ECC5004 DDI Study With Atorvastatin, Rosuvastatin, Digoxin and Midazolam in Healthy Participants

A Phase 1, Open Label, Fixed Sequence Study to Evaluate the Effect of ECC5004 on the Single Dose Pharmacokinetics of Atorvastatin, Rosuvastatin, Digoxin and Midazolam in Healthy Participants

This is a Phase 1, open-label, non-randomized, fixed sequence study designed to evaluate the effect of ECC5004 on single dose pharmacokinetics of Atorvastatin, Rosuvastatin, Digoxin and Midazolam in healthy participants.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Midazolam; Drug: ECC5004; Drug: Rosuvastatin; Drug: Digoxin; Drug: Atorvastatin

Detailed Description

The study consists of four parts (Part A, Part B, optional Part C and optional Part D), each with approximately 16 healthy participants enrolled. Part A and optional Part C of the study will have the same study design with two treatment periods, except that ECC5004 will be administered at a higher dose level in the optional Part C. Part B and optional Part D of the study will have the same study design with five treatment periods, except that ECC5004 will be administered at a higher dose level in optional Part D. Rosuvastatin and Digoxin will be administered alone or in combination with EC5004 in Part A and optional Part C. Atorvastatin and Midazolam will be administered alone or in combination with ECC5004 in Part B and optional Part D. The conduct of Part C and Part D with an increased dose of ECC5004 may be conducted as optional parts.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Eccogene Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male and female participants of non-childbearing potential (NCBP) between the ages of 18 to 65 years of age
• BMI of 18.0 to 32.0 kg/m2
• 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, clinical laboratory evaluations, concomitant medications, or medical/psychiatric history
• Able to understand and sign and date informed consent

Exclusion Criteria:

• Females who are pregnant, planning to become pregnant, or breastfeeding during the study or within 3 months after the study
• 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 treatment, or plan to donate blood during this trial and within 1 month after the last dose of 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
• 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
• Used or plan to use any drugs or substances that can modulate the activity of CYP3A4 within at least 14 days prior to the first dose of study treatment until after their final follow up visit
• Use of drugs with enzyme-inducing properties such as St. John's Wort within 3 weeks prior to the first dose of study treatment until after their final follow up visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Digoxin, Rosuvastatin, ECC5004 (Part A); Part A consists of 2 treatment periods. Participants will receive Digoxin and Rosuvastatin administered alone in treatment period 1 and in combination with ECC5004 in treatment period 2.	Drug: ECC5004; ECC5004 tablet will be administered orally.; Drug: Rosuvastatin; Rosuvastatin will be administered orally.; Drug: Digoxin; Digoxin will be administered orally.
