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
Overview
- Phase
- Phase 1
- Intervention
- ISIS 353512
- Conditions
- Inflammatory Diseases
- Sponsor
- Ionis Pharmaceuticals, Inc.
- Enrollment
- 103
- Locations
- 1
- Primary Endpoint
- To evaluate the safety and tolerability of single and multiple doses of ISIS 353512 administered intravenously and subcutaneously.
- Status
- Completed
- Last Updated
- 15 years ago
Overview
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.
Investigators
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)
Arms & Interventions
A
single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 355312 or placebo
Intervention: ISIS 353512
B
single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo
Intervention: ISIS 353512
C
single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo
Intervention: ISIS 353512
AA
multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving 353512 or placebo
Intervention: ISIS 353512
BB
multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo
Intervention: ISIS 353512
CC
multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo
Intervention: ISIS 353512
G
single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo
Intervention: ISIS 353512
H
single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo
Intervention: ISIS 353512
I
single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo
Intervention: ISIS 353512
GG
multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo
Intervention: ISIS 353512
HH
multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo
Intervention: ISIS 353512
II
multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo
Intervention: ISIS 353512
F (100 mg)
single-dose cohort (n=4, randomized 3 active: 1 placebo) receiving ISIS 353512 or placebo
Intervention: ISIS 353512
Dose-Titration 1
multiple-dose cohort (n=4, randomized 3 active: 1 placebo) receiving ISIS 353512 or placebo
Intervention: ISIS 353512
F (200 mg)
single-dose cohort (n=4, randomized 3 active: 1 placebo) receiving ISIS 353512 or placebo
Intervention: ISIS 353512
Dose-Titration 7
multiple-dose cohort (n=4, randomized 3 active: 1 placebo) receiving ISIS 353512 or placebo
Intervention: ISIS 353512
Outcomes
Primary Outcomes
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
Secondary Outcomes
- 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)