Why Collecting Pharmacokinetic Information After Intravenous Drug Administration Is Important
Clinical Pharmacology in Drug Development, EarlyView. (Source: Clinical Pharmacology in Drug Development)
Source: Clinical Pharmacology in Drug Development - January 13, 2020 Category: Drugs & Pharmacology Authors: Peter H. Hinderling, Thomas Papoian Tags: Commentary Source Type: research

Single ‐ and Multiple‐Dose Safety, Tolerability, and Pharmacokinetic Profiles of ASP8062: Results From 2 Phase 1 Studies
AbstractASP8062 is an orally active γ‐amino‐butyric acid type B (GABAB) receptor positive allosteric modulator currently in phase 2 development. Safety and pharmacokinetic (PK) profiles of ASP8062 were evaluated in 2 studies in healthy subjects. The first study (a first ‐in‐human study) evaluated single ascending doses (SAD) of ASP8062. The second study was composed of 2 parts: part 1 evaluated multiple ascending doses (MAD) of ASP8062 for 14 days, and part 2 was a single‐dose arm to assess the PK of ASP8062 in cerebrospinal fluid (CSF). Fifty‐six men (SAD ) and 56 subjects (24 women and 32 men; MAD)...
Source: Clinical Pharmacology in Drug Development - January 11, 2020 Category: Drugs & Pharmacology Authors: Mark Walzer, Gerard J. Marek, Ruishan Wu, Masanori Nagata, David Han Tags: Original Manuscript Source Type: research

Evaluation of Pharmacokinetics and Dose Proportionality of Diazepam After Intranasal Administration of NRL ‐1 to Healthy Volunteers
AbstractNRL ‐1 is a novel intranasal formulation of diazepam that is being evaluated as rescue medication in patients with epilepsy who experience bouts of increased seizure activity despite stable regimens of antiepileptic drugs. This phase 1, open‐label, randomized, crossover study in healthy adult volunt eers consisted of 3 single‐dose periods (5, 10, and 20 mg) followed by a 2‐dose period (2 × 10 mg) with a minimum 28‐day washout between treatments. Blood samples were taken at prespecified time points after intranasal dosing, and bioanalytic analysis of diazepam and nordiazepam was c...
Source: Clinical Pharmacology in Drug Development - January 9, 2020 Category: Drugs & Pharmacology Authors: Sarina Tanimoto, Luana Pesco Koplowitz, Richard E. Lowenthal, Barry Koplowitz, Adrian L. Rabinowicz, Enrique Carrazana Tags: Original Manuscript Source Type: research

Effect of Food on the Pharmacokinetics of Quizartinib
AbstractQuizartinib is an oral, highly potent, and selective type II FMS ‐like tyrosine kinase 3 inhibitor in development for acute myeloid leukemia. This parallel‐group study evaluated potential food effects on quizartinib absorption in healthy subjects who received a single 30‐mg dose after overnight fasting (n = 34) or a high‐fat, high‐calorie meal (n = 30). Blood samples were collected through 504 hours after dosing, and pharmacokinetic parameters calculated were maximum observed concentration (Cmax) and area under plasma concentration –time curve from time 0 to last quantifiable concentration (AUClast)...
Source: Clinical Pharmacology in Drug Development - January 8, 2020 Category: Drugs & Pharmacology Authors: Jianke Li, Melissa Holmes, Martin Kankam, Denise Trone, Jeanne Mendell, Guy Gammon Tags: Original Manuscript Source Type: research

Single ‐Dose Pharmacokinetics, Safety, and Tolerability of Avadomide (CC‐122) in Subjects With Mild, Moderate, or Severe Renal Impairment
AbstractCC ‐122 (Avadomide) is a nonphthalimide analogue of thalidomide that has multiple pharmacological activities including immune modulation of several immune cell subsets, antigrowth activity, antiproliferative activity, and antiangiogenic activity. CC‐122 as monotherapy and in combination with other agents is being evaluated for multiple indications including hematologic malignancies and advanced solid tumors. Given that renal clearance is one of the major routes of elimination for CC‐122 and its clearance/exposure could be affected by renal impairment, a total of 50 subjects with various deg rees of renal func...
Source: Clinical Pharmacology in Drug Development - December 31, 2019 Category: Drugs & Pharmacology Authors: Yan Li, Kimberly MacGorman, Liangang Liu, Jian Chen, Matthew Hoffmann, Maria Palmisano, Simon Zhou Tags: Original Manuscript Source Type: research

