None listed
Conditions
Brief summary
Semaglutide is a long-acting GLP-1 analogue used in the treatment of patients with type 2 diabetes (T2D), and has shown to improve glycaemic control and result in meaningful weight loss. The drug has a well described safety profile including a low risk of hypoglycaemia. Tirzepatide is a glucagon-like peptide 1 (GLP-1) receptor agonist and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, and has robust glucose-lowering and weight loss effects. This short duration pilot study will compare the biological activity of a single dose of 4 mg of oral semaglutide with 25 mg oral tirzepatide, both in Diabetology’s Axcess formulation. Five healthy volunteers will receive 4 mg of the encapsulated semaglutide on an empty stomach with a glass of 100 mL of water, on Day 0. Five additional healthy volunteers will receive 25 mg of the encapsulated tirzepatide on an empty stomach with a glass of 100 mL of water, on Day 0. Each participant would also receive a placebo 2 days prior to this (Day -2). Both the placebo and the semaglutide or tirzepatide will be administered at the same time of day, in a fasting state. An intravenous glucose tolerance test (IVGTT) will be conducted two hours after placebo and treatment, before any food is consumed. The IVGTT will also be performed at approximately the same time on days 1, 4 and 6 post-treatment. The primary aim of the study is to determine whether a single dose of orally delivered encapsulated semaglutide or tirzepatide is associated with a difference in plasma blood glucose levels during an intravenous glucose tolerance test (IVGTT). The secondary aims are to 1) explore changes in serum insulin during an IVGTT, and 2) to explore the duration of action over a span of 7 days.
Interventions
Semaglutide is a long-acting GLP-1 analogue used in the treatment of patients with type 2 diabetes (T2D), and has shown to improve glycaemic control and result in meaningful weight loss. The drug has a well described safety profile including a low risk of hypoglycaemia. Tirzepatide is a glucagon-like peptide 1 (GLP-1) receptor agonist and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, and has robust glucose-lowering and weight loss effects.
This short duration pilot study w
Semaglutide is a long-acting GLP-1 analogue used in the treatment of patients with type 2 diabetes (T2D), and has shown to improve glycaemic control and result in meaningful weight loss. The drug has a well described safety profile including a low risk of hypoglycaemia. Tirzepatide is a glucagon-like peptide 1 (GLP-1) receptor agonist and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, and has robust glucose-lowering and weight loss effects. This short duration pilot study will compare the biological activity of a single dose of 4 mg of oral semaglutide with 25 mg oral tirzepatide, both in Diabetology’s Axcess formulation. Five healthy volunteers will receive 4 mg of the encapsulated semaglutide on an empty stomach with a glass of 100 mL of water, on Day 0. Five additional healthy volunteers will receive 25 mg of the encapsulated tirzepatide on an empty stomach with a glass of 100 mL of water, on Day 0. Each participant would also receive a placebo 2 days prior to this (Day -2). Both the placebo and the semaglutide or tirzepatide will be administered at the same time of day, in a fasting state. An intravenous glucose tolerance test (IVGTT) will be conducted two hours after placebo and treatment, before any food is consumed. The IVGTT will also be performed at approximately the same time on days 1, 4 and 6 post-treatment. Participants are allocated 1:1 to receive either semaglutide or tirzepatide, with allocation turn-based (i.e. semaglutide, tirzepatide, semaglutide, ...). The primary aim of the study is to determine whether a single dose of orally delivered encapsulated semaglutide or tirzepatide is associated with a difference in plasma blood glucose levels during an intravenous glucose tolerance test (IVGTT). The secondary aims are to 1) explore changes in serum insulin during an IVGTT, and 2) to explore the duration of action over a span of 7 days. Screening visit: Will occur within 2 weeks of placebo. Prospective participants will have their medical history assessed and have 8 mLs of blood drawn to confirm inclusion criteria. Eligible participants will be informed that their General Practitioners will be notified of their enrolment in the study. Visit Day -2: An intravenous glucose tolerance test (IVGTT) will be performed in the morning of Day -2 with the participant having fasted for 10h, except for water. During this time, they are also to abstain from cigarettes, alcohol, caffeine, and vigorous exercise. All participants will receive one placebo capsule (capsule containing excipients only, i.e. formulation ingredients minus the semaglutide or tirzepatide (active ingredient)) with a glass of 100mL water. The IVGTT testing will be conducted by an experienced clinical research nurse, two hours after placebo and before any food is consumed. It will involve an intravenous administration of 0.5g/kg of intravenous glucose (50% sterile solution); to a maximum dose of 35g. Blood samples (32mls of blood) for serum total insulin and plasma glucose levels will be collected at 5min and 0min pre-glucose IV administration, and 5-, 15-, 25-, 35-, 45-, and 60 min post-glucose IV administration. The IV glucose is administered over 3mins. Subjects will be provided with a questionnaire (adverse event log) on Day-2 to be used for recording any potential study-related effects (e.g.: nausea, vomiting, diarrhoea, headache, vision irregularities, hunger, loss of appetite). The clinician will review this record at each subsequent visit to determine whether any of these signs are treatment related, and to ascertain the history of treatment emergent and concomitant medicines. Visit Day 0: The IVTT procedure for Day 0 will be performed at approximately the same time as Day -2 and the placebo will be replaced with a once off semaglutide or tirzepatide capsule (containing the same excipients as the placebo but with 4 mg of Semaglutide or 25 mg of Tirzepatide (active ingredient)). The clinician will review the adverse event log to determine whether any of these signs are treatment related. Visit Days 1, 4 and 6: The IVTT procedure will also be performed on Days 1, 4, and 6 at approximately the same time as on days -2 and 0. No capsules will be administered on these days. The clinician will review the adverse event log at each visit. Study participation is voluntary, and participants may withdraw at any time. Those who withdraw from the study after commencing on oral semaglutide or tirzepatide will be followed-up for adverse events and concomitant medications for the full week after taking the semaglutide. Should any treatment-emergent adverse events be reported, this will also be included in the Data and Safety Monitoring Board (DSMB) report. Participants who withdraw from the study will need to be replaced, as the study is powered for a sample size of 10 with completed data. Both placebo and oral semaglutide or tirzepatide capsules will be administered during the clinic visit. The clinical diabetes research nurse will ensure that participants ingest the whole capsule at their respective visit.
