Highlights d Findings are shared for the first 17 participants in a phase 1/2 trial of VC-02 d This investigational device was implanted into type 1 diabetes patients d VC-02 contains pluripotent stem cell-derived pancreatic endoderm cells d C-peptide levels and insulin expression correlate with engraftment in 63% of subjects Authors

BackgroundLactose intolerance (LI) is a common medical problem with limited treatment options. The primary symptoms are abdominal pain, diarrhea, bloating, flatulence, and cramping. Limiting dairy foods to reduce symptoms contributes to low calcium intake and the risk for chronic disease. Adaptation of the colon bacteria to effectively metabolize lactose is a novel and potentially useful approach to improve lactose digestion and tolerance. RP-G28 is novel galacto-oligosaccharide (GOS) being investigated to improve lactose digestion and the symptoms of lactose intolerance in affected patients.MethodsA randomized, double-blind, parallel group, placebo-controlled study was conducted at 2 sites in the United States. RP-G28 or placebo was administered to 85 patients with LI for 35 days. Post-treatment, subjects reintroduced dairy into their daily diets and were followed for 30 additional days to evaluate lactose digestion as measured by hydrogen production and symptom improvements via a patient-reported symptom assessment instrument.ResultsLactose digestion and symptoms of LI trended toward improvement on RP-G28 at the end of treatment and 30 days post-treatment. A reduction in abdominal pain was also demonstrated in the study results. Fifty percent of RP-G28 subjects with abdominal pain at baseline reported no abdominal pain at the end of treatment and 30 days post treatment (p = 0.0190). RP-G28 subjects were also six times more likely to claim lactose tolerance post-treatment once dairy foods had been re-introduced into their diets (p = 0.0389).ConclusionsEfficacy trends and favorable safety/tolerability findings suggest that RP-G28 appears to be a potentially useful approach for improving lactose digestion and LI symptoms. The concurrent reduction in abdominal pain and improved overall tolerance could be a meaningful benefit to lactose intolerant individuals.Study registrationClinicalTrials.gov NCT01113619.

VC-01 is a novel cell replacement therapy being developed as a potential long-term diabetes therapy to more effectively control glycemia, reduce hypoglycemia risk and mitigate diabetes-related complications. VC-01 is derived from directed differentiation of human embryonic stem cells to pancreatic progenitor cells, which are loaded into a durable, retrievable delivery device and then implanted subcutaneously. Once implanted and matured, the cells secrete insulin and other islet hormones in response to blood glucose levels. The delivery device is immunoprotective to implanted cells. VC-01 is currently being evaluated in a 24-month open-label, dose-escalating Phase 1/2 study in T1D patients with minimal insulin-producing β-cell function. Cohort 1 has evaluated product at a subtherapeutic dose to assess initial safety and tolerability and establish implantation techniques. To date, 19 subjects have been implanted and evaluated throughout implantation duration until final product explant. Product has been safe and well tolerated; adverse events have been relatively minor and generally related to the surgical procedure. The delivery device has provided protection against the host adaptive immune system with no evidence of allogeneic or autoimmune rejection or sensitization based upon a sensitive panel of immune function tests. No off-target growth of donor cells has been detected. The potential for prolonged cell survival has been demonstrated, as long as 24 months, but has been inconsistent among subjects and primarily limited by a foreign body response to the device component. Positive immunohistochemical staining for pancreatic islet cell markers NKX6-1, insulin, and glucagon has been observed. These preliminary results demonstrate the immune-protective nature of the encapsulation device and safety of this human stem cell-derived product, but also indicate the ongoing requirement for optimization of the host response to device materials. Disclosure R.R. Henry: Consultant; Self; Abbott, Alere Inc., AstraZeneca. Research Support; Self; AstaReal. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Bristol-Myers Squibb Company. Advisory Panel; Self; Elcelyx Therapeutics, Inc.. Research Support; Self; Eli Lilly and Company, Hitachi, Ltd.. Advisory Panel; Self; AstraZeneca. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Intarcia Therapeutics, Inc.. Consultant; Self; Intarcia Therapeutics, Inc., Ionis Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Johnson & Johnson Services, Inc.. Research Support; Self; Lexicon Pharmaceuticals, Inc.. Consultant; Self; Ligand Pharmaceuticals, Inc.. Advisory Panel; Self; Merck & Co., Inc.. Consultant; Self; Merck & Co., Inc.. Research Support; Self; Viacyte, Inc.. Consultant; Self; Sanofi-Aventis. Advisory Panel; Self; Sanofi-Aventis. J. Pettus: Advisory Panel; Self; Sanofi, Novo Nordisk Inc.. Consultant; Self; MannKind Corporation. Advisory Panel; Self; Insulet Corporation. Consultant; Self; Senseonics. J. Wilensky: None. A. Shapiro: Consultant; Self; Viacyte, Inc., Protokinetix. P.A. Senior: Consultant; Self; Abbott, AstraZeneca. Research Support; Self; AstraZeneca, Prometic Life Sciences Inc., Novo Nordisk Inc., Sanofi. Consultant; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc., Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; AstraZeneca, Merck & Co., Inc., Abbott. Research Support; Self; Viacyte, Inc. B. Roep: Consultant; Self; Viacyte, Inc.. Research Support; Self; Viacyte, Inc. R. Wang: Employee; Self; Viacyte, Inc.. Stock/Shareholder; Self; Sanofi. E.J. Kroon: Employee; Self; Viacyte, Inc. M. Scott: Stock/Shareholder; Self; Viacyte, Inc.. K. D'Amour: None. H.L. Foyt: Employee; Self; Viacyte, Inc.. Stock/Shareholder; Self; Viacyte, Inc..

OBJECTIVE -The purpose of this study was to evaluate the long-term (2-year) safety and efficacy of inhaled human insulin (Exubera [insulin human (rDNA origin)] inhalation powder) (EXU) in adult patients with type 1 diabetes. , indicating that the significant difference between the treatment groups in FEV 1 developed during the first 3 months and was not progressive thereafter. Adverse event profiles were similar except for a higher incidence of cough (usually mild and unproductive) in patients receiving EXU (37.6 vs. 13.1%) that decreased to 1.3% by month 24. Glycemic control was sustained in both groups (adjusted mean treatment difference in change from baseline A1C at month 24 0.25 Ϯ 0.07% [0.13-0.37]). Although the overall hypoglycemic events were comparable between groups (4.0 vs. 3.8 events/subject-month), the incidence of severe hypoglycemic events was lower with EXU than with SC insulin (2.8 vs. 4.1 events/100 subject-months, risk ratio 0. RESEARCH DESIGN AND METHODS

Conduct of a large, multicenter trial of the aldose reductase inhibitor zenarestat provided data on the reproducibility of multiple electrophysiologic (nerve conduction studies, NCS) and quantitative sensory (QST) tests. Baseline and 12-month electrophysiologic data from approximately 1100 patients at multiple centers were available for analysis. Intersite variability contributed minimally to overall test variance. All NCS tests were highly reproducible. Cool thermal and vibration QST thresholds, as measured by CASE IV instrumentation, were also highly reproducible. Intersubject variance accounted for the majority of variance for all parameters measured. Repeating NCS and QST measures decreased sample sizes needed to show statistical significance. Consideration of these observations, particularly with regard to QST, should aid in the design of future clinical trials investigating neuropathy.