DiabetesPhase 3NCT02419612
A 52-week International, Multicenter Trial With a Long -Term Extension to Evaluate Saxagliptin With Dapagliflozin in Combination With Metformin Compared to Glimepiride in Combination With Metformin in Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Alone
A Phase 3 study testing Saxagliptin, Dapagliflozin and Glimepiride in people with Diabetes, run by AstraZeneca at 84 sites in 10 countries.
Trial summary
This clincial trial is evaluating if the co-administration of saxagliptin and dapagliflozin, in addition to metformin, results in better glycemic control, as measured by HbA1c, over a treatment period of 52 weeks, compared to the addition of glimepiride to metformin in subjects with Type 2 Diabetes Mellitus who have… Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Diabetes
- What is being tested?
- Saxagliptin, Dapagliflozin and Glimepiride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 444 participants
- Where
- 84 sitesin 10 countries
- Study dates
- 14 Aug 2015to 18 Sep 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must be willing and able to give signed and dated written informed consent
- Patients with Type 2 diabetes mellitus (T2DM) with inadequate glycemic control
- Subjects should have been taking the same daily dose of metformin ≥ 1500 mg
- Fasting Plasma Glucose ≤ 270 mg/dL (≤15 mmol/L)
- Males and females, aged ≥18 years old at time of screening visit
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test
- WOCBP and males must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug
Who cannot join
- Clinical diagnosis of type I diabetes
- History of diabetic ketoacidosis
- Cardiovascular/vascular diseases within 3 months of the enrollment
- Renal disease
- Hepatic diseases
- History of, or currently, acute or chronic pancreatitis
Show all 10Show fewer
- Hematological and oncological disease/conditions
- Patients who have contraindications to therapy being studied
- Patients on weight loss program(s)
- Replacement or chronic systemic corticosteroid therapy
Trial locations and contacts
84 sites in 10 countries.
84 sites in 10 countries
United States22 sites
Research Site
Birmingham, Alabama, 35211
Research Site
Bristol, Tennessee, 37620
Research Site
Chandler, Arizona, 85224
Research Site
Dallas, Texas, 75230
Research Site
Edina, Minnesota, 55435
Research Site
Greer, South Carolina, 29651
Research Site
Huntington Park, California, 90255
Research Site
Jacksonville, Florida, 32207
Research Site
Jacksonville, Florida, 32277
Research Site
Kissimmee, Florida, 34744
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Knoxville, Tennessee, 37912
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Las Vegas, Nevada, 89128
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Los Angeles, California, 90057
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Miami, Florida, 33126
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Miami, Florida, 33174
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New Port Richey, Florida, 34652
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Palm Harbor, Florida, 34684
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Sacramento, California, 95823
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San Antonio, Texas, 78229
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Tarzana, California, 91356
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Tempe, Arizona, 85283
Research Site
Waterbury, Connecticut, 06708
Hungary12 sites
Research Site
Ajka, 8400
Research Site
Balatonfüred, 8230
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Budapest, 1033
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Budapest, 1089
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Budapest
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Debrecen, 4032
Research Site
Eger, 3300
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Gyula, 5700
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Kaposvár, 7400
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Kecskemét, 6000
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Nyíregyháza, 4405
Research Site
Zalaegerszeg, 8900
Romania12 sites
Research Site
Brasov, 500269
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Bucharest, 020045
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Bucharest, 020359
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Buzău, 120203
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Galati, 800291
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Oradea, 410032
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Oradea, 410169
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Ploieşti, 100163
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Ploieşti, 100342
