insulin tregopil (IN-105) / Biocon - LARVOL DELTA

An open-label, multiple ascending dose trial of orally administered insulin Tregopil in patients with type 1 diabetes mellitus to evaluate its pharmacokinetics, pharmacodynamics, safety and tolerability. (PubMed, Diabetes Obes Metab) - P1 | "Fixed-dose insulin Tregopil reduced the requirement for insulin aspart supplementation, although it was not a viable stand-alone option for the daily management of T1DM. Insulin Tregopil could be explored with a flexible dosing approach and be titrated based on individual needs."

Journal • PK/PD data • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Three-Dimensional Heat Map: The OTA/AO Type 43C Pilon Fracture Lines Distribution. (PubMed, Int J Gen Med) - "CT scan was performed in105 fractures diagnosed with OTA/AO type 43C pilon fractures between January 2017 and December 2022...This study demonstrates that the articular surface fracture lines in the C type pilon fracture are formed by fixed main fracture lines. The understand of morphological and distribution characteristics of the fracture lines and size of fragments in OTA/AO type 43C pilon fractures would help the surgeons take suitable approach and fixation."

Journal • Musculoskeletal Diseases • Orthopedics

One Tube 23 Color Full Spectral Flow Cytometry Panel in Detecting Minimal Residual Disease in Pediatric B-Cell Acute Lymphoblastic Leukemia (ASH 2023) - "Results The limit of blank (LOB), limit of detection (LOD), and lower limit of quantitation (LLOQ) were firstly determined, the results showed reproducible sensitivity up to 0.001% (1-in-105) after acquisition of 4.8 million cells for 23-color panel...Conclusion Based on these evidences, SMFC-based one-tube 23-color MRD panel for B-ALL was convenient and maneuverable with higher sensitivity and specificity compared to conventional 8-color FC-MRD panel. It would be a promising method to improve the risk stratification."

Clinical • IO biomarker • Minimal residual disease • Residual disease • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • ANPEP • CD123 • CD133 • CD20 • CD200 • CD21 • CD22 • CD24 • CD34 • CD44 • CD58 • CD73 • CD81 • CD86 • CEACAM6 • IL3RA • MME • NCAM1 • NRP1 • PTPRC

Risk-Adapted SABR for Ultra-Central Lung Tumors Attaining High BED10 to Targets in a Steep Dose-Response Window of 72-105 Gy under Tumor Tracking: A Planning Study (ASTRO 2023) - " For scheme-A, mean BED 10 to PTV are 118.0 Gy (median) in105.5-133.5 Gy (range), and mean BED 10 dose to GTV are 132.2 (118.3-149.4 Gy)... Two risk-adapted SABR of 7.5Gyx8 and 4Gyx15 are implemented for treating ultra-central lung tumors with BED 10 =100 Gy to the distal sections of PTV and yet attain potent BED 10 =72-84 Gy to the proximal sections of PTV that abut or overlap with trachea, proximal bronchial tree or esophagus. Accurate dose calculation by a planning tool and real-time tumor tracking are essential for safe and accurate delivery of such high-risk SABR treatments."

Lung Cancer • Oncology • Solid Tumor

Risk-Adapted SABR for Ultra-Central Lung Tumors Attaining High BED to Targets in a Steep Dose-Response Window of 72-105 Gy under Tumor Tracking: A Planning Study. (PubMed, Int J Radiat Oncol Biol Phys) - "Two risk-adapted SABR of 7.5 Gyx8 and 4 Gyx15 are implemented for treating ultra-central lung tumors with BED ≥100 Gy to the distal sections of PTV and yet attain potent BED ≥72-84 Gy to the proximal sections of PTV that abut or overlap with trachea, proximal bronchial tree or esophagus. Accurate dose calculation by a planning tool and real-time tumor tracking are essential for safe and accurate delivery of such high-risk SABR treatments."

Journal • Lung Cancer • Oncology • Solid Tumor

Insulin Tregopil: An Ultra-Fast Oral Recombinant Human Insulin Analog: Preclinical and Clinical Development in Diabetes Mellitus. (PubMed, Drugs) - "It shows a good safety profile with a lower incidence of clinically significant hypoglycemia. This review covers the overall clinical development of insulin tregopil establishing it as an ultra-fast onset, short-acting oral insulin analog for optimizing post-prandial glucose."

Clinical • Journal • Preclinical • Diabetes • Gastrointestinal Disorder • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Efficacy and safety of Tregopil, a novel, ultra-rapid acting oral prandial insulin analog, as part of a basal-bolus regimen in type 2 diabetes: a randomized, active-controlled phase 2/3 study. (PubMed, Expert Opin Pharmacother) - P2/3 | "Efficacy and safety of ultra-rapid acting oral prandial insulin Tregopil was compared with insulin aspart (IAsp) in patients with type 2 diabetes (T2D) on insulin glargine and metformin...While Tregopil's early postprandial effects were comparable to IAsp, its late postprandial effects were inferior. The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT03430856)."

