Clinical trial NCT06293742: ECC5004 DDI Study With Atorvastatin, Rosuvastatin, Digoxin and Midazolam in Healthy Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Eccogene
Sponsor class: INDUSTRY
First posted: 2024-03-05
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Atorvastatin PK parameters: AUC(0-tlast)
timeFrame: Part B and optional Part D: up to Day 34
measure: Atorvastatin PK parameters: AUC(0-inf)
timeFrame: Part B and optional Part D: up to Day 34
measure: Atorvastatin PK parameters: Cmax
timeFrame: Part B and optional Part D: up to Day 34
measure: Rosuvastatin PK parameters: AUC(0-tlast)
timeFrame: Part A and optional Part C: up to Day 11
measure: Rosuvastatin PK parameters: AUC(0-inf)
timeFrame: Part A and optional Part C: up to Day 11
measure: Rosuvastatin PK parameters: Cmax
timeFrame: Part A and optional Part C: up to Day 11
measure: Digoxin PK parameters: AUC(0-tlast)
timeFrame: Part A and optional Part C: up to Day 11
measure: Digoxin PK parameters: AUC(0-inf)
timeFrame: Part A and optional Part C: up to Day 11
measure: Digoxin PK parameters: Cmax
timeFrame: Part A and optional Part C: up to Day 11
measure: Midazolam PK parameters: AUC(0-tlast)
timeFrame: Part B and optional Part D: up to Day 34
measure: Midazolam PK parameters: AUC(0-inf)
timeFrame: Part B and optional Part D: up to Day 34
measure: Midazolam PK parameters: Cmax
timeFrame: Part B and optional Part D: up to Day 34
Secondary outcomes:
measure: ECC5004 Safety parameters: Number of participants with adverse events (AEs)
timeFrame: Part A and optional Part C: up to Day 16; Part B and optional Part D: up to Day 40
measure: ECC5004 Safety parameters: Number of participants with vital sign abnormalities
timeFrame: Part A and optional Part C: up to Day 16; Part B and optional Part D: up to Day 40
measure: ECC5004 Safety parameters: Number of participants with electrocardiogram (ECG) abnormalities
timeFrame: Part A and optional Part C: up to Day 16; Part B and optional Part D: up to Day 40
measure: ECC5004 Safety parameters: Number of participants with physical examination abnormalities
timeFrame: Part A and optional Part C: up to Day 16; Part B and optional Part D: up to Day 40
measure: ECC5004 Safety parameters: Number of participants with clinical laboratory abnormalities
timeFrame: Part A and optional Part C: up to Day 16; Part B and optional Part D: up to Day 40
measure: Atorvastatin safety parameters: Number of participants with adverse events (AEs)
timeFrame: Part B and optional Part D: up to Day 40
measure: Atorvastatin safety parameters: Number of participants with vital sign abnormalities
timeFrame: Part B and optional Part D: up to Day 40
measure: Atorvastatin safety parameters: Number of participants with electrocardiogram (ECG)
timeFrame: Part B and optional Part D: up to Day 40
measure: Atorvastatin safety parameters: Number of participants with physical examination abnormalities
timeFrame: Part B and optional Part D: up to Day 40
measure: Atorvastatin safety parameters: Number of participants with clinical laboratory abnormalities
timeFrame: Part B and optional Part D: up to Day 40
measure: Rosuvastatin safety parameters: Number of participants with adverse events (AEs)
timeFrame: Part A and optional Part C: up to Day 16
measure: Rosuvastatin safety parameters: Number of participants with vital sign abnormalities
timeFrame: Part A and optional Part C: up to Day 16
measure: Rosuvastatin safety parameters: Number of participants with electrocardiogram (ECG) abnormalities
timeFrame: Part A and optional Part C: up to Day 16
measure: Rosuvastatin safety parameters: Number of participants with physical examination abnormalities
timeFrame: Part A and optional Part C: up to Day 16
measure: Rosuvastatin safety parameters: Number of participants with clinical laboratory abnormalities
timeFrame: Part A and optional Part C: up to Day 16
measure: Digoxin safety parameters: Number of participants with adverse events (AEs)
timeFrame: Part A and optional Part C: up to Day 16
measure: Digoxin safety parameters: Number of participants with vital sign abnormalities
timeFrame: Part A and optional Part C: up to Day 16
measure: Digoxin safety parameters: Number of participants with electrocardiogram (ECG) abnormalities
timeFrame: Part A and optional Part C: up to Day 16
measure: Digoxin safety parameters: Number of participants with physical examination abnormalities
timeFrame: Part A and optional Part C: up to Day 16
measure: Digoxin safety parameters: Number of participants with clinical laboratory abnormalities
timeFrame: Part A and optional Part C: up to Day 16
measure: Midazolam safety parameters: Number of participants with adverse events (AEs)
timeFrame: Part B and optional Part D: up to Day 40
measure: Midazolam safety parameters: Number of participants with vital sign abnormalities
timeFrame: Part B and optional Part D: up to Day 40
measure: Midazolam safety parameters: Number of participants with electrocardiogram (ECG) abnormalities
timeFrame: Part B and optional Part D: up to Day 40
measure: Midazolam safety parameters: Number of participants with physical examination abnormalities
timeFrame: Part B and optional Part D: up to Day 40
measure: Midazolam safety parameters: Number of participants with clinical laboratory abnormalities
timeFrame: Part B and optional Part D: up to Day 40
measure: ECC5004 PK parameters: AUC (0-τ)
timeFrame: Part A and optional Part C: up to Day 11; Part B and optional Part D: up to Day 34
measure: ECC5004 PK parameters: AUC(0-24)
timeFrame: Part A and optional Part C: up to Day 11; Part B and optional Part D: up to Day 34
measure: ECC5004 PK parameters: tmax
timeFrame: Part A and optional Part C: up to Day 11; Part B and optional Part D: up to Day 34
measure: ECC5004 PK parameters: t1/2
timeFrame: Part A and optional Part C: up to Day 11; Part B and optional Part D: up to Day 34
measure: ECC5004 PK parameters: CL/F
timeFrame: Part A and optional Part C: up to Day 11; Part B and optional Part D: up to Day 34
measure: ECC5004 PK parameters: Ctau
timeFrame: Part A and optional Part C: up to Day 11; Part B and optional Part D: up to Day 34
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Eccogene Investigational Site
state: California
Study officials:
affiliation: Eccogene Clinical Trials
name: Eccogene
role: STUDY_DIRECTOR
References: