Oligomalt, a New Slowly Digestible Carbohydrate, Is Well Tolerated in Healthy Young Men and Women at Intakes Up to 180 Gram per Day: A Randomized, Double-Blind, Crossover Trial.

In this randomized, double-blind triple-crossover study (NCT05142137), the digestive tolerance and safety of a novel, slowly digestible carbohydrate (SDC), oligomalt, an α-1,3/α-1,6-glucan α-glucose-based polymer, was assessed in healthy adults over three separate 7-day periods, comparing a high dose of oligomalt (180 g/day) or a moderate dose of oligomalt (80 g/day in combination with 100 g maltodextrin/day) with maltodextrin (180 g/day), provided as four daily servings in 300 mL of water with a meal. Each period was followed by a one-week washout. A total of 24 subjects (15 females, age 34 years, BMI 22.2 kg/m2, fasting blood glucose 4.9 mmol/L) were recruited, of whom 22 completed the course. The effects on the primary endpoint (the Gastrointestinal Symptom Rating Score (GSRS)) showed a statistically significant dose dependency, albeit of limited clinical relevance, between a high dose of oligomalt and maltodextrin (mean (95% CI) 2.29 [2.04, 2.54] vs. 1.59 [1.34, 1.83], respectively; difference: [-1.01, -0.4], p < 0.0001), driven by the GSRS-subdomains "Indigestion" and "Abdominal pain". The GSRS difference ameliorated with product exposure, and the GSRS in those who received high-dose oligomalt as their third intervention period was similar to pre-intervention (mean ± standard deviation: 1.6 ± 0.4 and 1.4 ± 0.3, respectively). Oligomalt did not have a clinically meaningful impact on the Bristol Stool Scale, and it did not cause serious adverse events. These results support the use of oligomalt across various doses as an SDC in healthy, normal weight, young adults.

A Novel Inhaled Dry-Powder Formulation of Ribavirin Allows for Efficient Lung Delivery in Healthy Participants and Those with Chronic Obstructive Pulmonary Disease in a Phase 1 Study.

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung condition, causing progressive decline in lung function leading to premature death. Acute exacerbations in COPD patients are predominantly associated with respiratory viruses. Ribavirin is a generic broad-spectrum antiviral agent that could be used for treatment of viral respiratory infections in COPD. Using the Particle Replication In Nonwetting Templates (PRINT) technology, which produces dry-powder particles of uniform shape and size, two new inhaled formulations of ribavirin (ribavirin-PRINT-CFI and ribavirin-PRINT-IP) were developed for efficient delivery to the lung and to minimize bystander exposure. Ribavirin-PRINT-CFI was well tolerated in healthy participants after single dosing and ribavirin-PRINT-IP was well tolerated in healthy and COPD participants after single and repeat dosing. Ribavirin-PRINT-CFI was replaced with ribavirin-PRINT-IP since the latter formulation was found to have improved physicochemical properties and it had a higher ratio of active drug to excipient per unit dose. Ribavirin concentrations were measured in lung epithelial lining fluid in both healthy and COPD participants and achieved target concentrations. Both formulations were rapidly absorbed with approximately dose proportional pharmacokinetics in plasma. Exposure to bystanders was negligible based on both the plasma and airborne ribavirin concentrations with the ribavirin-PRINT-IP formulation. Thus, ribavirin-PRINT-IP allowed for an efficient and convenient delivery of ribavirin to the lungs while minimizing systemic exposure. Further clinical investigations would be required to demonstrate ribavirin-PRINT-IP antiviral characteristics and impact on COPD viral-induced exacerbations. (The clinical trials discussed in this study have been registered at ClinicalTrials.gov under identifiers NCT03243760 and NCT03235726.).