Journal • P2/3 data • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Evaluation of Pharmacokinetics , Safety, Tolerability and Pharmacodynamics of Biocon Insulin Tregopil (clinicaltrials.gov) - P1 | N=55 | Terminated | Sponsor: Biocon Limited | Phase classification: P1/2 ➔ P1 | Completed ➔ Terminated; Part 1 completed. Part 2 not initiated

Phase classification • Trial termination • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Evaluation of Pharmacokinetics , Safety, Tolerability and Pharmacodynamics of Biocon Insulin Tregopil (clinicaltrials.gov) - P1/2 | N=60 | Completed | Sponsor: Biocon Limited | Recruiting ➔ Completed | Trial completion date: Jan 2022 ➔ Apr 2021

Trial completion • Trial completion date • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Evaluation of Pharmacokinetics , Safety, Tolerability and Pharmacodynamics of Biocon Insulin Tregopil (clinicaltrials.gov) - P1/2; N=60; Recruiting; Sponsor: Biocon Limited; Phase classification: P1 ➔ P1/2

Clinical • Phase classification • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Comparison of Insulin Tregopil (IN-105) With Insulin Aspart in Type 2 Diabetes Mellitus Patients (clinicaltrials.gov) - P2/3; N=143; Completed; Sponsor: Biocon Limited; N=91 ➔ 143

Clinical • Enrollment change • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Impact of Insulin Tregopil and its Permeation Enhancer on Pharmacokinetics of Metformin in Healthy Volunteers: Randomized, Open-label, Placebo Controlled, Crossover Study. (PubMed, Clin Transl Sci) - "Under fasting conditions, upper bound margin of C was just beyond this range (i.e. 1.27) and was concluded as functionally not relevant. There was no clinically significant effect of sodium caprate/IN-105 on pharmacokinetics of metformin under fasting/fed conditions and it was safe."

Clinical • Journal • PK/PD data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

CR845-CLIN3105: A Study to Evaluate the Safety and Effectiveness of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus (clinicaltrials.gov) - P3; N=222; Completed; Sponsor: Cara Therapeutics, Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion • Dermatology • Pruritus • Renal Disease

CR845-CLIN3105: A Study to Evaluate the Safety and Effectiveness of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus (clinicaltrials.gov) - P3; N=223; Active, not recruiting; Sponsor: Cara Therapeutics, Inc.; Recruiting ➔ Active, not recruiting

Enrollment closed

Comparison of Pharmacokinetics , Safety, Tolerability and Pharmacodynamics of Biocon Insulin Tregopil and Insulin Aspart (clinicaltrials.gov) - P1; N=60; Recruiting; Sponsor: Biocon Limited; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

Comparison of Pharmacokinetics , Safety, Tolerability and Pharmacodynamics of Biocon Insulin Tregopil and Insulin Aspart (clinicaltrials.gov) - P1; N=60; Not yet recruiting; Sponsor: Biocon Limited

Clinical • New P1 trial

CR845-CLIN3105: A Study to Evaluate the Safety and Effectiveness of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus (clinicaltrials.gov) - P3; N=250; Recruiting; Sponsor: Cara Therapeutics, Inc.; N=400 ➔ 250

Clinical • Enrollment change

Enterically-delivered Insulin Tregopil Exhibits Rapid Absorption Characteristics and a Pharmacodynamic Effect Similar to Human Insulin in Conscious Dogs. (PubMed, Diabetes Obes Metab) - "Enterically-delivered tregopil is rapidly absorbed and restores a portal-to-peripheral vascular distribution. These characteristics should improve post-prandial hyperglycemia in types 1 and 2 diabetes."

Journal • PK/PD data

Pharmacokinetics and Pharmacodynamics of Insulin Tregopil in Relation to Premeal Dosing Time, Between Meal Interval, and Meal Composition in Patients With Type 2 Diabetes Mellitus. (PubMed, Clin Pharmacol Drug Dev) - "A 5-hour between-meal interval minimizes the impact of a meal on absorption of subsequent (afternoon) insulin tregopil dose, and the pharmacodynamic response of insulin tregopil is not altered by meal composition. Insulin tregopil was well tolerated in patients with type 2 diabetes mellitus."

Clinical • Journal • PK/PD data

Comparison of Insulin Tregopil (IN-105) With Insulin Aspart in Type 2 Diabetes Mellitus Patients (clinicaltrials.gov) - P2/3; N=91; Completed; Sponsor: Biocon Limited; Recruiting ➔ Completed; N=358 ➔ 91; Trial completion date: Sep 2020 ➔ Feb 2019; Trial primary completion date: Jul 2020 ➔ Feb 2019

Clinical • Enrollment change • Trial completion • Trial completion date • Trial primary completion date

CR845-CLIN3105: A Study to Evaluate the Safety and Effectiveness of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus (clinicaltrials.gov) - P3; N=400; Recruiting; Sponsor: Cara Therapeutics, Inc.

Clinical • New P3 trial