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Comparative Pharmacokinetic Profiles of a Novel Low ‐Dose Micronized Formulation of Raloxifene 45 mg (AD‐101) and the Conventional Raloxifene 60 mg in Healthy Subjects
This study was designed as an open-label, randomized, 2-treatment-period, crossover study with a 2-week washout period. Two treatments consisted of micronized raloxifene 45  mg daily; and conventional raloxifene 60 mg daily administered in fasting conditions. Plasma raloxifene concentrations were determined by a validated method using ultra-fast liquid chromatography–tandem mass spectrometry, and pharmacokinetic parameters were calculated using a noncompartmental m odel. In total, 49 subjects completed the study. The geometric mean ratio (micronized/conventional) of the maximum concentration and the area under the plas...
Source: Clinical Pharmacology in Drug Development - August 26, 2023 Category: Drugs & Pharmacology Authors: Hae Won Lee, Woo Youl Kang, Mi ‐Ri Gwon, Soo‐Jin Park, Kyunghee Cho, Sook Jin Seong, Young‐Ran Yoon Tags: Original Article Source Type: research

Safety, Pharmacokinetics, and Exposure –Response Modeling of Nedosiran in Participants With Severe Chronic Kidney Disease
AbstractNedosiran is an investigational RNA-interference therapeutic in development for primary hyperoxaluria (PH). Because nedosiran undergoes renal clearance, we assessed its pharmacokinetic profile in non-PH participants with normal kidney function and Stages 4/5 chronic kidney disease (CKD), the latter with/without dialysis. Nedosiran exposure –response modeling in patients with PH Subtype 1 (PH1) with different renal function level was performed to recommend a nedosiran dose for this subpatient population. In this open-label, single-dose, Phase 1 study, 24 participants with estimated glomerular filtration rate<30...
Source: Clinical Pharmacology in Drug Development - August 23, 2023 Category: Drugs & Pharmacology Authors: Aniruddha Amrite, Ernesto Fuentes, Thomas C. Marbury, Steven Zhang Tags: Original Article Source Type: research

Absolute and Relative Bioavailability of Oral Solid Dosage Formulations of Deucravacitinib in Humans
Abstractitinib is an oral, selective, allosteric inhibitor of tyrosine kinase 2, an intracellular signaling kinase involved in the pathogenesis of immune-mediated inflammatory diseases. The absolute and relative bioavailability (BA) were evaluated in phase 1, open-label studies in healthy adults to assess (1) the absolute BA of the deucravacitinib tablet formulation following single oral administration of a 12-mg tablet and an intravenous microdose infusion of 0.1-mg carbon-13 and nitrogen-15 –labeled deucravacitinib ([13C2,15N3] deucravacitinib) solution in 8 subjects, and (2) the relative oral BA of deucravacitinib tab...
Source: Clinical Pharmacology in Drug Development - August 17, 2023 Category: Drugs & Pharmacology Authors: Anjaneya Chimalakonda, Wenying Li, David Marchisin, Bing He, Shalabh Singhal, Prashant Deshpande, Jonathan Brown, Urvi Aras, Bindu Murthy Tags: Original Article Source Type: research

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ZY ‐IL1 in Three Patients with Cryopyrin‐Associated Periodic Syndromes
We present the first results of the proof-of-concept phase 2a study of oral NLRP3 inflammasome inhibitor in subjects with cryopyrin-associated periodic syndromes (CAPS). Three adult subjects with a confirmed diagnosis of CAPS were enrolled and administered 50  mg of ZYIL1 twice daily for 7 days. A total of 5 treatment-emergent adverse events (TEAEs) were reported in 2 subjects. All 5 TEAEs were mild in severity and considered unrelated to the study drug. At steady state, the average plasma concentration and trough concentration ranged from 2.5 to 4.2 an d 1.4 to 2.5 μg/mL, respectively. Inflammatory markers and disease ...
Source: Clinical Pharmacology in Drug Development - August 15, 2023 Category: Drugs & Pharmacology Authors: Pravin Hissaria, Kevinkumar Kansagra, Hardik Patel, Taufik Momin, Ashok Ghoghari, Harilal Patel, Bhavesh Sharma Tags: Original Article Source Type: research

