Inflammatory DiseasesPhase 1NCT00734240
Safety and Tolerability of Single and Multiple Doses of ISIS 353512 in Healthy Volunteers
A Phase 1 study testing ISIS 353512 in people with Inflammatory Diseases, run by Ionis Pharmaceuticals, Inc. at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Inflammatory Diseases
- What is being tested?
- ISIS 353512
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 103 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2008to Mar 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 20Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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
- Being tested
- ISIS 353512
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ISIS 353512Drug
50 mg via 2 hour IV infusion, single dose
ISIS 353512Drug
50 mg via 2 hour IV infusion, 6 doses over 22 days
ISIS 353512Drug
50 mg via SC injection, single dose
ISIS 353512Drug
50 mg via SC injection, 6 doses over 22 days
ISIS 353512Drug
2 hour IV infusion, 50 mg on day 3, 100 mg on day 5, and 200 mg on day 8
ISIS 353512Drug
100 mg via 2 hour IV infusion, single dose
ISIS 353512Drug
200 mg via 2 hour IV infusion, single dose
ISIS 353512Drug
100 mg via SC injection, single dose
ISIS 353512Drug
200 mg via SC injection, single-dose
ISIS 353512Drug
100 mg via 2 hour IV infusion, 6 doses over 22 days
ISIS 353512Drug
200 mg via 2 hour IV infusion, 6 doses over 22 days
ISIS 353512Drug
100 mg via SC injection, 6 doses over 22 days
ISIS 353512Drug
200 mg via SC injection, 6 doses over 22 days
ISIS 353512Drug
100 mg via SC injection PLUS an oral treatment of a NSAID, acetaminophen, or oral placebo
ISIS 353512Drug
200 mg via SC injection PLUS an oral treatment of a NSAID, acetaminophen, or steroid
ISIS 353512Drug
2 hour IV infusion, 50 mg on day 1, 100 mg on day 3, 100 mg on day 5 and 200mg on day 8
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 355312 or placebo Receives: Drug: ISIS 353512 |
| B | Experimental | single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo Receives: Drug: ISIS 353512 |
| C | Experimental | single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo Receives: Drug: ISIS 353512 |
| AA | Experimental | multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving 353512 or placebo Receives: Drug: ISIS 353512 |
| BB | Experimental | multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo Receives: Drug: ISIS 353512 |
| CC | Experimental | multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo Receives: Drug: ISIS 353512 |
| G | Experimental | single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo Receives: Drug: ISIS 353512 |
| H | Experimental | single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo Receives: Drug: ISIS 353512 |
| I | Experimental | single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo Receives: Drug: ISIS 353512 |
| GG | Experimental | multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo Receives: Drug: ISIS 353512 |
| HH | Experimental | multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo Receives: Drug: ISIS 353512 |
| II | Experimental | multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo Receives: Drug: ISIS 353512 |
| F (100 mg) | Experimental | single-dose cohort (n=4, randomized 3 active: 1 placebo) receiving ISIS 353512 or placebo Receives: Drug: ISIS 353512 |
| Dose-Titration 1 | Experimental | multiple-dose cohort (n=4, randomized 3 active: 1 placebo) receiving ISIS 353512 or placebo Receives: Drug: ISIS 353512 |
| F (200 mg) | Experimental | single-dose cohort (n=4, randomized 3 active: 1 placebo) receiving ISIS 353512 or placebo Receives: Drug: ISIS 353512 |
| Dose-Titration 7 | Experimental | multiple-dose cohort (n=4, randomized 3 active: 1 placebo) receiving ISIS 353512 or placebo Receives: Drug: ISIS 353512 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the safety and tolerability of single and multiple doses of ISIS 353512 administered intravenously and subcutaneously.
Measured: 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.
Measured: 14 Days post treatment of each cohort
To evaluate the pharmacodynamics of ISIS 353512 administered intravenously and subcutaneously.
