Relative Bioavailability Study of Midazolam Intramuscularly Administered with the Needle-Free Auto-Injector ZENEO in Healthy Adults.

Introduction: Intramuscular (IM) midazolam is indicated for the treatment of status epilepticus. Administration must be efficient to rapidly terminate prolonged seizures and prevent complications. The objective of this study was to compare, in terms of relative bioavailability and bioequivalence, IM midazolam injection by needle-free auto-injector, in different settings, to IM midazolam injection by a conventional syringe and needle.

Safety and efficacy of platelet glycoprotein VI inhibition in acute ischaemic stroke (ACTIMIS): a randomised, double-blind, placebo-controlled, phase 1b/2a trial.

Background: Antagonists of glycoprotein VI-triggered platelet activation used in combination with recanalisation therapies are a promising therapeutic approach in acute ischaemic stroke. Glenzocimab is an antibody fragment that inhibits the action of platelet glycoprotein VI. We aimed to determine and assess the safety and efficacy of the optimal dose of glenzocimab in patients with acute ischaemic stroke eligible to receive alteplase with or without mechanical thrombectomy.

Evaluation of the efficacy and safety of TREM-1 inhibition with nangibotide in patients with COVID-19 receiving respiratory support: the ESSENTIAL randomised, double-blind trial.

Background: Activation of the TREM-1 pathway is associated with outcome in life threatening COVID-19. Data suggest that modulation of this pathway with nangibotide, a TREM-1 modulator may improve survival in TREM-1 activated patients (identified using the biomarker sTREM-1).

Methods: Phase 2 double-blind randomized controlled trial assessing efficacy, safety, and optimum treatment population of nangibotide (1.

Prospective evaluation of the efficacy, safety, and optimal biomarker enrichment strategy for nangibotide, a TREM-1 inhibitor, in patients with septic shock (ASTONISH): a double-blind, randomised, controlled, phase 2b trial.

Background: Activation of the triggering receptor expressed on myeloid cells-1 (TREM-1) pathway is associated with septic shock outcomes. Data suggest that modulation of this pathway in patients with activated TREM-1 might improve survival. Soluble TREM-1 (sTREM-1), a potential mechanism-based biomarker, might facilitate enrichment of patient selection in clinical trials of nangibotide, a TREM-1 modulator.

Evaluation of PXL065 - deuterium-stabilized (R)-pioglitazone in patients with NASH: A phase II randomized placebo-controlled trial (DESTINY-1).

Background & Aims: Pioglitazone (Pio) is efficacious in NASH, but its utility is limited by PPARγ-driven side effects. Pio is a mixture of two enantiomers (R, S). PXL065, deuterium-stabilized R-Pio, lacks PPARγ activity but retains non-genomic activity.

Efficacy, safety and patient reported outcomes in patients with active relapsing multiple sclerosis treated with ocrelizumab: Final results from the PRO-MSACTIVE study.

Background: Ocrelizumab, a humanized anti-CD20 monoclonal antibody, has been approved in Europe for the treatment of adult patients with active relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS), on the basis of previous phase III studies. However, limited data were available on ocrelizumab efficacy in RMS according to the Lublin definition of activity (clinical and/or imaging features) used in the current drug label. The PRO-MSACTIVE study was thus designed to provide additional data on ocrelizumab efficacy according to this definition, and also on safety and patient reported outcomes (PROs).

Rubus idaeus extract improves symptoms in knee osteoarthritis patients: results from a phase II double-blind randomized controlled trial.

Background: Osteoarthritis (OA) is the most frequent cause of disability in elderly people. In daily practice, the main objective of the physician is to reduce patient symptoms using treatments without adverse effects. However, the most prescribed treatment to manage OA symptoms remains nonsteroidal anti-inflammatory drugs which are associated with severe adverse effects.

Pharmacodynamic effects of direct AMP kinase activation in humans with insulin resistance and non-alcoholic fatty liver disease: A phase 1b study.