Research Site
Satu Mare, 440055
Research Site
Târgu Gânguleşti, 540142
Research Site
Timișoara, 300736
Poland11 sites
Research Site
Bialystok, 15-351
Research Site
Katowice, 40-648
Research Site
Krakow, 31-156
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Krakow, 31-261
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Lodz, 90-242
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Opole, 45-367
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Oświęcim, 32-600
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Poznan, 61-655
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Warsaw, 00-465
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Warsaw, 02-507
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Wroclaw, 50-349
Czechia7 sites
Research Site
Cheb, 350 02
Research Site
Hradec Králové, 503 41
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Krnov, 794 01
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Kroměříž, 767 01
Research Site
Náchod, 54701
Research Site
Prague, 140 00
Research Site
Prague, 149 00
Mexico7 sites
Research Site
Aguascalientes, 20230
Research Site
Chihuahua City, 31237
Research Site
Cuautla, 62746
Research Site
Guadalajara, 44600
Research Site
Guanajuato City, 38000
Research Site
Monterrey, 64460
Research Site
Veracruz, 91910
Russia7 sites
Research Site
Novosibirsk, 630087
Research Site
Saint Petersburg, 190013
Research Site
Saint Petersburg, 194354
Research Site
Saint Petersburg, 195176
Research Site
Saint Petersburg, 195257
Research Site
Saint Petersburg, 196084
Research Site
Smolensk, 214018
Sweden3 sites
Research Site
Gothenburg, 413 45
Research Site
Helsingborg, 25220
Research Site
Rättvik, 79530
About this study
Official title: A 52-week International, Multicenter, Randomized, Double-Blind, Active-Controlled, Parallel Group, Phase 3bTrial With a Blinded 104-week Long -Term Extension Period to Evaluate the Efficacy and Safety of Saxagliptin Co-administered With Dapagliflozin in Combination With Metformin Compared to Glimepiride in Combination With Metformin ≥1500 mg in Adult Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Therapy Alone
This clincial trial is evaluating if the co-administration of saxagliptin and dapagliflozin, in addition to metformin, results in better glycemic control, as measured by HbA1c, over a treatment period of 52 weeks, compared to the addition of glimepiride to metformin in subjects with Type 2 Diabetes Mellitus who have inadequate glycemic control on Metformin Alone. We will compare the change from baseline in HbA1c achieved with saxagliptin, in co-administration with dapagliflozin, added to current background therapy with metformin compared to glimepiride added to current background therapy with metformin ≥1500 mg at Week 52.
- Conditions
- Diabetes
- Being tested
- Saxagliptin, Dapagliflozin, Glimepiride, Placebo
- Medical subject headings
- Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SaxagliptinDrug
DapagliflozinDrug
GlimepirideDrug
PlaceboOther
| Study group | Role | What they receive |
|---|---|---|
| Saxagliptin 5 mg/ dapagliflozin 10mg or Placebo | Experimental | Saxagliptin 5 mg /dapagliflozin 10 mg Placebo once a day orally Receives: Drug: Saxagliptin; Drug: Dapagliflozin; Other: Placebo |
| Glimepiride or Placebo | Experimental | Glimepiride or placebo 1mg or 2mg or 3mg or 4mg or 6mg once a day orally Receives: Drug: Glimepiride; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 52
To examine whether the mean change from baseline in HbA1c with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin is superior to titrated glimepiride plus metformin after 52 weeks of double-blind treatment.
Measured: Baseline and Week 52
Secondary outcomes (7)
Change From Baseline in Total Body Weight at Week 52
To examine whether the mean change from baseline in total body weight with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin is superior to titrated glimepiride plus metformin after 52 weeks of double-blind treatment.
Measured: Baseline and Week 52
Percentage of Subjects Achieving a Therapeutic Glycemic Response, Defined as HbA1c < 7.0%, at Week 52
Therapeutic glycemic response was defined as HbA1c <7.0%. Subjects rescued or discontinued prior to, and subjects with missing measurements at Week 52 were treated as non-responders. The percentage of subjects with a therapeutic glycemic response is based on the logistic regression method with adjustment for baseline HbA1c.
Measured: At Week 52
Change From Baseline in Systolic Blood Pressure (SBP) at Week 52
To examine whether the change from baseline in SBP with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin is superior to titrated glimepiride plus metformin after 52 weeks of double-blind treatment.
