Diabetes Mellitus, Type 2Phase 4NCT00384085

Insulin Glargine "All to Target" Trial

A Phase 4 study testing Insulin Glulisine, Insulin Glargine and Premixed Insulin in people with Diabetes Mellitus, Type 2, run by Sanofi at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The primary objectives were: To demonstrate the superiority of Lantus plus stepwise addition of mealtime Apidra® (Lantus/Apidra-3) versus twice-daily Premixed insulin based on the proportion of patients achieving target glycemic control (as measured by hemoglobin A1c [HbA1c] <7.0%) at Week 60 To demonstrate the… Read more about this study

Who is it for?: Ages 30 to 80 years
Conditions the study is for: Diabetes Mellitus, Type 2
What is being tested?: Insulin Glulisine, Insulin Glargine and Premixed Insulin
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 588 participants
Where: 1 siteUnited States
Study dates: May 2006to Mar 2010
Phase: Phase 4
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 30 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Male or female patients
30 to 80 years of age
Body Mass Index <45 kg/m2
With Type 2 diabetes mellitus for at least 2 years
With an HbA1c level at screening of >7.5% and >7.0% at randomization
On stable dual or triple oral therapy for at least 3 months
Oral agents in 2 or 3 of the following classes: SU or repaglinide, biguanide, or TZD, willing and able to perform self-monitoring of BG
Females of child-bearing potentially were required to be willing and able to use adequate contraception

Trial locations and contacts

1 site in 1 country.

United States1 site

Sanofi-Aventis Administrative Office
Bridgewater, New Jersey

Other trials in United States

About this study

Official title: All to Target Trial Lantus® (Insulin Glargine) With Stepwise Addition of APIDRA® (Insulin Glulisine) or Lantus With One Injection of Apidra vs a Twice-Daily Premixed Insulin Regimen (Novolog® Mix 70/30) in Adult Subjects With Type 2 Diabetes Failing Dual or Triple Therapy With Oral Agents: a 64-week, Multi-center, Randomized, Parallel, Open-label Clinical Study.

The primary objectives were:

To demonstrate the superiority of Lantus plus stepwise addition of mealtime Apidra® (Lantus/Apidra-3) versus twice-daily Premixed insulin based on the proportion of patients achieving target glycemic control (as measured by hemoglobin A1c [HbA1c] <7.0%) at Week 60
To demonstrate the noninferiority of Lantus plus addition of 1 mealtime Apidra injection (Lantus/Apidra-1) versus twice-daily Premixed insulin based on the reduction from Baseline to Week 60 in HbA1c

Conditions: Diabetes Mellitus, Type 2
Being tested: Insulin Glulisine, Insulin Glargine, Premixed Insulin
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Insulin GlulisineDrug
Also called Apidra
Subcutaneous injection up to 1 injection per day
Insulin GlargineDrug
Also called Lantus
Subcutaneous injection once-a-day
Premixed InsulinDrug
Also called Novolog Mix 70/30
Subcutaneous injection twice-a-day.
Insulin GlulisineDrug
Also called Apidra
Subcutaneous injection up to 3 injections per day.

Study groups in NCT00384085
Study group	Role	What they receive
Lantus/Apidra-3	Experimental	Insulin glargine (Lantus) plus up to 3 injections of insulin glulisine (Apidra) added to oral agents. Receives: Drug: Insulin Glargine; Drug: Insulin Glulisine
Lantus/Apidra-1	Experimental	Insulin glargine (Lantus) plus up to 1 injection of insulin glulisine (Apidra) added to oral agents. Receives: Drug: Insulin Glulisine; Drug: Insulin Glargine
Novolog Mix 70/30	Experimental	Premixed insulin (Novolog® Mix 70/30) added to oral agents. Receives: Drug: Premixed Insulin

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Patients Achieving Glycosylated Hemoglobin A1c (HbA1c) < 7.0% at Week 60 (Lantus/Apidra-3 Versus Novolog Mix 70/30 - Intent To Treat (ITT) Population Without Good Clinical Practices (GCP) Noncompliant Sites)
Responders defined as patients who achieved an HbA1c value <7.0% versus nonresponders. Patients who did not achieve an HbA1c value <7.0% and patients with a missing HbA1c value at Week 60 were considered to be nonresponders.
Measured: At week 60
Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Week 60 (Lantus/Apidra-1 Versus Novolog Mix 70/30)Per Protocol Population
Absolute Change in HbA1c from Baseline to Week 60. If the Week 60 HbA1c evaluation was missing, the patient was counted as having not completed per protocol.
Measured: At week 60
Percentage of Patients Achieving Glycosylated Hemoglobin A1c (HbA1c) < 7.0% at Week 60 (Lantus/Apidra-3 Versus Novolog Mix 70/30 - ITT Population With All Sites) (Sensitivity Analysis)
Responders defined as patients who achieved an HbA1c value <7.0% versus nonresponders. Patients who did not achieve an HbA1c value <7.0% and patients with a missing HbA1c value at Week 60 were considered to be nonresponders.
Measured: At week 60