AMPK is an energy sensor modulating metabolism, inflammation, and a target for metabolic disorders. Metabolic dysfunction results in lower AMPK activity. PXL770 is a direct AMPK activator, inhibiting lipogenesis (DNL) and producing efficacy in preclinical models.

Efficacy and safety of imeglimin add-on to insulin monotherapy in Japanese patients with type 2 diabetes (TIMES 3): A randomized, double-blind, placebo-controlled phase 3 trial with a 36-week open-label extension period.

Aims: To evaluate the efficacy and safety of imeglimin for up to 52 weeks as combination therapy with insulin in Japanese patients with type 2 diabetes.

Materials And Methods: This double-blind, randomized, parallel-group phase 3 trial was performed at 35 sites in Japan. Eligible patients were individuals aged ≥20 years with type 2 diabetes and inadequate glycaemic control with insulin.

Long-term safety and efficacy of imeglimin as monotherapy or in combination with existing antidiabetic agents in Japanese patients with type 2 diabetes (TIMES 2): A 52-week, open-label, multicentre phase 3 trial.

Aim: To evaluate the safety and efficacy of imeglimin for 52 weeks as monotherapy or combination therapy with existing antidiabetic agents in Japanese patients with type 2 diabetes.

Materials And Methods: TIMES 2 was a phase 3, pivotal, open-label trial including patients with type 2 diabetes inadequately controlled despite diet/exercise or despite treatment with a single agent from one of several available classes of antidiabetic drugs along with diet/exercise. All patients received imeglimin 1000 mg twice-daily orally for 52 weeks as monotherapy or combination therapy.

Efficacy and safety of PXL770, a direct AMP kinase activator, for the treatment of non-alcoholic fatty liver disease (STAMP-NAFLD): a randomised, double-blind, placebo-controlled, phase 2a study.

Background: AMP kinase (AMPK) is an energy sensor implicated in regulation of lipid metabolism, inflammation, and insulin sensitivity. We aimed to assess efficacy and safety of PXL770, a novel direct AMPK activator, in patients with non-alcoholic fatty liver disease (NAFLD).

Methods: STAMP-NAFLD, a randomised, double-blind, placebo-controlled phase 2a study, was done across 15 US clinical sites.

Rationale and protocol for the efficacy, safety and tolerability of nangibotide in patients with septic shock (ASTONISH) phase IIb randomised controlled trial.

Introduction: Septic shock is the subgroup of patients with sepsis, which presents as vasopressor dependence, an elevated blood lactate concentration and is associated with a mortality of at least 30%. Expression of the triggering receptor expressed on myeloid cells 1 (TREM-1) pathway, measured using a serum biomarker of pathway activation (soluble TREM-1, sTREM-1) has been associated with outcome in septic shock. Preclinical and early phase patient data suggest that therapeutic modulation of this pathway may improve survival.

Efficacy and Safety of Imeglimin Monotherapy Versus Placebo in Japanese Patients With Type 2 Diabetes (TIMES 1): A Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multicenter Phase 3 Trial.

Objective: The aim of this study was to investigate the efficacy and safety of imeglimin, the first in a new class of oral antidiabetic agent, in Japanese patients with type 2 diabetes.

Research Design And Methods: This was a double-blind, randomized, parallel-group, placebo-controlled phase 3 trial in 30 sites in Japan. Eligible participants were individuals aged ≥20 years with type 2 diabetes treated with diet and exercise, stable for ≥12 weeks prior to screening, and whose HbA was 7.

Efficacy and safety of imeglimin in Japanese patients with type 2 diabetes: A 24-week, randomized, double-blind, placebo-controlled, dose-ranging phase 2b trial.

Aim: To assess the efficacy and safety of imeglimin monotherapy compared with placebo for 24 weeks in Japanese patients with type 2 diabetes (T2D).

