluation of Absolute Oral Bioavailability and Bioequivalence of Ribociclib, a Cyclin ‐Dependent Kinase 4/6 Inhibitor, in Healthy Subjects
AbstractRibociclib, a selective and potent cyclin ‐dependent kinase 4/6 inhibitor, has demonstrated safety and efficacy in combination with endocrine therapy in hormone receptor‐positive, human epidermal growth factor receptor‐2‐negative advanced breast cancer. In 2 open‐label crossover studies in healthy participants, the absolute bioava ilability of a single oral dose of a ribociclib 600‐mg tablet (n = 16) was compared with a single intravenous ribociclib infusion of 150 mg (n = 16), and the bioequivalence of a ribociclib 600‐mg tablet (n = 31) and a ribociclib 600‐mg capsule (n = 31) was evaluated. ...
Source: Clinical Pharmacology in Drug Development - July 24, 2020 Category: Drugs & Pharmacology Authors: Yan Ji, Ahmed M. Abdelhady, Tanay S. Samant, Shu Yang, Karen Rodriguez Lorenc Tags: Original Manuscript Source Type: research

In Vitro Dissolution and In Vivo Bioequivalence Evaluation of Two Metformin Extended ‐Release Tablets
The objective of the present study was to evaluate the bioequivalence between generic and branded metformin extended ‐release (ER) tablets in Chinese subjects. We tested bioequivalence in vitro and in vivo using a comparative dissolution study and a comparative pharmacokinetic trial. Safety assessments were conducted throughout the entire trial period. The dissolution profiles of the generic formulation expresse d obvious extended‐release properties, similar to those of the branded formulation (f2> 60.0%). Consistent with the result of the in vitro study, no remarkable differences were found in terms of pharmacokine...
Source: Clinical Pharmacology in Drug Development - July 24, 2020 Category: Drugs & Pharmacology Authors: Ziye Zhou, Chenxiang Wang, Min Li, Qin Lan, Chao Yu, Guoxin Yu, Yan Xia, Huafang Chen, Xiuhua Zhang Tags: Original Manuscript Source Type: research

Issue Information
Clinical Pharmacology in Drug Development, Volume 9, Issue S1, Page S1-S4, July 2020. (Source: Clinical Pharmacology in Drug Development)
Source: Clinical Pharmacology in Drug Development - July 24, 2020 Category: Drugs & Pharmacology Tags: Issue Information Source Type: research

Parameter Estimation and Reporting in Noncompartmental Analysis of Clinical Pharmacokinetic Data
This article provides a systematic review of issues related to the estimation of plasma and urine PK parameters with the intent of encouraging rigor in the performance of NCAs so as to provide reliable and informative analysis results. (Source: Clinical Pharmacology in Drug Development)
Source: Clinical Pharmacology in Drug Development - July 24, 2020 Category: Drugs & Pharmacology Authors: Dennis A. Noe Tags: Supplement Article Source Type: research

Evaluation of Absolute Oral Bioavailability and Bioequivalence of Ribociclib, a Cyclin ‐Dependent Kinase 4/6 Inhibitor, in Healthy Subjects
AbstractRibociclib, a selective and potent cyclin ‐dependent kinase 4/6 inhibitor, has demonstrated safety and efficacy in combination with endocrine therapy in hormone receptor‐positive, human epidermal growth factor receptor‐2‐negative advanced breast cancer. In 2 open‐label crossover studies in healthy participants, the absolute bioava ilability of a single oral dose of a ribociclib 600‐mg tablet (n = 16) was compared with a single intravenous ribociclib infusion of 150 mg (n = 16), and the bioequivalence of a ribociclib 600‐mg tablet (n = 31) and a ribociclib 600‐mg capsule (n = 31) was evaluated. ...
Source: Clinical Pharmacology in Drug Development - July 24, 2020 Category: Drugs & Pharmacology Authors: Yan Ji, Ahmed M. Abdelhady, Tanay S. Samant, Shu Yang, Karen Rodriguez Lorenc Tags: Original Manuscript Source Type: research

