Randomized controlled phase I trial for a novel peripheral parenteral nutrition formula containing dextrose, amino acids, fat emulsion, electrolytes, and FDA2000 recommendation-based vitamins.

BACKGROUND & AIMS: We developed the world's first all-in-one type peripheral parenteral nutrition product containing dextrose, amino acids, fat emulsion, electrolytes and vitamins, according to the FDA 2000 recommendation. This phase I trial examined the safety and changes in nutritional parameters in healthy participants. METHODS: A single-center, randomized, open-label, active-controlled trial was performed in single ascending dose (SAD: Step 1-3) and multiple dose (Step 4) studies. Participants were administered a single dose of OPF-105 (test solution: 150 g of dextrose, 60 g of amino acids, 40 g of fat, 1240 kcal of total energy per 2200 mL, and 106 NPC/N ratio, with multivitamins, n = 17) or BFI (control solution: 150 g of dextrose, 60 g of amino acids, 840 kcal of total energy per 2000 mL, and 64 NPC/N ratio, with vitamin B1, n = 18) with three ascending doses (Step 1: 550 mL, Step 2: 1100 mL, and Step 3: 2200 mL) in the SAD study, or received multiple doses with Step 3 amount of OPF-105 (n = 5) or BFI (n = 6) for 3 days (Step 4) via peripherally inserted venous catheters. The safety and nutritional parameters were assessed. RESULTS: There were no serious adverse events or events requiring discontinuation of the solution administration in either group. Blood urea nitrogen (BUN) levels remained within the normal range in both groups (Step 1-4). However, they gradually increased during the time course of the study in the BFI group but not in the OPF group (Step 4), suggesting the prevention of body protein breakdown. Blood triglyceride (TG) levels increased after administration in the OPF group but promptly returned to the pre-administration level (Step 1-4). Blood total ketone body levels increased the day after administration in both groups, which may imply a lower degree of starvation (Step 1-3), but the increase in the OPF group was milder than that in the BFI group (Step 4). Blood vitamin B6 and folic acid levels were maintained within the normal ranges in the OPF group but were near the lower limit in the BFI group (Step 1-4). Blood vitamin C levels showed almost lower limit in the two groups (Step 1-3), but increased only in the OPF group (Step 4). Blood vitamin K levels in the BFI group remained near the lower limit of the normal range, but those in the OPF group were higher than the upper limit at the end of administration and quickly returned to the pre-administration level (Step 1-4). CONCLUSIONS: This trial suggests that the newly developed formula (OPF-105) improves fat metabolism, maintains vitamin profiles, and may prevent body protein and fat breakdown and can be safely administered to healthy participants. Registration number of Clinical Trial: UMIN000046915; https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000053479.

Postoperative Vitamin Profile after Receiving a Novel Peripheral Parenteral Nutrition Solution: Multicenter Randomized Controlled Phase III Trial.

INTRODUCTION: We assessed the efficacy and safety of OPF-105, a novel all-in-one peripheral parenteral nutrition (PPN) solution containing multivitamins by the U.S. Food and Drug Administration in 2000 (FDA2000 recommendation). METHODS: We conducted a phase III trial administering OPF-105 or BFL (combination of a commercially available PPN solution and fat emulsion) to patients after gastrointestinal (GI) tract surgery from postoperative day (POD) 1 up to POD14. Until POD7, nutrients were provided only with OPF-105 or BFL. After blood sampling on POD8, oral food intake was permitted. PPN was administered according to the amount of food intake. RESULTS: Efficacy endpoints were assessed in 99 subjects (OPF group: 52; BFL group: 47). The levels of blood proteins and fatty acids in the two groups were similar on POD8. The transition of these mean levels was similar in both groups from POD1 or 2 to POD9 to 15. The mean preoperative blood vitamin levels were within reference intervals (RIs). On POD1 (before administration), the mean levels of most blood vitamins decreased compared to those of the preoperative levels. In the BFL group, the mean blood levels of vitamin B2, B6, pantothenic acid (PA), folic acid (FA), biotin, and C decreased below or near the lower limit of RIs on POD8, and the mean blood levels of vitamin B6 and C remained low from POD9 to 15. In the OPF group, the mean blood levels of vitamins, excluding vitamin K, were within RIs on POD8 and POD9 to 15. The mean levels of blood vitamin K increased over the upper limit of RIs on POD8 but within RIs from POD9 to 15. There was no obvious difference in the incidence of adverse events between the two groups, which is common after GI tract surgeries. CONCLUSION: Blood vitamin levels decreased when patients were administered PPN without vitamin supplementation during the first week after surgery. The novel PPN formula containing multivitamins recommended by FDA2000 can be safely administered to postoperative patients to maintain blood vitamin levels.

Optimizing Vitamin and Trace Element Profiles in Blood after Gastrointestinal Tract Surgery by a New Parenteral Nutrition Formula.

INTRODUCTION: Though micronutrient formulations for parenteral nutrition (PN) have been revised, the impacts of these changes on nutritional parameters, blood micronutrient levels, and safety have yet to be clarified. We examined the efficacy and safety of a new PN formulation with a micronutrient composition based on the Food and Drug Administration 2000 recommendation in surgical patients. METHODS: This phase III clinical trial (JapicCTI-No. 142610) was a prospective, randomized, controlled, parallel-group, open-label, multicenter study. Two types of PN, OPF-108 (revised formula, n = 51) and ELN (previous formula mainly based on American Medical Association 1975 guidelines, n = 59), were given to patients from POD1 or 2 to POD7 after surgery. OPF-108 contains more vitamin B1, B6, C, and folic acid, a much lower dose of vitamin K, and less iron than ELN. Nutritional parameters and micronutrient profiles in blood and safety were evaluated. RESULTS: Nutritional parameters on POD5 and 8 were similar between the 2 groups. Blood vitamin B1, B6, and folic acid levels on POD 5 and 8 were higher in the OPF-108 group than in the ELN group. Only OPF-108 restored vitamin C levels to within the normal range on POD5 and 8. Vitamin K levels far exceeded the upper limit of the standard range on POD5 and 8 in the ELN group, whereas OPF-108 essentially maintained these levels within the standard ranges. Serum iron levels on POD8 were nearly normal in both the OPF-108 and ELN groups. CONCLUSION: Beneficial effects of the new micronutrient formulation were demonstrated in surgical patients.