A Phase Ib, Double-blind, Placebo-controlled, Randomised Trial Investigating the Effect of AZD3427 on Renal Perfusion in HFrEF Patients With Renal Impairment Using Positron Emission Tomography (PET)

The present study is designed to test the effect of AZD3427 on renal perfusion in participants with heart failure and reduced eGFR (30 to 90 mL/min/1.73m2).

开始日期2024-09-17

申办/合作机构

AstraZeneca PLC

[+2]

NCT06360640 / Not yet recruiting临床1期

A First-in-human, Randomised, Double-blind, Placebo-controlled, Single Ascending Dose Trial to Evaluate Safety, Tolerability, and Pharmacokinetics of APC148 in Healthy Adults

The purpose of this first-in-human trial is to investigate the safety, tolerability, and pharmacokinetics of APC148 after intravenous (IV) infusion of single ascending doses in healthy adults.

开始日期2024-06-01

申办/合作机构

AdjuTec Pharma AS

[+1]

NCT06463275 / RecruitingN/A

Determination of the 99th Percentile Upper Reference Limits (URLs) for the SpinChip High Sensitivity Cardiac Troponin I (SpinChip Hs-cTnI) Test

During a heart attack, the protein troponin I is released from the heart muscle into the bloodstream. Measurements of cardiac troponin in blood are used as an aid in the diagnosis of heart attack. Low levels of troponin are also present in the blood stream of healthy individuals and can be detected by high-sensitive troponin tests. The SpinChip hs-cTnI test is a new high-sensitive test for measuring the amount of cardiac troponin I in the bloodstream as an aid in the diagnosis of heart attack.
The purpose of this study is to determine the upper reference limits (URLs) for the SpinChip hs-cTnI test in a healthy population.

开始日期2024-05-20

申办/合作机构

SpinChip Diagnostics AS

[+1]

100 项与 CTC Clinical Trial Consultants AB 相关的临床结果

登录后查看更多信息

0 项与 CTC Clinical Trial Consultants AB 相关的专利（医药）

登录后查看更多信息

项与 CTC Clinical Trial Consultants AB 相关的文献（医药）

2024-05-01·European Journal of Clinical Pharmacology

ACD856, a novel positive allosteric modulator of Trk receptors, single ascending doses in healthy subjects: Safety and pharmacokinetics

Article

作者: Rother, Matthias ; Halldin, Magnus M ; Önnestam, Kristin ; Nilsson, Boel ; Segerdahl, Märta ; Rein-Hedin, Erik ; Bylund, Johan

AbstractPurposeAlzeCure Pharma AB is developing novel positive allosteric modulators of Trk-receptors for treatment of Alzheimer’s disease, depression, other psychiatric conditions and other disorders where cognition is impaired. The preceding candidate drug ACD855 was shown to have a too long half-life in humans to allow further development. To de-risk the development of the follow-up compound ACD856, the oral single ascending dose study of ACD856 in humans was preceded by an intravenous microdose study, assessing the elimination half-life in plasma.MethodsA phase 0 study with a microdose of ACD856 (0.100 mg), was conducted in six healthy male subjects all receiving ACD856. Sequentially, a randomized, placebo-controlled, double-blind Phase I single ascending oral dose study (1 – 150 mg) was conducted, including 56 healthy subjects. Both studies assessed the safety and tolerability, as well as the PK properties of ACD856 after single dose intravenous and oral administration.ResultsACD856 was well tolerated with no treatment emergent, or dose related adverse events or other safety assessments. In the microdose study, ACD856 exhibited a bi-exponential plasma decline, low distribution volume, low plasma clearance with a half-life of approximately 20 hours. Orally, ACD856 exhibited rapid absorption, an almost complete bioavailability and a dose proportional increase in exposure. While the Cmax was lowered and delayed by food intake, the effect on plasma half-life and the overall bioavailability was low. No renal elimination of ACD856 was detected. ConclusionThe prediction proved accurate demonstrating the value of conducting a microdose study prior to ascending dose studies.Trial registrationNCT05783830 March 24, 2023 (microdose study, retrospectively registered) and NCT05077631 October 14, 2021 (single ascending dose study).

