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
- Conditions
- Type 2 Diabetes MellitusMetabolic and Endocrine - Diabetes
- Registration Number
- ACTRN12620001214921
- Lead Sponsor
- CMC Magnetics Corporation
- Brief Summary
This was a 2-center, Phase 1, placebo-controlled, randomized, double-blind, single and multiple ascending dose study, with formulation bridging and bioavailability cohorts. The study included following parts: Part 1 – Single ascending doses and food-effect study (Cohorts 1 through 5), Part 2 – Formulation bridging cohort (on the basis of SRC review this part was not conducted), Part 3 – Multiple ascending doses: healthy Cohort 6 and patient Cohorts 7 through 9, and Part 4 – Bioavailability cohort. In Part 1, 40 subjects were randomized, and 38 subjects were able to complete the study. In Part 3 and 4, in total 32 and 12 subjects were randomized and completed the study, respectively. In Part 1, 9 of 40 subjects (22.5%) experienced 11 TEAEs related to the study drug (headache, dizziness, nausea, flatulence, and decreased appetite [ALP001E]; migraine, fatigue, and rash [Placebo]). The most frequently experienced treatment-related TEAE in Part 1 was nausea (3 of 40 subjects [7.5%]; all 3 events possibly related to ALP001E). In Part 3, 12 of 32 subjects (37.5%) experienced 25 TEAEs related to the study drug (abdominal pain lower, memory impairment, somnolence, ALT increased, and pyuria [ALP001E]; nausea, diarrhea, abdominal discomfort, abdominal distension, abdominal pain, constipation, and dizziness [ALP001E and Placebo]; and headache [Placebo]). The most frequently experienced treatment-related TEAE in Part 3 was nausea (4 of 32 subjects [12.5%]; 2 events possibly related to ALP001E; 1 event probably related to ALP001E; 1 event possibly related to placebo). In Part 4, 1 of 12 subjects (8.3%) experienced 1 TEAE of headache related to the Test treatment (test formulation: four 20 mg ALP001 dried granulation capsules). There were no deaths or SAEs reported during the study and no subjects were discontinued from the study due to a TEAE in any part of the study. In all parts, no dose-related trends were observed for liver function tests, lipid profile, blood pressure, or vital signs. Overall, ALP001E was safe and generally well tolerated by heathy subjects in the SAD and MAD cohorts and by diabetic patients in the MAD cohorts. Both formulations of ALP001E 80 mg (reference formulation: spray dried powder capsules; test formulation: granulation capsules) were safe and well tolerated by the healthy subjects.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 84
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.
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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method