Measured: 14 Days post treatment of each cohort
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2008 (estimated)
- Study startJul 2008
- Primary completionFeb 2010
- Study completionMar 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Inflammatory DiseasesStudies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Anapharm
- Investigators
- Richard Larouche, M.D., Principal investigator, Anapharm
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00734240
- Sponsor's protocol ID
- ISIS 353512 CS1
- Status last verified
- Jul 2010
- First submitted
- 12 Aug 2008
- Last updated
- 29 Jul 2010
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00734240
- Acronym / sponsor ID
- ISIS 353512 CS1
- Conditions
- Inflammatory Diseases
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Anapharm
- Study start
- Jul 2008
- Primary completion
- Feb 2010 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 14 Aug 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 16
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: ISIS 353512single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 355312 or placebo |
| B | Experimental | Drug: ISIS 353512single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo |
| C | Experimental | Drug: ISIS 353512single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo |
| AA | Experimental | Drug: ISIS 353512multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving 353512 or placebo |
| BB | Experimental | Drug: ISIS 353512multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo |
| CC | Experimental | Drug: ISIS 353512multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo |
| G | Experimental | Drug: ISIS 353512single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo |
| H | Experimental | Drug: ISIS 353512single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo |
| I | Experimental | Drug: ISIS 353512single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo |
| GG | Experimental | Drug: ISIS 353512multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo |
| HH | Experimental | Drug: ISIS 353512multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo |
| II | Experimental | Drug: ISIS 353512multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo |
| F (100 mg) | Experimental | Drug: ISIS 353512single-dose cohort (n=4, randomized 3 active: 1 placebo) receiving ISIS 353512 or placebo |
| Dose-Titration 1 | Experimental | Drug: ISIS 353512multiple-dose cohort (n=4, randomized 3 active: 1 placebo) receiving ISIS 353512 or placebo |
| F (200 mg) | Experimental | Drug: ISIS 353512single-dose cohort (n=4, randomized 3 active: 1 placebo) receiving ISIS 353512 or placebo |
| Dose-Titration 7 | Experimental | Drug: ISIS 353512multiple-dose cohort (n=4, randomized 3 active: 1 placebo) receiving ISIS 353512 or placebo |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ISIS 35351250 mg via 2 hour IV infusion, single dose | Drug | A |
| ISIS 35351250 mg via 2 hour IV infusion, 6 doses over 22 days | Drug | AA |
| ISIS 35351250 mg via SC injection, single dose | Drug | G |
| ISIS 35351250 mg via SC injection, 6 doses over 22 days | Drug | GG |
| ISIS 3535122 hour IV infusion, 50 mg on day 3, 100 mg on day 5, and 200 mg on day 8 | Drug | Dose-Titration 1 |
| ISIS 353512100 mg via 2 hour IV infusion, single dose | Drug | B |
| ISIS 353512200 mg via 2 hour IV infusion, single dose | Drug | C |
| ISIS 353512100 mg via SC injection, single dose | Drug | H |
| ISIS 353512200 mg via SC injection, single-dose | Drug | I |
| ISIS 353512100 mg via 2 hour IV infusion, 6 doses over 22 days | Drug | BB |
| ISIS 353512200 mg via 2 hour IV infusion, 6 doses over 22 days | Drug | CC |
| ISIS 353512100 mg via SC injection, 6 doses over 22 days | Drug | HH |
| ISIS 353512200 mg via SC injection, 6 doses over 22 days | Drug | II |
| ISIS 353512100 mg via SC injection PLUS an oral treatment of a NSAID, acetaminophen, or oral placebo | Drug | F (100 mg) |
| ISIS 353512200 mg via SC injection PLUS an oral treatment of a NSAID, acetaminophen, or steroid | Drug | F (200 mg) |
| ISIS 3535122 hour IV infusion, 50 mg on day 1, 100 mg on day 3, 100 mg on day 5 and 200mg on day 8 | Drug | Dose-Titration 7 |
Primary outcome
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
2 secondary outcomes
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
To evaluate the pharmacodynamics of ISIS 353512 administered intravenously and subcutaneously.
Time frame: 14 Days post treatment of each cohort
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2010.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard Larouche, M.D. principal investigator
Anapharm
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ISIS 353512 in people with Inflammatory Diseases, run by Ionis Pharmaceuticals, Inc. at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jul 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2010.