2022-11-01·International Journal of Pharmaceutics

Oral transmucosal delivery of eletriptan for neurological diseases

Article

作者: Sultana, Kaiser ; Björklund, Sebastian ; Rönn, Robert ; Prgomet, Zdenka ; Feiler, Adam ; Doko, Anemona ; Dahlström, Bengt ; Eskandari, Mahboubeh ; Valetti, Sabrina ; Engblom, Johan ; Riaz, Azra

Migraine is a highly prevalent neurological disease affecting circa 1 billion patients worldwide with severe incapacitating symptoms, which significantly diminishes the quality of life. As self-medication practice, oral administration of triptans is the most common option, despite its relatively slow therapeutic onset and low drug bioavailability. To overcome these issues, here we present, to the best of our knowledge, the first study on the possibility of oral transmucosal delivery of one of the safest triptans, namely eletriptan hydrobromide (EB). Based on a comprehensive set of in vitro and ex vivo experiments, we highlight the conditions required for oral transmucosal delivery, potentially giving rise to similar, or even higher, drug plasma concentrations expected from conventional oral administration. With histology and tissue integrity studies, we conclude that EB neither induces morphological changes nor impairs the integrity of the mucosal barrier following 4 h of exposure. On a cellular level, EB is internalized in human oral keratinocytes within the first 5 min without inducing toxicity at the relevant concentrations for transmucosal delivery. Considering that the pK_a of EB falls within the physiologically range, we systematically investigated the effect of pH on both solubility and transmucosal permeation. When the pH is increased from 6.8 to 10.4, the drug solubility decreases drastically from 14.7 to 0.07 mg/mL. At pH 6.8, EB gave rise to the highest drug flux and total permeated amount across mucosa, while at pH 10.4 EB shows greater permeability coefficient and thus higher ratio of permeated drug versus applied drug. Permeation experiments with model membranes confirmed the pH dependent permeation profile of EB. The distribution of EB in different cellular compartments of keratinocytes is pH dependent. In brief, high drug ionization leads to higher association with the cell membrane, suggesting ionic interactions between EB and the phospholipid head groups. Moreover, we show that the chemical permeation enhancer DMSO can be used to enhance the drug permeation significantly (i.e., 12 to 36-fold increase). Taken together, this study presents important findings on transmucosal delivery of eletriptan via the oral cavity and paves the way for clinical investigations for a fast and safe migraine treatment.

2022-09-06·Neurology

Pharmacokinetics of Intravenously (DIZ101), Subcutaneously (DIZ102), and Intestinally (LCIG) Infused Levodopa in Advanced Parkinson Disease

Article

作者: Svenningsson, Per ; Ehrnebo, Mats ; Lundin, Fredrik ; Nyholm, Dag ; Johansson, Anders ; Eriksson, Elias ; Odin, Per ; Bergquist, Filip ; Dizdar, Nil ; Bring, Leif ; Hansson, Fredrik

Background and ObjectivesIntestinal levodopa/carbidopa gel infusion (LCIG) is superior to oral treatment in advanced Parkinson disease. The primary objective of this trial was to investigate whether continuous subcutaneous or intravenous infusion with a continuously buffered acidic levodopa/carbidopa solution yields steady-state plasma concentrations of levodopa that are equivalent in magnitude, and noninferior in variability, to those obtained with LCIG in patients with advanced Parkinson disease.MethodsA concentrated acidic levodopa/carbidopa (8:1) solution buffered continuously and administered intravenously (DIZ101) or subcutaneously (DIZ102) was compared with an approved LCIG in a randomized, 3-period crossover, open-label, multicenter trial. Formulations were infused for 16 hours to patients with Parkinson disease who were using LCIG as their regular treatment. Patients were recruited from several university neurology clinics but came to the same phase I unit for treatment. Pharmacokinetic variables and safety including dermal tolerance are reported. The primary outcomes were bioequivalence and noninferior variability of DIZ101 and DIZ102 vs LCIG with respect to levodopa plasma concentrations.ResultsWith dosing adjusted to estimated bioavailability, DIZ101 and DIZ102 produced levodopa plasma levels within standard bioequivalence limits compared with LCIG in the 18 participants who received all treatments. Although the levodopa bioavailability for DIZ102 was complete, it was 80% for LCIG. Therapeutic concentrations of levodopa were reached as quickly with subcutaneous administration of DIZ102 as with LCIG and remained stable throughout the infusions. Owing to poor uptake of LCIG, carbidopa levels in plasma were higher with DIZ101 and DIZ102 than with the former. All individuals receiving any of the treatments (n = 20) were included in the evaluation of safety and tolerability. Reactions at the infusion sites were mild and transient.DiscussionIt is feasible to rapidly achieve high and stable levodopa concentrations by means of continuous buffering of a subcutaneously administered acidic levodopa/carbidopa-containing solution.Trial Registration Information ClinicalTrials.gov identifier: NCT03419806. Registration first posted on February 5, 2018, first patient enrolled on February 16, 2018.

100 项与 CTC Clinical Trial Consultants AB 相关的药物交易

登录后查看更多信息

100 项与 CTC Clinical Trial Consultants AB 相关的转化医学

登录后查看更多信息