A Phase I, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of ALP001E in Healthy Subjects and Patients with Type 2 Diabetes
CMC Magnetics Corporation
96 participants
Feb 3, 2021
Interventional
Conditions
Summary
This study is the first clinical study conducted with ALP001E and is designed to assess the safety and tolerability, pharmacokinetics (how the drug is absorbed by the body) and pharmacodynamics (the effect the drug has on the body) of ALP001E when administered as single and multiple ascending doses in healthy participants and as multiple doses in patient with type 2 diabetes mellitus. The study will start with a low single dose and safety information will be reviewed by a safety review committee to confirm if higher doses can be given to sequential cohorts before giving multiple doses.
Eligibility
Inclusion Criteria15
- All study participates:
- body weight greater than or equal to 50.0 kg for males and greater than or equal to 45.0 kg for females
- non-smokers
- Females of childbearing potential and male subjects who are not vasectomized for at least 6 months who are sexually active must be willing to use acceptable contraceptive method throughout the study (from the screening) and for 30 days after the last study drug administration.
- Healthy volunteers:
- Body mass index (BMI) > 18.5 and < 30.0 kg/m^2
- the absence of clinically significant illness and surgery within 4 weeks prior to first dosing
- the absence of significant history of biliary tract disease
- has FPG between 70 mg/dL and 110 mg/dL (3.9 to 6.1 mmol/L) (inclusive)
- Type 2 Diabetics Patients:
- BMI between 20 and 42 kg/m^2;
- Subjects with established diagnosis of T2DM of at least 1 year duration at the time of screening;
- FPG greater than or equal to 6.94 mmol/L and less than or equal to 14.43 mmol/dL (260 mg/dL) at screening;
- Subjects must be on a stable dose of metformin for greater than or equal to 12 weeks without use of other antidiabetic medications for >3 weeks prior to randomization and maintain the dose until the end of the study;
- HbA1C greater than or equal to 6.5 and less than or equal to 10% at screening.
Exclusion Criteria9
- All study participates:
- Any confirmed clinically significant abnormality at physical examination, clinically significant abnormal laboratory test results or positive test for hepatitis B, hepatitis C, or HIV found during medical screening.
- Evidence of clinically significant hepatic, biliary tract disease or renal impairment including ALT and AST > 10% × ULN; creatinine clearance levels (Cockcroft Gault of <60mL, min); serum triglyceride level > 4.52 mmol/L (>400 mg/dL), total bilirubin is above ULN.
- Use of medications, with the exception of hormonal contraceptives and medications exempted by the Investigator on a case-by-case basis because they are judged unlikely to affect the pharmacokinetic profile of the study drug or subject safety (e.g., topical drug products without significant systemic absorption).
- Healthy volunteers:
- Clinically significant electrocardiogram (ECG) abnormalities or vital sign abnormalities (systolic blood pressure lower than 90 or over 140 mmHg, diastolic blood pressure lower than 50 or over 90 mmHg, or heart rate less than 40 or over 100 bpm) at screening
- Type 2 Diabetics Patients:
- Type 1 diabetes mellitus, maturity-onset diabetes of the young or any rare form of diabetes other than type 2, hyperglycemia due to secondary causes such as hyperadrenocorticalism caused by Cushing’s syndrome, pheochromocytoma, acromegaly or untreated hyperthyroidism
- Clinically significant ECG abnormalities or vital sign abnormalities (systolic blood pressure lower than 90 or over 150 mmHg, diastolic blood pressure lower than 50 or over 95 mmHg, or heart rate less than 40 or over 100 bpm) at screening.
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Interventions
Part 1 – Single ascending doses and food-effect: Cohorts 1 to 5 Planned a single oral dose of ALP001E capsules under fasting conditions: 25 mg, 75 mg, 150 mg, 300 mg, 600 mg. Subjects from Cohort 3 will be administered the same dose in a second period after ingestion of a high-fat meal. Subjects will be served a high-fat, high-caloric meal of approximately 800 to 1000 calories (approximately 50% of total caloric content of the meal derived from fat). This test meal should derive approximately 150, 250, and 500-600 calories from protein, carbohydrate, and fat, respectively. An example would be a meal consisting of two eggs fried in butter, 2 slices of toast with butter, 2 strips of bacon, approximately 120 g of hash brown potatoes, and 240 mL of whole milk. Part 2 – Formulation bridging cohort (if needed) If needed, one dose level is planned for Part 2 after evaluation of bioavailability and safety data of Cohort 3 of Part 1 as determined by the SRC. In this bridging cohort, dose in suspension will be then repeated using a lower step down dose administered in previous cohort, final dose to be determined by dose escalation committee based on preceding safety and PK data. A single oral dose of ALP001E given by staff in the study unit. Part 3 – Multiple ascending doses: Healthy Cohort 6 and type 2 diabetes (T2DM) Cohort 7 to 9 Planned dose of ALP001E capsules to healthy volunteers (Cohorts 6): 150 mg Planned dose of ALP001E capsules to T2DM (Cohorts 7 to 9): 50 mg, 100 mg, and 150 mg Oral given by staff in the study unit once daily for 14 days. The strategies of adherence to the doses: For Part 1, Study medication capsules will be administered to each subject with approximately 240 mL of water. For Part 2 (if needed), suspension formulation will be prepared and orally administered to study subjects. For Part 3, drug administration will be done at the same time every day. A hand and mouth check will be performed to ensure consumption of the medication to all subjects.
Locations(1)
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ACTRN12620001214921