Measured: Baseline and Week 52
Percentage of Subjects With Treatment Intensification During the 52-week Short-term Treatment Period
Treatment intensification was defined as the addition of insulin or other glucose-lowering agent for rescue therapy or discontinuation for lack of glycemic control. Time to treatment intensification was censored after the 52-week treatment period if treatment intensification had not occurred by then. Subjects rescued at Week 52 were counted as having an event for the analysis. The values presented are the percentage of subjects requiring the addition of insulin or other glucose-lowering agent for rescue therapy or discontinuation for lack of glycemic control during the 52-week short -term treatment period.
Measured: Up to Week 52
Percentage of Subjects With Treatment Intensification During the 156-Week Short-term Plus Long-Term Treatment Period.
Treatment intensification was defined as the addition of insulin or other glucose-lowering agent for rescue therapy or discontinuation for lack of glycemic control. Time to treatment intensification was censored after 156-week treatment period if treatment intensification had not occurred by then. Subjects rescued at Week 156 were counted as having an event for the analysis. The values presented are the percentage of subjects requiring the addition of insulin or other glucose-lowering agent for rescue therapy or discontinuation for lack of glycemic control during the 156-week treatment period.
Measured: Up to Week 156
Percentage of Subjects Achieving a Therapeutic Glycemic Response, Defined as HbA1c < 7.0%, at Week 156
Therapeutic glycemic response was defined as HbA1c <7.0%. Subjects rescued or discontinued prior to, and subjects with missing measurements at Week 156 were treated as non-responders. The percentage of subjects with a therapeutic glycemic response is based on the logistic regression method with adjustment for baseline HbA1c.
Measured: At Week 156
Time to Treatment Intensification During the 156-Week Short-term Plus Long-Term Treatment Period.
Treatment intensification was defined as the addition of insulin or other glucose-lowering agent for rescue therapy or discontinuation for lack of glycemic control. Time to treatment intensification was censored after 156-week treatment period if treatment intensification had not occurred by then. Subjects rescued at Week 156 were counted as having an event for the analysis. Time to treatment intensification curves were generated using Kaplan-Meier estimates and compared using a Cox proportional hazards model.
Measured: Up to Week 156
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2015 (estimated)
- Study start14 Aug 2015
- Primary completion29 Aug 2017
- Study completion18 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for DiabetesStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 444 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02419612
- Sponsor's protocol ID
- CV181-365
- Status last verified
- Jun 2020
- First submitted
- 14 Apr 2015
- Last updated
- 23 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Publications
Frias JP, Gonzalez-Galvez G, Johnsson E, Maaske J, Testa MA, Simonson DC, Dronamraju N, Garcia-Sanchez R, Peters AL. Efficacy and safety of dual add-on therapy with dapagliflozin plus saxagliptin versus glimepiride in patients with poorly controlled type 2 diabetes on a stable dose of metformin: Results from a 52-week, randomized, active-controlled trial. Diabetes Obes Metab. 2020 Jul;22(7):1083-1093. doi: 10.1111/dom.13997. Epub 2020 Mar 9.
