Diabetes Mellitus, Type 2Phase 4S019NCT00393705
Lispro Mid Mixture (MM) Intensive Mixture Therapy With Progressive Dose-Titration of Lispro Low Mixture (LM) or Biphasic Insulin Aspart 30/70 (S019)
A Phase 4 study testing Insulin Biphasic Aspart 30/70, insulin lispro LM and insulin lispro MM in people with Diabetes Mellitus, Type 2, run by Eli Lilly and Company at 9 sites in 5 countries.
Trial summary
Investigation into patients with type 2 diabetes mellitus not achieving adequate glycemic control while treated with combination of premixed insulin analogue formulations twice daily and metformin will be randomly assigned to follow one of two insulin treatment strategies used in combination with metformin… Read more about this study
- Who is it for?
- Ages 30 to 75 years
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- Insulin Biphasic Aspart 30/70, insulin lispro LM and insulin lispro MM
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 302 participants
- Where
- 9 sitesin 5 countries
- Study dates
- Oct 2006to Mar 2009
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have type 2 diabetes (World Health Organization [WHO] classification).
- Are at least 30 years of age and less than 75 years of age.
- Have been receiving hypoglycemic treatment with premixed insulin analogue (either with insulin lispro LM or biphasic insulin aspart 30/70) administered twice daily in combination with at least 1500 milligrams (mg) of metformin per day for at least 60 days immediately prior to the study.
- Have a hemoglobin A1c 1.2 to 1.8 times the upper limit of the normal reference range at the local laboratory at Visit 1 or
- Have at least 6 of 9 of the postprandial blood glucose values recorded in the period between Visit 1 and Visit 2 exceeding 180 milligrams per 100 milliliters (mg/dl) (10.0 millimole per liter [mmol/l]).
- Have given written informed consent to participate in this study in accordance with local regulations.
Who cannot join
- Are taking any other oral anti-diabetic medication (OAM) not mentioned in inclusion criterion.
- