Safety and Tolerability of Single and Multiple Doses of ISIS 353512 in Healthy Volunteers

NCT00734240 | Completed Phase 1

• 1 other identifier: ISIS 353512 CS1
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of single and multiple doses of ISIS 353512, to evaluate the blood concentration and rate elimination of ISIS 353512 from the blood, and to evaluate the effectiveness of ISIS 353512 in lowering a protein in the blood associated with inflammation.

Conditions

Inflammatory Diseases

Outcome Measures

Primary Outcomes (1)

• To evaluate the safety and tolerability of single and multiple doses of ISIS 353512 administered intravenously and subcutaneously.

  14 Days post treatment of each cohort

Secondary Outcomes (2)

• To evaluate the pharmacokinetic profile of single and multiple doses of ISIS 353512 administered intravenously and subcutaneously.

  14 Days post treatment of each cohort

• To evaluate the pharmacodynamics of ISIS 353512 administered intravenously and subcutaneously.

  14 Days post treatment of each cohort

Study Arms (16)

A

EXPERIMENTAL

single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 355312 or placebo

Drug: ISIS 353512

B

EXPERIMENTAL

single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo

Drug: ISIS 353512

C

EXPERIMENTAL

single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo

Drug: ISIS 353512

AA

EXPERIMENTAL

multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving 353512 or placebo

Drug: ISIS 353512

BB

EXPERIMENTAL

multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo

Drug: ISIS 353512

CC

EXPERIMENTAL

multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo

Drug: ISIS 353512

G

EXPERIMENTAL

single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo

Drug: ISIS 353512

H

EXPERIMENTAL

single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo

Drug: ISIS 353512

I

EXPERIMENTAL

single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo

Drug: ISIS 353512

GG

EXPERIMENTAL

multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo

Drug: ISIS 353512

HH

EXPERIMENTAL

multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo

Drug: ISIS 353512

II

EXPERIMENTAL

multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo

Drug: ISIS 353512

F (100 mg)

EXPERIMENTAL

single-dose cohort (n=4, randomized 3 active: 1 placebo) receiving ISIS 353512 or placebo

Drug: ISIS 353512

Dose-Titration 1

EXPERIMENTAL

multiple-dose cohort (n=4, randomized 3 active: 1 placebo) receiving ISIS 353512 or placebo

Drug: ISIS 353512

F (200 mg)

EXPERIMENTAL

single-dose cohort (n=4, randomized 3 active: 1 placebo) receiving ISIS 353512 or placebo

Drug: ISIS 353512

Dose-Titration 7

EXPERIMENTAL

multiple-dose cohort (n=4, randomized 3 active: 1 placebo) receiving ISIS 353512 or placebo

Drug: ISIS 353512

Interventions

ISIS 353512 DRUG

50 mg via 2 hour IV infusion, single dose

A

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 to 55 years
• Male or female although females must be post-menopausal or surgically sterile
• In good health
• BMI \< 32 kg/m2
• Give written informed consent to participate in the study
• hsCRP at Screening ≥ 0.50 mg/L and ≤ 5.0 mg/L (for 2 measurements ≥ 2 weeks apart; with difference between measurements ≤ 2.5 mg/L)(Multiple Dose Subjects only, not including dose-titration cohorts)

You may not qualify if:

• Pregnant women, nursing mothers or women of childbearing potential
• Clinically significant abnormalities in medical history or physical examination
• Clinically significant ECG abnormalities or vital sign abnormalities (systolic blood pressure \< 90 mm Hg or \> 140 mm Hg, diastolic blood pressure \< 50 mm Hg or \> 90 mm Hg or heat rate \< 50 or \> 100 bpm) at Screening
• Clinically significant abnormalities on laboratory examination, other than hsCRP
• Clinically significant abnormalities in coagulation parameters
• Positive test for HIV, TB (PPD test) or hepatitis B or C at Screening
• History of latent or active tuberculosis or exposure to endemic areas within 8 weeks prior to PPD test at Screening
• History of positive PPD test or positive PPD test result (≥ 5 mm) indicating possible tuberculosis infection
• Fasting triglycerides \> 400 mg/dL at Screening
• Malignancy (with the exception of basal or squamous cell carcinoma of the skin if adequately treated and no recurrence for \> 1 year)
• Evidence of ongoing chronic inflammatory condition or infection
• Any other concurrent condition which, in the opinion of the Investigator, would preclude participation in this study or interfere with compliance
• Regular use of alcohol within 6 months prior to Screening (\> 14 units of alcohol per week; 1 unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol)
• Use of soft drugs (such as marijuana) within 3 months prior to Screening or hard drugs (such as cocaine, phencyclidine \[PCP\] and crack) within 1 year prior to Screening, or positive urine drug screen at Screening
• Smoking \> 10 cigarettes per day

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead
• Anapharm: collaborator

Study Sites (1)

Anapharm

Montreal, Quebec, H3X 2H9, Canada

Location

Study Officials

• Richard Larouche, M.D.

  Anapharm

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: August 12, 2008
• First Posted: August 14, 2008
• Study Start: July 1, 2008
• Primary Completion: February 1, 2010
• Study Completion: March 1, 2010
• Last Updated: July 29, 2010

Record last verified: 2010-07

Locations

CA (1)