Trial record 1 of 1 for:    isis 353512
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Safety and Tolerability of Single and Multiple Doses of ISIS 353512 in Healthy Volunteers

This study has been completed.
Sponsor:
Collaborator:
Anapharm
Information provided by:
Isis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00734240
First received: August 12, 2008
Last updated: July 28, 2010
Last verified: July 2010
  Purpose

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.


Condition Intervention Phase
Inflammatory Diseases
Drug: ISIS 353512
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Double Blind, Placebo-Controlled, Dose-Escalation, Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of ISIS 353512 Administered Intravenously and Subcutaneously to Healthy Volunteers

Further study details as provided by Isis Pharmaceuticals:

Primary Outcome Measures:
  • To evaluate the safety and tolerability of single and multiple doses of ISIS 353512 administered intravenously and subcutaneously. [ Time Frame: 14 Days post treatment of each cohort ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the pharmacokinetic profile of single and multiple doses of ISIS 353512 administered intravenously and subcutaneously. [ Time Frame: 14 Days post treatment of each cohort ] [ Designated as safety issue: No ]
  • To evaluate the pharmacodynamics of ISIS 353512 administered intravenously and subcutaneously. [ Time Frame: 14 Days post treatment of each cohort ] [ Designated as safety issue: No ]

Enrollment: 103
Study Start Date: July 2008
Study Completion Date: March 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 355312 or placebo
Drug: ISIS 353512
50 mg via 2 hour IV infusion, single dose
Experimental: B
single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo
Drug: ISIS 353512
100 mg via 2 hour IV infusion, single dose
Experimental: C
single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo
Drug: ISIS 353512
200 mg via 2 hour IV infusion, single dose
Experimental: AA
multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving 353512 or placebo
Drug: ISIS 353512
50 mg via 2 hour IV infusion, 6 doses over 22 days
Experimental: BB
multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo
Drug: ISIS 353512
100 mg via 2 hour IV infusion, 6 doses over 22 days
Experimental: CC
multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo
Drug: ISIS 353512
200 mg via 2 hour IV infusion, 6 doses over 22 days
Experimental: G
single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo
Drug: ISIS 353512
50 mg via SC injection, single dose
Experimental: H
single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo
Drug: ISIS 353512
100 mg via SC injection, single dose
Experimental: I
single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo
Drug: ISIS 353512
200 mg via SC injection, single-dose
Experimental: GG
multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo
Drug: ISIS 353512
50 mg via SC injection, 6 doses over 22 days
Experimental: HH
multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo
Drug: ISIS 353512
100 mg via SC injection, 6 doses over 22 days
Experimental: II
multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo
Drug: ISIS 353512
200 mg via SC injection, 6 doses over 22 days
Experimental: F (100 mg)
single-dose cohort (n=4, randomized 3 active: 1 placebo) receiving ISIS 353512 or placebo
Drug: ISIS 353512
100 mg via SC injection PLUS an oral treatment of a NSAID, acetaminophen, or oral placebo
Experimental: Dose-Titration 1
multiple-dose cohort (n=4, randomized 3 active: 1 placebo) receiving ISIS 353512 or placebo
Drug: ISIS 353512
2 hour IV infusion, 50 mg on day 3, 100 mg on day 5, and 200 mg on day 8
Experimental: F (200 mg)
single-dose cohort (n=4, randomized 3 active: 1 placebo) receiving ISIS 353512 or placebo
Drug: ISIS 353512
200 mg via SC injection PLUS an oral treatment of a NSAID, acetaminophen, or steroid
Experimental: Dose-Titration 7
multiple-dose cohort (n=4, randomized 3 active: 1 placebo) receiving ISIS 353512 or placebo
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00734240

Locations
Canada, Quebec
Anapharm
Montreal, Quebec, Canada, H3X 2H9
Sponsors and Collaborators
Isis Pharmaceuticals
Anapharm
Investigators
Principal Investigator: Richard Larouche, M.D. Anapharm
  More Information

No publications provided

Responsible Party: Isis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00734240     History of Changes
Other Study ID Numbers: ISIS 353512 CS1
Study First Received: August 12, 2008
Last Updated: July 28, 2010
Health Authority: Canada: Health Canada

ClinicalTrials.gov processed this record on July 23, 2014