In Vitro Dissolution and In Vivo Bioequivalence Evaluation of Two Metformin Extended ‐Release Tablets
The objective of the present study was to evaluate the bioequivalence between generic and branded metformin extended ‐release (ER) tablets in Chinese subjects. We tested bioequivalence in vitro and in vivo using a comparative dissolution study and a comparative pharmacokinetic trial. Safety assessments were conducted throughout the entire trial period. The dissolution profiles of the generic formulation expresse d obvious extended‐release properties, similar to those of the branded formulation (f2> 60.0%). Consistent with the result of the in vitro study, no remarkable differences were found in terms of pharmacokine...
Source: Clinical Pharmacology in Drug Development - July 24, 2020 Category: Drugs & Pharmacology Authors: Ziye Zhou, Chenxiang Wang, Min Li, Qin Lan, Chao Yu, Guoxin Yu, Yan Xia, Huafang Chen, Xiuhua Zhang Tags: Original Manuscript Source Type: research

Assessment of Pharmacokinetic Interaction Between Letermovir and Fluconazole in Healthy Participants
AbstractLetermovir is a prophylactic agent for cytomegalovirus infection and disease in adult cytomegalovirus ‐seropositive recipients of allogeneic hematopoietic stem cell transplant. As the antifungal agent fluconazole is administered frequently in transplant recipients, a drug–drug interaction study was conducted between oral letermovir and oral fluconazole. A phase 1 open‐label, fixed‐sequence study was performed in healthy females (N = 14, 19‐55 years). In Period 1, a single dose of fluconazole 400 mg was administered. Following a 14‐day washout, a single dose of letermovir 480 mg was adminis...
Source: Clinical Pharmacology in Drug Development - July 22, 2020 Category: Drugs & Pharmacology Authors: Adedayo Adedoyin, Craig Fancourt, Karsten Menzel, Tian Zhao, Charles Tomek, Deborah Panebianco, Jacqueline B. McCrea, S. Aubrey Stoch, Marian Iwamoto Tags: Original Manuscript Source Type: research

Correction
Clinical Pharmacology in Drug Development, EarlyView. (Source: Clinical Pharmacology in Drug Development)
Source: Clinical Pharmacology in Drug Development - July 21, 2020 Category: Drugs & Pharmacology Tags: Correction Source Type: research

Effect of Hepatic Impairment on Cobimetinib Pharmacokinetics: The Complex Interplay Between Physiological Changes and Drug Characteristics
In this study, we investigated the impact of HI on the pharmacokinetics (PK) and safety of cobimetinib. Subjects with normal hepatic function and mild to severe HI were enrolled. All subjects received a single oral dose of 10 mg cobimetinib, and serial blood samples were collected at specified times. Cobimetinib PK in subjects with mild and moderate HI was similar to that in those with normal liver function. However, subjects with severe HI, on average, showed ∼30% lower total AUC0 ‐∞ and ∼2‐fold higher unbound AUC0 ‐∞ compared with those with normal hepatic function. These exposure differences ca...
Source: Clinical Pharmacology in Drug Development - July 21, 2020 Category: Drugs & Pharmacology Authors: Sravanthi Cheeti, Yuzhong Deng, Ilsung Chang, Isabela Georgescu, Ian Templeton, Nicholas Choong, Kit Wun Kathy Cheung, Sandhya Girish, Luna Musib Tags: Original Manuscript Source Type: research

Correction
Clinical Pharmacology in Drug Development, EarlyView. (Source: Clinical Pharmacology in Drug Development)
Source: Clinical Pharmacology in Drug Development - July 21, 2020 Category: Drugs & Pharmacology Tags: Correction Source Type: research

Effect of Hepatic Impairment on Cobimetinib Pharmacokinetics: The Complex Interplay Between Physiological Changes and Drug Characteristics
In this study, we investigated the impact of HI on the pharmacokinetics (PK) and safety of cobimetinib. Subjects with normal hepatic function and mild to severe HI were enrolled. All subjects received a single oral dose of 10 mg cobimetinib, and serial blood samples were collected at specified times. Cobimetinib PK in subjects with mild and moderate HI was similar to that in those with normal liver function. However, subjects with severe HI, on average, showed ∼30% lower total AUC0 ‐∞ and ∼2‐fold higher unbound AUC0 ‐∞ compared with those with normal hepatic function. These exposure differences ca...
Source: Clinical Pharmacology in Drug Development - July 21, 2020 Category: Drugs & Pharmacology Authors: Sravanthi Cheeti, Yuzhong Deng, Ilsung Chang, Isabela Georgescu, Ian Templeton, Nicholas Choong, Kit Wun Kathy Cheung, Sandhya Girish, Luna Musib Tags: Original Manuscript Source Type: research