Population Pharmacokinetics of Paliperidone Palmitate (Once ‐Monthly Formulation) in Japanese, Korean, and Taiwanese Patients With Schizophrenia
AbstractThe paliperidone pharmacokinetics after intramuscular administration of once ‐monthly paliperidone palmitate in Japanese patients were studied in 3 phase 1 studies and in 2 phase 3 studies performed in Japan, Korea, and Taiwan. These data (Japanese, n = 509; Korean, n = 31; Taiwanese, n = 47) were used to describe the paliperidone palmitate pharmacokinetics in Japanese, to compare with non‐Japanese, and to validate the historical population pharmacokinetic (Pop‐PK) model for paliperidone palmitate, developed using data from studies in patients with schizophrenia outside Japan. The final historical Pop‐PK mo...
Source: Clinical Pharmacology in Drug Development - December 25, 2019 Category: Drugs & Pharmacology Authors: Hiroko Shimizu, Martine Neyens, Marc De Meulder, Srihari Gopal, Yuko Tsukamoto, Mahesh N. Samtani, Bart Remmerie Tags: Original Manuscript Source Type: research

A Mass Balance Study of 14C ‐Labeled JTZ‐951 (Enarodustat), a Novel Orally Available Erythropoiesis‐Stimulating Agent, in Patients With End‐Stage Renal Disease on Hemodialysis
AbstractThe mass balance, pharmacokinetics, and biotransformation of JTZ ‐951 (enarodustat), a novel hypoxia‐inducible factor prolyl hydroxylase inhibitor, were characterized in patients (N = 6) with end‐stage renal disease on hemodialysis. Following a 10‐mg (100 µCi) oral dose of14C ‐JTZ‐951, whole blood, feces, dialysate, and, if feasible, urine were obtained for pharmacokinetic assessments and for metabolite profiling and identification in appropriate matrices. Fecal excretion was the major route of elimination of radioactivity, and urinary excretion a minor route, with m ean (coefficient of variation ...
Source: Clinical Pharmacology in Drug Development - December 25, 2019 Category: Drugs & Pharmacology Authors: Sudhakar M. Pai, Jeffrey Connaire, Hiroyuki Yamada, Seiji Enya, Barbara Gerhardt, Michihide Maekawa, Hiromasa Tanaka, Ryosuke Koretomo, Tomohiro Ishikawa Tags: Original Manuscript Source Type: research

Population Pharmacokinetics of Paliperidone Palmitate (Once ‐Monthly Formulation) in Japanese, Korean, and Taiwanese Patients With Schizophrenia
AbstractThe paliperidone pharmacokinetics after intramuscular administration of once ‐monthly paliperidone palmitate in Japanese patients were studied in 3 phase 1 studies and in 2 phase 3 studies performed in Japan, Korea, and Taiwan. These data (Japanese, n = 509; Korean, n = 31; Taiwanese, n = 47) were used to describe the paliperidone palmitate pharmacokinetics in Japanese, to compare with non‐Japanese, and to validate the historical population pharmacokinetic (Pop‐PK) model for paliperidone palmitate, developed using data from studies in patients with schizophrenia outside Japan. The final historical Pop‐PK mo...
Source: Clinical Pharmacology in Drug Development - December 25, 2019 Category: Drugs & Pharmacology Authors: Hiroko Shimizu, Martine Neyens, Marc De Meulder, Srihari Gopal, Yuko Tsukamoto, Mahesh N. Samtani, Bart Remmerie Tags: Original Manuscript Source Type: research

A Mass Balance Study of 14C ‐Labeled JTZ‐951 (Enarodustat), a Novel Orally Available Erythropoiesis‐Stimulating Agent, in Patients With End‐Stage Renal Disease on Hemodialysis
AbstractThe mass balance, pharmacokinetics, and biotransformation of JTZ ‐951 (enarodustat), a novel hypoxia‐inducible factor prolyl hydroxylase inhibitor, were characterized in patients (N = 6) with end‐stage renal disease on hemodialysis. Following a 10‐mg (100 µCi) oral dose of14C ‐JTZ‐951, whole blood, feces, dialysate, and, if feasible, urine were obtained for pharmacokinetic assessments and for metabolite profiling and identification in appropriate matrices. Fecal excretion was the major route of elimination of radioactivity, and urinary excretion a minor route, with m ean (coefficient of variation ...
Source: Clinical Pharmacology in Drug Development - December 25, 2019 Category: Drugs & Pharmacology Authors: Sudhakar M. Pai, Jeffrey Connaire, Hiroyuki Yamada, Seiji Enya, Barbara Gerhardt, Michihide Maekawa, Hiromasa Tanaka, Ryosuke Koretomo, Tomohiro Ishikawa Tags: Original Manuscript Source Type: research

