Type 2 Diabetes MellitusPhase 1NCT00836225
Safety, Tolerability and Activity Study of Multiple Doses of ISIS-SGLT2Rx in Healthy Volunteers
A Phase 1 study testing ISIS 388626 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 and tolerability of ISIS-SGLT2Rx when given at increasing single doses and to assess the safety and tolerability 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 388626
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 103 participants
- Where
- 1 siteNetherlands
- Study dates
- Jan 2009to Jan 2012
- 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
- Male or female gender although females must be post-menopausal or surgically sterile (hysterectomy, oophorectomy or tubal ligation)
- Give written informed consent to participate in the 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
- Agree to maintain steady hydration throughout study participation and agree not to fluid restrict
Who cannot join
- Pregnant women, nursing mothers or women of childbearing potential
- Clinically significant abnormalities in medical history or physical examination
- Clinically significant abnormalities in laboratory examination (including 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)
- Estimated GFR < 60 mL/min per 1.73m²
- History of clinically significant abnormalities in coagulation parameters
- Positive test result for HIV, hepatitis B virus, and/or hepatitis C virus
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- Active infection requiring antiviral or antimicrobial therapy
- Subjects on chronic or acute prescription medication may be permitted after discussion with the Isis Medical Monitor
- 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
- Past and present history of alcohol or drug abuse (defined as > 3 units daily)
- 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 388626 Administered to Healthy Volunteers
The primary purpose of this trial is to assess the safety and tolerability of ISIS-SGLT2Rx when given at increasing single doses and to assess the safety and tolerability of the same doses when given multiple times.
Read the detailed description
To evaluate the safety and tolerability of a single subcutaneous injection of ISIS-SGLT2Rx administered at four increasing dose levels (50, 100, 200, 400 mg) and to evaluate the safety and tolerability of multiple doses of ISIS 388626 administered subcutaneously of either 6 or 13 weeks.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- ISIS 388626
- Keywords
- diabetes, SGLT2 inhibitor
- 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 388626Drug
4 arms of single dose s.c. injections: A 50 mg, B 100 mg, C 200 mg, D 400 mg, 2 arms of multi-dose: 3 s.c. injections over 1 week followed by 5 weekly s.c. injections: AA 50 mg, BB 100 mg 3 arms of multi-dose 13 weekly s.c. injections: AAA 50 mg, BBB 100 mg, CCC 200 mg, FFF 50 mg
Placebo: 0.9% sterile saline
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | 50 mg ISIS 388626 vs Placebo, s.c. injection Receives: Drug: ISIS 388626 |
| B | Experimental | 100 mg ISIS 388626 vs Placebo, s.c. injection Receives: Drug: ISIS 388626 |
| C | Experimental | 200 mg ISIS 388626 vs Placebo, s.c. injection Receives: Drug: ISIS 388626 |
| D | Experimental | 400 mg ISIS 388626 vs Placebo, s.c. injection Receives: Drug: ISIS 388626 |
| AA | Experimental | 50 mg ISIS 388626, 3x over 1 week s.c. injection, weekly s.c. injection for 5 weeks vs Placebo Receives: Drug: ISIS 388626 |
| BB | Experimental | 100 mg ISIS 388626, 3x over 1 week s.c. injection, weekly s.c. injection for 5 weeks vs Placebo Receives: Drug: ISIS 388626 |
| AAA | Experimental | 50 mg ISIS 388626, weekly s.c. injection for 13 weeks vs Placebo Receives: Drug: ISIS 388626 |
| BBB | Experimental | 100 mg ISIS 388626, weekly s.c. injection for 13 weeks vs Placebo Receives: Drug: ISIS 388626 |
| CCC | Experimental | 200 mg ISIS 388626, weekly s.c. injection for 13 weeks vs Placebo Receives: Drug: ISIS 388626 |
| FFF | Experimental | 50 mg ISIS 388626, weekly s.c. injection for 13 weeks vs Placebo Receives: Drug: ISIS 388626 |
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-SGLT2Rx administered subcutaneously
Measured: 30 days for single dose, 11 weeks for 6-week dosing, 18 weeks for 13-week dosing
Secondary outcomes (1)
Pharmacokinetic profile all doses and Pharmacodynamics for multi-dose groups
Measured: 3 days for single dose, 11 weeks for 6-week dosing, 18 weeks for 13-week dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2009 (estimated)
- Study startJan 2009
- Primary completionOct 2011
- Study completionJan 2012
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
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Adam Cohen, MD, PhD, Principal investigator, Center for Human Drug Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00836225
- Sponsor's protocol ID
- ISIS 388626-CS1
- Status last verified
- Feb 2012
- First submitted
- 2 Feb 2009
- Last updated
- 3 Feb 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Tekendo-Ngongang C, Gleeson JG, Mignon L. Treating the Untreatable: Antisense Oligonucleotides as an Individualized Therapy for Rare Genetic Kidney Diseases. J Am Soc Nephrol. 2024 Dec 1;35(12):1774-1777. doi: 10.1681/ASN.0000000532. Epub 2024 Sep 27. No abstract available.
