HypercholesterolemiaPhase 2NCT00216463
Safety and Tolerability of Varying Load and Dose of ISIS 301012 in People With Elevated LDL-cholesterol Levels
A Phase 2 study of Hypercholesterolemia, run by Kastle Therapeutics, LLC at 1 site in Germany.
Trial summary
The aim of this study is to assess the safety and tolerability of varying dose and load regimens of ISIS 301012 in people who have elevated LDL-cholesterol levels. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hypercholesterolemia
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteGermany
- Study dates
- Aug 2005to Aug 2007
- Phase
- Phase 2
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- BMI >/= 25 to </= 32 kg/m^2
- fasting stable LDL-cholesterol >/= 130 mg/dL (3.36 mmol/L) and triglycerides < 400 mg/dL (4.55 mmol/L)
- Females not of childbearing potential
Who cannot join
- No endocrine, hematologic, renal, hepatic, metabolic, psychiatric, neurology, pulmonary or cardiovascular disease
- Subjects who test positive for hepatitis B, C or HIV
- Current diagnosis or known history of liver disease, such as acute or chronic hepatitis, liver cirrhosis, liver steatosis, or liver function abnormalities such as AST, ALT, GGT, or total bilirubin >/= 1.5 x ULN at Screening
- A systolic blood pressure >/= 160 mmHg or a diastolic blood pressure >/= 95 mmHg on 2 occasions during Screening
- Concomitant medications within 14 days of dosing, except hormone replacement therapy for post-menopausal women and acetylsalicylic acid or paracetamol dosed for fewer than five consecutive days
- Subject has taken any lipid-lowering drug within 30 days or five half-lives (of the lipid-lowering drug) whichever is longer, prior to Screening
Show all 9Show fewer
- Alcohol or drug abuse within 2 years of Screening
- Donated blood (450 mL) within the 3 months prior to Screening or suffered significant blood loss equal to a blood donor portion
- Subject smokes > 10 cigarettes, or more than one pipe or one cigar per day
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2, Randomized, Double Blind, Placebo-Controlled, Parallel Group Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Varying Loading and Maintenance Dosing Regimens of ISIS 301012 Administered to Hypercholesterolemic Subjects
The aim of this study is to assess the safety and tolerability of varying dose and load regimens of ISIS 301012 in people who have elevated LDL-cholesterol levels.
- Conditions
- Hypercholesterolemia
- Being tested
- ISIS 301012 or Placebo
- Keywords
- LDL-cholesterol, apoB-100, apoB-48
- Medical subject headings
- Hypercholesterolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ISIS 301012 or PlaceboDrug
200 mg subcutaneous injection - 4 loading doses within the first 11 days followed by: 200 mg subcutaneous injection - every other week for 11 weeks
ISIS 301012 or PlaceboDrug
200 mg subcutaneous injection - 4 loading doses within the first 11 days followed by: 100 mg subcutaneous injection - every other week for 11 weeks
ISIS 301012 or PlaceboDrug
300 mg subcutaneous injection - every week for 13 weeks
ISIS 301012 or PlaceboDrug
400 mg subcutaneous injection - every week for 13 weeks
ISIS 301012 or PlaceboDrug
200 mg subcutaneous injection - every week for 13 weeks
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Slow load with every other week maintenance Receives: Drug: ISIS 301012 or Placebo |
| B | Experimental | Slow load with every other week maintenance Receives: Drug: ISIS 301012 or Placebo |
| C | Experimental | No load; once weekly maintenance Receives: Drug: ISIS 301012 or Placebo |
| D | Experimental | No load; once weekly maintenance Receives: Drug: ISIS 301012 or Placebo |
| E | Experimental | No load; once weekly maintenance Receives: Drug: ISIS 301012 or Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent reduction in LDL-cholesterol from baseline
Measured: 14 days post dosing
Secondary outcomes (3)
Percent reduction in apoB-100 from baseline
Measured: 14 days post dosing
Percent change from baseline in HDL-cholesterol, triglycerides, total cholesterol, non-HDL cholesterol, VLDL and LP(a)
Measured: 14 days post dosing
Percent change from baseline in LDL/HDL and apoB-100/apo-A1 ratios
Measured: 14 days post dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2005 (estimated)
- Study startAug 2005
- Primary completionMar 2007
- Study completionAug 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypercholesterolemiaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kastle Therapeutics, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ionis Pharmaceuticals, Inc.
- Investigators
- Medical Monitor, Study director, Genzyme, a Sanofi Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00216463
- Sponsor's protocol ID
- 301012CS3
- Other IDs
- EudraCT No.: 2004-003934-32
- Status last verified
- Aug 2016
- First submitted
- 19 Sep 2005
- Last updated
- 3 Aug 2016
- Results posted
- No
Publications
Akdim F, Tribble DL, Flaim JD, Yu R, Su J, Geary RS, Baker BF, Fuhr R, Wedel MK, Kastelein JJ. Efficacy of apolipoprotein B synthesis inhibition in subjects with mild-to-moderate hyperlipidaemia. Eur Heart J. 2011 Nov;32(21):2650-9. doi: 10.1093/eurheartj/ehr148. Epub 2011 May 18.
