Sharan Sidhu

Quotient Clinical (United Kingdom)

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Hazel Hunt

Corcept Therapeutics (United States)

Lars Weidolf

AstraZeneca (Sweden)

Iain Shaw

Quotient Clinical (United Kingdom)

Ryan A. Bragg

AstraZeneca (United Kingdom)

Malin Gränfors

AstraZeneca (Sweden)

Jing Xie

Anhui Provincial Center for Disease Control and Prevention

Clinical Trials

Richard Kim

University of Southern California

Ulrika Wählby Hamrén

AstraZeneca (Sweden)

Ganesh Moorthy

AstraZeneca (United States)

Cooperative Institutions

AstraZeneca (United Kingdom)

AstraZeneca (Sweden)

Quotient Clinical (United Kingdom)

Netherlands Organisation for Applied Scientific Research

AstraZeneca (Brazil)

AstraZeneca (United States)

University of Ottawa

Columbus Oncology and Hematology Associates

Hudson Institute

John Wiley & Sons (United States)

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IGF-F1-1, A PEPTIDE ANTAGONIST OF IGF-1

Kurt Deshayes MK Schäffer Nicholas J. Skelton Gerald Nakamura S Kadkhodayan

10.2210/pdb1lb7/pdb

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A study in healthy male volunteers to assess how the radiolabelled test medicine enters, is broken down and is removed from the body when given by mouth in the form of a tablet and liquid, and when given by short infusion into a vein

http://isrctn.com/ (2022)

Michelle Beharry Sharan Sidhu

10.1186/isrctn15620353

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Characterization of Clinical Absorption, Distribution, Metabolism, and Excretion and Pharmacokinetics of Velsecorat Using an Intravenous Microtracer Combined with an Inhaled Dose in Healthy Subjects

Drug Metabolism and Disposition (2021)

Ann Aurell Holmberg Lars Weidolf Sofia Necander Peter Bold Sharan Sidhu

This open-label, single-period study describes the human absorption, distribution, metabolism, excretion, and pharmacokinetics of velsecorat (AZD7594). Healthy subjects received inhaled velsecorat (non-radiolabeled; 720 µg) followed by intravenous infusion of carbon 14 (¹⁴C)-velsecorat (30 µg). Plasma, urine, and feces were collected up to 168 hours post-dose. Objectives included identification and quantification of velsecorat and its metabolites (i.e., drug-related material) in plasma and excreta, and determining the elimination pathways of velsecorat by measuring the rate and route of excretion, plasma half-life (t_1/2), clearance, volume of distribution and mean recovery of radioactivity. On average, 76.0% of administered ¹⁴C dose was recovered by the end of the sampling period (urine = 24.4%; feces = 51.6%), with no unchanged compound recovered in excreta, suggesting that biliary excretion is the main elimination route. Compared with intravenous ¹⁴C-velsecorat, inhaled velsecorat had a longer t_1/2 (27 versus 2 hours), confirming that plasma elimination is absorption-rate-limited from the lungs. Following intravenous administration, t_1/2 of ¹⁴C-drug-related material was longer than for unchanged velsecorat, and 20% of the ¹⁴C plasma content was related to unchanged velsecorat. The geometric mean plasma clearance of velsecorat was high (70.7 l/h) and the geometric mean volume of distribution at steady state was 113 l. Velsecorat was substantially metabolized via O-dealkylation of the indazole ether followed by sulfate conjugation, forming the M1 metabolite, the major metabolite in plasma. There were 15 minor metabolites. Velsecorat was well tolerated, and these results support the progression of velsecorat to phase 3 studies.

SIGNIFICANCE STATEMENT

This study describes the human pharmacokinetics and metabolism of velsecorat, a selective glucocorticoid receptor modulator, evaluated via co-administration of a radiolabeled intravenous microtracer dose and a non-radiolabeled inhaled dose. This study provides a comprehensive assessment of the disposition of velsecorat in humans. It also highlights a number of complexities associated with determining human absorption, distribution, metabolism, and excretion for velsecorat, related to the inhaled route, the high metabolic clearance, sequential metabolite formation and the low intravenous dose.

10.1124/dmd.121.000632

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A study in healthy volunteers to look at how different formulations (recipes) of the test medicine Firibastat (QGC001) are taken up and broken down by the body

http://isrctn.com/ (2022)

Sharan Sidhu B. Besse Codou Mariette

10.1186/isrctn24120533

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An open-label, two-period study designed to evaluate and compare the mass balance recovery and metabolite profile of 14 c deutetrabenazine and 14 c-tetrabenazine in healthy male subjects

Drug Metabolism and Pharmacokinetics (2018)

Margaret Bradbury David Stamler Thomas A. Baillie Stuart Mair Sharan Sidhu

Tetrabenazine

Gender balance

10.1016/j.dmpk.2017.11.250

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Effect of Miricorilant, a Selective Glucocorticoid Receptor Modulator, on Olanzapine-Associated Weight Gain in Healthy Subjects

Journal of Clinical Psychopharmacology (2021)

Hazel Hunt Kirsteen Donaldson Mark Strem Iulia Cristina Tudor Suzanne Sweet-Smith

Abstract Purpose Antipsychotic medications, including olanzapine, are associated with substantial weight gain and metabolic disturbances. We sought to determine whether coadministration of miricorilant, a selective glucocorticoid receptor modulator, with olanzapine can ameliorate these effects. Methods Sixty-six healthy men were enrolled in a 2-week, randomized, double-blind, placebo-controlled trial. The primary objective was to evaluate changes in body weight after 14 days coadministration of olanzapine (10 mg) + miricorilant (600 mg) compared with olanzapine (10 mg) + placebo. Secondary objectives included evaluating (a) the safety and tolerability of the combination; (b) the effects of the combination on glucose, insulin, insulin resistance, and triglycerides; and (c) the impact of the combination on hepatic enzymes. Results Subjects administered olanzapine + miricorilant gained less weight than subjects administered olanzapine + placebo (mean weight gain on day 15, 3.91 kg vs 4.98 kg; difference between groups, −1.07 kg; 95% confidence interval, −1.94 to −0.19; P = 0.017]). Compared with the placebo group, coadministration of miricorilant with olanzapine was associated with smaller increases in insulin (difference, −3.74 mIU/L; P = 0.007), homeostatic model assessment of insulin resistance (difference, −0.47; P = 0.007), triglycerides (difference, −0.29 mmol/L; P = 0.057), aspartate aminotransferase (difference, −32.24 IU/L; P = 0.009), and alanine aminotransferase (difference, −49.99 IU/L; P = 0.030). Conclusions Miricorilant may provide a promising option for ameliorating the detrimental effects of olanzapine, and investigation of this medication in patients affected by antipsychotic-induced weight gain is warranted. Two phase 2 studies of miricorilant in patients with recent and long-standing antipsychotic-induced weight gain are currently in progress.

10.1097/jcp.0000000000001470

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A study in healthy male volunteers to investigate how the radiolabelled test medicine [14C]-CORT125236 is taken up, broken down and removed from the body (Part 1) and to investigate how the test medicine CORT125236 is taken up by the body in healthy male and female volunteers when given as a new tablet recipe with and without food (Part 2)

http://isrctn.com/ (2024)

Hazel Hunt Sharan Sidhu

10.1186/isrctn16855040

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A study in healthy volunteers to discover how the test medicine interacts with other approved medicines

http://isrctn.com/ (2023)

Sharan Sidhu Sharan Sidhu Sharan Sidhu

10.1186/isrctn10379288

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Pharmacokinetics and Metabolism of Ziritaxestat (GLPG1690) in Healthy Male Volunteers Following Intravenous and Oral Administration

Clinical Pharmacology in Drug Development (2021)

Eric Helmer Ashley Willson Christopher Brearley Mark Westerhof Stephane Delage

Ziritaxestat is a novel inhibitor of autotaxin, an enzyme responsible for the production of lysophosphatidic acid, the downstream signaling of which mediates responses to tissue injury and has been implicated in the pathogenesis of fibrotic conditions such as idiopathic pulmonary fibrosis and systemic sclerosis. This study (Clinical Trial Registration: NCT03787186) was designed to assess the absorption, distribution, metabolism, and excretion of orally administered 600-mg ziritaxestat labeled with a carbon-14 tracer (

MicroDose

Pathogenesis

Autotaxin

10.1002/cpdd.1021

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Citations (9)

P095 Help stopping infant oral mutilation – a global child abuse and public health issue

British Journal of Oral and Maxillofacial Surgery (2023)

Leo Cheng Leo Cheng Arthur Kemoli Sharan Sidhu

10.1016/j.bjoms.2023.08.166

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