Type 2 Diabetes MellitusPhase 1NCT00519727
Safety Study of ISIS 325568 in Healthy Volunteers
A Phase 1 study testing ISIS 325568 in people with Type 2 Diabetes Mellitus, run by Ionis Pharmaceuticals, Inc. at 1 site in Netherlands.
Trial summary
The primary purpose of this trial is to assess the safety of ISIS 325568 when given at increasing single doses and to assess the safety of the same doses when given multiple times. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- ISIS 325568
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteNetherlands
- Study dates
- Aug 2007to Jun 2008
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 18 to 65 years
- Males or females. Females must be non-pregnant and non-lactating, and either surgically sterile (hysterectomy, oophorectomy, or tubal ligation) or post-menopausal. Males must be surgically sterile, abstinent or if engaged in sexual relations of child-bearing potential, subject or partner must be using an acceptable contraceptive method during the trial and for 9 weeks after the last dose of study drug.
- Give written informed consent to participate in study and availability for all study requirements
- Fasting plasma glucose ≤ the upper limit of the laboratory's reference range (ULN)
- HbA1C ≤ ULN
- BMI < 30 kg/m2
Who cannot join
- Clinically significant abnormalities in medical history or physical examination
- Abnormalities on laboratory examination (ALT > ULN, AST > ULN, bilirubin > ULN, creatinine > ULN, urine protein positive by urine dipstick, platelets < lower limit of normal and any other clinically significant laboratory findings)
- History of clinically significant abnormalities in coagulation parameters
- Positive test result for HIV, hepatitis B virus, and/or hepatitis C virus
- Active infection requiring antiviral or antimicrobial therapy
- Subjects on chronic or acute prescription medication may be permitted after discussion with the Isis Medical Monitor.
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- Malignancy (with the exception of basal or squamous cell carcinoma of the skin if adequately treated and no recurrence for > 1 year)
- Any other concurrent condition which, in the opinion of the Investigator, would preclude participation in this study or interfere with compliance
- History of alcohol or drug abuse
- Undergoing or have undergone treatment with another investigational drug, biologic agent or device within 90 days prior to Screening.
- Blood donation within three months of screening
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Double-Blind, Placebo-Controlled, Dose- Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of ISIS 325568 Administered to Healthy Volunteers
The primary purpose of this trial is to assess the safety of ISIS 325568 when given at increasing single doses and to assess the safety of the same doses when given multiple times.
Read the detailed description
To evaluate the safety of a single subcutaneous injection of ISIS 325568 administered at four increasing dose levels (50, 100, 200, 400 mg/week) and to evaluate the safety and tolerability of multiple doses of ISIS 325568 (three intravenous doses during Study Week 1, followed by once weekly subcutaneous administration for 5 weeks) at each of the four dose levels
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- ISIS 325568
- Keywords
- diabetes
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ISIS 325568Drug
4 arms of single dose s.c. injections: A 50 mg B 100 mg C 200 mg D 400 mg 4 arms of multi-dose: 3 i.v. infusions over 1 week followed by 5 weekly s.c. injections AA 50 mg BB 100 mg CC 200 mg DD 400 mg or EE 50 mg
Placebo: 0.9% Sodium Chloride
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | 50 mg ISIS 325568 vs Placebo, s.c. injection Receives: Drug: ISIS 325568 |
| B | Experimental | 100 mg ISIS 325568 vs Placebo , s.c. injection Receives: Drug: ISIS 325568 |
| C | Experimental | 200 mg ISIS 325568 vs Placebo , s.c. injection Receives: Drug: ISIS 325568 |
| D | Experimental | 400 mg ISIS 325568 vs Placebo, s.c. injection Receives: Drug: ISIS 325568 |
| AA | Experimental | 50 mg ISIS 325568, 3x over 1 week i.v. infusion, weekly s.c. injection for 5 weeks vs Placebo Receives: Drug: ISIS 325568 |
| BB | Experimental | 100 mg ISIS 325568, 3x over 1 week i.v. infusion, weekly s.c. injection for 5 weeks vs Placebo Receives: Drug: ISIS 325568 |
| CC | Experimental | 200 mg ISIS 325568, 3x over 1 week i.v. infusion, weekly s.c. injection for 5 weeks vs Placebo Receives: Drug: ISIS 325568 |
| DD | Experimental | 400 mg ISIS 325568, 3x over 1 week i.v. infusion, weekly s.c. injection for 5 weeks vs Placebo Receives: Drug: ISIS 325568 |
What is being measured
The primary outcome is the main question the study is designed to answer.
safety and tolerability
Measured: 30 days for single dose, 16 weeks for multi-dose
Secondary outcomes (1)
Pharmacokinetic profile all doses and Pharmacodynamics for multi-dose groups.
Measured: 4 days for single dose, 16 weeks for multi-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2007 (estimated)
- Study startAug 2007
- Primary completionApr 2008
- Study completionJun 2008
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 Type 2 Diabetes MellitusStudies 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
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- J. Burggraaf, MD PhD, Principal investigator, Centre for Human Drug Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00519727
- Sponsor's protocol ID
- ISIS 325568-CS1
- Other IDs
- EudraCT No: 2007-000235-25
- Status last verified
- Aug 2008
- First submitted
- 21 Aug 2007
- Last updated
- 19 Aug 2008
- Results posted
- No
- Data monitoring committee
- No
Publications
Burel SA, Machemer T, Baker BF, Kwoh TJ, Paz S, Younis H, Henry SP. Early-Stage Identification and Avoidance of Antisense Oligonucleotides Causing Species-Specific Inflammatory Responses in Human Volunteer Peripheral Blood Mononuclear Cells. Nucleic Acid Ther. 2022 Dec;32(6):457-472. doi: 10.1089/nat.2022.0033. Epub 2022 Aug 17.