Pharmacokinetics and Safety of a Single Oral Dose of Peficitinib (ASP015K) in Japanese Subjects With Normal and Impaired Hepatic Function
AbstractPeficitinib (ASP015K) is a novel Janus kinase inhibitor developed for the treatment of rheumatoid arthritis (RA). The impact of hepatic impairment on the peficitinib pharmacokinetic (PK) and safety profile was investigated in non ‐RA subjects (n = 24) in an open‐label, parallel‐group, multicenter comparative study in Japan. Subjects received a single, clinically relevant, oral dose of a peficitinib 150 mg tablet under fasting conditions. Plasma PK parameters were measured for peficitinib and its metabolites H1 (sulfa te and methylated metabolite), H2 (sulfate metabolite), and H4 (methylated metaboli...
Source: Clinical Pharmacology in Drug Development - December 12, 2019 Category: Drugs & Pharmacology Authors: Daisuke Miyatake, Tomohisa Shibata, Junko Toyoshima, Yuichiro Kaneko, Kazuo Oda, Tetsuya Nishimura, Masataka Katashima, Masashi Sakaki, Kazuaki Inoue, Takayoshi Ito, Naoki Uchida, Kenichi Furihata, Akinori Urae Tags: Original Manuscript Source Type: research

Evaluation of Clinical Cardiac Safety of Itacitinib, a JAK1 Inhibitor, in Healthy Participants
AbstractItacitinib is a JAK1 ‐selective inhibitor in phase 3 development in graft‐versus‐host disease. A post hoc electrocardiogram (ECG) analysis and a plasma concentration‐QTc (C‐QTc) analysis were performed to assess cardiac safety using data from the first‐in‐human itacitinib study. The study included 2 cohort s of 12 healthy participants each in an interleaving dosing design with single doses of 10‐300 mg or placebo; 500 and 1000 mg doses were subsequently added with 12 participants randomized to itacitinib or placebo. Continuous Holter recordings were collected from 1 hour predose to 8 hours postdose ...
Source: Clinical Pharmacology in Drug Development - December 10, 2019 Category: Drugs & Pharmacology Authors: Xiaohua Gong, Borje Darpo, Hongqi Xue, Naresh Punwani, Kevin He, April M. Barbour, Noam Epstein, Robert Landman, Xuejun Chen, Swamy Yeleswaram Tags: Original Manuscript Source Type: research

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Novel Non –Bile Acid FXR Agonist Tropifexor (LJN452) in Healthy Volunteers
AbstractTropifexor (LJN452) is a potent, orally available, non –bile acid farnesoid X receptor agonist under clinical development for chronic liver diseases. Here, we present results from a first‐in‐human study of tropifexor following single‐ and multiple‐ascending doses (SAD/MAD) and food effect substudy in healthy volunteers. The SAD study included 6 fasted cohorts receiving 10‐ to 3000‐µg tropifexor or placebo and 1 cohort receiving 300‐µg tropifexor with a high‐fat meal. The MAD study included 4 lean cohorts receiving 10 to 100 µg and 1 obese cohort receiving 30‐µg o...
Source: Clinical Pharmacology in Drug Development - December 10, 2019 Category: Drugs & Pharmacology Authors: Michael K. Badman, Jin Chen, Sachin Desai, Soniya Vaidya, Srikanth Neelakantham, Jie Zhang, Lu Gan, Kate Danis, Bryan Laffitte, Lloyd B. Klickstein Tags: Original Manuscript Source Type: research

Pharmacokinetics, Pharmacodynamics, and Safety of a Single Escalating Dose and Repeated Doses of Rasagiline Transdermal Patch in Healthy Chinese Subjects
AbstractA rasagiline transdermal patch can be used to offer continuous rasagiline to patients with Parkinson's disease who cannot take their usual oral medications. This was the first study to investigate the pharmacokinetics, pharmacodynamics, and safety of the rasagiline transdermal patch in healthy Chinese subjects. Thirty subjects were randomized to 3 groups with 10 subjects in each group. The 10 subjects of group 1 received a single 1 ‐mg dose of rasagiline as a tablet; the 20 subjects of groups 2 and 3 received a single transdermal patch (48‐hour patch‐on period) containing 1.25 mg and 2.5 mg rasagiline, r...
Source: Clinical Pharmacology in Drug Development - December 10, 2019 Category: Drugs & Pharmacology Authors: Meng Wang, Wenjia Zhou, Quanying Zhang, Shunlin Zong, Chengzhe Lv Tags: Original Manuscript Source Type: research