PubMed 32052516
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 52-week International, Multicenter, Randomized, Double-Blind, Active-Controlled, Parallel Group, Phase 3bTrial With a Blinded 104-week Long -Term Extension Period to Evaluate the Efficacy and Safety of Saxagliptin Co-administered With Dapagliflozin in Combination With Metformin Compared to Glimepiride in Combination With Metformin ≥1500 mg in Adult Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Therapy Alone
- ClinicalTrials.gov ID
- NCT02419612
- Acronym / sponsor ID
- CV181-365
- Conditions
- Diabetes
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 444 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 14 Aug 2015 (actual)
- Primary completion
- 29 Aug 2017 (actual)
- Study completion
- 18 Sep 2019 (actual)
- First posted
- 17 Apr 2015 (estimated)
- Results
- Posted 19 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clincial trial is evaluating if the co-administration of saxagliptin and dapagliflozin, in addition to metformin, results in better glycemic control, as measured by HbA1c, over a treatment period of 52 weeks, compared to the addition of glimepiride to metformin in subjects with Type 2 Diabetes Mellitus who have inadequate glycemic control on Metformin Alone. We will compare the change from baseline in HbA1c achieved with saxagliptin, in co-administration with dapagliflozin, added to current background therapy with metformin compared to glimepiride added to current background therapy with metformin ≥1500 mg at Week 52.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Saxagliptin 5 mg/ dapagliflozin 10mg or Placebo | Experimental | Drug: Saxagliptin, Drug: Dapagliflozin, Other: PlaceboSaxagliptin 5 mg /dapagliflozin 10 mg Placebo once a day orally |
| Glimepiride or Placebo | Experimental | Drug: Glimepiride, Other: PlaceboGlimepiride or placebo 1mg or 2mg or 3mg or 4mg or 6mg once a day orally |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subjects must be willing and able to give signed and dated written informed consent
- Patients with Type 2 diabetes mellitus (T2DM) with inadequate glycemic control
- Subjects should have been taking the same daily dose of metformin ≥ 1500 mg
- Fasting Plasma Glucose ≤ 270 mg/dL (≤15 mmol/L)
- Males and females, aged ≥18 years old at time of screening visit
Key exclusion criteria (10 listed)
- Clinical diagnosis of type I diabetes
- History of diabetic ketoacidosis
- Cardiovascular/vascular diseases within 3 months of the enrollment
- Renal disease
- Hepatic diseases
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 |
|---|---|---|
| Saxagliptin | Drug | Saxagliptin 5 mg/ dapagliflozin 10mg or Placebo |
| Dapagliflozin | Drug | Saxagliptin 5 mg/ dapagliflozin 10mg or Placebo |
| Glimepiride | Drug | Glimepiride or Placebo |
| Placebo | Other | Glimepiride or Placebo, Saxagliptin 5 mg/ dapagliflozin 10mg or Placebo |
Primary outcome
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 52
Time frame: Baseline and Week 52
To examine whether the mean change from baseline in HbA1c with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin is superior to titrated glimepiride plus metformin after 52 weeks of double-blind treatment.
7 secondary outcomes
Change From Baseline in Total Body Weight at Week 52
Time frame: Baseline and Week 52
Percentage of Subjects Achieving a Therapeutic Glycemic Response, Defined as HbA1c < 7.0%, at Week 52
Time frame: At Week 52
Change From Baseline in Systolic Blood Pressure (SBP) at Week 52
Time frame: Baseline and Week 52
Percentage of Subjects With Treatment Intensification During the 52-week Short-term Treatment Period
Time frame: Up to Week 52
Percentage of Subjects With Treatment Intensification During the 156-Week Short-term Plus Long-Term Treatment Period.
Time frame: Up to Week 156
Percentage of Subjects Achieving a Therapeutic Glycemic Response, Defined as HbA1c < 7.0%, at Week 156
Time frame: At Week 156
Time to Treatment Intensification During the 156-Week Short-term Plus Long-Term Treatment Period.
Time frame: Up to Week 156
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32052516Frias JP, Gonzalez-Galvez G, Johnsson E, Maaske J, Testa MA, Simonson DC, Dronamraju N, Garcia-Sanchez R, Peters AL. Efficacy and safety of dual add-on therapy with dapagliflozin plus saxagliptin versus glimepiride in patients with poorly controlled type 2 diabetes on a stable dose of metformin: Results from a 52-week, randomized, active-controlled trial. Diabetes Obes Metab. 2020 Jul;22(7):1083-1093. doi: 10.1111/dom.13997. Epub 2020 Mar 9.
- CV181365\_CSP\_redactedLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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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.
The record lists no contact. Use the official record to reach the sponsor.
84 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Saxagliptin, Dapagliflozin and Glimepiride in people with Diabetes, run by AstraZeneca at 84 sites in 10 countries.
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 10 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 23 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 84 sites in United States, Hungary, Romania, Poland, Czechia and 5 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Hemoglobin A1c (HbA1c) at Week 52 (time frame: Baseline and Week 52). 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 NCT02419612, 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 23 Jun 2020.