Secondary outcomes (5)

Absolute Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Week 60 (Lantus/Apidra-3 Versus Novolog Mix 70/30)
Absolute Change in HbA1c from Baseline to Week 60.
Measured: From baseline to week 60
Percentage of Patients Achieving Glycosylated Hemoglobin A1c (HbA1c) <7.0% at Week 60 (Lantus/Apidra-1 Versus Novolog Mix 70/30)
Patients who achieved an HbA1c value <7.0% were defined as responders. Patients who did not achieve HbA1c values <7.0% and patients with missing HbA1c values were considered nonresponders.
Measured: At week 60
Percentage of Patients Achieving Glycosylated Hemoglobin A1c (HbA1c) <7.0% at Week 60 Without a Severe Hypoglycemic Event or a Symptomatic Hypoglycemic Event With an Self Monitoring Blood Glucose (SMBG) <50 mg/dl
Severe hypoglycemia was defined as an event with clinical symptoms that are considered to result from hypoglycemia in which the patient required assistance of another person and one of the following: the event was associated with a measured blood glucose level below 36 mg/dL or the event was associated with prompt recovery after oral carbohydrate, iv glucose, or glucagon administration.
A symptomatic hypoglycemic event was defined as a hypoglycemic episode with an associated SMBG value of <50 mg/dL with reported symptoms.
Measured: At week 60
Adjusted Incidence Rate of Hypoglycemia
Adjusted incidence rate of hypoglycemia: estimated percent of patients having at least 1 event of a given type of hypoglycemia.
A severe Hypoglycemic Event (HE) is one where patient requires assistance. It is confirmed either by a prompt response to certain countermeasures or by a blood Glucose (BG) <36 mg/dL during or soon after the event.
A serious HE is one where the patient has loss of consciousness, coma, seizure, or convulsion.
Nocturnal = events occurring between 00:00 \& 06:00 based on a 24-hour clock.
An event is included if the HE start date is within the treatment period.
Measured: Week 60
Adjusted Hypoglycemic Event Rates (Event/Patient-year)
Adjusted Hypoglycemic event rate: Total # of events for a given type of hypoglycemia divided by the total exposure to study drug (patient-years). Rates are estimated from a general linear model adjusted for baseline BMI and oral agent combination of antidiabetic medications on which the patient entered the study.
An event is included if the hypoglycemic event start date is within the treatment period (i.e., from the Randomization date to \& including 1 day after the date of last dose of study drug).
Measured: Week 60

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2006Mar 2010

First posted4 Oct 2006 (estimated)
Study startMay 2006
Primary completionMar 2010
Study completionMar 2010

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 Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
More trials run by SanofiThe 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 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 588 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00384085
Sponsor's protocol ID: HMR1964A_3515
Status last verified: May 2011
First submitted: 3 Oct 2006
Last updated: 6 May 2011
Results posted: Yes, on ClinicalTrials.gov

Publications

Polonsky WH, Thompson S, Wei W, Riddle MC, Chaudhari S, Jackson J, Bruno AS. Greater fear of hypoglycaemia with premixed insulin than with basal-bolus insulin glargine and glulisine: patient-reported outcomes from a 60-week randomised study. Diabetes Obes Metab. 2014 Nov;16(11):1121-7. doi: 10.1111/dom.12328. Epub 2014 Jul 12.
PubMed 24919603

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 6 May 2011. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: All to Target Trial Lantus® (Insulin Glargine) With Stepwise Addition of APIDRA® (Insulin Glulisine) or Lantus With One Injection of Apidra vs a Twice-Daily Premixed Insulin Regimen (Novolog® Mix 70/30) in Adult Subjects With Type 2 Diabetes Failing Dual or Triple Therapy With Oral Agents: a 64-week, Multi-center, Randomized, Parallel, Open-label Clinical Study.
ClinicalTrials.gov ID: NCT00384085
Acronym / sponsor ID: HMR1964A_3515
Conditions: Diabetes Mellitus, Type 2
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 588 participants (actual)
Lead sponsor: SanofiIndustry (pharma, biotech, devices)
Study start: May 2006
Primary completion: Mar 2010 (actual)
Study completion: Mar 2010 (actual)
First posted: 4 Oct 2006 (estimated)
Results: Posted 26 Apr 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The primary objectives were:

To demonstrate the superiority of Lantus plus stepwise addition of mealtime Apidra® (Lantus/Apidra-3) versus twice-daily Premixed insulin based on the proportion of patients achieving target glycemic control (as measured by hemoglobin A1c [HbA1c] <7.0%) at Week 60
To demonstrate the noninferiority of Lantus plus addition of 1 mealtime Apidra injection (Lantus/Apidra-1) versus twice-daily Premixed insulin based on the reduction from Baseline to Week 60 in HbA1c

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Lantus/Apidra-3	Experimental	Drug: Insulin Glargine, Drug: Insulin GlulisineInsulin glargine (Lantus) plus up to 3 injections of insulin glulisine (Apidra) added to oral agents.
Lantus/Apidra-1	Experimental	Drug: Insulin Glulisine, Drug: Insulin GlargineInsulin glargine (Lantus) plus up to 1 injection of insulin glulisine (Apidra) added to oral agents.
Novolog Mix 70/30	Experimental	Drug: Premixed InsulinPremixed insulin (Novolog® Mix 70/30) added to oral agents.

Who may qualify

Ages: 30 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

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
Insulin GlulisineAlso: ApidraSubcutaneous injection up to 1 injection per day	Drug	Lantus/Apidra-1
Insulin GlargineAlso: LantusSubcutaneous injection once-a-day	Drug	Lantus/Apidra-1, Lantus/Apidra-3
Premixed InsulinAlso: Novolog Mix 70/30Subcutaneous injection twice-a-day.	Drug	Novolog Mix 70/30
Insulin GlulisineAlso: ApidraSubcutaneous injection up to 3 injections per day.	Drug	Lantus/Apidra-3

Primary outcome

Percentage of Patients Achieving Glycosylated Hemoglobin A1c (HbA1c) < 7.0% at Week 60 (Lantus/Apidra-3 Versus Novolog Mix 70/30 - Intent To Treat (ITT) Population Without Good Clinical Practices (GCP) Noncompliant Sites)
Time frame: At week 60
Responders defined as patients who achieved an HbA1c value <7.0% versus nonresponders. Patients who did not achieve an HbA1c value <7.0% and patients with a missing HbA1c value at Week 60 were considered to be nonresponders.
Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Week 60 (Lantus/Apidra-1 Versus Novolog Mix 70/30)Per Protocol Population
Time frame: At week 60
Absolute Change in HbA1c from Baseline to Week 60. If the Week 60 HbA1c evaluation was missing, the patient was counted as having not completed per protocol.
Percentage of Patients Achieving Glycosylated Hemoglobin A1c (HbA1c) < 7.0% at Week 60 (Lantus/Apidra-3 Versus Novolog Mix 70/30 - ITT Population With All Sites) (Sensitivity Analysis)
Time frame: At week 60
Responders defined as patients who achieved an HbA1c value <7.0% versus nonresponders. Patients who did not achieve an HbA1c value <7.0% and patients with a missing HbA1c value at Week 60 were considered to be nonresponders.

5 secondary outcomes

Absolute Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Week 60 (Lantus/Apidra-3 Versus Novolog Mix 70/30)
Time frame: From baseline to week 60
Percentage of Patients Achieving Glycosylated Hemoglobin A1c (HbA1c) <7.0% at Week 60 (Lantus/Apidra-1 Versus Novolog Mix 70/30)
Time frame: At week 60
Percentage of Patients Achieving Glycosylated Hemoglobin A1c (HbA1c) <7.0% at Week 60 Without a Severe Hypoglycemic Event or a Symptomatic Hypoglycemic Event With an Self Monitoring Blood Glucose (SMBG) <50 mg/dl
Time frame: At week 60
Adjusted Incidence Rate of Hypoglycemia
Time frame: Week 60
Adjusted Hypoglycemic Event Rates (Event/Patient-year)
Time frame: Week 60

Results and safety

Results posted to the registry on 26 Apr 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Lantus/Apidra-3	195	156
Lantus/Apidra-1	196	150
Novolog Mix 70/30	197	141

