Leveraging patient-centric sampling for clinical drug development and decentralized clinical trials: Promise to reality.

Advances in the technologies to enable patient-centric sampling (PCS) have the potential to improve blood sample collection by enabling clinical trial participants to collect samples via self-collection or with the help of a caregiver in their home. Typically, blood samples to assess pharmacokinetics and pharmacodynamics of a drug during clinical development are collected at a clinical site via venous blood draw. In this position paper by the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ), the potential value PCS can bring to patients, to the clinical datasets generated, and to clinical trial sponsors is discussed, along with considerations for program decision making, bioanalytical feasibility, operations, and regulatory implications. With an understanding of the value of PCS and considerations when implementing during clinical drug development, we can bring the promise of PCS closer to reality and enable decentralized clinical trials.

Gastric mucosal damage following repeat administration of melanocortin subtype-4 receptor ligands to Fischer 344 rats.

Since the melanocortin system plays a role in the central control of feeding, melanocortin receptor ligands may be efficacious in treating human obesity. Ten structurally similar melanocortin subtype-4 receptor (MC4R) ligands from an aryl piperazine chemical platform were evaluated in female Fischer 344 rats to assess the toxicity of this class of compounds. Rats were orally gavaged with 100, 250, or 500 mg/kg of each compound in 10% acacia and purified water daily for 4 days. In treated rats, notable clinical observations included a dose-dependent decrease in mean body weight and food consumption. A morphologically unique compound-related histologic lesion occurred in the nonglandular gastric mucosa. The lesions consisted of multiple, raised, sometimes ulcerated, white foci which, microscopically, were discrete, intraepithelial vesicles containing dense accumulations of neutrophils continuous with inflammation in the submucosa. Ruptured vesicles resulted in ulcers and occasionally gastric perforation. The morphologic characteristics of this acute lesion were described and concluded to be a direct toxicity of the compounds unrelated to melanocortin-mediated pharmacology.