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Novel Non –Bile Acid FXR Agonist Tropifexor (LJN452) in Healthy Volunteers
AbstractTropifexor (LJN452) is a potent, orally available, non –bile acid farnesoid X receptor agonist under clinical development for chronic liver diseases. Here, we present results from a first‐in‐human study of tropifexor following single‐ and multiple‐ascending doses (SAD/MAD) and food effect substudy in healthy volunteers. The SAD study included 6 fasted cohorts receiving 10‐ to 3000‐µg tropifexor or placebo and 1 cohort receiving 300‐µg tropifexor with a high‐fat meal. The MAD study included 4 lean cohorts receiving 10 to 100 µg and 1 obese cohort receiving 30‐µg o...
Source: Clinical Pharmacology in Drug Development - December 10, 2019 Category: Drugs & Pharmacology Authors: Michael K. Badman, Jin Chen, Sachin Desai, Soniya Vaidya, Srikanth Neelakantham, Jie Zhang, Lu Gan, Kate Danis, Bryan Laffitte, Lloyd B. Klickstein Tags: Original Manuscript Source Type: research

Pharmacokinetics, Pharmacodynamics, and Safety of a Single Escalating Dose and Repeated Doses of Rasagiline Transdermal Patch in Healthy Chinese Subjects
AbstractA rasagiline transdermal patch can be used to offer continuous rasagiline to patients with Parkinson's disease who cannot take their usual oral medications. This was the first study to investigate the pharmacokinetics, pharmacodynamics, and safety of the rasagiline transdermal patch in healthy Chinese subjects. Thirty subjects were randomized to 3 groups with 10 subjects in each group. The 10 subjects of group 1 received a single 1 ‐mg dose of rasagiline as a tablet; the 20 subjects of groups 2 and 3 received a single transdermal patch (48‐hour patch‐on period) containing 1.25 mg and 2.5 mg rasagiline, r...
Source: Clinical Pharmacology in Drug Development - December 10, 2019 Category: Drugs & Pharmacology Authors: Meng Wang, Wenjia Zhou, Quanying Zhang, Shunlin Zong, Chengzhe Lv Tags: Original Manuscript Source Type: research

Evaluation of Clinical Cardiac Safety of Itacitinib, a JAK1 Inhibitor, in Healthy Participants
AbstractItacitinib is a JAK1 ‐selective inhibitor in phase 3 development in graft‐versus‐host disease. A post hoc electrocardiogram (ECG) analysis and a plasma concentration‐QTc (C‐QTc) analysis were performed to assess cardiac safety using data from the first‐in‐human itacitinib study. The study included 2 cohort s of 12 healthy participants each in an interleaving dosing design with single doses of 10‐300 mg or placebo; 500 and 1000 mg doses were subsequently added with 12 participants randomized to itacitinib or placebo. Continuous Holter recordings were collected from 1 hour predose to 8 hours postdose ...
Source: Clinical Pharmacology in Drug Development - December 10, 2019 Category: Drugs & Pharmacology Authors: Xiaohua Gong, Borje Darpo, Hongqi Xue, Naresh Punwani, Kevin He, April M. Barbour, Noam Epstein, Robert Landman, Xuejun Chen, Swamy Yeleswaram Tags: Original Manuscript Source Type: research

Preemptive Anti –Stress Response Effects of Oxycodone Versus Sufentanil for Patients Undergoing Cardiac Valve Replacement—A Randomized Controlled Trial
AbstractPatients undergoing cardiac valve replacement may experience cardiovascular adverse events during the preoperative period before anesthesia. The study was to compare the preemptive anti –stress response effects of oxycodone versus sufentanil for patients undergoing cardiac valve replacement. Ninety‐four patients were enrolled and assigned to group Oxy, group Suf and group NS. Patients in group Oxy were administrated with oxycodone 0.1 mg/kg, group Suf received sufentanil 0.1  μg/kg and group NS were given equivalent volume of normal saline. The primary outcomes included serum levels of cortisol...
Source: Clinical Pharmacology in Drug Development - December 9, 2019 Category: Drugs & Pharmacology Authors: Jian Zhang, Qing Tu, Jianhui Gan, Shuai Miao, Ying Zhou, Qiang Li, Chuandong Zheng Tags: Original Manuscript Source Type: research

