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

Catabasis Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Hypercholesterolemia

Treatments: Drug: CAT-2054-C; Drug: CAT-2054; Drug: Atorvastatin; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02374047

CAT-2054-101

Details and patient eligibility

About

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.

Enrollment: 118 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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118 participants in 12 patient groups

Cohort A1, Dose Level 1: CAT-2054 or placebo fasting

Experimental group

Description:

Single dose

Treatment:

Drug: CAT-2054

Drug: Placebo

Cohort A2, Dose Level 2: CAT-2054 or placebo fasting and fed

Experimental group

Description:

Single dose

Treatment:

Drug: CAT-2054

Drug: Placebo

Cohort A3, Dose Level 3: CAT-2054 or placebo fasting and fed

Experimental group

Description:

Single dose

Treatment:

Drug: CAT-2054

Drug: Placebo

Cohort A4, Dose Level 4: CAT-2054 or placebo fasting and fed

Experimental group

Description:

Single dose

Treatment:

Drug: CAT-2054

Drug: Placebo

Cohort A5, Dose Level 5: CAT-2054-C or placebo fasting and fed

Experimental group

Description:

Single dose

Treatment:

Drug: CAT-2054-C

Drug: Placebo

Cohort B1, Dose Level 1: CAT-2054 or placebo

Experimental group

Description:

Multiple dose for 14 days

Treatment:

Drug: CAT-2054

Drug: Placebo

Cohort B2, Dose Level 2: CAT-2054 or placebo

Experimental group

Description:

Multiple dose for 14 days

Treatment:

Drug: CAT-2054

Drug: Placebo

Cohort B3, Dose Level 3: CAT-2054 or placebo

Experimental group

Description:

Multiple dose for 14 days

Treatment:

Drug: CAT-2054

Drug: Placebo

Cohort B4, Dose Level 4: CAT-2054 or placebo

Experimental group

Description:

Multiple dose for 14 days

Treatment:

Drug: CAT-2054

Drug: Placebo

Cohort B5, Dose Level 5: CAT-2054 or placebo

Experimental group

Description:

Multiple dose for 14 days

Treatment:

Drug: CAT-2054

Drug: Placebo

Cohort B6, Dose Level 6: CAT-2054 with atorvastatin

Experimental group

Description:

Multiple dose for 14 days

Treatment:

Drug: CAT-2054

Drug: Atorvastatin

Cohort B7, Dose Level 7: CAT-2054 or placebo

Experimental group

Description:

Multiple dose for 14 days

Treatment:

Drug: CAT-2054

Drug: Placebo