Experimental: Midazolam, Atorvastatin, ECC5004 (Part B); Part B consists of 5 treatment periods. In treatment period 1, participants will receive Midazolam administered alone followed by treatment period 2 in which participants will receive Atorvastatin administered alone. In treatment period 3, participants will receive ECC5004 alone. In treatment period 4, participants will receive ECC5004 in combination with Midazolam. In treatment period 5, ECC5004 will be administered alone and co-administered with Atorvastatin.	Drug: Midazolam; Midazolam will be administered orally.; Drug: ECC5004; ECC5004 tablet will be administered orally.; Drug: Atorvastatin; Atorvastatin will be administered orally.
Experimental: Digoxin, Rosuvastatin, ECC5004 (optional Part C); Optional Part C consists of 2 treatment periods. Participants will receive Digoxin and Rosuvastatin administered alone in treatment period 1 and in combination with ECC5004 in treatment period 2.	Drug: ECC5004; ECC5004 tablet will be administered orally.; Drug: Rosuvastatin; Rosuvastatin will be administered orally.; Drug: Digoxin; Digoxin will be administered orally.
Experimental: Midazolam, Atorvastatin, ECC5004 (optional Part D); Optional Part D consists of 5 treatment periods. In treatment period 1, participants will receive Midazolam administered alone followed by treatment period 2 in which participants will receive Atorvastatin administered alone. In treatment period 3, participants will receive ECC5004 alone. In treatment period 4, participants will receive ECC5004 in combination with Midazolam. In treatment period 5, ECC5004 will be administered alone and co-administered with Atorvastatin.	Drug: Midazolam; Midazolam will be administered orally.; Drug: ECC5004; ECC5004 tablet will be administered orally.; Drug: Atorvastatin; Atorvastatin will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Atorvastatin PK parameters: AUC(0-tlast)	Area under the Plasma Concentration-Time Curve from Time 0 to the Last Measurable Non Zero Concentration	Part B and optional Part D: up to Day 34
Atorvastatin PK parameters: AUC(0-inf)	Area under the Plasma Concentration-Time Curve from Time 0 Extrapolated to Infinity	Part B and optional Part D: up to Day 34
Atorvastatin PK parameters: Cmax	Maximum observed plasma concentration	Part B and optional Part D: up to Day 34
Rosuvastatin PK parameters: AUC(0-tlast)	Area under the Plasma Concentration-Time Curve from Time 0 to the Last Measurable Non Zero Concentration	Part A and optional Part C: up to Day 11
Rosuvastatin PK parameters: AUC(0-inf)	Area under the Plasma Concentration-Time Curve from Time 0 Extrapolated to Infinity	Part A and optional Part C: up to Day 11
Rosuvastatin PK parameters: Cmax	Maximum observed plasma concentration	Part A and optional Part C: up to Day 11
Digoxin PK parameters: AUC(0-tlast)	Area under the Plasma Concentration-Time Curve from Time 0 to the Last Measurable Non Zero Concentration	Part A and optional Part C: up to Day 11
Digoxin PK parameters: AUC(0-inf)	Area under the Plasma Concentration-Time Curve from Time 0 Extrapolated to Infinity	Part A and optional Part C: up to Day 11
Digoxin PK parameters: Cmax	Maximum observed plasma concentration	Part A and optional Part C: up to Day 11
Midazolam PK parameters: AUC(0-tlast)	Area under the Plasma Concentration-Time Curve from Time 0 to the Last Measurable Non Zero Concentration	Part B and optional Part D: up to Day 34
Midazolam PK parameters: AUC(0-inf)	Area under the Plasma Concentration-Time Curve from Time 0 Extrapolated to Infinity	Part B and optional Part D: up to Day 34
Midazolam PK parameters: Cmax	Maximum observed plasma concentration	Part B and optional Part D: up to Day 34

