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Two ‐Part Phase 1 Study to Evaluate the Taste Profile of Novel Belumosudil Oral Suspensions and Assess the Relative Bioavailability and Food Effect of the Selected Belumosudil Oral Suspension Compared With Oral Tablet Reference in Healthy Male Participants
This study (NCT04735822) assessed the taste and palatability of oral suspensions of belumosudil, evaluated the relative bioavailability of an oral suspension versus the tablet formulation, and characterized the effect of food on the pharmacokinetics of an oral suspension. Addition of sweetener and/or flavor vehicle improved the taste. Relative bioavailability of 200-mg doses of the oral suspension and tablet in the fed state was similar for belumosudil and its metabolites (KD025m1 and KD025m2), but absorption was faster with the oral suspension (median time to maximum concentration: 2 vs 3 hours). Administration of the ora...
Source: Clinical Pharmacology in Drug Development - February 12, 2024 Category: Drugs & Pharmacology Authors: Olivier Schueller, Galit Regev, Nand Singh, Ashley Willson, Mark Beville, Nazim Kanji, Lauren Lohmer, Jeegar Patel Tags: Original Article Source Type: research

2023 CPDD Peer Reviewer List
(Source: Clinical Pharmacology in Drug Development)
Source: Clinical Pharmacology in Drug Development - February 12, 2024 Category: Drugs & Pharmacology Tags: List of Reviewers Source Type: research

Safety, Tolerability, and Pharmacokinetics of Voriconazole for Injection in Two Preparations in Chinese Healthy Adult Volunteers
AbstractVoriconazole is a second-generation, synthetic, triazole antifungal drug based on the structure of fluconazole. We compared the safety, tolerability, and pharmacokinetic characteristics of voriconazole for injection (200  mg) manufactured by at a dose of 6 mg/kg in Chinese healthy adult volunteers. This was a single-center, randomized, open, 2-preparation, single-dose, 2-period, 2-sequence, crossover bioequivalence clinical trial. Twenty-four eligible, healthy, male, and female volunteers were assigned randomly to one of 2 dose-sequence groups (test-reference group or reference-test group) in a 1:1 block. The vor...
Source: Clinical Pharmacology in Drug Development - February 8, 2024 Category: Drugs & Pharmacology Authors: Jin Yu, Yi Wu, Sisi Lin, Ying Wang Tags: Original Article Source Type: research

Population Pharmacokinetics of Fasinumab in Healthy Volunteers and Patients With Pain Due to Osteoarthritis of the Knee or Hip
AbstractOsteoarthritis (OA) pain management options are currently limited. Fasinumab, an anti-nerve growth factor monoclonal antibody, has been investigated in healthy volunteers and patients with OA-related pain, among other conditions. Data from 12 Phase I-III clinical trials of 92 healthy volunteers and 7430 patients with OA were used to develop a population pharmacokinetic model to characterize fasinumab concentration-time profiles and assess the covariates ’ effect on fasinumab pharmacokinetic parameters. Participants received single or repeated fasinumab doses intravenously (IV)/subcutaneously (SC), based on body w...
Source: Clinical Pharmacology in Drug Development - February 7, 2024 Category: Drugs & Pharmacology Authors: Kuan ‐Ju Lin, Kenneth C. Turner, Hazem E. Hassan, Lutz O. Harnisch, John D. Davis, Albert Thomas DiCioccio Tags: Original Article Source Type: research

Pharmacokinetics and Pharmacodynamics of Etripamil, an Intranasally Administered, Fast ‐Acting, Nondihydropyridine Calcium Channel Blocker
We report detailed pharmacokinetics and pharmacodynamics of intranasally administered etripamil in healthy adults from 2 Phase 1, randomized, double-blind studies: Study MSP-2017-1096 (sequential dose-escalation, crossover study design, n = 64) and NODE-102 (single dose, 4-way crossover study, n = 24). Validated bioanalytical assays determined plasma concentrations of etripamil and its inactive metabolite. Noncompartmental pharmacokinetic parameters were calculated. Pharmacodynamic parameters were determined for PR interval, blood pressure, and heart rate. Etripamil was rapidly absorbed intranasally, with time to maximal p...
Source: Clinical Pharmacology in Drug Development - February 6, 2024 Category: Drugs & Pharmacology Authors: James E. Ip, Douglas Wight, Corinne Seng Yue, David Nguyen, Francis Plat, Bruce S. Stambler Tags: Original Article Source Type: research

Results from a Phase 1 Study Assessing the Pharmacokinetics of the Aldosterone Synthase Inhibitor Baxdrostat in Participants with Varying Degrees of Renal Function
AbstractBaxdrostat is a selective small-molecule aldosterone synthase inhibitor in development for treatment of hypertension and chronic kidney disease. This phase 1, open-label, parallel-group study assessed the safety and pharmacokinetics (PK) of baxdrostat in participants with varying degrees of renal function. Participants were enrolled into control (estimated glomerular filtration rate [eGFR] ≥60 mL/min), moderate to severe renal impairment (eGFR 15-59 mL/min), or kidney failure (eGFR<15  mL/min) groups and received a single 10-mg baxdrostat dose followed by 7 days of inpatient PK blood and urine sampling. Saf...
Source: Clinical Pharmacology in Drug Development - February 5, 2024 Category: Drugs & Pharmacology Authors: Mason W. Freeman, Yuan ‐Di Halvorsen, Mary Bond, Brian Murphy, Jonathan Isaacsohn Tags: Original Article Source Type: research

Issue Information
(Source: Clinical Pharmacology in Drug Development)
Source: Clinical Pharmacology in Drug Development - February 2, 2024 Category: Drugs & Pharmacology Tags: Issue Information Source Type: research

Can Intranasal Nalmefene Reduce the Number of Opioid Overdose Deaths?
(Source: Clinical Pharmacology in Drug Development)
Source: Clinical Pharmacology in Drug Development - January 31, 2024 Category: Drugs & Pharmacology Authors: Edward M. Sellers, Myroslava K. Romach Tags: Letter to the Editor Source Type: research

Comment on: Can Intranasal Nalmefene Reduce the Number of Opioid Overdose Deaths?
(Source: Clinical Pharmacology in Drug Development)
Source: Clinical Pharmacology in Drug Development - January 30, 2024 Category: Drugs & Pharmacology Authors: Phil Skolnick Tags: Letter to the Editor Source Type: research

Concentration ‐QTcF Modeling of Icenticaftor from a Randomized, Placebo‐ and Positive‐Controlled Thorough QT Study in Healthy Participants
AbstractIcenticaftor (QBW251) is a potentiator of the cystic fibrosis transmembrane receptor. Based on its mechanism of action, icenticaftor is expected to provide benefits in patients with chronic obstructive pulmonary disease by restoring mucociliary clearance, which would eventually lead to a reduction of bacterial colonization and related inflammatory cascade. A placebo- and positive-controlled, 4-way crossover thorough QT study was conducted in 46 healthy participants with the objective to assess the effect of therapeutic (300  mg twice daily for 6 days) and supratherapeutic (750 mg twice daily for 6 days) oral dose...
Source: Clinical Pharmacology in Drug Development - January 30, 2024 Category: Drugs & Pharmacology Authors: Ganesh R. Iyer, Borje Darpo, Hongqi Xue, Jean Lecot, Julia Zack, Lidiya Bebrevska, Wendy Weis, Ieuan Jones, Anton Drollmann Tags: Original Article Source Type: research

Safety and Pharmacokinetics of Quizartinib Combination Therapy With Standard Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia: Results from Two Phase 1 Trials in Japan and China
AbstractQuizartinib is a potent, oral, second-generation, selective type II FMS-like receptor tyrosine kinase 3 (FLT3) inhibitor. It has shown improved overall survival in a randomized, multinational, Phase 3 (QuANTUM-First) study in patients withFLT3-internal tandem duplication (ITD)-positive newly diagnosed acute myeloid leukemia. We conducted 2 Phase 1b studies in Japan and China to evaluate the safety, pharmacokinetics, and efficacy of quizartinib in combination with standard induction and consolidation chemotherapy in patients with newly diagnosed acute myeloid leukemia. Quizartinib was started at a dose level of 20 �...
Source: Clinical Pharmacology in Drug Development - January 29, 2024 Category: Drugs & Pharmacology Authors: Junyuan Qi, Ilseung Choi, Shuichi Ota, Satoshi Ichikawa, Naohito Fujishima, Hiroatsu Iida, Isamu Sugiura, Koichi Sugiura, Yasuharu Murata, Hiroyuki Inoue, Shoichi Ohwada, Jianxiang Wang Tags: Original Article Source Type: research

