Clinical trial NCT01587365: Single Ascending Dose Safety Study of BMS-962476 in Healthy Subjects and Patients With Elevated Cholesterol on Statins
Official title: Randomized, Double-Blind, Placebo-Controlled, Ascending Single-Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BMS-962476 in Healthy Subjects and in Patients With Hypercholesterolemia on Statin Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Atherosclerosis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2012-04-30
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To obtain safety and tolerability information in healthy subjects is administered as a single dose

Detailed description: * Study Classification: Pharmacokinetics and Pharmacodynamics
* Intervention Model: Single Ascending Dose (SAD) study
* Allocation: Randomized Non-Stratified

Eligibility criteria: Inclusion Criteria:

* Healthy population

  * Untreated low density lipoprotein cholesterol (LDL-c) ≥ 130 and ≤ 190 mg/dL and triglycerides ≤ 200 mg/dL
  * Body Mass Index (BMI) of 18 to 35 kg/m2 inclusive
  * Men and women, ages 18 to 65 years, inclusive
* Statin population

  * Patients with hypercholesterolemia on stable statin therapy for 6 weeks prior to enrollment
  * At enrollment, LDL-c ≥ 100mg/dL and triglycerides ≤ 200 mg/dL
  * Patients with controlled hypertension on a stable dose of no more than two antihypertensive drugs
  * BMI of 18 to 37 kg/m2 inclusive
  * Men and women, ages 18 to 75 years inclusive

Exclusion Criteria:

* Healthy Population

  * Subjects with fasting LDL-c \< 130 or \> 190 mg/dL, or fasting triglycerides \> 200 mg/dL
  * Subjects at increased 10-year cardiovascular risk of ≥ 20% based on Framingham risk score
  * Subjects with any significant acute or chronic medical illness at the time of screening, including history of cancer, known history of sickle cell disease or trait, and known history of thalassemia
* Statin population

  * Patients with fasting LDL-c \< 100mg/dL, or fasting triglycerides \> 200 mg/dL on statin therapy
  * Patients on prescription or over the counter lipid-lowering therapy other than statin therapy
  * Patients with established atherosclerotic vascular disease
  * Patients with diabetes who are requiring oral or injectable anti-diabetic drug therapy
  * Patients with uncontrolled hypertension or controlled hypertension requiring more than two antihypertensive drugs
  * Patients with any significant acute or chronic medical illness that is severe, progressive or uncontrolled at the time of screening
* Use of any lipid lowering medication including over the counter products (eg, niacin \> 500 mg; omega-3 fatty acids \> 1000 mg; red rice yeast; phytosterols or stanol esters) for lipid lowering within 30 days prior to screening visit (42 days for fibrates) with the exception of stable statin therapy in the target disease population
* Prior treatment with any monoclonal antibody or investigational protein biologic within the preceding one year before study drug administration
* Concurrent or use within 3 months of study drug administration of marketed or investigational systemic or inhaled corticosteroids or other immunosuppressant drugs, and within 6 weeks for topical corticosteroids

Primary outcomes:
measure: Safety and tolerability of BMS-962476 as measured by the number of subjects with serious adverse events, deaths or discontinuations due to adverse events (AEs), AEs of injection site reactions, or potentially clinically significant changes in vital signs
timeFrame: Up to Day 43
Secondary outcomes:
measure: Pharmacodynamic effects of single subcutaneous (SC) and intravenous (IV) doses of BMS-962476
timeFrame: Up to Day 43
measure: Maximum observed plasma concentration (Cmax) of single dose pharmacokinetics (PK) and dose proportionality of BMS-962476 following SC and IV administration
timeFrame: 17 time points up to Day 43
measure: Time of maximum observed plasma concentration (Tmax) of single dose pharmacokinetics (PK) and dose proportionality of BMS-962476 following SC and IV administration
timeFrame: 17 time points up to Day 43
measure: Area under the plasma concentration-time curve from time zero to the time of last quantifiable plasma concentration [AUC(0-T)] of single dose pharmacokinetics (PK) and dose proportionality of BMS-962476 following SC and IV administration
timeFrame: 17 time points up to Day 43
measure: Area under the plasma concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of single dose pharmacokinetics (PK) and dose proportionality of BMS-962476 following SC and IV administration
timeFrame: 17 time points up to Day 43
measure: Plasma elimination half-life (T-HALF) of single dose pharmacokinetics (PK) and dose proportionality of BMS-962476 following SC and IV administration
timeFrame: 17 time points up to Day 43
measure: Total body clearance (CL/F) of BMS-962476 SC Dosing
timeFrame: 15 time points up to Day 43
measure: Total body clearance (CL) of BMS-962476 IV Dosing
timeFrame: 17 time points up to Day 43
measure: Volume of distribution at steady state (Vss/F) of BMS-962476 SC Dosing
timeFrame: 15 time points up to Day 43
measure: Volume of distribution at steady state (Vss) of BMS-962476 IV Dosing
timeFrame: 15 time points up to Day 43
measure: Absolute bioavailability (F) of total and free BMS-962476
timeFrame: 15 time points up to Day 43
measure: Frequency of anti-BMS-962476 antibodies (immunogenicity) following single SC and IV doses of BMS-962476
timeFrame: Up to Day 43
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Metabolic And Atherosclerosis Research Center/ Medpace Clinical Pharmacology
state: Ohio
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: