Evaluation of Pharmacokinetics , Safety, Tolerability and Pharmacodynamics of Biocon Insulin Tregopil

NCT04141423 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: TREGO-DM1-01-G-02
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

Multi-centre, open label, multiple ascending dose trial in patients with type 1 diabetes mellitus

Conditions

Type 1 Diabetes Mellitus (T1DM)

Keywords

Oral Insulin

Outcome Measures

Primary Outcomes (15)

• Adverse events (AEs)

  Number of patients with Adverse Events (Part I)

  Between screening (up to Day -21) and End of study ( up to Day 6)

• Laboratory safety parameters

  Number of patients with clinically significant changes in Laboratory safety parameters (Part I)

  Between screening (up to Day -21) and End of study ( up to Day 6)

• Physical examination

  Number of patients with clinically significant changes in Physical examination (Part I)

  Between screening (up to Day -21) and End of study ( up to Day 6)

• Vital signs, clinically

  Number of patients with clinically significant changes in Vital signs (Part I)

  Between screening (up to Day -21) and End of study ( up to Day 6)

• Hypoglycaemic events

  Number of patients with Hypoglycaemia events (Part I)

  Between screening (up to Day -21) and End of study ( up to Day 6)

• Hyperglycaemia events

  Number of patients with Hyperglycaemia events (Part I)

  Between screening (up to Day -21) and End of study ( up to Day 6)

• Electrocardiograms

  Number of patients with clinically significant changes in Electrocardiogram (ECG) (Part I)

  Between screening (up to Day -21) and End of Treatment ( up to Day 6)

• Adverse events (AEs)

  Number of patients with Adverse Events (Part II)

  Day of screening to Day 20 (Diary) and During follow up Via (Telephone)

• Hypoglycaemic events

  Number of patients with Hypoglycaemia events (Part II)

  Day of screening to Day 20 (Diary) and During follow up Via (Telephone)

• Hyperglycaemia events

  Number of patients with Hyperglycaemia events (Part II)

  Day of Run-in to Day 20 (Diary) and During follow up Via (Telephone)

• Laboratory safety parameters

  Number of patients with clinically significant changes in Laboratory safety parameters (Part II)

  Day of screening and Day 20

• Physical examination

  Number of patients with clinically significant changes in Physical examination (Part II)

  Day of screening, Dosing day 1 and Day 20

• Vital signs

  Number of patients with clinically significant changes in Vital signs (Part II)

  Day of screening, Day1-6 and Day 20)

• Electrocardiograms

  Number of patients with clinically significant changes in Electrocardiogram (ECG) (Part II)

  Day of screening and Day 20

• Anti-insulin Tregopil antibodies

  Change in antibody levels (Part II)

  Day -1 and Day 20

Secondary Outcomes (60)

• Pharmacokinetics (PK) endpoint-Area under the insulin concentration curve(AUCins).

  0 to 1 hour

• PK endpoint-Area under the insulin concentration curve(AUCins).

  0 to 2 hour

• PK endpoint-Area under the insulin concentration curve(AUCins).

  0 to 3 hour

• PK endpoint-Area under the insulin concentration curve(AUCins).

  0 to 4 hour

• PK endpoint-Area under the insulin concentration curve(AUCins).

  Time zero to the last measurable concentration (6 hours)

Study Arms (4)

Tregopil 30 mg

ACTIVE COMPARATOR

Dose level cohort with a sentinel dosing design

Drug: Tregopil

Tregopil 45 mg

ACTIVE COMPARATOR

Dose level cohort with a sentinel dosing design

Drug: Tregopil

Tregopil 60 mg

ACTIVE COMPARATOR

Dose level cohort with a sentinel dosing design

Drug: Tregopil

Derived Dose level

ACTIVE COMPARATOR

Derived Dose level cohort with a sentinel dosing design (60 mg fixed preprandial dose plus an additional 30 mg postprandial rescue dose, if required)

Drug: Tregopil

Interventions

Tregopil DRUG

Insulin Tregopil is recombinant human insulin modified by a single amphiphilic oligomer covalently linked via an amide bond to lysine at position 29 of the B-chain. This alters the physicochemical characteristics of the molecule, leading to enhanced stability and resistance to intestinal degradation following oral administration.

