Phase 2a Randomized Open-Label Crossover Study of Oral NHS7108 in Adults with Exocrine Pancreatic Insufficiency

The primary objective is to assess the safety of different daily doses of oral NHS7108 over 14 days in participants with exocrine pancreatic insufficiency. The coefficient of nitrogen absorption is also measured as part of the safety evaluation, providing information relevant to nutrient absorption and treatment tolerability. The secondary objectives are to evaluate the effect of different NHS7108 doses on fat absorption and to assess effects on gastrointestinal symptoms, which are clinically relevant outcomes in exocrine pancreatic insufficiency because they reflect digestive function and symptom control.

The trial population comprised 37 participants with exocrine pancreatic insufficiency. The study included male and female participants 18 to 85 years of age, with clinically confirmed chronic established disease and a clinical indication for pancreatic enzyme replacement therapy. Participants were selected on the basis of screening criteria that included fecal elastase below 200 µg/g, coefficient of fat absorption off therapy below 80%, and a body mass index between 17.0 and 35.0 kg/m², reflecting adequate control of the condition in the investigator’s opinion. The source did not provide additional information on general health status, lifestyle characteristics such as diet, physical activity, or habits.

This is a randomized, open-label, active-controlled, crossover phase 2a study in adults with exocrine pancreatic insufficiency. The trial evaluates the safety of different daily doses of oral NHS7108 over 14 days and explores efficacy in comparison with Zenpep delayed-release capsule. The overall study period is estimated to run from 29 May 2026 to 19 April 2027. Study participation begins with a screening visit to confirm eligibility, including clinical confirmation of chronic EPI, fecal elastase assessment if needed, coefficient of fat absorption off pancreatic enzyme replacement therapy, and other protocol-defined criteria. Eligible participants then enter the treatment period and complete scheduled follow-up assessments during and after the 14-day dosing phase to evaluate adverse events, laboratory tests, vital signs, electrocardiogram, physical examination, coefficient of nitrogen absorption, coefficient of fat absorption, omega-3 absorption, gastrointestinal symptoms, stool frequency, and stool consistency. An end-of-study visit is performed after completion of the assigned study periods and assessments. Expected participant involvement is approximately 14 days per treatment period within the crossover design, with possible early termination if study treatment is discontinued, eligibility criteria are no longer met, safety concerns arise, or withdrawal from the study occurs.

NHS7108 capsules were the investigational treatment. The pharmaceutical form was a capsule for oral use. The administered dose was 240 mg, given orally once daily for 14 days. The study evaluated different doses of NHS7108 in participants with exocrine pancreatic insufficiency. Coefficient of nitrogen absorption was measured as part of the safety assessment. Compliance with the dosing regimen was monitored during the treatment period.

Zenpep delayed-release capsules were used as the active comparator. The pharmaceutical form was a delayed-release capsule for oral use. The administered dose was 600000 U, given orally. This comparator contained amylase, lipase, and protease. The study used an open-label, active-controlled, crossover design, and treatment administration followed the protocol-defined dosing schedule. Compliance monitoring was performed during the study.

Efficacy will be assessed by coefficient of fat absorption after 14-day treatment with NHS7108, compared with Zenpep. Efficacy will also be evaluated by the omega-3 absorption test, using changes from baseline in post-prandial eicosapentaenoic acid and docosahexaenoic acid content of plasma over a 24-hour period following a standard breakfast after 14-day NHS7108 treatment. Additional efficacy assessments include change from baseline in the GI symptoms score recorded in the eDiary, stool frequency as assessed by the eDiary, and stool consistency as assessed by the Bristol Stool Scale.