PubMed 35976085
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Double-Blind, Placebo-Controlled, Dose- Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of ISIS 325568 Administered to Healthy Volunteers
- ClinicalTrials.gov ID
- NCT00519727
- Acronym / sponsor ID
- ISIS 325568-CS1
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- diabetes
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Aug 2007
- Primary completion
- Apr 2008 (actual)
- Study completion
- Jun 2008 (actual)
- First posted
- 23 Aug 2007 (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 primary purpose of this trial is to assess the safety of ISIS 325568 when given at increasing single doses and to assess the safety of the same doses when given multiple times.
Detailed description
To evaluate the safety of a single subcutaneous injection of ISIS 325568 administered at four increasing dose levels (50, 100, 200, 400 mg/week) and to evaluate the safety and tolerability of multiple doses of ISIS 325568 (three intravenous doses during Study Week 1, followed by once weekly subcutaneous administration for 5 weeks) at each of the four dose levels
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: ISIS 32556850 mg ISIS 325568 vs Placebo, s.c. injection |
| B | Experimental | Drug: ISIS 325568100 mg ISIS 325568 vs Placebo , s.c. injection |
| C | Experimental | Drug: ISIS 325568200 mg ISIS 325568 vs Placebo , s.c. injection |
| D | Experimental | Drug: ISIS 325568400 mg ISIS 325568 vs Placebo, s.c. injection |
| AA | Experimental | Drug: ISIS 32556850 mg ISIS 325568, 3x over 1 week i.v. infusion, weekly s.c. injection for 5 weeks vs Placebo |
| BB | Experimental | Drug: ISIS 325568100 mg ISIS 325568, 3x over 1 week i.v. infusion, weekly s.c. injection for 5 weeks vs Placebo |
| CC | Experimental | Drug: ISIS 325568200 mg ISIS 325568, 3x over 1 week i.v. infusion, weekly s.c. injection for 5 weeks vs Placebo |
| DD | Experimental | Drug: ISIS 325568400 mg ISIS 325568, 3x over 1 week i.v. infusion, weekly s.c. injection for 5 weeks vs Placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age 18 to 65 years
- Males or females. Females must be non-pregnant and non-lactating, and either surgically sterile (hysterectomy, oophorectomy, or tubal ligation) or post-menopausal. Males must be surgically sterile, abstinent or if engaged in sexual relations of child-bearing potential, subject or partner must be using an acceptable contraceptive method during the trial and for 9 weeks after the last dose of study drug.
- Give written informed consent to participate in study and availability for all study requirements
- Fasting plasma glucose ≤ the upper limit of the laboratory's reference range (ULN)
- HbA1C ≤ ULN
Key exclusion criteria (11 listed)
- Clinically significant abnormalities in medical history or physical examination
- Abnormalities on laboratory examination (ALT > ULN, AST > ULN, bilirubin > ULN, creatinine > ULN, urine protein positive by urine dipstick, platelets < lower limit of normal and any other clinically significant laboratory findings)
- History of clinically significant abnormalities in coagulation parameters
- Positive test result for HIV, hepatitis B virus, and/or hepatitis C virus
- Active infection requiring antiviral or antimicrobial therapy
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 3255684 arms of single dose s.c. injections: A 50 mg B 100 mg C 200 mg D 400 mg 4 arms of multi-dose: 3 i.v. infusions over 1 week followed by 5 weekly s.c. injections AA 50 mg BB 100 mg CC 200 mg DD 400 mg or EE 50 mg Placebo: 0.9% Sodium Chloride | Drug | A, AA, B, BB, C, CC, D, DD |
Primary outcome
safety and tolerability
Time frame: 30 days for single dose, 16 weeks for multi-dose
1 secondary outcome
Pharmacokinetic profile all doses and Pharmacodynamics for multi-dose groups.
Time frame: 4 days for single dose, 16 weeks for multi-dose
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 19 Aug 2008.
- Derived from this study: PubMed 35976085Burel SA, Machemer T, Baker BF, Kwoh TJ, Paz S, Younis H, Henry SP. Early-Stage Identification and Avoidance of Antisense Oligonucleotides Causing Species-Specific Inflammatory Responses in Human Volunteer Peripheral Blood Mononuclear Cells. Nucleic Acid Ther. 2022 Dec;32(6):457-472. doi: 10.1089/nat.2022.0033. Epub 2022 Aug 17.
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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.
J. Burggraaf, MD PhD principal investigator
Centre for Human Drug Research
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 325568 in people with Type 2 Diabetes Mellitus, run by Ionis Pharmaceuticals, Inc. at 1 site in Netherlands.
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 11 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 19 Aug 2008. 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 Netherlands. 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?
safety and tolerability (time frame: 30 days for single dose, 16 weeks for multi-dose). 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 NCT00519727, 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 19 Aug 2008.