Bioavailability, Biopotency and Food Effect Study of SCD0503 Compared to Subcutaneous Regular Human Insulin

Официальное название

A Trial to Investigate the Relative Bioavailability, Relative Biopotency and Food Effect of SCD0503 (Oral Insulin) in Comparison to Subcutaneous Regular Human Insulin Under Euglycaemic Clamp Conditions and After Food Intake in People With Type I Diabetes

Обзор

Reason for the study The participants have been diagnosed with type 1 diabetes and are being treated with standard insulin therapy. The sponsor of the study is developing a new insulin-based medicine that can be taken by mouth (orally). For this reason, the investigational product named SCD0503 is to be tested in the study. The sponsor wants to investigate the course of blood concentrations and the blood sugar-lowering effect of the investigational product and to find out whether SCD0503 is safe. Investigational product tested in this study The investigational product tested, SCD0503, is still under clinical evaluation and has not yet been approved for your treatment. The active ingredient is regular human insulin, which has been used for many years in approved medicines for the treatment of diabetes. SCD0503 is being used in humans for the first time in this study. Study procedures The study will last for approximately 1 to 4 months. During this time, the participant will come to the investigational site 8 times for visits. During 4 visits the participant will undergo a clamp examination. The blood sugar-lowering effect of the investigational product is determined using a clamp device, a computer-controlled device that maintains blood sugar at a constant level within the normal range. This is achieved by infusing a sugar solution. During 2 further visits the participant will have a meal test. During the meal test, the blood sugar-lowering effect of the investigational product is determined after intake of a standardized meal as breakfast. You will have catheters in your arms to take blood, measure your blood sugar level and to infuse glucose (sugar) or insulin, if needed. SCD0503 is compared with a regular human insulin already approved for the treatment of diabetes. The participant will receive SCD0503 and the comparator product during different visits to the investigational site. The participant will also receive a placebo together with the investigational or the comparator product. The placebo looks identical but contains no active ingredient. As the investigational product is administered orally and the comparator product is injected under the skin, two placebos are used in this study. The order of medications given will be decided by chance, using a pre-defined method called randomization (a procedure similar to flipping a coin). Neither the participant nor the study physician will know which of the 2 medicines is administered at the respective dosing occasion. However, in case of emergency, this information will be quickly available.

Вмешательства

• Биопрепарат oral insulin
  test product
• Другое Placebo A
  placebo for test product
• Биопрепарат subcutaneous insulin
  reference product/comparator
• Другое Placebo B
  placebo for reference product

Первичные конечные точки

• AUCins.0-6h, area under the serum insulin concentration curve from 0 to 6 hours [Срок оценки: From enrollment to the end of treatment in 4 months]
• Cins.max, maximum observed insulin concentration [Срок оценки: From enrollment to the end of treatment in 4 months]
• AUCGIR.0-6h, area under the insulin concentration-time curve from 0 to 6 hours [Срок оценки: From enrollment to the end of treatment in 4 months]
• GRELcl, Relative biopotency (will be derived of the dose corrected ratio of AUCGIR.0-6h for oral and sc insulin) [Срок оценки: From enrollment to the end of treatment in 4 months]

Вторичные конечные точки (12)

• AUCins.0-1h, AUCins.0-2h, AUCins.0-4h, areas under the serum insulin concentration curve in the indicated time intervals [Срок оценки: From enrollment to the end of treatment in 4 months]
• tmax.ins., time to maximum observed insulin concentration [Срок оценки: From enrollment to the end of treatment in 4 months]
• λz, terminal elimination rate constant of insulin [Срок оценки: From enrollment to the end of treatment in 4 months]
• t½ is the terminal serum elimination half-life calculated as t½=ln2/λz [Срок оценки: From enrollment to the end of treatment in 4 months]
• MRT, Mean residence time (h) [Срок оценки: From enrollment to the end of treatment in 4 months]
• CL/F, Systemic clearance after oral administration (mL/min) [Срок оценки: From enrollment to the end of treatment in 4 months]
• V/F, volume of distribution (L) [Срок оценки: From enrollment to the end of treatment in 4 months]
• FRELcl, Relative bioavailability (will be derived from the dose corrected ratio of AUCins.0-6h for oral and sc insulin) [Срок оценки: From enrollment to the end of treatment in 4 months]
• Cins.max.fed, maximum observed insulin concentration after meal test [Срок оценки: From enrollment to the end of treatment in 4 months]
• AUCins.fed.0-1h, AUCins.fed.0-2h, AUCins.fed.0-4h, AUCins.fed.0-6h, areas under the serum insulin concentration curve in the indicated time intervals after meal test [Срок оценки: From enrollment to the end of treatment in 4 months]
• FRELfed, Relative bioavailability (will be derived of the dose corrected ratio of AUCins.fed.0-6 for oral and sc insulin) [Срок оценки: From enrollment to the end of treatment in 4 months]
• Food effect is investigated by comparing the total and maximum oral insulin exposure in the fasted state and after food intake [Срок оценки: From enrollment to the end of treatment in 4 months]

Критерии участия

Критерии включения

• Male person with type 1 diabetes mellitus
• Age between 18 and 64 years, both inclusive
• Body Mass Index (BMI) between 18.5 and 29.9 kg/m2, both inclusive
• HbA1c ≤ 8.5%
• Fasting C-peptide <= 0.20 nmol/L
• Total insulin dose of <1.2 (I)U/kg/day
• Diabetes duration of at least 12 months at the time of screening
• Stable insulin regimen for at least 2 months prior to inclusion into the trial

Критерии исключения

• Systolic blood pressure < 90 mmHg or >139 mmHg and/or diastolic blood pressure < 50 mmHg or > 89 mmHg
• Heart rate at rest outside the range of 50- 90 beats per minute
• Clinically significant abnormal standard 12-lead electrocardiogram (ECG) after 5 minutes resting in supine position at screening
• Proliferative retinopathy or maculopathy as judged by the investigator based on a recent (<1 year) ophthalmologic examination
• Peripheral neuropathy
• More than one episode of severe hypoglycaemia with seizure, coma or requiring assistance of another person during the past 6 months pior to screening
• Hospitalisation for diabetic ketoacidosis during the previous 6 months prior to screening
• Significant history of alcoholism or drug abuse
• Smoking more than 5 cigarettes or the equivalent per day
• Tested positive for hepatitis Bs antigen
• Tested positive for hepatitis C antibodies
• Positive result to the test for HIV-1/2 antibodies or HIV-1 antigen
• Estimated glomerular filtration rate (eGFR) < 60.0 mL/min/1.73m2

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Двойное слепое

Основная цель

Фундаментальное исследование

Центры проведения

Германия · 1 центр

• Profil Institut für Stoffwechselforschung GmbH — Neuss

Идентификаторы

NCT: NCT07634770 · SCD-4E001 · 2024-519502-12

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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