Effects of ABCB1, UGT1A1, and UGT1A9 Genetic Polymorphisms on the Pharmacokinetics of Sitafloxacin Granules in Healthy Subjects
In conclusion, sitafloxacin granules were safe at single doses and multiple doses up to 200 and 100 mg/day, respectively, with a linear plasma PK profile. However,ABCB1 (rs1045642),UGT1A1 (rs2741049), andUGT1A9 (rs3832043) genetic polymorphisms are likely to influence the Cmax or t1/2 and thereby merit further clinical evaluation. (Source: Clinical Pharmacology in Drug Development)
Source: Clinical Pharmacology in Drug Development - July 20, 2020 Category: Drugs & Pharmacology Authors: Lu ‐Ning Sun, Guo‐Xian Sun, Yu‐Qing Yang, Ye Shen, Feng‐Ru Huang, Li‐Jun Xie, Juan Cheng, Hong‐Wen Zhang, Xue‐Hui Zhang, Yun Liu, Yong‐Qing Wang Tags: Original Manuscript Source Type: research

Evaluation of the Potential for QTc Prolongation With Repeated Oral Doses of Fedratinib in Patients With Advanced Solid Tumors
AbstractThe impact of repeated daily 500 ‐mg fedratinib (an oral selective Janus kinase [JAK] 2 inhibitor) on QTc and other electrocardiogram (ECG) parameters was assessed in 60 patients with advanced solid tumors. Patients received placebo on day 1 and fedratinib 500 mg daily for 14 days. Concentration‐QTc analysis was performed with change‐from‐baseline QTc corrected by Fridericia's formula (ΔQTcF) as the dependent variable. Fedratinib median time to maximum plasma concentration (Cmax) was observed 3 hours postdose on day 15. The largest difference between means for fedratinib and placebo was 0.5 bpm (...
Source: Clinical Pharmacology in Drug Development - July 16, 2020 Category: Drugs & Pharmacology Authors: Ken Ogasawara, Christine Xu, Jian Yin, Borje Darpo, Leon Carayannopoulos, Hongqi Xue, Maria Palmisano, Gopal Krishna Tags: Original Manuscript Source Type: research

Issue Information
Clinical Pharmacology in Drug Development, Volume 9, Issue 5, Page 547-551, July 2020. (Source: Clinical Pharmacology in Drug Development)
Source: Clinical Pharmacology in Drug Development - July 13, 2020 Category: Drugs & Pharmacology Tags: Issue Information Source Type: research

Effect of Mild and Moderate Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of a Single Dose of Oral Ivosidenib in Otherwise Healthy Participants
AbstractIvosidenib, a small ‐molecule inhibitor of mutant isocitrate dehydrogenase 1, is primarily cleared by hepatic metabolism. This open‐label study investigated the impact of hepatic impairment on ivosidenib pharmacokinetics (ClinicalTrials.gov: NCT03282513). Otherwise healthy participants with mild (n = 9) or moderate (n = 8) hepatic impairment (Child‐Pugh score) and matched participants with normal hepatic function (n = 16) received 1 oral dose of 500‐mg ivosidenib. Mild hepatic impairment had a negligible effect on total ivosidenib plasma exposure, with geometric mean ratios (90% confidence interval [CI]) of...
Source: Clinical Pharmacology in Drug Development - July 9, 2020 Category: Drugs & Pharmacology Authors: Bin Fan, David Dai, Marvin Cohen, Huansheng Xu, Feng Yin, Raj Nagaraja, Michelle Mobilia, Caroline Almon, Frank G. Basile, Hua Yang Tags: Original Manuscript Source Type: research

