A Randomized, Double-Blind, Placebo-Controlled, Single and Repeated Dose Escalation, First-Time-In-Human Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ECC5004 in Healthy Participants and in Patients With Type 2 Diabetes Mellitus
Overview
- Phase
- Phase 1
- Intervention
- Placebo
- Conditions
- Type 2 Diabetes Mellitus
- Sponsor
- Eccogene
- Enrollment
- 69
- Locations
- 1
- Primary Endpoint
- Number of participants with adverse events, with abnormal laboratory test results, abnormal ECGs, abnormal vital signs, and abnormal physical examinations
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose and multiple ascending dose study of ECC5004 in healthy participants and in patients with Type 2 Diabetes Mellitus
Detailed Description
This study will be conducted in two cohorts of Single Ascending Dose (SAD) with a dose range from 1mg to 300mg, and in four cohorts of Multiple Ascending Dose (MAD) with a dose range of 10mg to 150mg to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ECC5004 in Healthy Participants and in Patients with Type 2 Diabetes Mellitus
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy male and female participants of non-childbearing potential
- •Age of 18 to 65 years
- •BMI of 18.0 to 32.0 kg/m2
- •Hemoglobin A1c ≤ 6.0%
- •Female participants who are postmenopausal, confirmed by FSH test, or surgically sterile, confirmed by medical documentation, or agree to practice true abstinence
- •Male participants agree to use contraception, or agree to practice true abstinence
- •No clinically significant findings in physical examination, 12-lead electrocardiogram (ECG), vital sign measurements, laboratory tests, or medical/psychiatric history
- •Able to understand and sign and date informed consent
- •Additional Inclusion Criteria for Part 2 (MAD)
- •Diagnosed Type 2 Diabetes Mellitus of 18 to 70 years of age inclusive
Exclusion Criteria
- •Concomitant participation in any investigational study of any nature
- •Blood loss of non-physiological reasons ≥ 200 ml (i.e. trauma, blood collection, blood donation) within 2 months prior to the first dose of study drug, or plan to donate blood during this trial and within 1 month after the last dosing
- •Unable to refrain from taking any non-metformin anti-diabetic medication including insulin within ≥ 3 months prior to the study treatment
- •Serum calcitonin \> 20 ng/L
- •Clinically relevant acute or chronic medical conditions or diseases of the cardiovascular, gastrointestinal, hepatic, renal, endocrine, pulmonary, neurologic, psychiatric, immune or dermatologic systems
- •Diagnosis of T1DM or secondary forms of diabetes
- •Individual or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia 2 (MEN2), or suspected MTC
- •History of pancreatitis
- •Significant allergic reaction to active ingredients or excipients of the study drug.
- •Any clinically significant abnormal findings in the participant's physical examination, laboratory tests, pregnancy test, urine drug screen, alcohol test, or medical history which in the opinion of the Investigator would prevent the participants from participating in the study.
Arms & Interventions
SAD Cohorts 1 to 2: Participants receiving Placebo
Participants in each SAD cohort will be randomized to receive placebo.
Intervention: Placebo
SAD Cohorts 1 to 2: Participants receiving ECC5004
Participants in each SAD cohort will be randomized to receive up to 4 escalating doses of ECC5004 ranging from 1 mg to 300 mg.
Intervention: ECC5004
MAD Cohorts 1 to 4: Participants receiving Placebo
Participants will be randomized to receive a once-daily dose of placebo for 28 days.
Intervention: Placebo
MAD Cohorts 1 to 4: Participants receiving ECC5004
Participants will be randomized to receive a once-daily dose of 1 of 4 escalating doses of ECC5004 ranging from 10 mg to 150 mg for 28 days.
Intervention: ECC5004
Outcomes
Primary Outcomes
Number of participants with adverse events, with abnormal laboratory test results, abnormal ECGs, abnormal vital signs, and abnormal physical examinations
Time Frame: SAD: Up to Day 8 and MAD: Up to Day 35
Safety Assessment evaluated through adverse events, laboratory evaluations, vital signs, ECGs, and physical examination.
Secondary Outcomes
- Pharmacokinetic Parameters: AUC0-infinity(SAD: Up to Day 3)
- Pharmacokinetic Parameters: tmax(SAD: Up to Day 3 and MAD: Up to Day 30)
- Pharmacokinetic Parameters: tlast(SAD: Up to Day 3)
- Pharmacokinetic Parameters: AUC0-tau(MAD: Up to Day 30)
- Pharmacokinetic Parameters: C24(SAD: Up to Day 3 and MAD: Up to Day 30)
- Pharmacokinetic Parameters: t1/2(SAD: Up to Day 3 and MAD: Up to Day 30)
- Pharmacokinetic Parameters: CL/F(SAD: Up to Day 3 and MAD: Up to Day 30)
- Pharmacodynamic Parameters: AUC0-4 for insulin(MAD: Up to Day 30)
- Pharmacodynamic Parameters: AUC0-4 for glucagon(MAD: Up to Day 30)
- Pharmacodynamic Parameters: Body Weight and Waist Circumference(MAD: Up to Day 30)
- Pharmacokinetic Parameters: tlag(SAD: Up to Day 3 and MAD: Up to Day 30)
- Pharmacodynamic Parameters: AUC0-4 for C-peptide(MAD: Up to Day 30)
- Pharmacodynamic Parameters: Fasting plasma glucose(MAD: Up to Day 30)
- Pharmacodynamic Parameters: Fasting plasma glucose homeostatic model assessment(MAD: Up to Day 30)
- Pharmacodynamic Parameters: Fasting plasma insulin homeostatic model assessment(MAD: Up to Day 30)
- Pharmacokinetic Parameters: AUC0-24(SAD: Up to Day 3 and MAD: Up to Day 30)
- Pharmacokinetic Parameters: AUC0-tlast(SAD: Up to Day 3)
- Pharmacokinetic Parameters: Cmax(SAD: Up to Day 3 and MAD: Up to Day 30)
- Pharmacokinetic Parameters: Ctau(MAD: Up to Day 30)
- Pharmacokinetic Parameters: Clast(SAD: Up to Day 3)
- Pharmacodynamic Parameters: AUC0-4 for glucose(MAD: Up to Day 30)
- Pharmacodynamic Parameters: Mean daily glucose(MAD: Up to Day 30)