Sponsors
The Kids Research Institute Australia
Study design
Allocation
Non-randomised trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
•Adequate renal function defined as a GFR greater than or equal to 30 mL/min/1.73m2. •Female patients of childbearing potential must have a negative serum pregnancy test at screening and practice effective birth control for the duration of the trial. •Male patients must agree to practice effective contraceptive methods during the course of the study. •Are able and willing to sign an informed consent to participate in the study. •Able and willing to adhere to the study requirements, specifically: follow the study visit and assessment schedules, take the study medications as indicated.
Exclusion criteria
•Type 1 diabetes •Type 2 diabetes •Diabetes attributable to other secondary causes (e.g., genetic syndromes, secondary pancreatic diabetes, diabetes due to endocrinopathies, drug- or chemical-induced, and post-organ transplant). •Treatment involving GLP-1 receptor agonists within 3 months prior to Visit 1. •Have a history of acute or chronic pancreatitis. •Have a known clinically significant gastric emptying abnormality (e.g., severe diabetic gastroparesis or gastric outlet obstruction). •Have undergone or plan to have bariatric surgery during the course of the study. •Have uncontrolled hypertension defined as SBP/DBP greater than or equal to 160/100 mmHg. •Have a history of cardiac disease. •Have an estimated GFR < 30 mL/min/1.73m2 •Any condition that is currently being treated or may be treated with systemic corticosteroids or biologics during the course of the study; topical, intra-nasal and inhaled corticosteroids are allowed. •Any current or history of any condition that may affect the patient’s participation in the study. •Any current or history of any condition that in the opinion of the investigator participation in the study may increase the risk to the patient. •Female patients that are pregnant or are breastfeeding or plan to breastfeed during the course of the study. •Laboratory abnormalities at screening including: o C-peptide < 0.4 ng/mL o Abnormal serum thyrotropin (TSH) levels below the lower limit of normal or >1.5X the upper limit of normal; a single repeat test is allowable. o Elevated liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) >3X the upper limit of normal; a single repeat test is allowable. o Very high fasting triglyceride levels (>600 mg/dL); a single repeat test is allowable. •Any relevant abnormality that would interfere with the study assessments. •History of or current active liver disease (other than non-alcoholic hepatic steatosis), primary biliary cirrhosis, or active symptomatic gallbladder disease. •Positive results for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus ribonucleic acid (RNA). •Active or history of neoplastic disease (except for adequately treated non-invasive basal cell and/or squamous cell carcinoma or carcinoma in situ of the cervix) within the past 5 years prior to Baseline. •Use of the following medications: o Thyroid preparations or thyroxine (except in subjects on stable replacement therapy) within 6 weeks prior to screening. o Systemic (oral, intravenous, intramuscular) glucocorticoid therapy (in the last 12 months) or may require them for more than 2 weeks during the study period. Intra-articular and/or topical corticosteroids are not considered systemic. o Any medications known to modify glucose metabolism or to decrease the ability to recover from hypoglycemia such as oral, parenteral, and immunosuppressive or immunomodulating agents. Inhaled nasal steroids are permissible. •Involvement in a weight loss program and is not in the maintenance phase, or subject has started weight loss medication (e.g., orlistat or liraglutide) within 3 months prior to screening. •Subject is a user of recreational or illicit drugs or has had a recent history (within 1 year of screening) 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) at screening. Occasional intermittent use of cannabinoid products will be allowed provided that no cannabinoid products have been used during the 1 week prior to each visit. •A history of gastrointestinal disorders (e.g., hypochlorhydria) or gastroparesis with the potential to interfere with drug absorption. •Any condition or other factor (at the Investigator's discretion) that is deemed unsuitable for subject enrolment into the study. •Enrolled in another clinical trial involving an investigational product within 30 days of the screening visit. •Is not able to understand and sign the informed consent of the study.
Outcome results
None listed