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

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.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: Placebo; Drug: Atorvastatin; Drug: CAT-2054; Drug: CAT-2054-C

• Study Type: Interventional
• Enrollment (Actual): 118
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • West Bend, Wisconsin, United States, 53095
      • Spaulding Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A1, Dose Level 1: CAT-2054 or placebo fasting; Single dose	Drug: Placebo; Drug: CAT-2054
Experimental: Cohort A2, Dose Level 2: CAT-2054 or placebo fasting and fed; Single dose	Drug: Placebo; Drug: CAT-2054
Experimental: Cohort A3, Dose Level 3: CAT-2054 or placebo fasting and fed; Single dose	Drug: Placebo; Drug: CAT-2054
Experimental: Cohort A4, Dose Level 4: CAT-2054 or placebo fasting and fed; Single dose	Drug: Placebo; Drug: CAT-2054
Experimental: Cohort A5, Dose Level 5: CAT-2054-C or placebo fasting and fed; Single dose	Drug: Placebo; Drug: CAT-2054-C
Experimental: Cohort B1, Dose Level 1: CAT-2054 or placebo; Multiple dose for 14 days	Drug: Placebo; Drug: CAT-2054
Experimental: Cohort B2, Dose Level 2: CAT-2054 or placebo; Multiple dose for 14 days	Drug: Placebo; Drug: CAT-2054
Experimental: Cohort B3, Dose Level 3: CAT-2054 or placebo; Multiple dose for 14 days	Drug: Placebo; Drug: CAT-2054
Experimental: Cohort B4, Dose Level 4: CAT-2054 or placebo; Multiple dose for 14 days	Drug: Placebo; Drug: CAT-2054
Experimental: Cohort B5, Dose Level 5: CAT-2054 or placebo; Multiple dose for 14 days	Drug: Placebo; Drug: CAT-2054
Experimental: Cohort B6, Dose Level 6: CAT-2054 with atorvastatin; Multiple dose for 14 days	Drug: Atorvastatin; Drug: CAT-2054
Experimental: Cohort B7, Dose Level 7: CAT-2054 or placebo; Multiple dose for 14 days	Drug: Placebo; Drug: CAT-2054

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Frequency and severity of adverse events	up to 3 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
AUCinf of CAT-2054	Days 1 through 4
Cmax of CAT-2054	up to 3 weeks
Changes from baseline for hematology, chemistry, coagulation and urinalysis	up 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 Atorvastatin	up to 3 weeks

Collaborators and Investigators

• Sponsor: Catabasis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: February 2, 2015
• First Submitted That Met QC Criteria: February 23, 2015
• First Posted (Estimate): February 27, 2015

Study Record Updates

• Last Update Posted (Actual): January 28, 2021
• Last Update Submitted That Met QC Criteria: January 27, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: CAT-2054-101