Pharmacokinetic Analysis of Weekly Versus Biweekly IgPro20 Dosing in Patients With Primary Immunodeficiency
AbstractFlexible dosing of IgPro20 (Hizentra ®, CSL Behring, King of Prussia, Pennsylvania) maintains normal serum immunoglobulin G (IgG) levels in patients with primary immunodeficiencies (PID). Until now, clinical trials testing the pharmacokinetic (PK) characteristics of serum IgG of weekly and biweekly subcutaneous IgG therapy were not pu blished. This is the first study assessing PK characteristics following weekly and biweekly IgPro20 in patients with PID. The PK study was conducted in 2 parts: weekly dosing (12 weeks) and biweekly dosing (up to 12 months). Serum IgG concentration‐time data were analyzed u...
Source: Clinical Pharmacology in Drug Development - December 8, 2019 Category: Drugs & Pharmacology Authors: Mikhail A. Rojavin, Hugo Chapdelaine, Michael A. Tortorici, Michaela Praus, Gautam Baheti, Ying Zhang, Jutta Hofmann, Roxane Labrosse, Ren ée Dicaire, Elie Haddad Tags: Original Manuscript Source Type: research

Pharmacokinetics, Bioequivalence, and Safety Studies of Prucalopride in Healthy Chinese Subjects
This study was designed as a randomized, open ‐label, fasting, single‐dose, crossover, and dual‐period trial. After overnight fasting, 12 subjects were given prucalopride tablets via oral administration, and blood specimens were obtained up to 96 hours after dosing. Prucalopride concentrations in plasma were measured using ultraprecision liquid chromatography–tandem mass spectrometry followed by calculation of pharmacokinetic parameters. The safety of prucalopride was assessed throughout the study. The pharmacokinetics of prucalopride can be defined as a 2‐compartment model with a long elimination phase. No s...
Source: Clinical Pharmacology in Drug Development - December 3, 2019 Category: Drugs & Pharmacology Authors: Ziye Zhou, Chenxiang Wang, Xuyong Zheng, Xuben Yu, Chao Yu, Dongchuan Zhang, Yan Xia, Huafang Chen, Xiaoxiao Huang, Xiuhua Zhang Tags: Original Manuscript Source Type: research

Filgotinib, a JAK1 Inhibitor, Has No Effect on QT Interval in Healthy Subjects
AbstractFilgotinib, a selective inhibitor of Janus kinase 1, is being developed for the treatment of chronic inflammatory diseases. Electrocardiograms evaluated the effect of filgotinib on the corrected QT (QTc) interval in 52 healthy subjects who received each of 4 treatments: filgotinib 200  mg (therapeutic dose), 450 mg (supratherapeutic dose), and placebo, each administered once daily for 7 days, and a single dose of moxifloxacin 400 mg (positive control). Plasma samples were collected for pharmacokinetic analysis. The QTc interval was calculated using Fridericia's correction fact or (QTcF) or an individ...
Source: Clinical Pharmacology in Drug Development - December 2, 2019 Category: Drugs & Pharmacology Authors: Kacey Anderson, Yan Xin, Hao Zheng, Chohee Yun, Ellen Kwan, Ann Qin, Florence Namour, Brian P. Kearney, Anita Mathias Tags: Original Manuscript Source Type: research

Lack of Effect of Rezafungin on QT/QTc Interval in Healthy Subjects
AbstractRezafungin is a new echinocandin in development for treatment of candidemia and invasive candidiasis, and for prophylaxis of invasive fungal infections. Rezafungin is the first echinocandin to undergo definitive QT/QTc study. This phase 1, single ‐center, randomized, double‐blind trial was conducted to assess effects of intravenous rezafungin vs intravenous placebo (with moxifloxacin as positive control) on the QT interval of the electrocardiogram, corrected for heart rate by Fridericia's formula (QTcF), in healthy adults. Therapeutic (6 00 mg) and supratherapeutic (1400 mg) rezafungin doses were selected ...
Source: Clinical Pharmacology in Drug Development - December 2, 2019 Category: Drugs & Pharmacology Authors: Shawn Flanagan, Daniel B. Goodman, Alena Jandourek, Terry O'Reilly, Taylor Sandison Tags: Original Manuscript Source Type: research

The Effect of Food on the Single ‐Dose Bioavailability and Tolerability of the Highest Marketed Strength of Duloxetine
AbstractDuloxetine is a combined serotonin and norepinephrine reuptake inhibitor indicated in adults for the treatment of major depressive disorder, diabetic peripheral neuropathic pain, and generalized anxiety disorder. The aim of these studies was to evaluate the effect of food on the pharmacokinetics and safety of duloxetine 60 ‐mg gastroresistant hard capsules following single‐dose administration. The data were obtained from 2 phase 1 bioequivalence studies, 1 in a fasting state and the other under fed conditions. Both studies have shown that, when administered as a single dose in the same prandial state, the test ...
Source: Clinical Pharmacology in Drug Development - December 2, 2019 Category: Drugs & Pharmacology Authors: Simona Rizea ‐Savu, Simona Nicoleta Duna, Adrian Ghita, Adriana Iordachescu, Marinela Chirila Tags: Original Manuscript Source Type: research

Phase 1 Pharmacokinetic Study of AZD5718 in Healthy Volunteers: Effects of Coadministration With Rosuvastatin, Formulation and Food on Oral Bioavailability
AbstractAZD5718 is a first ‐in‐class small‐molecule anti‐inflammatory drug with the potential to reduce the residual risk of cardiovascular events after myocardial infarction in patients receiving lipid‐lowering statin therapy. Leukotrienes are potent proinflammatory and vasoactive mediators synthesized in leukocyte s via 5‐lipoxygenase and 5‐lipoxygenase‐activating protein (FLAP). AZD5718 is a FLAP inhibitor that dose‐dependently reduced leukotriene biosynthesis in a first‐in‐human study. We enrolled 12 healthy men in a randomized, open‐label, crossover, single‐dose phase 1 pharmacokinetic stud y...
Source: Clinical Pharmacology in Drug Development - December 2, 2019 Category: Drugs & Pharmacology Authors: Hans Ericsson, Karin Nelander, Maria Heijer, Magnus Kjaer, Eva ‐Lotte Lindstedt, Muna Albayaty, Pablo Forte, Maria Lagerström‐Fermér, Stanko Skrtic Tags: Original Manuscript Source Type: research

Filgotinib, a JAK1 Inhibitor, Has No Effect on QT Interval in Healthy Subjects
AbstractFilgotinib, a selective inhibitor of Janus kinase 1, is being developed for the treatment of chronic inflammatory diseases. Electrocardiograms evaluated the effect of filgotinib on the corrected QT (QTc) interval in 52 healthy subjects who received each of 4 treatments: filgotinib 200  mg (therapeutic dose), 450 mg (supratherapeutic dose), and placebo, each administered once daily for 7 days, and a single dose of moxifloxacin 400 mg (positive control). Plasma samples were collected for pharmacokinetic analysis. The QTc interval was calculated using Fridericia's correction fact or (QTcF) or an individ...
Source: Clinical Pharmacology in Drug Development - December 2, 2019 Category: Drugs & Pharmacology Authors: Kacey Anderson, Yan Xin, Hao Zheng, Chohee Yun, Ellen Kwan, Ann Qin, Florence Namour, Brian P. Kearney, Anita Mathias Tags: Original Manuscript Source Type: research

Lack of Effect of Rezafungin on QT/QTc Interval in Healthy Subjects
AbstractRezafungin is a new echinocandin in development for treatment of candidemia and invasive candidiasis, and for prophylaxis of invasive fungal infections. Rezafungin is the first echinocandin to undergo definitive QT/QTc study. This phase 1, single ‐center, randomized, double‐blind trial was conducted to assess effects of intravenous rezafungin vs intravenous placebo (with moxifloxacin as positive control) on the QT interval of the electrocardiogram, corrected for heart rate by Fridericia's formula (QTcF), in healthy adults. Therapeutic (6 00 mg) and supratherapeutic (1400 mg) rezafungin doses were selected ...
Source: Clinical Pharmacology in Drug Development - December 2, 2019 Category: Drugs & Pharmacology Authors: Shawn Flanagan, Daniel B. Goodman, Alena Jandourek, Terry O'Reilly, Taylor Sandison Tags: Original Manuscript Source Type: research

The Effect of Food on the Single ‐Dose Bioavailability and Tolerability of the Highest Marketed Strength of Duloxetine
AbstractDuloxetine is a combined serotonin and norepinephrine reuptake inhibitor indicated in adults for the treatment of major depressive disorder, diabetic peripheral neuropathic pain, and generalized anxiety disorder. The aim of these studies was to evaluate the effect of food on the pharmacokinetics and safety of duloxetine 60 ‐mg gastroresistant hard capsules following single‐dose administration. The data were obtained from 2 phase 1 bioequivalence studies, 1 in a fasting state and the other under fed conditions. Both studies have shown that, when administered as a single dose in the same prandial state, the test ...
Source: Clinical Pharmacology in Drug Development - December 2, 2019 Category: Drugs & Pharmacology Authors: Simona Rizea ‐Savu, Simona Nicoleta Duna, Adrian Ghita, Adriana Iordachescu, Marinela Chirila Tags: Original Manuscript Source Type: research