Safety, Tolerability, and Pharmacokinetics of Valemetostat Tablets and the Effect of Food on Valemetostat Pharmacokinetics in Healthy Subjects: Two Phase 1 Studies
We report outcomes from 2 phase 1 trials in healthy Japanese participants, assessing the safety, tolerability, and pharmacokinetics (PK) of valemetostat tablets at single ascending doses (50, 100, and 200-mg), the relative bioavailability between capsules and tablets, and the effect of food (high-fat or low-fat meals) on the PK of valemetostat tablets. In the ascending-dose study, valemetostat maximum plasma concentration (Cmax) and area under the concentration –time curve (AUC) increased dose-proportionally. Valemetostat plasma PK parameters were similar between the capsule and tablet formulations following a single 200...
Source: Clinical Pharmacology in Drug Development - August 12, 2023 Category: Drugs & Pharmacology Authors: Masaya Tachibana, Shunji Matsuki, Kaoru Toyama, Yutaro Maekawa, Masato Fukae, Takako Shimizu, Junko Tsutsumi, Sayaka Shinohara, Hitoshi Ishizuka Tags: Original Article Source Type: research

Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Sibeprenlimab in Healthy Participants
AbstractSibeprenlimab blocks the cytokine “A Proliferation-InducingLigand ” (APRIL), which may play a key role in immunoglobulin A nephropathy pathogenesis. A phase 1 study of subcutaneous (SC) sibeprenlimab evaluated preliminary safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy participants. This was an open-label, single-ascending-dose study. Twe lve participants in each of 4 sequential dosing cohorts received 1 SC dose of sibeprenlimab (200 mg [1×1 mL injection], 400 mg [2×1 mL injections], 400 mg [1×2 mL injection], or 600 mg [1 mL+2 mL injections]) and underwent 16-week follow-up ...
Source: Clinical Pharmacology in Drug Development - August 11, 2023 Category: Drugs & Pharmacology Authors: Xiaoyan Zhang, Yanlin Wang, Jill Yarbrough, Mohit Mathur, Lee Andrews, Brian Pereira, Susan E. Sloan, Asher D. Schachter Tags: Original Article Source Type: research

Changes in Urinary Uric Acid Concentration after Dotinurad Administration to Patients with Hyperuricemia: A Post Hoc Analysis of Two Clinical Trials in Japan
This study highlights the significance of adequately managing urinary uric acid concentrations by increasing urine volume and alkalinizing urine to prevent uric acid crystallization during dotinurad administration. (Source: Clinical Pharmacology in Drug Development)
Source: Clinical Pharmacology in Drug Development - August 10, 2023 Category: Drugs & Pharmacology Authors: Toshinari Takahashi, Minoru Sasaki, Toru Shimizu, Satoshi Yamaguchi Tags: Original Article Source Type: research

Pharmacokinetics and Food Effect Between a 100 ‐mg Sustained‐Release Tablet and a 50‐mg Immediate‐Release Tablet of Vildagliptin in Healthy Subjects
This study aimed to compare vildagliptin exposure between 50-mg immediate-release (IR) and 100-mg new sustained-release (SR) tablets, and evaluate the food effect on the pharmacokinetics (PKs) of vildagliptin. A randomized, open-label, 3-period, 3-treatment, 6-sequence crossover study was conducted on healthy subjects. During each period, subjects received the SR tablet either in the fasted (T1) or high-fat fed (T2) state once a day, or IR tablets administered twice a day in the fasted state (R). Blood samples for PK analysis were obtained serially up to 24  hours after dosing. Thirty-four subjects completed the study. Th...
Source: Clinical Pharmacology in Drug Development - August 9, 2023 Category: Drugs & Pharmacology Authors: Hyounggyoon Yoo, Wonsuk Shin, BackHwan Lee, JinSoo Park, Yilseob Lee, Anhye Kim Tags: Original Article Source Type: research