Clinical Pharmacology in Drug Development This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

A Phase 1, Randomized, Double ‐Blind, Placebo‐Controlled, Single Ascending Dose Study to Evaluate the Pharmacokinetics, Immunogenicity, Safety, and Tolerability After Subcutaneous Administration of Tozorakimab in Healthy Chinese Participants
AbstractTozorakimab is a high-affinity human immunoglobulin G1 monoclonal antibody that neutralizes interleukin (IL)-33, an IL-1 family cytokine. This phase 1, single-center, randomized, double-blind, placebo-controlled, single ascending dose study (NCT05070312) evaluated tozorakimab in a healthy Chinese population. Outcomes included the characterization of the pharmacokinetic (PK) profile and immunogenicity of tozorakimab. Safety outcomes included treatment-emergent adverse events (TEAEs) and clinical laboratory, electrocardiogram, and vital sign parameters. Healthy, non-smoking, male, and female Chinese participants aged...
Source: Clinical Pharmacology in Drug Development - March 25, 2024 Category: Drugs & Pharmacology Authors: Yunfei Li, Hua Zhang, Hitesh Pandya, Liyan Miao, Fred Reid, Eulalia Jimenez, Muhammad Waqas Sadiq, Rachel Moate, Alejhandra Lei, Xiao ‐Hong Zhou, Chris Kell, Junjie Ding, Guanlin Zhang, Lina Zhao, Xiaoyun Ge Tags: Original Article Source Type: research

Clinical Pharmacology of GP40321 (Insulin Glulisine Biosimilar): Pharmacokinetic and Pharmacodynamic Comparability in a Hyperinsulinemic ‐Euglycemic Clamp Procedure
AbstractThe aim of the study was to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of T-glu (GP40321, test drug), and reference insulin glulisine in a hyperinsulinemic-euglycemic clamp procedure. During this study, 34 healthy male volunteers underwent the hyperinsulinemic-euglycemic clamp procedure following subcutaneous 0.3  U/kg injection of T-glu or reference insulin glulisine in a randomized, double-blind, crossover study. Plasma glucose levels were monitored every 5 minutes for 8 hours. Glucose infusion rate adjustment was based on the blood glucose measurements. Evaluation of PD was performed using th...
Source: Clinical Pharmacology in Drug Development - March 22, 2024 Category: Drugs & Pharmacology Authors: Ekaterina Koksharova, Roman Drai, Sergei Noskov, Artem Dorotenko, Ekaterina Protsenko, Kseniia Radaeva, Anna Arefeva, Maria Gefen, Gagik Galstyan, Igor Makarenko Tags: Original Article Source Type: research

Comparative Bioequivalence and Food Effect of Two Formulations of 30 ‐mg Nifedipine Controlled‐Release Tablets in Healthy Chinese Adults
The objective of this trial was to assess the bioequivalence of a 30-mg nifedipine controlled-release tablet and a reference drug in a cohort of healthy Chinese individuals. Two independent open-label, randomized, single-dose, crossover studies were conducted, 1 under fasting conditions (N = 44, with 1 participant dropping out midway) and the other under fed conditions (N = 44, with 4 participants dropping out midway). Plasma concentrations of nifedipine were determined using liquid chromatography-mass spectrometry, and pharmacokinetic (PK) parameters were calculated using noncompartmental analysis with Phoenix WinNonlin 8...
Source: Clinical Pharmacology in Drug Development - March 14, 2024 Category: Drugs & Pharmacology Authors: Huizi Zhang, Siyang Wang, Hongxia Wang, Tingting Zhi, Jian Ren, Yanhui Wang, Zhiqing Yao, Pan Zhang, Naobei Ye, Ruiqin Zhang Tags: Original Article Source Type: research