PubMed 21593041
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double Blind, Placebo-Controlled, Parallel Group Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Varying Loading and Maintenance Dosing Regimens of ISIS 301012 Administered to Hypercholesterolemic Subjects
- ClinicalTrials.gov ID
- NCT00216463
- Acronym / sponsor ID
- 301012CS3
- Conditions
- Hypercholesterolemia
- Keywords
- LDL-cholesterol, apoB-100, apoB-48
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Kastle Therapeutics, LLCIndustry (pharma, biotech, devices)
- Collaborators
- Ionis Pharmaceuticals, Inc.
- Study start
- Aug 2005
- Primary completion
- Mar 2007 (actual)
- Study completion
- Aug 2007 (actual)
- First posted
- 22 Sep 2005 (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 aim of this study is to assess the safety and tolerability of varying dose and load regimens of ISIS 301012 in people who have elevated LDL-cholesterol levels.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: ISIS 301012 or PlaceboSlow load with every other week maintenance |
| B | Experimental | Drug: ISIS 301012 or PlaceboSlow load with every other week maintenance |
| C | Experimental | Drug: ISIS 301012 or PlaceboNo load; once weekly maintenance |
| D | Experimental | Drug: ISIS 301012 or PlaceboNo load; once weekly maintenance |
| E | Experimental | Drug: ISIS 301012 or PlaceboNo load; once weekly maintenance |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- BMI >/= 25 to </= 32 kg/m^2
- fasting stable LDL-cholesterol >/= 130 mg/dL (3.36 mmol/L) and triglycerides < 400 mg/dL (4.55 mmol/L)
- Females not of childbearing potential
Key exclusion criteria (9 listed)
- No endocrine, hematologic, renal, hepatic, metabolic, psychiatric, neurology, pulmonary or cardiovascular disease
- Subjects who test positive for hepatitis B, C or HIV
- Current diagnosis or known history of liver disease, such as acute or chronic hepatitis, liver cirrhosis, liver steatosis, or liver function abnormalities such as AST, ALT, GGT, or total bilirubin >/= 1.5 x ULN at Screening
- A systolic blood pressure >/= 160 mmHg or a diastolic blood pressure >/= 95 mmHg on 2 occasions during Screening
- Concomitant medications within 14 days of dosing, except hormone replacement therapy for post-menopausal women and acetylsalicylic acid or paracetamol dosed for fewer than five consecutive days
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 301012 or Placebo200 mg subcutaneous injection - 4 loading doses within the first 11 days followed by: 200 mg subcutaneous injection - every other week for 11 weeks | Drug | A |
| ISIS 301012 or Placebo200 mg subcutaneous injection - 4 loading doses within the first 11 days followed by: 100 mg subcutaneous injection - every other week for 11 weeks | Drug | B |
| ISIS 301012 or Placebo300 mg subcutaneous injection - every week for 13 weeks | Drug | D |
| ISIS 301012 or Placebo400 mg subcutaneous injection - every week for 13 weeks | Drug | E |
| ISIS 301012 or Placebo200 mg subcutaneous injection - every week for 13 weeks | Drug | C |
Primary outcome
Percent reduction in LDL-cholesterol from baseline
Time frame: 14 days post dosing
3 secondary outcomes
Percent reduction in apoB-100 from baseline
Time frame: 14 days post dosing
Percent change from baseline in HDL-cholesterol, triglycerides, total cholesterol, non-HDL cholesterol, VLDL and LP(a)
Time frame: 14 days post dosing
Percent change from baseline in LDL/HDL and apoB-100/apo-A1 ratios
Time frame: 14 days post dosing
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 3 Aug 2016.
- Derived from this study: PubMed 21593041Akdim F, Tribble DL, Flaim JD, Yu R, Su J, Geary RS, Baker BF, Fuhr R, Wedel MK, Kastelein JJ. Efficacy of apolipoprotein B synthesis inhibition in subjects with mild-to-moderate hyperlipidaemia. Eur Heart J. 2011 Nov;32(21):2650-9. doi: 10.1093/eurheartj/ehr148. Epub 2011 May 18.
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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.
Medical Monitor study director
Genzyme, a Sanofi Company
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study of Hypercholesterolemia, run by Kastle Therapeutics, LLC at 1 site in Germany.
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 3 inclusion and 9 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 3 Aug 2016. 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 Germany. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Percent reduction in LDL-cholesterol from baseline (time frame: 14 days post dosing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00216463, which also lists 1 linked publication.
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 3 Aug 2016.