Pharmacokinetics of Ubrogepant in Healthy Japanese and White Adults
The objectives of this study were to evaluate (1) single-dose pharmacokinetics (PK) and dose proportionality of ubrogepant in Japanese participants, (2) the safety and tolerability of ubrogepant in healthy Japanese and White participants, and (3) to compare the PK of ubrogepant in Japanese versus White participants. A total of 48 participants were enrolled into 4 cohorts (N = 12 [9 active + 3 placebo] per cohort). A single dose was administered on Day 1 following an overnight fast to assess the PK of ubrogepant at 3 dose levels and test dose proportionality between 25 and 100  mg in Japanese participants. White participan...
Source: Clinical Pharmacology in Drug Development - January 24, 2024 Category: Drugs & Pharmacology Authors: Ramesh Boinpally, Joel Trugman Tags: Original Article Source Type: research

Cedirogant Population Pharmacokinetics and Pharmacodynamic Analyses of Interleukin ‐17A Inhibition in Two Phase I Studies in Healthy Participants and Participants with Moderate to Severe Psoriasis
AbstractCedirogant (ABBV-157) is an orally bioavailable inverse agonist of retinoic acid-related orphan receptor gamma thymus. Data from 2 Phase 1 studies were used to characterize cedirogant pharmacokinetics and evaluate target engagement. Cedirogant plasma concentrations and ex vivo interleukin 17A (IL-17A) concentrations from healthy participants and participants with moderate to severe psoriasis (PsO) were analyzed in a population pharmacokinetic and pharmacodynamic modeling framework to characterize cedirogant pharmacokinetics following single and multiple doses and assess ex vivo IL-17A inhibition in relation to cedi...
Source: Clinical Pharmacology in Drug Development - January 18, 2024 Category: Drugs & Pharmacology Authors: Corinna S. Maier, Doerthe Eckert, F. Stephen Laroux, Kinjal M. Hew, Ahmed A. Suleiman, Wei Liu, Mohamed ‐Eslam F. Mohamed Tags: Original Article Source Type: research

Intravenous Ganaxolone: Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability in Healthy Adults
AbstractGanaxolone, a neuroactive steroid anticonvulsant that modulates both synaptic and extrasynaptic γ-aminobutyric acid type A (GABAA) receptors, is in development for treatment of status epilepticus (SE) and rare epileptic disorders, and has been approved in the United States for treatment of seizures associated with cyclin-dependent kinase-like 5 deficiency disorder in patients ≥2 years old. This phase 1 study in 36 healthy volunteers evaluated the pharmacokinetics, pharmacodynamics, and safety of intravenous ganaxolone administered as a (i) single bolus, (ii) infusion, and (iii) bolus followed by continuous infus...
Source: Clinical Pharmacology in Drug Development - January 17, 2024 Category: Drugs & Pharmacology Authors: Maciej Gasior, Aatif Husain, Megan E. Barra, Shruti M. Raja, David MacLeod, Jeffrey T. Guptill, Henrikas Vaitkevicius, Eva Rybak Tags: Original Article Source Type: research

Pharmacokinetics, Bioequivalence, and Safety Evaluation of Two Oral Formulations of Calcium Dobesilate Capsules in Healthy Chinese Volunteers Under Fasting and Fed Conditions
AbstractTo determine the pharmacokinetics (PK), safety, and bioequivalence profiles of 0.5-g calcium dobesilate capsules in both fasting and fed states for the test drug and reference drug. A randomized-sequence, single-dose, open-label, 2-period crossover study was conducted in fasted and fed healthy Chinese volunteers (Chinese Clinical Trials Registry identifier: CTR202000268-01). The fasting and fed studies, both involving 24 subjects, were conducted. A single dosage of either the reference or the test preparation was given to each eligible subject in a 1:1 ratio, followed by a 7-day rest interval before the administrat...
Source: Clinical Pharmacology in Drug Development - January 17, 2024 Category: Drugs & Pharmacology Authors: Yanrong Wang, Ying Liu, Liyuan Tang, Jie Gao, Hongmin LI, Xinya Dai, Ran Chen, Fengqin Wang Tags: Original Article Source Type: research