Phase 1 Pharmacokinetic Study of AZD5718 in Healthy Volunteers: Effects of Coadministration With Rosuvastatin, Formulation and Food on Oral Bioavailability
AbstractAZD5718 is a first ‐in‐class small‐molecule anti‐inflammatory drug with the potential to reduce the residual risk of cardiovascular events after myocardial infarction in patients receiving lipid‐lowering statin therapy. Leukotrienes are potent proinflammatory and vasoactive mediators synthesized in leukocyte s via 5‐lipoxygenase and 5‐lipoxygenase‐activating protein (FLAP). AZD5718 is a FLAP inhibitor that dose‐dependently reduced leukotriene biosynthesis in a first‐in‐human study. We enrolled 12 healthy men in a randomized, open‐label, crossover, single‐dose phase 1 pharmacokinetic stud y...
Source: Clinical Pharmacology in Drug Development - December 2, 2019 Category: Drugs & Pharmacology Authors: Hans Ericsson, Karin Nelander, Maria Heijer, Magnus Kjaer, Eva ‐Lotte Lindstedt, Muna Albayaty, Pablo Forte, Maria Lagerström‐Fermér, Stanko Skrtic Tags: Original Manuscript Source Type: research

A Thorough QT Study to Evaluate the Effects of a Supratherapeutic Dose of Sertraline on Cardiac Repolarization in Healthy Subjects
AbstractThe effect of steady ‐state supratherapeutic sertraline (Zoloft) on QT interval was assessed in a single‐center, randomized, 3‐way crossover, double‐blind, placebo‐ and moxifloxacin‐controlled thorough QT study. Healthy adults received sertraline 400 mg/day, moxifloxacin 400 mg, and placebo, with a washout period (≥14 days) between treatments. A 12‐lead electrocardiogram was recorded in triplicate before dosing and at selected time points up to 72 hours after dosing. Analysis of covariance using a mixed‐effect model with sequence, period, treatment, time, and treatment‐by‐...
Source: Clinical Pharmacology in Drug Development - November 27, 2019 Category: Drugs & Pharmacology Authors: Richat Abbas, Steve Riley, Robert R. LaBadie, Mary Bachinsky, Phillip B. Chappell, Penelope H. Crownover, Bharat Damle Tags: Original Manuscript Source Type: research

Bioequivalence and Food Effect Assessment of 2 Fixed ‐Dose Combination Formulations of Dolutegravir and Lamivudine
AbstractThis single ‐dose study evaluated the bioequivalence, food effect, and safety of 2 experimental, 2‐drug, fixed‐dose formulations of 50 mg dolutegravir and 300 mg lamivudine (formulation AH and formulation AK) as compared with coadministration of single‐entity tablets of 50 mg dolutegravir and 300 mg lamivudine (reference). In fasted subjects, formulation AH lamivudine exposure was similar to the reference; however, dolutegravir exposure was consistently higher in formulation AH, with area under the concentration‐time curve (AUC) and maximum concentration (Cmax) approximately 27% to 28%...
Source: Clinical Pharmacology in Drug Development - November 14, 2019 Category: Drugs & Pharmacology Authors: Teodora Pene Dumitrescu, Kavita Peddiraju, Caifeng Fu, Kalpana Bakshi, Shui Yu, Zhiping Zhang, Allan R. Tenorio, Chris Spancake, Shashidhar Joshi, Allen Wolstenholme, Kimberly Adkison Tags: Original Manuscript Source Type: research

Phase 1 Dose ‐Escalation Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Tofacitinib in Japanese Healthy Volunteers
AbstractThe aim of the study was to characterize the pharmacokinetics, safety, and tolerability of tofacitinib, an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis in healthy Japanese volunteers, and to compare these outcomes with those of healthy Western volunteers. Twenty ‐five volunteers (Japanese, n = 16; Western [white], n = 9) were randomized to receive either 3 escalating single doses of tofacitinib (1, 5, and 30 mg), single‐dose tofacitinib (15 mg) followed by multiple doses (15 mg twice daily for 5 da...
Source: Clinical Pharmacology in Drug Development - November 11, 2019 Category: Drugs & Pharmacology Authors: So Miyoshi, Sriram Krishnaswami, Shigeyuki Toyoizumi, Hiroyuki Nakamura, Samuel H. Zwillich Tags: Original Manuscript Source Type: research