Materials And Methods: In this 24-week, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging, phase 2b clinical trial, Japanese adults (age ≥ 20 years) with T2D either treatment-naïve or previously treated with one oral antidiabetes agent were eligible for participation. Patients were randomly assigned (1:1:1:1) to receive orally imeglimin 500, 1000 or 1500 mg, or placebo twice-daily over a 24-week period.

6 months versus 12 months of adjuvant trastuzumab in early breast cancer (PHARE): final analysis of a multicentre, open-label, phase 3 randomised trial.

Background: In 2013, the interim analysis of the Protocol for Herceptin as Adjuvant therapy with Reduced Exposure (PHARE) trial could not show that 6 months of adjuvant trastuzumab was non-inferior to 12 months. Here, we report the planned final analysis based on the prespecified number of occurring events.

Methods: PHARE is an open-label, phase 3, non-inferiority randomised trial of patients with HER2-positive early breast cancer comparing 6 months versus 12 months of trastuzumab treatment concomitant with or following standard neoadjuvant or adjuvant chemotherapy.

IqYmune® is an effective maintenance treatment for multifocal motor neuropathy: A randomised, double-blind, multi-center cross-over non-inferiority study vs Kiovig®-The LIME Study.

Intravenous immunoglobulin (IVIg) is the gold-standard for maintenance treatment of multifocal motor neuropathy (MMN). This phase III, randomised, double-blind, multi-centre, active-control, crossover study, aimed to evaluate the non-inferiority of IqYmune® relative to Kiovig®, primarily based on efficacy criteria. Twenty-two adult MMN patients, treated with any brand of IVIg (except Kiovig® or IqYmune®) at a stable maintenance dose within the range of 1 to 2 g/kg every 4 to 8 weeks, were randomised to receive either Kiovig® followed by IqYmune®, or IqYmune® followed by Kiovig®.

Efficacy and safety of once-daily fluticasone furoate/vilanterol (FF/VI) versus twice-daily inhaled corticosteroids/long-acting β-agonists (ICS/LABA) in patients with uncontrolled asthma: An open-label, randomized, controlled trial.

Background: A variety of different fixed-dose combinations of inhaled corticosteroids/long-acting β-agonists (ICS/LABA) are available for the treatment of asthma. The aim of this 24-week, open-label, multicenter, Phase IIIb randomized controlled trial was to evaluate the efficacy and safety of once-daily fluticasone furoate/vilanterol (FF/VI; 100/25 or 200/25 μg) compared with twice-daily fixed combinations of ICS/LABA (fluticasone propionate/salmeterol [FP/S] and budesonide/formoterol [BUD/F]) as maintenance therapy in patients with uncontrolled asthma treated with ICS alone.

Methods: Adult patients with documented physician-diagnosed asthma ≥1 year with an Asthma Control Test (ACT) score ≥15 and < 20 were included.

Relative short-term efficacy and acceptability of agomelatine versus vortioxetine in adult patients suffering from major depressive disorder.

Agomelatine and vortioxetine are antidepressants with different mechanisms of action compared to other pharmaceutical treatment options. The objective of this present analysis is to determine the relative efficacy and acceptability of agomelatine (25-50 mg) compared to vortioxetine (10-15-20 mg) in adult patients with major depressive disorder. We performed an adjusted indirect comparison using placebo as a common control.

Fibrinogen concentrate as a treatment for postpartum haemorrhage-induced coagulopathy: A study protocol for a randomised multicentre controlled trial. The fibrinogen in haemorrhage of DELivery (FIDEL) trial.

Background: Postpartum haemorrhage (PPH) remains the leading cause for maternal mortality worldwide. Hypofibrinogenaemia has been identified as a major risk factor for progress towards severe PPH. The efficacy of fibrinogen concentrate supplementation in PPH has been shown in various clinical settings but the level of evidence is not sufficient to prove the benefit, evaluate the risks, and determine the value, timing and dose of fibrinogen supplementation in PPH.