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ECC5004 Safety parameters: Number of participants with adverse events (AEs)	Safety Assessment evaluated through adverse events	Part A and optional Part C: up to Day 16; Part B and optional Part D: up to Day 40
ECC5004 Safety parameters: Number of participants with vital sign abnormalities	Safety Assessment evaluated through vital signs	Part A and optional Part C: up to Day 16; Part B and optional Part D: up to Day 40
ECC5004 Safety parameters: Number of participants with electrocardiogram (ECG) abnormalities	Safety Assessment evaluated through electrocardiograms (ECGs)	Part A and optional Part C: up to Day 16; Part B and optional Part D: up to Day 40
ECC5004 Safety parameters: Number of participants with physical examination abnormalities	Safety Assessment evaluated through physical examination	Part A and optional Part C: up to Day 16; Part B and optional Part D: up to Day 40
ECC5004 Safety parameters: Number of participants with clinical laboratory abnormalities	Safety Assessment evaluated through clinical laboratory assessments	Part A and optional Part C: up to Day 16; Part B and optional Part D: up to Day 40
Atorvastatin safety parameters: Number of participants with adverse events (AEs)	Safety Assessment evaluated through adverse events	Part B and optional Part D: up to Day 40
Atorvastatin safety parameters: Number of participants with vital sign abnormalities	Safety Assessment evaluated through vital signs	Part B and optional Part D: up to Day 40
Atorvastatin safety parameters: Number of participants with electrocardiogram (ECG)	Safety Assessment evaluated through electrocardiograms (ECGs)	Part B and optional Part D: up to Day 40
Atorvastatin safety parameters: Number of participants with physical examination abnormalities	Safety Assessment evaluated through physical examination	Part B and optional Part D: up to Day 40
Atorvastatin safety parameters: Number of participants with clinical laboratory abnormalities	Safety Assessment evaluated through clinical laboratory assessments	Part B and optional Part D: up to Day 40
Rosuvastatin safety parameters: Number of participants with adverse events (AEs)	Safety Assessment evaluated through adverse events	Part A and optional Part C: up to Day 16
Rosuvastatin safety parameters: Number of participants with vital sign abnormalities	Safety Assessment evaluated through vital signs	Part A and optional Part C: up to Day 16
Rosuvastatin safety parameters: Number of participants with electrocardiogram (ECG) abnormalities	Safety Assessment evaluated through electrocardiograms (ECGs)	Part A and optional Part C: up to Day 16
Rosuvastatin safety parameters: Number of participants with physical examination abnormalities	Safety Assessment evaluated through physical examination	Part A and optional Part C: up to Day 16
Rosuvastatin safety parameters: Number of participants with clinical laboratory abnormalities	Safety Assessment evaluated through clinical laboratory assessments	Part A and optional Part C: up to Day 16
Digoxin safety parameters: Number of participants with adverse events (AEs)	Safety Assessment evaluated through adverse events	Part A and optional Part C: up to Day 16
Digoxin safety parameters: Number of participants with vital sign abnormalities	Safety Assessment evaluated through vital signs	Part A and optional Part C: up to Day 16
Digoxin safety parameters: Number of participants with electrocardiogram (ECG) abnormalities	Safety Assessment evaluated through electrocardiograms (ECGs)	Part A and optional Part C: up to Day 16
Digoxin safety parameters: Number of participants with physical examination abnormalities	Safety Assessment evaluated through physical examination	Part A and optional Part C: up to Day 16
Digoxin safety parameters: Number of participants with clinical laboratory abnormalities	Safety Assessment evaluated through clinical laboratory assessments	Part A and optional Part C: up to Day 16
Midazolam safety parameters: Number of participants with adverse events (AEs)	Safety Assessment evaluated through adverse events	Part B and optional Part D: up to Day 40
Midazolam safety parameters: Number of participants with vital sign abnormalities	Safety Assessment evaluated through vital signs	Part B and optional Part D: up to Day 40
Midazolam safety parameters: Number of participants with electrocardiogram (ECG) abnormalities	Safety Assessment evaluated through electrocardiograms (ECGs)	Part B and optional Part D: up to Day 40
Midazolam safety parameters: Number of participants with physical examination abnormalities	Safety Assessment evaluated through physical examination	Part B and optional Part D: up to Day 40
Midazolam safety parameters: Number of participants with clinical laboratory abnormalities	Safety Assessment evaluated through clinical laboratory assessments	Part B and optional Part D: up to Day 40
ECC5004 PK parameters: AUC (0-τ)	Area under the Plasma Concentration-Time Curve during the Dosing Interval	Part A and optional Part C: up to Day 11; Part B and optional Part D: up to Day 34
ECC5004 PK parameters: AUC(0-24)	Area under the Plasma Concentration-Time Curve from Time 0 to 24 Hours Post-dose	Part A and optional Part C: up to Day 11; Part B and optional Part D: up to Day 34
ECC5004 PK parameters: tmax	Time of the maximum observed plasma concentration	Part A and optional Part C: up to Day 11; Part B and optional Part D: up to Day 34
ECC5004 PK parameters: t1/2	Apparent terminal elimination half-life	Part A and optional Part C: up to Day 11; Part B and optional Part D: up to Day 34
ECC5004 PK parameters: CL/F	Apparent Clearance	Part A and optional Part C: up to Day 11; Part B and optional Part D: up to Day 34
ECC5004 PK parameters: Ctau	Observed Concentration at the End of the Dosing Interval	Part A and optional Part C: up to Day 11; Part B and optional Part D: up to Day 34

Collaborators and Investigators

• Sponsor: Eccogene
• Investigators: Study Director: Eccogene, Eccogene Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2024
• Primary Completion (Actual): April 15, 2024
• Study Completion (Actual): April 15, 2024

Study Registration Dates

• First Submitted: February 19, 2024
• First Submitted That Met QC Criteria: February 27, 2024
• First Posted (Actual): March 5, 2024

Study Record Updates

• Last Update Posted (Actual): July 22, 2024
• Last Update Submitted That Met QC Criteria: July 19, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Antimetabolites; Protective Agents; Cardiotonic Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Digoxin; Atorvastatin; Midazolam; Rosuvastatin Calcium
• Other Study ID Numbers: EC0007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No