Safety, Tolerability, and Pharmacokinetics of Single ‐ and Multiple‐Ascending Doses of Sunobinop in Healthy Participants
AbstractSunobinop is an investigational, potent, selective partial agonist at the nociceptin/orphanin FQ peptide receptor in vitro. Three phase 1 studies were conducted to evaluate the safety, tolerability, and pharmacokinetics (PK) of escalating single- and multiple-dose administration of sunobinop in healthy participants. Study 1 was a randomized, double-blind, placebo-controlled, single-ascending dose study. Study 2 was a randomized, double-blind, placebo-controlled, multiple-ascending dose study. Study 3 was a randomized, open-label, single-dose, 4-way crossover study of oral and sublingual sunobinop comparing morning ...
Source: Clinical Pharmacology in Drug Development - March 13, 2024 Category: Drugs & Pharmacology Authors: Alessandra Cipriano, Ram P. Kapil, Mingyan Zhou, Manjunath S. Shet, Garth T. Whiteside, Sandra K. Willsie, Stephen C. Harris Tags: Original Article Source Type: research

Pharmacokinetic and Safety Comparison of Fixed ‐Dose Combination of Cilostazol/Rosuvastatin (200 + 20 mg) Versus Concurrent Administration of the Separate Components in Healthy Adults
AbstractThe combined cilostazol and rosuvastatin therapy is frequently used for coronary artery disease treatment. This open-label, 3  × 3 crossover clinical trial evaluated the pharmacokinetics and safety of a fixed-dose combination (FDC) of cilostazol/rosuvastatin (200 + 20 mg) versus a concurrent administration of the separate components (SCs) under both fasted and fed conditions. Among 48 enrolled healthy adults, 38 comple ted the study. Participants were administered a single oral dose of cilostazol/rosuvastatin (200 + 20 mg), either as an FDC or SCs in a fasted state, or FDC in a fed state, in each period of the...
Source: Clinical Pharmacology in Drug Development - March 12, 2024 Category: Drugs & Pharmacology Authors: Jae Hoon Kim, Jang Hee Hong, Jin ‐Gyu Jung, Won Tae Jung, Kyu‐Yeol Nam, Jae Seok Roh, Youn Woong Choi, Junbae Bang, Hyunwook Huh, Hye J. Lee, JungHa Moon, Jaehee Kim, Jung Sunwoo Tags: Original Article Source Type: research

Nlmixr2 Versus NONMEM: An Evaluation of Maximum A Posteriori Bayesian Estimates Following External Evaluation of Gentamicin and Tobramycin Population Pharmacokinetic Models
The objective of this project is to compare the results of the same study carried out on NONMEM and nlmixr2. This analysis consists of evaluating previously published population pharmacokinetic models of gentamicin and tobramycin in our population of interest with sparse concentrations. A literature review was performed to determine the gentamicin and tobramycin models in critically ill adult patients. In parallel, gentamicin and tobramycin dosing data, information on the treatment, the patient, and the bacteria were collected retrospectively in 2 Quebec establishments. The external evaluations were previously performed us...
Source: Clinical Pharmacology in Drug Development - March 12, 2024 Category: Drugs & Pharmacology Authors: Alexandre Duong, Am élie Marsot Tags: Original Article Source Type: research

Cardiovascular Evaluation of Etrasimod, a Selective Sphingosine 1 ‐phosphate Receptor Modulator, in Healthy Adults: Results of a Randomized, Thorough QT/QTc Study
AbstractEtrasimod is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 modulator used as an oral treatment option for immune-mediated inflammatory disorders. This randomized, double-blind, placebo- and positive-controlled, parallel-group, healthy adult study investigated etrasimod's effect on the QT interval and other electrocardiogram parameters. All participants received etrasimod-matched placebo on day 1. Group A received once-daily, multiple ascending doses of etrasimod (2-4  mg) on days 1-14 and moxifloxacin-matched placebo on days 1 and 15. Group B received etrasimod-matched pla...
Source: Clinical Pharmacology in Drug Development - March 6, 2024 Category: Drugs & Pharmacology Authors: Borje Darpo, Kalvin Connor, Christopher H. Cabell, John S. Grundy Tags: Original Article Source Type: research

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(Source: Clinical Pharmacology in Drug Development)
Source: Clinical Pharmacology in Drug Development - March 1, 2024 Category: Drugs & Pharmacology Tags: Issue Information Source Type: research

Pharmacokinetic Evaluation of the CYP3A4 and CYP2C9 Drug ‐Drug Interaction of Avacopan in 2 Open‐Label Studies in Healthy Participants
AbstractAvacopan, a complement 5a receptor (C5aR) antagonist approved for treating severe active antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, was evaluated in 2 clinical drug-drug interaction studies. The studies assessed the impact of avacopan on the pharmacokinetics (PK) of CYP3A4 substrates midazolam and simvastatin and CYP2C9 substrate celecoxib, and the influence of CYP3A4 inhibitor itraconazole and inducer rifampin on the PKs of avacopan. The results indicated that twice-daily oral administration of 30  mg of avacopan increased the area under the curve (AUC) of midazolam by 1.81-fold and cel...
Source: Clinical Pharmacology in Drug Development - March 1, 2024 Category: Drugs & Pharmacology Authors: Shichang Miao, Pirow Bekker, Danielle Armas, Mary Lor, Yanyan Han, Kenneth Webster, Ashit Trivedi Tags: Original Article Source Type: research

Effect of Strong CYP3A4 Inhibition, CYP3A4 Induction, and OATP1B1/3 Inhibition on the Pharmacokinetics of a Single Oral Dose of Sotorasib
AbstractSotorasib is a small molecule that irreversibly inhibits the Kirsten rat sarcoma viral oncogene homolog (KRAS) protein with a G12C amino acid substitution mutant protein. The impact of cytochrome P450 (CYP) 3A4 inhibition and induction on sotorasib pharmacokinetics (PKs) was evaluated in 2 separate studies in healthy volunteers (N = 14/study). The impact of CYP3A4 inhibition was interrogated utilizing repeat doses of 200  mg of itraconazole, a strong CYP3A4 inhibitor, on 360 mg of sotorasib PKs. The impact of CYP3A4 induction was interrogated utilizing multiple doses of 600 mg of rifampin, a strong CYP3A4 induce...
Source: Clinical Pharmacology in Drug Development - February 29, 2024 Category: Drugs & Pharmacology Authors: Panli Cardona, Sandeep Dutta, Brett Houk Tags: Original Article Source Type: research

Pharmacokinetics, Safety, and Tolerability of Cedirogant in Healthy Japanese and Chinese Adults
This study aimed to characterize pharmacokinetics, pharmacodynamics, safety, and tolerability of cedirogant following a single oral dose in Japanese participants and multiple oral doses in Japanese and Chinese participants. The single doses evaluated in hea lthy Japanese participants were 75, 225, and 395 mg. The multiple doses evaluated in both healthy Japanese and Chinese participants was 375 mg once daily for 14 days. Cedirogant plasma exposure increased dose proportionally with administration of single doses. Maximum cedirogant plasma concentrati on was reached within a median time of 4-5 hours after dosing. The harm...
Source: Clinical Pharmacology in Drug Development - February 28, 2024 Category: Drugs & Pharmacology Authors: Mohamed ‐Eslam F Mohamed, Yuli Qian, Ronilda D'Cunha, Shuai Hao, Roberto Carcereri De Prati, Gweneth F Levy, Kinjal Hew, Wei Liu Tags: Original Article Source Type: research

Bioequivalence Assessment of Two Dapoxetine Hydrochloride Formulations in Healthy Chinese Males Under Fasted and Fed Conditions
This study evaluated the bioequivalence of the newly developed dapoxetine hydrochloride tablet relative to the marketed reference product by comparing their pharmacokinetic profiles under fasted and fed conditions. A total of 60 healthy Chinese male subjects participated in a single-center, 2-period, 2-sequence, randomized, open-label, self-crossover study with a washout period of 14 days, 30 in the fasted group and 30 in the fed group. Following a single 30-mg oral dose of the test or reference dapoxetine formulation, blood samples were collected before dosing to 72 hours after dosing. Liquid chromatography-tandem mass sp...
Source: Clinical Pharmacology in Drug Development - February 24, 2024 Category: Drugs & Pharmacology Authors: Yumin Li, Zhen Zhang, Jizhen Xie, Xianghua Lian, Guangtao Zhang, Cheng Wang Tags: Original Article Source Type: research

Physiologically Based Pharmacokinetic Absorption Model for Pexidartinib to Evaluate the Impact of Meal Contents and Intake Timing on Drug Exposure
AbstractPexidartinib is a systemic treatment for patients with tenosynovial giant cell tumor not amenable to surgery. Oral absorption of pexidartinib is affected by food; administration with a high-fat meal (HFM) or low-fat meal (LFM) increases absorption by approximately 100% and approximately 60%, respectively, compared with the fasted state. Pexidartinib is currently dosed 250  mg orally twice daily with an LFM (approximately 11-14 g of total fat). We developed a physiologically based pharmacokinetic model to determine the impact on drug exposure of dose timing with respect to meals, meal type, and caloric content. A 1...
Source: Clinical Pharmacology in Drug Development - February 24, 2024 Category: Drugs & Pharmacology Authors: Shintaro Nakayama, Viera Lukacova, Shuichi Tanabe, Akiko Watanabe, Jim Mullin, Sandra Suarez ‐Sharp, Takako Shimizu Tags: Original Article Source Type: research

Bioequivalence Between a New Omalizumab Prefilled Syringe With an Autoinjector or with a Needle Safety Device Compared with the Current Prefilled Syringe: A Randomized Controlled Trial in Healthy Volunteers
The objective of this randomized open-label 12-week study was to demonstrate pharmacokinetic bioequivalence between (1) new PFS with autoinjector (PFS-AI), (2) new PFS-NSD configuration, and (3) current PFS-NSD configuration. Each new configuration was considered bioequivalent to the current configuration if the confidence intervals (CIs) for the geometric mean ratios (GMR) were contained in the 0.80-1.25 range for maximum concentration (Cmax), area under the concentration-time curve until the last quantifiable measurement (AUClast), and AUC extrapolated to infinity (AUCinf). Safety was assessed throughout the study. In to...
Source: Clinical Pharmacology in Drug Development - February 23, 2024 Category: Drugs & Pharmacology Authors: Ramachandra Sangana, Yan Xu, Bharti Shah, Xianbin Tian, Julia Zack, Kasra Shakeri ‐Nejad, Sampath Kalluri, Ieuan Jones, Monica Ligueros‐Saylan, Angel Fowler Taylor, Devendra Kumar Jain, Emil Scosyrev, Alkaz Uddin, Nathalie Laurent, Paola Tags: Original Article Source Type: research

Phase 1 Healthy Volunteer Study of AL01211, an Oral, Non ‐brain Penetrant Glucosylceramide Synthase Inhibitor, to Treat Fabry Disease and Type 1 Gaucher Disease
AbstractGlycosphingolipid (GSL) storage diseases are caused by deficiencies in the enzymes that metabolize different GSLs in the lysosome. Glucosylceramide synthase (GCS) inhibitors reduce GSL production and have potential to treat multiple GSL storage diseases. AL01211 is a potent, oral GCS inhibitor being developed for the treatment of Type 1 Gaucher disease and Fabry disease. AL01211 has minimal central nervous system penetration, allowing for treatment of peripheral organs without risking CNS-associated adverse effects. AL01211 was evaluated in a Phase 1 healthy volunteer study with single ascending dose (SAD) and mult...
Source: Clinical Pharmacology in Drug Development - February 17, 2024 Category: Drugs & Pharmacology Authors: Michael Babcock, Jianhong Zheng, Jessica Gail Shurr, Li Li, Bing Wang, Pedro Huertas, Philip John Ryan, Yuqiao Shen, Marvin Garovoy Tags: Original Article Source Type: research