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

NCT ID: NCT00734240

Last Updated: 2010-07-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 103 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2010-03-31

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.

Detailed Description

This will be a Phase 1, double blind, placebo-controlled, dose-escalation study conducted at a single center to 1)evaluate the safety and tolerability of single and multiple doses of ISIS 353512 administered intravenously and subcutaneously, 2)evaluate the pharmacokinetic profile of single and multiple doses of ISIS 353512 administered intravenously and subcutaneously, and 3)evaluate the pharmacodynamics of ISIS 353512 in lowering constitutive levels of c-reactive proteins in healthy volunteers.

Conditions

Inflammatory Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

A

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

Group Type: EXPERIMENTAL

ISIS 353512

Intervention Type: DRUG

50 mg via 2 hour IV infusion, single dose

B

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

Group Type: EXPERIMENTAL

ISIS 353512

Intervention Type: DRUG

100 mg via 2 hour IV infusion, single dose

C

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

Group Type: EXPERIMENTAL

ISIS 353512

Intervention Type: DRUG

200 mg via 2 hour IV infusion, single dose

AA

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

Group Type: EXPERIMENTAL

ISIS 353512

Intervention Type: DRUG

50 mg via 2 hour IV infusion, 6 doses over 22 days

BB

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

Group Type: EXPERIMENTAL

ISIS 353512

Intervention Type: DRUG

100 mg via 2 hour IV infusion, 6 doses over 22 days

CC

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

Group Type: EXPERIMENTAL

ISIS 353512

Intervention Type: DRUG

200 mg via 2 hour IV infusion, 6 doses over 22 days

G

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

Group Type: EXPERIMENTAL

ISIS 353512

Intervention Type: DRUG

50 mg via SC injection, single dose

H

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

Group Type: EXPERIMENTAL

ISIS 353512

Intervention Type: DRUG

100 mg via SC injection, single dose

I

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

Group Type: EXPERIMENTAL

ISIS 353512

Intervention Type: DRUG

200 mg via SC injection, single-dose

GG

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

Group Type: EXPERIMENTAL

ISIS 353512

Intervention Type: DRUG

50 mg via SC injection, 6 doses over 22 days

HH

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

Group Type: EXPERIMENTAL

ISIS 353512

Intervention Type: DRUG

100 mg via SC injection, 6 doses over 22 days

II

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

Group Type: EXPERIMENTAL

ISIS 353512

Intervention Type: DRUG

200 mg via SC injection, 6 doses over 22 days

F (100 mg)

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

Group Type: EXPERIMENTAL

ISIS 353512

Intervention Type: DRUG

100 mg via SC injection PLUS an oral treatment of a NSAID, acetaminophen, or oral placebo

Dose-Titration 1

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

Group Type: EXPERIMENTAL

ISIS 353512

Intervention Type: DRUG

2 hour IV infusion, 50 mg on day 3, 100 mg on day 5, and 200 mg on day 8

F (200 mg)

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

Group Type: EXPERIMENTAL

ISIS 353512

Intervention Type: DRUG

200 mg via SC injection PLUS an oral treatment of a NSAID, acetaminophen, or steroid

Dose-Titration 7

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

Group Type: EXPERIMENTAL

ISIS 353512

Intervention Type: DRUG

2 hour IV infusion, 50 mg on day 1, 100 mg on day 3, 100 mg on day 5 and 200mg on day 8

Interventions

ISIS 353512

50 mg via 2 hour IV infusion, single dose

Intervention Type: DRUG

ISIS 353512

50 mg via 2 hour IV infusion, 6 doses over 22 days

Intervention Type: DRUG

ISIS 353512

50 mg via SC injection, single dose

Intervention Type: DRUG

ISIS 353512

50 mg via SC injection, 6 doses over 22 days

Intervention Type: DRUG

ISIS 353512

2 hour IV infusion, 50 mg on day 3, 100 mg on day 5, and 200 mg on day 8

Intervention Type: DRUG

ISIS 353512

100 mg via 2 hour IV infusion, single dose

Intervention Type: DRUG

ISIS 353512

200 mg via 2 hour IV infusion, single dose

Intervention Type: DRUG

ISIS 353512

100 mg via SC injection, single dose

Intervention Type: DRUG

ISIS 353512

200 mg via SC injection, single-dose

Intervention Type: DRUG

ISIS 353512

100 mg via 2 hour IV infusion, 6 doses over 22 days

Intervention Type: DRUG

ISIS 353512

200 mg via 2 hour IV infusion, 6 doses over 22 days

Intervention Type: DRUG

ISIS 353512

100 mg via SC injection, 6 doses over 22 days

Intervention Type: DRUG

ISIS 353512

200 mg via SC injection, 6 doses over 22 days

Intervention Type: DRUG

ISIS 353512

100 mg via SC injection PLUS an oral treatment of a NSAID, acetaminophen, or oral placebo

Intervention Type: DRUG

ISIS 353512

200 mg via SC injection PLUS an oral treatment of a NSAID, acetaminophen, or steroid

Intervention Type: DRUG

ISIS 353512

2 hour IV infusion, 50 mg on day 1, 100 mg on day 3, 100 mg on day 5 and 200mg on day 8

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

• 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
• Use of an investigational drug or participation in an investigational study involving a small molecule with 30 days prior to dosing or participation in an investigational study involving biologic compounds within 90 days prior to dosing
• Regularly taking OTC medications and/or vitamin supplements that may alter CRP, e.g., NSAIDs, aspirin, vitamin E, fish oil, within 14 days prior to Screening
• Receiving prescription medications, including hormone replacement therapy, statins, TNF-α inhibitors, or other anti-inflammatory or immunosuppressive drugs within 30 days prior to Screening
• Immunization with a live attenuated vaccine one month prior to dosing or planned vaccination during the course of the study
• Blood donation of 50 to 499 mL within 30 days of Screening or of > 499 mL within 60 days of Screening

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Anapharm

INDUSTRY

Sponsor Role: collaborator

Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Isis Pharmaceuticals, Inc.

Principal Investigators

Richard Larouche, M.D.

Role: PRINCIPAL_INVESTIGATOR

Anapharm

Locations

Anapharm

Montreal, Quebec, Canada

Countries

Canada

Other Identifiers

ISIS 353512 CS1

Identifier Type: -

Identifier Source: org_study_id