The Influence of Renal or Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Oliceridine
AbstractOliceridine is a G protein –biased ligand at the μ‐opioid receptor in development for treatment of moderate to severe acute pain. A phase 1, open‐label, single‐dose study investigated the pharmacokinetics and safety of oliceridine 0.5 mg intravenous (IV) in subjects with end‐stage renal disease (ESRD, n = 9) versus 1 mg in healthy controls (n = 8). A second phase 1, open‐label, single‐dose study investigated the pharmacokinetics and safety of a 0.5‐mg IV dose in hepatic impairment (mild, n = 10; moderate, n = 10; severe, n = 6) versus 1 mg in healthy controls (n = 8). The controls were sex an...
Source: Clinical Pharmacology in Drug Development - November 7, 2019 Category: Drugs & Pharmacology Authors: Anne N. Nafziger, Kelly A. Arscott, Kristina Cochrane, Franck Skobieranda, David A. Burt, Michael J. Fossler Tags: Original Manuscript Source Type: research

Issue Information
Clinical Pharmacology in Drug Development, Volume 8, Issue 8, Page 973-977, November/December 2019. (Source: Clinical Pharmacology in Drug Development)
Source: Clinical Pharmacology in Drug Development - November 4, 2019 Category: Drugs & Pharmacology Tags: Issue Information Source Type: research

Evaluation of the Pharmacokinetic Interaction Between the Voltage ‐ and Use‐Dependent Nav1.7 Channel Blocker Vixotrigine and Carbamazepine in Healthy Volunteers
AbstractVixotrigine is a voltage ‐ and use‐dependent Nav1.7 channel blocker under investigation for the treatment of peripheral neuropathic pain conditions, including trigeminal neuralgia. Vixotrigine is metabolized primarily via uridine diphosphate‐glucuronosyltransferases (UGTs). Carbamazepine, a UGT and cytochrome P450 3A4 inducer, is a first‐line treatment for trigeminal neuralgia. We conducted a double‐blind, randomized, placebo‐controlled, parallel‐group, single‐center phase 1 study to investigate the impact of coadministering vixotrigine and carbamazepine on their respective pharmacokinetics (PK) in ...
Source: Clinical Pharmacology in Drug Development - October 24, 2019 Category: Drugs & Pharmacology Authors: Joi Dunbar, Mark Versavel, Yuan Zhao, Simon Tate, Valerie Morisset, Gerard M. P. Giblin, Joanne Palmer, Beth Tidemann ‐Miller, Himanshu Naik Tags: Original Manuscript Source Type: research

Comparison of In Vitro and In Vivo Percutaneous Absorption Across Human Skin Using BAY1003803 Formulated as Ointment and Cream
In conclusion, in vitro skin absorption studies using human skin are suitable for the prediction of systemic exposu re and formulation effects in vivo; they can therefore be applied to guide the design of clinical investigations of dermatological preparations. (Source: Clinical Pharmacology in Drug Development)
Source: Clinical Pharmacology in Drug Development - October 24, 2019 Category: Drugs & Pharmacology Authors: Clemens G ünther, Kristin Kowal, Timm Schmidt, Alen Jambrecina, Frank Toner, Rüdiger Nave Tags: Original Manuscript Source Type: research

Pharmacokinetic Similarity of ABP 710, a Proposed Biosimilar to Infliximab: Results From a Randomized, Single ‐Blind, Single‐Dose, Parallel‐Group Study in Healthy Subjects
AbstractThis was a randomized, single ‐blind, single‐dose, 3‐arm parallel‐group study. Healthy subjects were randomized to receive ABP 710 (n = 50) or infliximab reference product (RP) sourced from the United States (infliximab US; n = 50) or the European Union (infliximab EU; n = 50) 5 mg/kg intravenously over 2 hours. Th e primary endpoint was area under the serum concentration–time curve from time 0 extrapolated to infinity (AUCinf) for the comparison of ABP 710 to infliximab US and infliximab EU. Secondary endpoints included safety, tolerability, and immunogenicity. AUCinf wa...
Source: Clinical Pharmacology in Drug Development - October 19, 2019 Category: Drugs & Pharmacology Authors: Vincent Chow, MyungShin Oh, Melissa A. Gessner, Gary Fanjiang Tags: Original Manuscript Source Type: research