Clinical trial NCT06485245: Study to Evaluate Safety, Tolerability and Pharmacokinetics of CS060304 in Healthy and Elevated LDL-C Subjects
Official title: A Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetics and Food Effect of Randomized, Double-Blind, Placebo-Controlled Single and Multiple Dose Escalations of CS060304 in Healthy and Elevated LDL-C Subjects
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: MASH
Lead sponsor: Cascade Pharmaceuticals, Inc
Sponsor class: OTHER
First posted: 2024-07-03
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study to Evaluate Safety, Tolerability and Pharmacokinetics of CS060304 in Healthy and Elevated LDL-C Subjects.

Detailed description: A Phase I study Evaluating the Safety, Tolerability, Pharmacokinetics and Food Effects of Randomised, Double-Blind, Placebo-Controlled Single and Multiple Dose Escalations of CS060304 in Healthy and Elevated LDL-C Subjects.

Eligibility criteria: Inclusion Criteria:

SAD

1. Sign and date the ICF.
2. Signing ICF age≥18 years≤55 years, male or female.
3. Weight: Male≥50kg, female≥45kg BMI: 18\~28kg/m².
4. Female or male subjects must be eligible for contraception during the study and for three months after the last dose.
5. Normal renal function.
6. Good general health.
7. No significant medical history, in good general health as assessed by the study during the Screening Period and no more than 28 days from the first dose.
8. Understand and comply with study procedures and limitations.

MAD

1. Sign and date the ICF.
2. Signing ICF age≥18 years≤65 years, male or female.
3. Weight: Male≥50kg, female≥45kg BMI: 18\~35kg/m².
4. Screening period, fasting LDL-C \> 110 mg/dL (2.85 mmol/L).
5. Female or male subjects must be eligible for contraception during the study and for three months after the last dose.
6. Normal renal function.
7. Good general health.
8. No significant medical history, in good general health as assessed by the study during the Screening Period and no more than 28 days from the first dose.
9. Understand and comply with study procedures and limitations. -

Exclusion Criteria:

SAD

1. Special dietary requirements, not following a uniform diet.
2. Pregnant or nursing females or females who have pregnancy plans during the trial or within 3 months after the trial.
3. History of febrile illness or active infection within 7 days prior to first dose.
4. Positive urine drug screens at screening or baseline.
5. History of substance/drug abuse in the 5 years prior to the start of the trial, or a positive screening or baseline drug screen result.
6. History of previous corrected QT interval (QTc) prolongation:

   1. Screening periods QTcF ≥ 450 ms.
   2. Family history of hypocalcaemia or long QT interval syndrome.
   3. Use of drugs causing QT/QTc prolongation.
   4. Investigator judgement of clinically significant abnormal ECG results.
7. Abnormal liver function: AST, ALT, ALP, GGT and TBIL\>ULN.
8. Smoking or use of nicotine products within 3 months prior to screening and during the study period.
9. Use of other investigational drugs 40 days prior to enrolment or within at least 5 half-lives of drug use.
10. Positive screening results for infectious diseases during the screening period, include HIV, HBsAg, HBcAb, HCV antibody tests.
11. Any abnormal results of laboratory tests judged by the investigator to be clinically significant during the screening period.
12. Blood loss within 40 days prior to administration 50\~500 mL, or loss of more than 500 mL of blood within 56 days prior to administration.
13. Men and women who consumed more than 1 unit per day prior to screening. \[1 unit = 150 ml of wine, 360 ml of beer or 45 ml of 40% alcohol\]. Subjects will not be permitted to consume alcohol 48 hours prior to dosing and while in the CRU.
14. Prescription and over-the-counter use within 14 days or at least 5 half-lives prior to the baseline period, or use of any drug or other substance that may affect CYP3A activity within 14 days or at least 5 half-lives before taking this study drug.
15. History of thyroid disease or clinically significant thyroid test abnormalities.
16. Allergy to thyroid medication.
17. Presence of any disease that may interfere with the absorption, distribution, metabolism or excretion of drugs, Including bile salt metabolism in the colon, such as gastrectomy, inflammatory bowel disease, etc.
18. According to the researcher's judgment, there are clinically significant diseases found, including but not limited to (gastrointestinal, kidney, liver, nervous, blood, endocrine, tumor, lung, immune, mental or cardiovascular diseases), researchers believe that participating in the study poses risks to participants.
19. Allergy to the investigational drug or any component of the investigational drug, Allergy history and constitution.
20. Diseases or conditions with clinical significance that researchers believe may pose a risk to the safety of subjects or interfere with the conduct, progress, or completion of the study.
21. Abnormal thyroid function test during screening.
22. Screening or baseline cardiac troponin\>ULN.

MAD

1. Special dietary requirements that cannot follow a unified diet.
2. Pregnant or lactating women who have a pregnancy plan during or within 3 months after the trial, female subjects tested positive for pregnancy during screening or baseline period.
3. Individuals with a history of febrile diseases or active infections within 7 days prior to the first administration of medication.
4. Positive urine drug screening results during screening or baseline period.
5. History of drug/drug abuse within 5 years prior to the start of the trial, or positive drug screening results during screening or baseline period.
6. Subjects who are receiving lipid-lowering treatment or have LDL-C\>190 mg/dL and have a family history of coronary heart disease, arrhythmia, unexplained syncope, or cardiac arrest.
7. Existing history of QTc extension in the past:

