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

Type 2 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06293742
• Other study ID #: EC0007
• Status: Recruiting
• Phase: Phase 1
• Start date: February 9, 2024
• Est. completion date: April 19, 2024

Study information

• Verified date: February 2024
• Source: Eccogene
• Contact: Eccogene Clinical Trials
• Phone: 86-21-61053022
• Email: contact[@]eccogene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 64
• Est. completion date: April 19, 2024
• Est. primary completion date: April 19, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• ECC5004
ECC5004 tablet will be administered orally.
• Midazolam
Midazolam will be administered orally.
• Rosuvastatin
Rosuvastatin will be administered orally.
• Digoxin
Digoxin will be administered orally.
• Atorvastatin
Atorvastatin will be administered orally.

Locations

Country	Name	City	State
United States	Eccogene Investigational Site	Anaheim	California

Sponsors (1)

Lead Sponsor	Collaborator
Eccogene

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Atorvastatin PK parameters: Cmax	Maximum observed plasma concentration	Part B and optional Part D: up to Day 34
Primary	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
Primary	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
Primary	Rosuvastatin PK parameters: Cmax	Maximum observed plasma concentration	Part A and optional Part C: up to Day 11
Primary	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
Primary	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
Primary	Digoxin PK parameters: Cmax	Maximum observed plasma concentration	Part A and optional Part C: up to Day 11
Primary	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
Primary	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
Primary	Midazolam PK parameters: Cmax	Maximum observed plasma concentration	Part B and optional Part D: up to Day 34
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	ECC5004 PK parameters: AUC (0-t)	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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