Also known as: IN-105

Derived Dose level; Tregopil 30 mg; Tregopil 45 mg; Tregopil 60 mg

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female patient with diabetes mellitus type 1 on insulin therapy for at least 1 year before screening
• Age between 18 and 64 years, both inclusive.
• Body Mass Index (BMI) between 18.5 and 29.0 kg/m2, both inclusive.
• Body weight between 60 kg and 100 kg, both inclusive and a stable weight +/- 5% for at least 3 months prior to screening (evaluated by patient history or medical history documents).
• Beta-N-1-deoxy fructosyl haemoglobin (HbA1c) between 6.5 to 9%, both inclusive.
• Total insulin dose of \< 1.2 (I)U/kg/day.
• Daily dose of prandial insulin analogues or regular human insulin not exceeding 70% of total daily insulin dose at screening.
• Fasting C-peptide \<= 0.20 nmol/L.
• Daily dose of prandial insulin analogues or regular human insulin of at least 21 (I)U per day at screening.
• Stable basal-bolus insulin regimen for at least 3 months prior to screening (stable as per Investigator's discretion).
• Patients with experience in insulin titration and self-treatment of hypoglycemic events.
• Considered generally healthy (apart from conditions associated with T1DM) upon completion of medical history and screening safety assessments including safety lab results, as judged by the Investigator.

You may not qualify if:

• Use of continuous subcutaneous insulin infusion (CSII) in the last 3 months prior to screening.
• History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction.
• History of autoimmune disorders other than T1DM as judged clinically relevant by the Investigator (obtained by patient history), except a stable thyroid disorder treated with a stable dose of thyroxin.
• Hospitalization for diabetic ketoacidosis during the previous 6 months.
• More than one episode of severe hypoglycemia (as per American Diabetes Association classification) with seizure, coma or requiring assistance of another person during the past 6 months.
• Hypoglycemic unawareness (defined as individuals with a score of 3 or more \[reduced awareness and intermediate awareness\] as assessed by the Clarke score).
• Presence of clinically significant acute gastrointestinal (GI) symptoms (e.g. nausea, vomiting, heartburn or diarrhea) within 2 weeks prior to dosing, as judged by the investigator.
• Presence of chronic GI disorders or conditions known to significantly alter the absorption of orally administered drugs or significantly alter upper GI or pancreatic function, as judged by the Investigator.
• Patient with previous gastrointestinal surgery, except patients that underwent uncomplicated surgical procedures such as appendectomy, hernia surgery, biopsies, as wells as colonic- and gastric endoscopy.
• Treatment with glucagon-like peptide 1 (GLP-1) receptor agonists within the last 12 weeks prior to screening visit.
• The use of any prescribed medication that would interfere with trial endpoints or the safe completion of the trial procedures like e.g. warfarin, indomethacin or systemic non-selective ß-blocker, as judged by the investigator.
• Any clinically significant abnormality in ECG or safety laboratory tests (liver function, renal function, hematology, urinalysis or any other laboratory result judged as clinically relevant by the investigator) at screening.
• Clinically significant cardiovascular and/or cerebrovascular disease within 12 months before Screening, as judged by the Investigator.
• Active proliferative retinopathy as confirmed by ophthalmoscopy / retinal photography examination performed (by a qualified person as per local legislation) within 6 months prior to screening.
• Renal impairment with estimated Glomerular Filtration Rate (eGFR) \< 60 mL

Sponsors & Collaborators

• Biocon Limited: lead
• Profil Institut für Stoffwechselforschung GmbH: collaborator
• Juvenile Diabetes Research Foundation: collaborator

Study Sites (1)

Profil Mainz GmbH & Co. KG Malakoff-Passage,Rheinstraße 4C D-55116

Mainz, Germany

Location

Related Publications (1)

• Latres E, Plum-Moerschel L, Murugesan SMN, Lou O, Panda J, Marwah A, Samsonraj R, Gopu CL, Loganathan S, Athalye SN. 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. Diabetes Obes Metab. 2025 Jun;27(6):3154-3164. doi: 10.1111/dom.16327. Epub 2025 Apr 10.

  PMID: 40211481 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Indium-105

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Ulrike Hövelmann, MD

  Profil Institut für Stoffwechselforschung GmbH Hellersbergstraße 9 (Acting as Coordinating Investigator)

  PRINCIPAL INVESTIGATOR

• Leona Plum Mörschel, MD

  Profil Institut für Stoffwechselforschung GmbH Hellersbergstraße 9

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2019
• First Posted: October 28, 2019
• Study Start: October 28, 2019
• Primary Completion: April 23, 2021
• Study Completion: April 23, 2021
• Last Updated: June 27, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)