Diabetes Mellitus, Type 2Phase 1NCT02009488
Treatment Differences Between Canagliflozin and Placebo in Insulin Secretion in Subjects With Type 2 Diabetes Mellitus (T2DM)
A Phase 1 study testing Canagliflozin, 100 mg and Canagliflozin, 300 mg in people with Diabetes Mellitus, Type 2, run by Janssen Research & Development, LLC at 2 sites in United States.
Trial summary
The purpose of this study is to assess changes from baseline in insulin sensitivity, hepatic fat content and beta cell function after approximately 24-25 weeks of treatment with canagliflozin compared to placebo in participants with type 2 diabetes mellitus (T2DM) with inadequate glycemic (blood sugar) control on… Read more about this study
- Who is it for?
- Ages 25 to 70 years
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- Canagliflozin, 100 mg and Canagliflozin, 300 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 59 participants
- Where
- 2 sitesUnited States
- Study dates
- 8 Sep 2014to 3 Jan 2017
- 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 25 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must have a diagnosis of T2DM for at least 3 months and be on either metformin monotherapy at a stable dose of >=1,000 mg per day or on combination therapy of metformin >=1,000 mg per day and a DPP-4 inhibitor at stable daily doses for at least 12 weeks prior to screening with an HbA1c of >=7.0% and <= 9.5% at Screening
- Fasting plasma glucose >=120 mg/dL and <=240 mg/dL at the Week -4 visit
- Fasting fingerstick glucose >=120 mg/dL and <=240 mg/dL performed at clinical research center on Day -14
- Must be medically stable on the basis of clinical laboratory tests performed at screening
Who cannot join
- Has a history of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or β-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy
- Has claustrophobia or anxiety, related to previous negative experiences with magnetic resonance imaging procedures which cannot be managed with an anxiolytic drug
- Has a history of brittle or labile glycemic control, with widely varying glucose measurements
- Has proliferative diabetic retinopathy (based on an eye examination within one year prior to Screening), currently receiving or requiring treatment
- Has a history of 1 or more severe hypoglycemic episodes within 6 months before screening
- Has history of hereditary glucose-galactose malabsorption or primary renal glucosuria.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Study site
Gainesville, Florida
Study site
San Diego, La Jolla, California
About this study
Official title: A Double-Blind, Placebo-Controlled, Randomized, Parallel Groups, Multicenter Study to Investigate the Effects of Canagliflozin on Insulin Sensitivity, Hepatic Fat Content and Beta Cell Function in Subjects With Type 2 Diabetes Mellitus
The purpose of this study is to assess changes from baseline in insulin sensitivity, hepatic fat content and beta cell function after approximately 24-25 weeks of treatment with canagliflozin compared to placebo in participants with type 2 diabetes mellitus (T2DM) with inadequate glycemic (blood sugar) control on metformin monotherapy or on combination therapy with metformin and a dipeptidyl peptidase-4 (DPP-4) inhibitor.
Read the detailed description
This is a double-blind (neither physician nor participants knows the treatment that the participant receives), randomized (the study medication is assigned by chance), placebo-controlled (an inactive substance is compared with a medication to test whether the medication has a real effect in a clinical study), parallel-groups study which will be conducted at 2 clinical research centers (CRC) in the US. Approximately 56 participants, ages 25-70 years, with T2DM inadequately controlled on either metformin monotherapy or combination therapy with metformin and a DPP-4 inhibitor, will be enrolled. The study has 3 phases: pre-treatment, double-blind treatment, and post-treatment.
Pre-Treatment Phase will consist of a screening visit (Week -5), 14 days Single- Blind Placebo Run-in period, followed by 14 days of Single-Blind Placebo Baseline Period, during which participants will be randomized (1:1) to one of 2 treatment groups, either canagliflozin or placebo. Double-Blind Treatment Phase begins on Day 1, and ends at approximately Week 25, during which participants will be assessed at least biweekly at outpatient visits or by telephone contact. Canagliflozin treatment will be initiated at 100 mg/day, with up-titration to 300 mg/day, consistent with the approved INVOKANA® US Prescribing Information 2013. During post-treatment phase, a follow-up visit will occur within approximately 28 days after the last dose of study drug.
At baseline and after 24 weeks of treatment with canagliflozin, hepatic and peripheral insulin sensitivity will be assessed using tracer labeled euglycemic clamp technique; hepatic fat content will be determined using 1H nuclear magnetic resonance spectroscopy (MRS); beta cell function (insulin secretion rate and beta cell glucose sensitivity) will be assessed during mixed meal tolerance test (MMTT); substrate oxidation and energy production rates will be measured using indirect calorimetry during euglycemic clamp and MMTT.
During the study, participants will remain on their stable dose regimens of metformin or combination metformin DPP-4 inhibitor therapy, unless the investigator considers dose modification to be medically necessary. The total study duration for each participant participating in this study will be up to approximately 34 weeks.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- Canagliflozin, 100 mg, Canagliflozin, 300 mg, Placebo
- Keywords
- Diabetes Mellitus, Type 2, Metformin, Canagliflozin, INVOKANA®, Insulin sensitivity, DPP-4 inhibitor, dipeptidyl peptidase-4
- Medical subject headings
- Diabetes Mellitus, Type 2, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Canagliflozin, 100 mgDrug
One 100 mg capsule taken orally (by mouth) once daily
Canagliflozin, 300 mgDrug
One 300 mg capsule taken orally (by mouth) once daily
PlaceboDrug
One placebo capsule (inactive medication) once daily.
| Study group | Role | What they receive |
|---|---|---|
| Canagliflozin (JNJ-28431754) | Experimental | Each patient will receive canagliflozin 100 mg once daily during the first 4 weeks of the 25 weeks double-blind period, then the dose may be increased to 300 mg once daily, till the end of the period. Receives: Drug: Canagliflozin, 100 mg; Drug: Canagliflozin, 300 mg |
| Placebo | Placebo comparator | One placebo capsule taken orally (by mouth) once daily for approximately 28 days during the Pre-Treatment Run-In and the Baseline Periods, then during double-blind study for 178 days (approximately 24-25 weeks). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in hepatic insulin sensitivity
Measured: Baseline, 25 weeks
Change from baseline in peripheral tissue insulin sensitivity
Measured: Baseline, 25 weeks
Change from baseline in liver fat content, determined using magnetic resonance spectroscopy (MRS)
Measured: Baseline, 25 weeks
Change from baseline in insulin secretion rate (ISR) during mixed-meal tolerance test (MMTT)
Measured: Baseline, 25 weeks
Change from baseline in beta-cell glucose sensitivity, determined as a slope of ISR vs. plasma glucose concentration during MMTT
Measured: Baseline, 25 weeks
Secondary outcomes (5)
Changes from baseline in substrate oxidation and energy production rates during MMTT and euglycemic clamp
Measured: Baseline, 25 weeks
Changes from baseline in insulin clearance during MMTT and euglycemic clamp
Measured: Baseline, 25 weeks
Change from baseline in suppression of free fatty acids (FFAs) during euglycemic clamp
Measured: Baseline, 25 weeks
Changes from baseline in basal and postprandial plasma glucagon, FFAs and β-hydroxybutyrate during MMTT
Measured: Baseline, 25 weeks
Change from baseline in renal threshold for glucose (RTG), estimated using an MMTT-based method
Measured: Baseline, 25 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2013 (estimated)
- Study start8 Sep 2014
- Primary completion3 Jan 2017
- Study completion3 Jan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe 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
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02009488
- Sponsor's protocol ID
- CR103062
- Other IDs
- 28431754DIA1054
- Status last verified
- Jan 2018
- First submitted
- 9 Dec 2013
- Last updated
- 4 Jan 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Placebo-Controlled, Randomized, Parallel Groups, Multicenter Study to Investigate the Effects of Canagliflozin on Insulin Sensitivity, Hepatic Fat Content and Beta Cell Function in Subjects With Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT02009488
- Acronym / sponsor ID
- CR103062
- Conditions
- Diabetes Mellitus, Type 2
- Keywords
- Diabetes Mellitus, Type 2, Metformin, Canagliflozin, INVOKANA®, Insulin sensitivity, DPP-4 inhibitor, dipeptidyl peptidase-4
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- 8 Sep 2014 (actual)
- Primary completion
- 3 Jan 2017 (actual)
- Study completion
- 3 Jan 2017 (actual)
- First posted
- 12 Dec 2013 (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 assess changes from baseline in insulin sensitivity, hepatic fat content and beta cell function after approximately 24-25 weeks of treatment with canagliflozin compared to placebo in participants with type 2 diabetes mellitus (T2DM) with inadequate glycemic (blood sugar) control on metformin monotherapy or on combination therapy with metformin and a dipeptidyl peptidase-4 (DPP-4) inhibitor.
Detailed description
This is a double-blind (neither physician nor participants knows the treatment that the participant receives), randomized (the study medication is assigned by chance), placebo-controlled (an inactive substance is compared with a medication to test whether the medication has a real effect in a clinical study), parallel-groups study which will be conducted at 2 clinical research centers (CRC) in the US. Approximately 56 participants, ages 25-70 years, with T2DM inadequately controlled on either metformin monotherapy or combination therapy with metformin and a DPP-4 inhibitor, will be enrolled. The study has 3 phases: pre-treatment, double-blind treatment, and post-treatment.
Pre-Treatment Phase will consist of a screening visit (Week -5), 14 days Single- Blind Placebo Run-in period, followed by 14 days of Single-Blind Placebo Baseline Period, during which participants will be randomized (1:1) to one of 2 treatment groups, either canagliflozin or placebo. Double-Blind Treatment Phase begins on Day 1, and ends at approximately Week 25, during which participants will be assessed at least biweekly at outpatient visits or by telephone contact. Canagliflozin treatment will be initiated at 100 mg/day, with up-titration to 300 mg/day, consistent with the approved INVOKANA® US Prescribing Information 2013. During post-treatment phase, a follow-up visit will occur within approximately 28 days after the last dose of study drug.