   1. Screening period QTcF ≥ 450 ms.
   2. Family history of hypocalcemia or long QT interval syndrome.
   3. Using drugs that cause QT/QTc prolongation.
   4. Abnormal results of ECG with clinical significance determined by researchers.
8. Abnormal liver function: AST, ALT, ALP, GGT and TBIL\>ULN.
9. Screening for smoking or using nicotine products within the first 3 months and during the study period.
10. Use of other investigational drugs 40 days prior to enrolment or within at least 5 half-lives of drug use.
11. Positive screening results for infectious diseases during the screening period, include HIV, HBsAg, HBcAb, HCV antibody Tests.
12. Any abnormal results of laboratory tests judged by the investigator to be clinically significant during the screening period.
13. Blood loss within 40 days prior to administration 50\~500 mL, or loss of more than 500 mL of blood within 56 days prior to administration.
14. Men and women who consumed more than 1 unit per day prior to screening. \[1 unit = 150 ml of wine, 360 ml of beer or 45 ml of 40% alcohol\]. Subjects will not be permitted to consume alcohol 48 hours prior to dosing and while in the CRU.
15. Prescription and over-the-counter use within 14 days or at least 5 half-lives prior to the baseline period, or use of any drug or other substance that may affect CYP3A activity within 14 days or at least 5 half-lives before taking this study drug.
16. History of thyroid disease or clinically significant thyroid test abnormalities.
17. Allergy to thyroid medication.
18. Presence of any disease that may interfere with the absorption, distribution, metabolism or excretion of drugs, Including bile salt metabolism in the colon, such as gastrectomy, inflammatory bowel disease, etc.
19. According to the researcher's judgment, there are clinically significant diseases found, including but not limited to (gastrointestinal, kidney, liver, nervous, blood, endocrine, tumor, lung, immune, mental or cardiovascular diseases), researchers believe that participating in the study poses risks to participants.
20. Allergy to the investigational drug or any component of the investigational drug, Allergy history and constitution.
21. Diseases or conditions with clinical significance that researchers believe may pose a risk to the safety of subjects or interfere with the conduct, progress, or completion of the study.
22. Abnormal thyroid function test during screening.
23. Screening or baseline cardiac troponin\>ULN.

Primary outcomes:
measure: Safety and tolerability
timeFrame: Day1 to Day 28
Secondary outcomes:
measure: Single-Dose Pharmacokinetic (PK) Parameter (AUC0-∞)
timeFrame: Day 1
measure: Single-Dose Pharmacokinetic (PK) Parameter (AUC0-last)
timeFrame: Day 1
measure: Single-Dose Pharmacokinetic (PK) Parameter (Cmax)
timeFrame: Day 1
measure: Single-Dose Pharmacokinetic (PK) Parameter (Tmax)
timeFrame: Day 1
measure: Single-Dose Pharmacokinetic (PK) Parameter (T1/2)
timeFrame: Day 1
measure: Single-Dose Pharmacokinetic (PK) Parameter (CL/F)
timeFrame: Day 1
measure: Single-Dose Pharmacokinetic (PK) Parameter (Kel)
timeFrame: Day 1
measure: Single-Dose Pharmacokinetic (PK) Parameter (MRT)
timeFrame: Day 1
measure: Single-Dose Pharmacokinetic (PK) Parameter (Vz/F)
timeFrame: Day 1
measure: Multiple-Dose Pharmacokinetic (PK) Parameter (Ct_max)
timeFrame: Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.
measure: Multiple-Dose Pharmacokinetic (PK) Parameter (Ct_min)
timeFrame: Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.
measure: Multiple-Dose Pharmacokinetic (PK) Parameter (AUCtau)
timeFrame: Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.
measure: Multiple-Dose Pharmacokinetic (PK) Parameter (Tmax)
timeFrame: Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.
measure: Multiple-Dose Pharmacokinetic (PK) Parameter (T1/2)
timeFrame: Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.
measure: Multiple-Dose Pharmacokinetic (PK) Parameter (CL/F)
timeFrame: Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.
measure: Multiple-Dose Pharmacokinetic (PK) Parameter (DF)
timeFrame: Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.
measure: Multiple-Dose Pharmacokinetic (PK) Parameter (Ct_av)
timeFrame: Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.
measure: Multiple-Dose Pharmacokinetic (PK) Parameter (Rac)
timeFrame: Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.
Other outcomes:
measure: Pharmacodynamic (PD) Characteristics (Fasting serum LDL-C)
timeFrame: Day 1, day3, day 5, day 7, day 14, day 15, day 17.
measure: Pharmacodynamic (PD) Characteristics (HDL-C)
timeFrame: Day 1, day3, day 5, day 7, day 14, day 15, day 17.
measure: Pharmacodynamic (PD) Characteristics (TG)
timeFrame: Day 1, day 3, day 7, day 10, day 14, day 15, day 17.
measure: Pharmacodynamic (PD) Characteristics (TC)
timeFrame: Day 1, day3, day 5, day 7, day 14, day 15, day 17.
measure: Pharmacodynamic (PD) Characteristics (Apo B)
timeFrame: Day 1, day3, day 5, day 7, day 14, day 15, day 17.
measure: Pharmacodynamic (PD) Characteristics (SHBG)
timeFrame: Day 1, day3, day 7, day 10, day 14, day 15, day 17.
measure: Thyroid function indicators (total serum T3)
timeFrame: Day 1, day3, day 7, day 10, day 14, day 15, day 17.
measure: Thyroid function indicators (T3)
timeFrame: Day 1, day3, day 7, day 10, day 14, day 15, day 17.
measure: Thyroid function indicators (T4)
timeFrame: Day 1, day3, day 7, day 10, day 14, day 15, day 17.
measure: Thyroid function indicators (disassociate T4)
timeFrame: Day 1, day3, day 7, day 10, day 14, day 15, day 17.
measure: Thyroid function indicators (TSH)
timeFrame: Day 1, day3, day 7, day 10, day 14, day 15, day 17.
measure: Drug concentration (QTcF)
timeFrame: Day 1, day 2.
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
References: