FTIH of ECC5004 in Healthy and Diabetic Participants

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Placebo
* Drug: ECC5004


Participation Criteria
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Eligibility Criteria
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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 Type 2 Diabetes Mellitus with lifestyle modification only or with stable dose of metformin for ≥ 2 months prior to the study treatment BMI of 24.0 to 40.0 kg/m2 with a minimum body weight of 50.0 kg (110 lbs) HbA1c ≥ 7.0% and ≤ 10.5%, and fasting plasma glucose ≤ 270 mg/dL Blood pressure (BP) with or without medication: Systolic BP ≤ 160 mmHg, AND Diastolic BP ≤ 100 mmHg Not taking any active treatment regimen 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: SAD Cohorts 1 to 2: Participants receiving Placebo<br>Participants in each SAD cohort will be randomized to receive placebo. | Drug: Placebo<br>* Matching Placebo will be administered as oral tablet. Matching Placebo will be given orally during each dosing day.<br>|
| Experimental: SAD Cohorts 1 to 2: Participants receiving ECC5004<br>Participants in each SAD cohort will be randomized to receive up to 4 escalating doses of ECC5004 ranging from 1 mg to 300 mg. | Drug: ECC5004<br>* ECC5004 will be administered as oral tablet(s) during each dosing day.<br>|
| Placebo Comparator: MAD Cohorts 1 to 4: Participants receiving Placebo<br>Participants will be randomized to receive a once-daily dose of placebo for 28 days. | Drug: Placebo<br>* Matching Placebo will be administered as oral tablet. Matching Placebo will be given orally during each dosing day.<br>|
| Experimental: MAD Cohorts 1 to 4: Participants receiving ECC5004<br>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. | Drug: ECC5004<br>* ECC5004 will be administered as oral tablet(s) during each dosing day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events, with abnormal laboratory test results, abnormal ECGs, abnormal vital signs, and abnormal physical examinations | Safety Assessment evaluated through adverse events, laboratory evaluations, vital signs, ECGs, and physical examination. | SAD: Up to Day 8 and MAD: Up to Day 35 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Parameters: AUC0-24 | AUC from time 0 to 24 hour dosing interval | SAD: Up to Day 3 and MAD: Up to Day 30 | 
| Pharmacokinetic Parameters: AUC0-tlast | AUC from time 0 to the time of last quantifiable non-zero concentration | SAD: Up to Day 3 | 
| Pharmacokinetic Parameters: AUC0-tau | AUC over a dosing interval from time 0 to time of last quantifiable concentration | MAD: Up to Day 30 | 
| Pharmacokinetic Parameters: AUC0-infinity | AUC from time 0 extrapolated to infinity | SAD: Up to Day 3 | 
| Pharmacokinetic Parameters: Cmax | Maximum observed plasma concentration | SAD: Up to Day 3 and MAD: Up to Day 30 | 
| Pharmacokinetic Parameters: C24 | Observed concentration at 24 hours post dose | SAD: Up to Day 3 and MAD: Up to Day 30 | 
| Pharmacokinetic Parameters: Ctau | Observed concentration at the end of the dosing interval | MAD: Up to Day 30 | 
| Pharmacokinetic Parameters: tmax | Time of the maximum observed plasma concentration | SAD: Up to Day 3 and MAD: Up to Day 30 | 
| Pharmacokinetic Parameters: tlag | Lag time (time delay between dosing and first observed plasma concentration) | SAD: Up to Day 3 and MAD: Up to Day 30 | 
| Pharmacokinetic Parameters: t1/2 | Apparent terminal elimination half-life | SAD: Up to Day 3 and MAD: Up to Day 30 | 
| Pharmacokinetic Parameters: Clast | Last measurable non-zero concentration | SAD: Up to Day 3 | 
| Pharmacokinetic Parameters: tlast | Time of last measurable non-zero concentration | SAD: Up to Day 3 | 
| Pharmacokinetic Parameters: CL/F | Apparent Clearance | SAD: Up to Day 3 and MAD: Up to Day 30 | 
| Pharmacodynamic Parameters: AUC0-4 for glucose | AUC from time 0 to 4 hour dosing interval | MAD: Up to Day 30 | 
| Pharmacodynamic Parameters: AUC0-4 for insulin | AUC from time 0 to 4 hour dosing interval | MAD: Up to Day 30 | 
| Pharmacodynamic Parameters: AUC0-4 for glucagon | AUC from time 0 to 4 hour dosing interval | MAD: Up to Day 30 | 
| Pharmacodynamic Parameters: AUC0-4 for C-peptide | AUC from time 0 to 4 hour dosing interval | MAD: Up to Day 30 | 
| Pharmacodynamic Parameters: Fasting plasma glucose | Change from baseline | MAD: Up to Day 30 | 
| Pharmacodynamic Parameters: Mean daily glucose | Change from baseline | MAD: Up to Day 30 | 
| Pharmacodynamic Parameters: Body Weight and Waist Circumference | Change from baseline | MAD: Up to Day 30 | 
| Pharmacodynamic Parameters: Fasting plasma glucose homeostatic model assessment | Fasting plasma glucose homeostatic model assessment | MAD: Up to Day 30 | 
| Pharmacodynamic Parameters: Fasting plasma insulin homeostatic model assessment | Fasting plasma insulin homeostatic model assessment | MAD: Up to Day 30 |