Primary outcome: Percentage of Patients Achieving Glycosylated Hemoglobin A1c (HbA1c) < 7.0% at Week 60 (Lantus/Apidra-3 Versus Novolog Mix 70/30 - Intent To Treat (ITT) Population Without Good Clinical Practices (GCP) Noncompliant Sites)

Time frame: At week 60. Number. Unit: percentage of participants

Measure	Lantus/Apidra-3 n = 187	Novolog Mix 70/30 n = 189
HbA1c < 7.0%	43.3	38.6
HbA1c ≥ 7.0%	35.3	32.3
Missing data	21.4	29.1

Lantus/Apidra-3 vs Novolog Mix 70/30: Adjusted Odds Ratio: 1.56 (95% CI 0.97 to 2.52), p = 0.0628, Regression, Logistic

Population analysed: Analysis was performed on Intent-To-Treat population which consisted of all patients who were randomized and for whom there was any post-baseline follow-up information. Patients from nonGCP compliant sites were excluded from this analysis. Additional analysis including those patients were completed to ensure that study results were not compromised.

Primary outcome: Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Week 60 (Lantus/Apidra-1 Versus Novolog Mix 70/30)Per Protocol Population

Time frame: At week 60. Least squares mean (Standard Error). Unit: percent HbA1c

Measure	Lantus/Apidra-1 n = 138	Novolog Mix 70/30 n = 134
baseline HbA1c	9.30 (0.176)	9.06 (0.187)
Absolute change in HbA1c from baseline	-2.30 (0.126)	-1.97 (0.132)

Lantus/Apidra-1 vs Novolog Mix 70/30: Adjusted Mean of difference: -0.34 (95% CI -0.82 to 0.15), p = 0.0359, Mixed Models Analysis

Population analysed: Analysis was performed on the Per Protocol (PP) population which included randomized patients who had no major protocol violation and who had HbA1c recorded for both Baseline \& Week 60. Patients from non-GCP compliant sites were, by population definition, excluded from this analysis.

Primary outcome: Percentage of Patients Achieving Glycosylated Hemoglobin A1c (HbA1c) < 7.0% at Week 60 (Lantus/Apidra-3 Versus Novolog Mix 70/30 - ITT Population With All Sites) (Sensitivity Analysis)

Time frame: At week 60. Number. Unit: percentage of participants

Measure	Lantus/Apidra-3 n = 195	Novolog Mix 70/30 n = 197
HbA1c < 7.0%	44.1	38.1
HbA1c ≥ 7.0%	34.4	32.0
Missing data	21.5	29.9

Lantus/Apidra-3 vs Novolog Mix 70/30: Adjusted Odds Ratio: 1.66 (95% CI 1.04 to 2.64), p = 0.0313, Regression, Logistic

Population analysed: Analysis was performed on the Intent To Treat (ITT) population which consisted of all patients who were randomized, and for whom there was any post-baseline follow-up information. Patients from non-GCP compliant sites were included in this analysis. This analysis was performed to ensure that study results were not compromised.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: All Adverse Events (AE) regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent Form up to the last visit were collected.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Lantus/Apidra-3	22 of 194 (11.3%)	140 of 194 (72.2%)	Not reported
Lantus/Apidra-1	23 of 194 (11.9%)	150 of 194 (77.3%)	Not reported
Novolog Mix 70/30	21 of 194 (10.8%)	152 of 194 (78.4%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2011.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 24919603Polonsky WH, Thompson S, Wei W, Riddle MC, Chaudhari S, Jackson J, Bruno AS. Greater fear of hypoglycaemia with premixed insulin than with basal-bolus insulin glargine and glulisine: patient-reported outcomes from a 60-week randomised study. Diabetes Obes Metab. 2014 Nov;16(11):1121-7. doi: 10.1111/dom.12328. Epub 2014 Jul 12.

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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 Affairs study director

Sanofi

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Insulin Glulisine, Insulin Glargine and Premixed Insulin in people with Diabetes Mellitus, Type 2, run by Sanofi at 1 site 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?

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 6 May 2011. 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 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 26 Apr 2011). 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?

Percentage of Patients Achieving Glycosylated Hemoglobin A1c (HbA1c) < 7.0% at Week 60 (Lantus/Apidra-3 Versus Novolog Mix 70/30 - Intent To Treat (ITT) Population Without Good Clinical Practices (GCP) Noncompliant Sites) (time frame: At week 60). The study lists 3 primary outcomes in all. 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 NCT00384085, 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 6 May 2011.