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A 2-Part, Phase 1, Single and Multiple Ascending Dose Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of CAT-2054 in Healthy Subjects

Phase 1
Completed
Conditions
Hypercholesterolemia
Interventions
Drug: Placebo
Drug: CAT-2054-C
Registration Number
NCT02374047
Lead Sponsor
Catabasis Pharmaceuticals
Brief Summary

This is a 2-part, Phase 1, placebo-controlled, double-blind, randomized, single and multiple ascending dose study. CAT-2054 will be administered either as an uncoated capsule (CAT-2054) or a coated capsule (CAT-2054-C). In Part A, CAT-2054 or placebo is administered as a single dose in a fasting state at 4 dose levels; at 3 dose levels, subjects will return for a second dose of the study drug after a high-fat meal. Additionally, at 1 dose level, CAT-2054-C or placebo will be administered as a single dose in a fasting state, and subjects will return for a second dose of the study drug after a high-fat meal. In Part B, CAT-2054 will be administered as multiple ascending doses at 4 dose levels for 14 consecutive days. In selected cohorts, CAT-2054, CAT-2054-C or CAT-2054 with atorvastatin will be dosed to assess safety in anticipation of future clinical trials.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
118
Inclusion Criteria
  • Provision of written informed consent before any study-specific procedure

  • Good health as determined by medical history, physical examination, vital sign measurements, ECG, and clinical laboratory measurements

  • Satisfies one of the following:

    1. Females not of childbearing potential: non-pregnant and non-lactating surgically sterile or postmenopausal 2 years or less with a follicle-stimulating hormone assessment greater than or equal to 40 IU/L
    2. Males: surgically sterile, abstinent, or subject or partner is utilizing an acceptable contraceptive method during and 3 months after the last study dose
  • For Part B only, measured at Screening: Fasting LDL-C ≥100 mg/dL; or (Cohort B6 only) fasting LDL-C ≥130 mg/dL

  • Body mass index (BMI) between 18 and 30 kg/m², inclusive, for Part A and between 18 and 40 kg/m², inclusive, for Part B, and body weight >50 kg at Screening

Exclusion Criteria
  • Use of prescription drugs or non-prescription drugs including herbals, and dietary supplements (including multivitamins and any product containing niacin or omega-3 fatty acids above the Recommended Daily Allowance) within 2 weeks before dosing. Additionally for Part B only, use of any lipid-regulating prescription drug, non-prescription drug, herbal, or dietary supplement within 6 weeks before dosing
  • Clinically significant disease that requires a physician's care and/or would interfere with study evaluations
  • Clinically significant electrocardiogram (ECG) abnormalities or laboratory results as assessed by the investigator, such as QTcF >450
  • Use of any investigational drug or participation in any investigational study within 30 days prior to screening or 5 half-lives of the study agent, whichever is longer

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cohort A3, Dose Level 3: CAT-2054 or placebo fasting and fedPlaceboSingle dose
Cohort A5, Dose Level 5: CAT-2054-C or placebo fasting and fedCAT-2054-CSingle dose
Cohort B1, Dose Level 1: CAT-2054 or placeboCAT-2054Multiple dose for 14 days
Cohort B1, Dose Level 1: CAT-2054 or placeboPlaceboMultiple dose for 14 days
Cohort B3, Dose Level 3: CAT-2054 or placeboPlaceboMultiple dose for 14 days
Cohort B4, Dose Level 4: CAT-2054 or placeboCAT-2054Multiple dose for 14 days
Cohort B4, Dose Level 4: CAT-2054 or placeboPlaceboMultiple dose for 14 days
Cohort A1, Dose Level 1: CAT-2054 or placebo fastingCAT-2054Single dose
Cohort A1, Dose Level 1: CAT-2054 or placebo fastingPlaceboSingle dose
Cohort A2, Dose Level 2: CAT-2054 or placebo fasting and fedCAT-2054Single dose
Cohort A2, Dose Level 2: CAT-2054 or placebo fasting and fedPlaceboSingle dose
Cohort A3, Dose Level 3: CAT-2054 or placebo fasting and fedCAT-2054Single dose
Cohort B2, Dose Level 2: CAT-2054 or placeboCAT-2054Multiple dose for 14 days
Cohort B2, Dose Level 2: CAT-2054 or placeboPlaceboMultiple dose for 14 days
Cohort A4, Dose Level 4: CAT-2054 or placebo fasting and fedCAT-2054Single dose
Cohort A4, Dose Level 4: CAT-2054 or placebo fasting and fedPlaceboSingle dose
Cohort A5, Dose Level 5: CAT-2054-C or placebo fasting and fedPlaceboSingle dose
Cohort B5, Dose Level 5: CAT-2054 or placeboCAT-2054Multiple dose for 14 days
Cohort B5, Dose Level 5: CAT-2054 or placeboPlaceboMultiple dose for 14 days
Cohort B6, Dose Level 6: CAT-2054 with atorvastatinCAT-2054Multiple dose for 14 days
Cohort B6, Dose Level 6: CAT-2054 with atorvastatinAtorvastatinMultiple dose for 14 days
Cohort B7, Dose Level 7: CAT-2054 or placeboCAT-2054Multiple dose for 14 days
Cohort B7, Dose Level 7: CAT-2054 or placeboPlaceboMultiple dose for 14 days
Cohort B3, Dose Level 3: CAT-2054 or placeboCAT-2054Multiple dose for 14 days
Primary Outcome Measures
NameTimeMethod
Frequency and severity of adverse eventsup to 3 weeks
Secondary Outcome Measures
NameTimeMethod
Changes from baseline for hematology, chemistry, coagulation and urinalysisup to 3 weeks
AUCinf of CAT-2054Days 1 through 4
Cmax of CAT-2054up to 3 weeks
Assess the pharmacodynamic effects of multiple doses of CAT-2054 on serum lipids LDL-C, non-HDL-C, total cholesterol, triglycerides, HDL-C, apoB, and PCSK9.up to 3 weeks
AUC48 of Atorvastatinup to 3 weeks

Trial Locations

Locations (1)

Spaulding Clinical Research

🇺🇸

West Bend, Wisconsin, United States

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