An investigator-initiated, comparative, two-arm, randomized, open-labelled, single centre study to evaluate the safety, tolerability and efficacy of oral insulin twice daily and oral insulin once daily along with metformin 500 mg in subjects with type 2 diabetes mellitus (dm) who are currently on insulin.
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- To assess the safety and tolerability of oral Insulin administered as a liquid oral spray in the study participants
Study Overview
Brief Summary
Background and Objectives: Diabetes mellitus encompasses a group of metabolic disorders affecting carbohydrate metabolism. It leads to inadequate utilization of glucose as an energy source and excessive glucose production due to inappropriate gluconeogenesis and glycogenolysis, resulting in hyperglycemia.
The global prevalence of diabetes has reached alarming levels, affecting 10.5% of individuals aged 20 to 79 (536.6 million people) and projected to rise to 12.2% (783.2 million) by 2045. This increase is predominantly seen in low- and middle-income countries due to the adoption of Western lifestyle habits such as sedentary behavior, physical inactivity and high-energy diet.
Diabetes diagnosis involves elevated glucose levels in venous plasma or increased glycated hemoglobin (A1C) levels. It is classified into type 1 and type 2 diabetes, gestational diabetes mellitus, and other types. Type 1 is characterized by insulin deficiency requiring lifelong insulin therapy. Insulin therapy is pivotal for managing hyperglycemia and associated metabolic disturbances like ketoacidosis and hypertriglyceridemia.
For both type 1 and type 2 diabetes (T2DM), insulin therapy plays a crucial role as the disease progresses. Basal, mealtime, and correction insulin regimens are tailored to meet individual patient needs to optimize glycemic control. Currently, insulin is administered through subcutaneous injections and this delivery system has several drawbacks including lipohypertrophy, obesity, retinopathy, hypoglycemia, neuropathy, lipoatrophy, allergic reactions and peripheral hyperinsulinemia. Also, the need to take multiple injections throughout the day can be burdensome to the patients leading to noncompliance.
Recent advancements include ultra-rapid-acting insulin formulations that enhance postprandial glucose control with reduced hypoglycemia risk compared to traditional insulin therapies. Nanomedicine offers promising solutions by improving medication targeting and stability, potentially reducing administration frequency and minimizing the risk of hypoglycemia thereby revolutionizing diabetes care. Among the various drug delivery mechanisms, Oral insulin delivery is promising as it has the potential to improve patient adherence and quality of life. The harsh conditions of the cavity pose significant challenges to the oral absorption of peptide drugs.
The investigational product is a nano-particulate liquid formulation containing nano particles encapsulating the active Human Insulin. These particles are covered by another layer of encapsulation that prevents the exposure of Insulin to harsh gastric environment.
Purpose: The purpose of this Investigator-initiated, Comparative, Two-Arm, Randomized, Open-Labelled, Single-Centre clinical trial is to evaluate the equivanlency, safety, tolerability and efficacy of an oral insulin spray administered in adults with stable type 2 diabetes (T2D). This trial aims to explore whether this novel delivery method can offer a safer and more convenient alternative to traditional insulin injections, potentially improving adherence and overall diabetes management.
Results:
Out of the 20 participants (male and female) enrolled in the age group of 18–60 years, 19 completed the study (10 in each arm - Arm A and Arm B respectively; 1 from Arm B was lost to follow-up due to relocation). The study was conducted at a single center in India. The total duration of participation per subject was approximately 100 days, including screening, 90 days of treatment, wth interim follow-up visits and End of the Study (EOS) visit.
A small pilot sample of 3 Subjects were dosed and monitored closely by the Investigator to establish the equivalence, following the accomplishment of which remaining 17 Subjects were prescribed with an adjusted dose. Participants in Arm A were instructed to use Oral Insulin Spray twice daily and those in Arm B were instructed to use Oral Insulin Spray once daily along with Metformin 500 mg. The spray was titrated to replace their injectable insulin dose.
All participants had normal physiological vital signs.
Primary Endpoiints: The liquid oral insulin spray was found to be safe and well tolerated. No serious adverse events or hypoglycemic emergencies were reported during the study. All adverse events observed were mild and self-limiting. This indicates the safety profile was in alignment with the expected tolerability of the oral insulin. No clinically significant changes were observed in vital signs or laboratory parameters supporting its use in target population.
Secondary Endpoint: Blood Glucose Levels
The study demonstrated significant improvements in glycemic control over the 90-day treatment period. In Arm A, HbA1c reduced from 8.34% to 7.41%, Fasting Blood Sugar (FBS) from 168.38 mg/dL at Baseline gradually decreased over time to 136.47 mg/dL at Day 90, and Post-Prandial Blood Sugar (PPBS) at Baseline was 217.25 mg/dL and gradually decreased to 187.84 mg/dL on Day 90. In Arm B, at Baseline, HbA1c was 8.45% which decreased to 7.9% at Day 90, FBS from 166.7 mg/dL at Baseline decreased to 141.65 mg/dL at Day 90 and PPBS from 240.03 mg/dL at Baseline decreased to 209.53 mg/dL at Day 90.
