CYP11B2 inhibitor dexfadrostat phosphate suppresses the aldosterone-to-renin ratio, an indicator of sodium retention, in healthy volunteers.

Aims: High aldosterone is a key driver of hypertension and long-term negative sequelae. We evaluated the safety and efficacy of dexfadrostat phosphate (DP13), a novel aldosterone synthase (CYP11B2) inhibitor, in healthy participants.

Methods: This randomized, double-blind, placebo-controlled study was conducted in two parts.

Changes in Biomarkers of Exposure on Switching From a Conventional Cigarette to Tobacco Heating Products: A Randomized, Controlled Study in Healthy Japanese Subjects.

Background: Smoking is a leading cause of numerous human disorders including pulmonary disease, cardiovascular disease, and cancer. Disease development is primarily caused by exposure to cigarette smoke constituents, many of which are known toxicants. Switching smokers to modified risk tobacco products (MRTPs) has been suggested as a potential means to reduce the risks of tobacco use, by reducing such exposure.

SELECT-3: a phase I study of selumetinib in combination with platinum-doublet chemotherapy for advanced NSCLC in the first-line setting.

Background: We investigated selumetinib (AZD6244, ARRY-142886), an oral, potent, and highly selective, allosteric MEK1/2 inhibitor, plus platinum-doublet chemotherapy for patients with advanced/metastatic non-small cell lung cancer.

Methods: In this Phase I, open-label study (NCT01809210), treatment-naïve patients received selumetinib (50, 75, 100 mg BID PO) plus standard doses of gemcitabine or pemetrexed plus cisplatin or carboplatin. Primary objectives were safety, tolerability, and determination of recommended Phase II doses.

A randomised, controlled, two-Centre open-label study in healthy Japanese subjects to evaluate the effect on biomarkers of exposure of switching from a conventional cigarette to a tobacco heating product.

Background: Smoking is a leading cause of numerous human disorders including lung cancer, chronic obstructive pulmonary disease, and atherosclerotic cardiovascular disease. The development of modified risk tobacco products (MRTPs) has been suggested as a possible way to reduce the risks of tobacco smoking by reducing exposure to cigarette smoke toxicants. This study is designed to investigate whether biomarkers of such exposure are reduced when smokers switch from smoking commercial cigarettes to using either a novel or a commercially-available tobacco heating product (THP).

Safety, Pharmacokinetics, and Pharmacodynamics Study in Healthy Subjects of Oral NEO6860, a Modality Selective Transient Receptor Potential Vanilloid Subtype 1 Antagonist.

Unlabelled: Most previous transient receptor potential vanilloid subtype 1 (TRPV1) antagonist programs have been put on hold, mainly because of on-target adverse events: hyperthermia and impaired noxious heat sensation. NEO6860 is a TRPV1 antagonist, blocking capsaicin activation of the target, with little or no effect against pH or heat activation. The hypothesis is that this pharmacological profile will translate into analgesia without undesired effects on the body temperature or heat-pain threshold.

Randomized clinical trial: pharmacokinetics and safety of multimatrix mesalamine for treatment of pediatric ulcerative colitis.

Background: Limited data are available on mesalamine (5-aminosalicylic acid; 5-ASA) use in pediatric ulcerative colitis (UC).

Aim: To evaluate pharmacokinetic and safety profiles of 5-ASA and metabolite acetyl-5-ASA (Ac-5-ASA) after once-daily, oral administration of multimatrix mesalamine to children and adolescents with UC.

Methods: Participants (5-17 years of age; 18-82 kg, stratified by weight) with UC received multi-matrix mesalamine 30, 60, or 100 mg/kg/day once daily (to 4,800 mg/day) for 7 days.

A phase 1 randomized study evaluating the effect of omeprazole on the pharmacokinetics of a novel 5-hydroxytryptamine receptor 4 agonist, revexepride (SSP-002358), in healthy adults.

Background: About 30% of patients with gastroesophageal reflux disease continue to experience symptoms despite treatment with proton pump inhibitors. The 5-hydroxytryptamine 4 receptor agonist revexepride (SSP-002358) is a novel prokinetic that stimulates gastrointestinal motility, which has been suggested as a continued cause of symptoms in these patients. The aim of this study was to assess whether revexepride pharmacokinetics were affected by co-administration of omeprazole, in preparation for a proof-of-concept evaluation of revexepride added to proton pump inhibitor treatment.

Assessment of pharmacodynamic equivalence and tolerability of lanthanum carbonate oral powder and tablet formulations: a single-center, randomized, open-label, 2-period crossover study in healthy subjects.

Background: Phosphate binders are commonly used in tablet form to help patients with hyperphosphatemia limit their absorption of dietary phosphate. These patients frequently have a heavy tablet burden so alternative formulations provide choice and may support adherence. Lanthanum carbonate (LC) is a phosphate binder currently available as a chewable tablet.

The effect of sevelamer carbonate and lanthanum carbonate on the pharmacokinetics of oral calcitriol.

Background: Lanthanum carbonate and sevelamer carbonate are non-calcium-based phosphate binders used to manage hyperphosphataemia in patients with chronic kidney disease (CKD). Patients with CKD may require intravenous or oral active vitamin D. We investigated the effects of lanthanum carbonate and sevelamer carbonate on the bioavailability of oral calcitriol.

A solid-state approach to enable early development compounds: selection and animal bioavailability studies of an itraconazole amorphous solid dispersion.

A solid-state approach to enable compounds in preclinical development is used by identifying an amorphous solid dispersion in a simple formulation to increase bioavailability. Itraconazole (ITZ) was chosen as a model crystalline compound displaying poor aqueous solubility and low bioavailability. Solid dispersions were prepared with different polymers (PVP K-12, K29/32, K90; PVP VA S-630; HPMC-P 55; and HPMC-AS HG) at varied concentrations (1:5, 1:2, 2:1, 5:1 by weight) using two preparation methods (evaporation and freeze drying).