Characterization of the Effect of Upadacitinib on the Pharmacokinetics of Bupropion, a Sensitive Cytochrome P450 2B6 Probe Substrate
AbstractThis phase 1 study characterized the effect of multiple doses of upadacitinib, an oral Janus kinase 1 selective inhibitor, on the pharmacokinetics of the cytochrome P450 (CYP) 2B6 substrate bupropion. Healthy subjects (n = 22) received a single oral dose of bupropion 150 mg alone (study period 1) and on day 12 of a 16 ‐day regimen of upadacitinib 30 mg once daily (study period 2). Serial blood samples for measurement of bupropion and hydroxybupropion plasma concentrations were collected in each study period. The central values (90% confidence intervals) for the ratios of change were 0.87 (0.79‐0.96) for bu...
Source: Clinical Pharmacology in Drug Development - July 9, 2020 Category: Drugs & Pharmacology Authors: Mohamed ‐Eslam F. Mohamed, Mukul Minocha, Sheryl Trueman, Tian Feng, Jeffrey Enejosa, Ogert Fisniku, Ahmed A. Othman Tags: Original Manuscript Source Type: research

Effect of Mild and Moderate Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of a Single Dose of Oral Ivosidenib in Otherwise Healthy Participants
AbstractIvosidenib, a small ‐molecule inhibitor of mutant isocitrate dehydrogenase 1, is primarily cleared by hepatic metabolism. This open‐label study investigated the impact of hepatic impairment on ivosidenib pharmacokinetics (ClinicalTrials.gov: NCT03282513). Otherwise healthy participants with mild (n = 9) or moderate (n = 8) hepatic impairment (Child‐Pugh score) and matched participants with normal hepatic function (n = 16) received 1 oral dose of 500‐mg ivosidenib. Mild hepatic impairment had a negligible effect on total ivosidenib plasma exposure, with geometric mean ratios (90% confidence interval [CI]) of...
Source: Clinical Pharmacology in Drug Development - July 9, 2020 Category: Drugs & Pharmacology Authors: Bin Fan, David Dai, Marvin Cohen, Huansheng Xu, Feng Yin, Raj Nagaraja, Michelle Mobilia, Caroline Almon, Frank G. Basile, Hua Yang Tags: Original Manuscript Source Type: research

Characterization of the Effect of Upadacitinib on the Pharmacokinetics of Bupropion, a Sensitive Cytochrome P450 2B6 Probe Substrate
AbstractThis phase 1 study characterized the effect of multiple doses of upadacitinib, an oral Janus kinase 1 selective inhibitor, on the pharmacokinetics of the cytochrome P450 (CYP) 2B6 substrate bupropion. Healthy subjects (n = 22) received a single oral dose of bupropion 150 mg alone (study period 1) and on day 12 of a 16 ‐day regimen of upadacitinib 30 mg once daily (study period 2). Serial blood samples for measurement of bupropion and hydroxybupropion plasma concentrations were collected in each study period. The central values (90% confidence intervals) for the ratios of change were 0.87 (0.79‐0.96) for bu...
Source: Clinical Pharmacology in Drug Development - July 9, 2020 Category: Drugs & Pharmacology Authors: Mohamed ‐Eslam F. Mohamed, Mukul Minocha, Sheryl Trueman, Tian Feng, Jeffrey Enejosa, Ogert Fisniku, Ahmed A. Othman Tags: Original Manuscript Source Type: research

A Randomized, Double ‐Blind Study Comparing Pharmacokinetics and Pharmacodynamics of Proposed Biosimilar ABP 798 With Rituximab Reference Product in Subjects With Moderate to Severe Rheumatoid Arthritis
AbstractABP 798 is a proposed biosimilar to rituximab reference product (RP), an anti ‐CD20 monoclonal antibody. Pharmacokinetics (PK), pharmacodynamics (PD), and safety results from the comparative clinical study that evaluated the PK, PD, safety, efficacy, and immunogenicity of ABP 798 versus rituximab RP are presented here. Subjects with moderate to severe rheumatoid arthritis (RA) received 2 doses of ABP 798, United States‐sourced RP (rituximab US) or European Union‐sourced RP (rituximab EU), each consisting of two 1000‐mg infusions 2 weeks apart. For the second dose (week 24), ABP 798‐ and rituximab EU...
Source: Clinical Pharmacology in Drug Development - July 5, 2020 Category: Drugs & Pharmacology Authors: Gerd Burmester, David Chien, Vincent Chow, Melissa Gessner, Jean Pan, Stanley Cohen Tags: Original Manuscript Source Type: research