The Mean Plasma Glucose levels also showed a consistent decline across both arms from Baseline (Day 0) to Day 90, with Arm A dropping from 189 mg/dL to 164.58 mg/dL and Arm B from 202.52 mg/dL to 180.61 mg/dL, indicating better glycemic stability.
Laboratory values (hematological, liver, renal, lipid, and thyroid function parameters) remained stable throughout the study in both the Arms. Minor laboratory fluctuations were observed, but were not clinically significant. Patient compliance was 95%.with no instances of consent withdrawal or non-compliance to the Protocol except one Subject who was lost to follow-up due to relocation to another city.
These results confirm that the Oral Insulin Spray is safe, well-tolerated, and effective in improving glycemic control in Subjects with Type 2 Diabetes Mellitus. The formulation also showed promise as a patient-friendly, non-invasive alternative to injectable insulin and supports the need to conduct large-scale studies to validate these results.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Masking
- None
Eligibility Criteria
- Ages
- 18.00 Year(s) to 60.00 Year(s) (—)
- Sex
- All
Inclusion Criteria
- •Informed consent signed
- •Adults of both sex aged greter than equal to 18 and less than equal to 60 years
- •BMI greter than equal to 18 and less than equal to 33 kg/m2
- •Patients diagnosed with T2DM since more than 1 year
- •Fasting Blood Glucose greter 126mg/dL & less than 200mg/dL
- •Glycated hemoglobin HbA1c greter than equal to 7 and less than equal to 10 % at screening visit
- •Patients with total daily insulin less than equal to 30 insulin units
- •No severe hypoglycemic or ketoacidosis episode requiring third-party intervention within the past 12 months.
Exclusion Criteria
- •Subjects with Type 1 Diabetes Mellitus and C peptide less than one nanogram per milliliter.
- •Refusal or inability to provide informed consent.
- •Participation in or administration of any clinical trials or investigational drugs within thirty days before the screening visit.
- •Presence of clinically significant endocrine disease, except euthyroid subjects on stable thyroxine therapy for at least three months prior to screening.
- •Presence of Type 1 diabetes.
- •Any clinically significant condition that might interfere with the evaluation of study medication.
- •Presence or history of cancer within the past five years.
- •Subjects with Type 1 Diabetes Mellitus and C peptide less than one nanogram per milliliter, refusal or inability to provide informed consent, participation in or administration of any clinical trials or investigational drugs within thirty days before the screening visit, clinically significant endocrine disease (except euthyroid subjects on stable thyroxine therapy for at least three months prior to screening), Type 1 diabetes, any condition that might interfere with the evaluation of study medication, presence or history of cancer within the past five years, laboratory abnormalities (including C peptide less than one nanogram per milliliter, positive urine pregnancy test in females of childbearing potential.
- •Any relevant abnormality that interferes with efficacy or safety assessments during study drug administration.
- •Laboratory abnormalities include C peptide less than one nanogram per milliliter, a positive urine pregnancy test in females of childbearing potential at screening, abnormal serum thyrotropin levels at screening, a positive test for hepatitis B surface antigen or hepatitis C antibody at screening, and glycated hemoglobin (HbA1c) less than ten percent at screening.
- •Antidiabetic drugs other than metformin within three months prior to screening.
- •Thyroid preparations or thyroxine within three months prior to screening.
- •Systemic long-acting corticosteroids within two months or prolonged use of other systemic corticosteroids or inhaled corticosteroids (daily dosage less than one thousand milligrams equivalent beclomethasone) within thirty days prior to screening.
- •Pregnancy or breastfeeding.
- •Current tobacco use of more than ten cigarettes per day or equivalent.
- •Known allergy to some insulins.
- •Clarkes score greater than or equal to four
- •Severe late complications of diabetes, including severe neuropathy, nonstabilized proliferative retinopathy, estimated glomerular filtration rate less than fortyfive milliliters per minute, myocardial infarction, or stroke within the last three months.
- •Planned travel within fifteen days of the study.
- •Persons under guardianship or incapable of judgment.
Outcomes
Primary Outcomes
To assess the safety and tolerability of oral Insulin administered as a liquid oral spray in the study participants
Time Frame: Day -3, Day 1, Day 14, Day 30, Day 60, Day 90, Day 97
Secondary Outcomes
- 1. Proportion of participants with treatment emergent AEs TEAEs and laboratory abnormalities(2. Proportion of participants with TEAEs leading to study treatment discontinuation)
Investigators
Dr Manjunath U
Currex Hospital, Bengaluru