Type 2 Diabetes Treated With Insulin
Conditions
Brief summary
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.
Interventions
DRUGOral insulin
Capsule administered by mouth with a glass of water two times per day, once before breakfast and once before supper
Sponsors
Roger New
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A randomised twelve-week open-label study.
Eligibility
Sex/Gender
ALL
Age
35 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c | 12 weeks | Change in HbA1c Relative to Baseline at Start of Study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fasting Plasma Glucose | 12 weeks | Change in Fasting Plasma Glucose Relative to Baseline at Start of Study |
| Change in Post-Prandial Glucose | 12 weeks | Change in Post-Prandial Glucose Relative to Baseline at Start of study |
| Changes in Triglycerides | 12 weeks | Change in Triglycerides Relative to Baseline at Start of Study |
Countries
United Kingdom
Participant flow
Recruitment details
204 patients were assessed for eligibility - 51 did not meet the inclusion criteria. Recruitment was conducted in hospital clinics and commenced one month before the start of study in October 2018
Pre-assignment details
153 patients were randomised to allocated treatment groups. A proportion of these patients (7) did not commence treatment, and full baseline characteristics were not collected for the whole group
Participants by arm
| Arm | Count |
|---|---|
| 75iu Capsule containing 75iu recombinant human insulin administered two times per day
Oral insulin: Capsule administered by mouth with a glass of water two times per day, once before breakfast and once before supper | 33 |
| 150iu Capsule containing 150iu recombinant human insulin administered two times per day
Oral insulin: Capsule administered by mouth with a glass of water two times per day, once before breakfast and once before supper | 29 |
| 300iu Capsule containing 300iu recombinant human insulin administered two times per day
Oral insulin: Capsule administered by mouth with a glass of water two times per day, once before breakfast and once before supper | 38 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Did not take medication | 2 | 3 | 2 |
| Overall Study | No data from Central lab (protocol violation) | 14 | 9 | 4 |
| Overall Study | Starting HbA1c below 7% | 0 | 1 | 1 |
| Overall Study | Uncontrolled hyperglycaemia | 1 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 6 | 5 |
Baseline characteristics
| Characteristic | 150iu | 300iu | Total | 75iu |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants | 38 Participants | 100 Participants | 33 Participants |
| Age, Customized | 46.6 years STANDARD_DEVIATION 6.3 | 49.7 years STANDARD_DEVIATION 7.1 | 48.5 years STANDARD_DEVIATION 6.7 | 48.8 years STANDARD_DEVIATION 6.4 |
| BMI (kg/m2) | 25.8 kg/m2 STANDARD_DEVIATION 2.7 | 25.7 kg/m2 STANDARD_DEVIATION 2.9 | 25.7 kg/m2 STANDARD_DEVIATION 2.8 | 25.6 kg/m2 STANDARD_DEVIATION 3 |
| Body weight (kg) | 66.1 kg STANDARD_DEVIATION 8.8 | 66.9 kg STANDARD_DEVIATION 12.5 | 65.7 kg STANDARD_DEVIATION 10.2 | 63.9 kg STANDARD_DEVIATION 8.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 38 Participants | 100 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Fasting plasma glucose (mg/dL) | 148.2 mg/dL STANDARD_DEVIATION 39 | 136.7 mg/dL STANDARD_DEVIATION 47.8 | 144.0 mg/dL STANDARD_DEVIATION 47.2 | 148.8 mg/dL STANDARD_DEVIATION 53 |
| HbA1c (%) | 8.13 % STANDARD_DEVIATION 0.65 | 7.93 % STANDARD_DEVIATION 0.61 | 8.1 % STANDARD_DEVIATION 0.65 | 8.27 % STANDARD_DEVIATION 0.66 |
| Region of Enrollment India | 29 participants | 38 participants | 100 participants | 33 participants |
| Sex: Female, Male Female | 16 Participants | 16 Participants | 52 Participants | 20 Participants |
| Sex: Female, Male Male | 13 Participants | 22 Participants | 48 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 29 | 0 / 38 |
| other Total, other adverse events | 0 / 33 | 0 / 29 | 0 / 38 |
| serious Total, serious adverse events | 0 / 33 | 0 / 29 | 0 / 38 |
Outcome results
Primary
Change in HbA1c
Change in HbA1c Relative to Baseline at Start of Study
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 75iu | Change in HbA1c | -0.20 % of glycated haemoglobin | Standard Deviation 1.06 |
| 150iu | Change in HbA1c | -0.53 % of glycated haemoglobin | Standard Deviation 1.04 |
| 300iu | Change in HbA1c | -0.31 % of glycated haemoglobin | Standard Deviation 1.04 |
p-value: 0.0039t-test, 2 sided
Secondary
Change in Fasting Plasma Glucose
Change in Fasting Plasma Glucose Relative to Baseline at Start of Study
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 75iu | Change in Fasting Plasma Glucose | -14.8 mg/dL | Standard Deviation 53.6 |
| 150iu | Change in Fasting Plasma Glucose | -18.8 mg/dL | Standard Deviation 39.8 |
| 300iu | Change in Fasting Plasma Glucose | -2.7 mg/dL | Standard Deviation 60.09 |
p-value: 0.0166t-test, 2 sided
Secondary
Change in Post-Prandial Glucose
Change in Post-Prandial Glucose Relative to Baseline at Start of study
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 75iu | Change in Post-Prandial Glucose | -17.4 mg/dL | Standard Deviation 83.74 |
| 150iu | Change in Post-Prandial Glucose | -21.0 mg/dL | Standard Deviation 86.4 |
| 300iu | Change in Post-Prandial Glucose | -31.0 mg/dL | Standard Deviation 97.7 |
Secondary
Changes in Triglycerides
Change in Triglycerides Relative to Baseline at Start of Study
Time frame: 12 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 75iu | Changes in Triglycerides | -7.06 mg/dL | Standard Error 10.23 |
| 150iu | Changes in Triglycerides | -22.13 mg/dL | Standard Error 11.02 |
| 300iu | Changes in Triglycerides | 20.56 mg/dL | Standard Error 9.61 |
p-value: 0.0474ANCOVA