PubMed 39331470
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2012. 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 388626 Administered to Healthy Volunteers
- ClinicalTrials.gov ID
- NCT00836225
- Acronym / sponsor ID
- ISIS 388626-CS1
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- diabetes, SGLT2 inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Jan 2009
- Primary completion
- Oct 2011 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 4 Feb 2009 (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 and tolerability of ISIS-SGLT2Rx when given at increasing single doses and to assess the safety and tolerability of the same doses when given multiple times.
Detailed description
To evaluate the safety and tolerability of a single subcutaneous injection of ISIS-SGLT2Rx administered at four increasing dose levels (50, 100, 200, 400 mg) and to evaluate the safety and tolerability of multiple doses of ISIS 388626 administered subcutaneously of either 6 or 13 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: ISIS 38862650 mg ISIS 388626 vs Placebo, s.c. injection |
| B | Experimental | Drug: ISIS 388626100 mg ISIS 388626 vs Placebo, s.c. injection |
| C | Experimental | Drug: ISIS 388626200 mg ISIS 388626 vs Placebo, s.c. injection |
| D | Experimental | Drug: ISIS 388626400 mg ISIS 388626 vs Placebo, s.c. injection |
| AA | Experimental | Drug: ISIS 38862650 mg ISIS 388626, 3x over 1 week s.c. injection, weekly s.c. injection for 5 weeks vs Placebo |
| BB | Experimental | Drug: ISIS 388626100 mg ISIS 388626, 3x over 1 week s.c. injection, weekly s.c. injection for 5 weeks vs Placebo |
| AAA | Experimental | Drug: ISIS 38862650 mg ISIS 388626, weekly s.c. injection for 13 weeks vs Placebo |
| BBB | Experimental | Drug: ISIS 388626100 mg ISIS 388626, weekly s.c. injection for 13 weeks vs Placebo |
| CCC | Experimental | Drug: ISIS 388626200 mg ISIS 388626, weekly s.c. injection for 13 weeks vs Placebo |
| FFF | Experimental | Drug: ISIS 38862650 mg ISIS 388626, weekly s.c. injection for 13 weeks vs Placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age 18 to 65 years
- Male or female gender although females must be post-menopausal or surgically sterile (hysterectomy, oophorectomy or tubal ligation)
- Give written informed consent to participate in the 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 (13 listed)
- Pregnant women, nursing mothers or women of childbearing potential
- Clinically significant abnormalities in medical history or physical examination
- Clinically significant abnormalities in laboratory examination (including 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)
- Estimated GFR < 60 mL/min per 1.73m²
- History of 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 3886264 arms of single dose s.c. injections: A 50 mg, B 100 mg, C 200 mg, D 400 mg, 2 arms of multi-dose: 3 s.c. injections over 1 week followed by 5 weekly s.c. injections: AA 50 mg, BB 100 mg 3 arms of multi-dose 13 weekly s.c. injections: AAA 50 mg, BBB 100 mg, CCC 200 mg, FFF 50 mg Placebo: 0.9% sterile saline | Drug | A, AA, AAA, B, BB, BBB, C, CCC, D, FFF |
Primary outcome
To evaluate the safety and tolerability of single and multiple doses of ISIS-SGLT2Rx administered subcutaneously
Time frame: 30 days for single dose, 11 weeks for 6-week dosing, 18 weeks for 13-week dosing
1 secondary outcome
Pharmacokinetic profile all doses and Pharmacodynamics for multi-dose groups
Time frame: 3 days for single dose, 11 weeks for 6-week dosing, 18 weeks for 13-week 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 Feb 2012.
- Derived from this study: PubMed 39331470Tekendo-Ngongang C, Gleeson JG, Mignon L. Treating the Untreatable: Antisense Oligonucleotides as an Individualized Therapy for Rare Genetic Kidney Diseases. J Am Soc Nephrol. 2024 Dec 1;35(12):1774-1777. doi: 10.1681/ASN.0000000532. Epub 2024 Sep 27. No abstract available.
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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.
Adam Cohen, MD, PhD principal investigator
Center 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 388626 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 7 inclusion and 13 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 Feb 2012. 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?
To evaluate the safety and tolerability of single and multiple doses of ISIS-SGLT2Rx administered subcutaneously (time frame: 30 days for single dose, 11 weeks for 6-week dosing, 18 weeks for 13-week 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 NCT00836225, 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 Feb 2012.