At baseline and after 24 weeks of treatment with canagliflozin, hepatic and peripheral insulin sensitivity will be assessed using tracer labeled euglycemic clamp technique; hepatic fat content will be determined using 1H nuclear magnetic resonance spectroscopy (MRS); beta cell function (insulin secretion rate and beta cell glucose sensitivity) will be assessed during mixed meal tolerance test (MMTT); substrate oxidation and energy production rates will be measured using indirect calorimetry during euglycemic clamp and MMTT.
During the study, participants will remain on their stable dose regimens of metformin or combination metformin DPP-4 inhibitor therapy, unless the investigator considers dose modification to be medically necessary. The total study duration for each participant participating in this study will be up to approximately 34 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Canagliflozin (JNJ-28431754) | Experimental | Drug: Canagliflozin, 100 mg, Drug: Canagliflozin, 300 mgEach patient will receive canagliflozin 100 mg once daily during the first 4 weeks of the 25 weeks double-blind period, then the dose may be increased to 300 mg once daily, till the end of the period. |
| Placebo | Placebo comparator | Drug: PlaceboOne placebo capsule taken orally (by mouth) once daily for approximately 28 days during the Pre-Treatment Run-In and the Baseline Periods, then during double-blind study for 178 days (approximately 24-25 weeks). |
Who may qualify
- Ages
- 25 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Must have a diagnosis of T2DM for at least 3 months and be on either metformin monotherapy at a stable dose of >=1,000 mg per day or on combination therapy of metformin >=1,000 mg per day and a DPP-4 inhibitor at stable daily doses for at least 12 weeks prior to screening with an HbA1c of >=7.0% and <= 9.5% at Screening
- Fasting plasma glucose >=120 mg/dL and <=240 mg/dL at the Week -4 visit
- Fasting fingerstick glucose >=120 mg/dL and <=240 mg/dL performed at clinical research center on Day -14
- Must be medically stable on the basis of clinical laboratory tests performed at screening
Key exclusion criteria (6 listed)
- Has a history of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or β-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy
- Has claustrophobia or anxiety, related to previous negative experiences with magnetic resonance imaging procedures which cannot be managed with an anxiolytic drug
- Has a history of brittle or labile glycemic control, with widely varying glucose measurements
- Has proliferative diabetic retinopathy (based on an eye examination within one year prior to Screening), currently receiving or requiring treatment
- Has a history of 1 or more severe hypoglycemic episodes within 6 months before screening
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 |
|---|---|---|
| Canagliflozin, 100 mgOne 100 mg capsule taken orally (by mouth) once daily | Drug | Canagliflozin (JNJ-28431754) |
| Canagliflozin, 300 mgOne 300 mg capsule taken orally (by mouth) once daily | Drug | Canagliflozin (JNJ-28431754) |
| PlaceboOne placebo capsule (inactive medication) once daily. | Drug | Placebo |
Primary outcome
Change from baseline in hepatic insulin sensitivity
Time frame: Baseline, 25 weeks
Change from baseline in peripheral tissue insulin sensitivity
Time frame: Baseline, 25 weeks
Change from baseline in liver fat content, determined using magnetic resonance spectroscopy (MRS)
Time frame: Baseline, 25 weeks
Change from baseline in insulin secretion rate (ISR) during mixed-meal tolerance test (MMTT)
Time frame: Baseline, 25 weeks
Change from baseline in beta-cell glucose sensitivity, determined as a slope of ISR vs. plasma glucose concentration during MMTT
Time frame: Baseline, 25 weeks
5 secondary outcomes
Changes from baseline in substrate oxidation and energy production rates during MMTT and euglycemic clamp
Time frame: Baseline, 25 weeks
Changes from baseline in insulin clearance during MMTT and euglycemic clamp
Time frame: Baseline, 25 weeks
Change from baseline in suppression of free fatty acids (FFAs) during euglycemic clamp
Time frame: Baseline, 25 weeks
Changes from baseline in basal and postprandial plasma glucagon, FFAs and β-hydroxybutyrate during MMTT
Time frame: Baseline, 25 weeks
Change from baseline in renal threshold for glucose (RTG), estimated using an MMTT-based method
Time frame: Baseline, 25 weeks
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 4 Jan 2018.
- A Double-Blind, Placebo-Controlled, Randomized, Parallel Groups, Multicenter Study to Investigate the Effects of Canagliflozin on Insulin Sensitivity, Hepatic Fat Content and Beta Cell Function in Subjects with Type 2 Diabetes MellitusLink provided by the sponsor.
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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.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Canagliflozin, 100 mg and Canagliflozin, 300 mg in people with Diabetes Mellitus, Type 2, run by Janssen Research & Development, LLC at 2 sites in United States.
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 4 inclusion and 6 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 4 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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. Some participants in this study may receive a placebo. 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?
Change from baseline in hepatic insulin sensitivity (time frame: Baseline, 25 weeks). The study lists 5 primary outcomes in all. 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 4 Jan 2018.