Study to Evaluate the Safety and Efficacy of Oral Insulin Formulation in Type 2 Diabetes Mellitus Subjects

A Phase 2b, Open-label Randomized Comparative Study to Evaluate the Safety and Efficacy of Oral Insulin Formulation in Type 2 Diabetes Mellitus Subjects Uncontrolled With Metformin Hydrochloride Treatment

The aim of the study was to compare the pharmacodynamic properties of different doses of regular human insulin administered in capsule form twice daily in a randomised twelve-week open-label trial.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Treated With Insulin
• Intervention / Treatment: Drug: Oral insulin

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, NW1 0NH
    • Diabetology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female aged 35 to 60 years (both inclusive)
2. Type 2 diabetes mellitus diagnosed < 2 years prior to enrolment
3. Glycated haemoglobin level ≥ 7% and ≤ 9.5%
4. On stable oral monotherapy with metformin hydrochloride (1000 mg to 2500 mg/day) and regular diet and exercise regimen at least 12 weeks prior to enrolment
5. Body mass index between 18 to 30 kg/m2
6. Ability to perform capillary blood glucose measurements
7. Willing to provide informed and written consent for the clinical trial
8. Able to comply with all requirements of clinical trial protocol

Exclusion Criteria:

1. Subject with history or evidence of hypersensitivity to insulin or metformin hydrochloride or its excipients
2. Suffering from type 1 diabetes mellitus
3. Received treatment with sulphonylureas or alpha-glucosidase inhibitors, Glucagonlike peptide-1 (GLP-1) receptor agonists or Sodium-glucose co-transporter 2 (SGLT2) inhibitors or meglitinides or pramlintide or thiazolidinediones within 3 months prior to enrolment
4. Previously treated with insulin within 3 months prior to enrolment
5. History of episodes of hypoglycaemia during 3 months prior to enrolment.
6. Reduced awareness of hypoglycaemia or inability to identify and tackle hypoglycaemic episodes
7. History of substantial weight loss defined as 5% decrease in body weight within the last 6 months
8. Medical history of unstable angina within 1 year prior to enrolment
9. History of tobacco or nicotine more than two packs/day within 3 months prior to enrolment
10. Is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within 1 year prior to enrolment) of drug or alcohol abuse or dependence. (Note: Alcohol abuse includes heavy alcohol intake as defined by >3 drinks per day or >14 drinks per week, or binge drinking).
11. History of gastrointestinal disorders which may potentially interfere with absorption of the investigational product
12. Treatment with systemic corticosteroids or with inhalational corticosteroids (Beclomethasone or budesonide) within the 3 months prior to enrolment
13. Likelihood of requiring treatment during the study period with prohibited medications mentioned (as defined in this clinical trial protocol)
14. Female subject who is pregnant, lactating or planning pregnancy during the trial
15. Female subject of childbearing age who is not willing to use adequate method of contraception during the study period
16. Life expectancy of less than 6 months from screening
17. Elective surgery or any other surgical procedure/s requiring general anaesthesia during the clinical trial
18. Has participated in another research trial within 12 weeks prior to screening

19. History of diabetic ketoacidosis requiring hospitalization within 6 months prior to enrolment, case of proliferative retinopathy or advanced neuropathy

    1. Subject having any of the following laboratory results at screening
    2. Estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2
    3. Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) >3 times of upper limit normal
20. Blood urea nitrogen (BUN) > 30 mg/dL
21. Subject who has a positive serology for hepatitis B virus (HBV) or hepatitis C (HCV) or human immunodeficiency virus (HIV) infections at screening
22. Subject who has undergone pancreatectomy or pancreas islet transplant or renal transplant
23. Subject receiving or has received any immunomodulation medications within 1 year prior to enrolment
24. Subject with history or evidence of diabetic complications (e.g. diabetic retinopathy, diabetic neuropathy, or diabetic nephropathy, etc.), cardiac disorders, or any other systemic complication due to diabetes, which in the opinion of the Investigator signifies subjects' ineligibility for the trial
25. Has any concurrent disease or medical/surgical condition, which required treatment of more than 3 months and which in the opinion of the Investigator does not allow participation of the subject in this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 75iu; Capsule containing 75iu recombinant human insulin administered two times per day	Drug: Oral insulin; Capsule administered by mouth with a glass of water two times per day, once before breakfast and once before supper
Experimental: 150iu; Capsule containing 150iu recombinant human insulin administered two times per day	Drug: Oral insulin; Capsule administered by mouth with a glass of water two times per day, once before breakfast and once before supper
Experimental: 300iu; Capsule containing 300iu recombinant human insulin administered two times per day	Drug: Oral insulin; Capsule administered by mouth with a glass of water two times per day, once before breakfast and once before supper

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fall in HbA1c	Fall in HbA1c	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fasting Plasma Glucose	Change in Fasting Plasma Glucose	12 weeks
Change in Post-Prandial Glucose	Change in Post-Prandial Glucose	12 weeks
Changes in Lipids	Change in plasma cholesterol and triglyceride	12 weeks

Collaborators and Investigators

• Sponsor: Roger New

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2018
• Primary Completion (Actual): July 11, 2020
• Study Completion (Actual): July 11, 2020

Study Registration Dates

• First Submitted: June 19, 2024
• First Submitted That Met QC Criteria: June 19, 2024
• First Posted (Actual): June 25, 2024

Study Record Updates

• Last Update Posted (Actual): June 25, 2024
• Last Update Submitted That Met QC Criteria: June 19, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: Diabetology Ltd

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No