Clinical trial NCT02374047: A 2-Part, Phase 1, Single and Multiple Ascending Dose Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of CAT-2054 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypercholesterolemia
Lead sponsor: Catabasis Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2015-02-27
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


Eligibility criteria: 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

Primary outcomes:
measure: Frequency and severity of adverse events
timeFrame: up to 3 weeks
Secondary outcomes:
measure: AUCinf of CAT-2054
timeFrame: Days 1 through 4
measure: Cmax of CAT-2054
timeFrame: up to 3 weeks
measure: Changes from baseline for hematology, chemistry, coagulation and urinalysis
timeFrame: up to 3 weeks
measure: 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.
timeFrame: up to 3 weeks
measure: AUC48 of Atorvastatin
timeFrame: up to 3 weeks
Other outcomes:
Locations:
city: West Bend
country: United States
facility: Spaulding Clinical Research
state: Wisconsin
Study officials:
References: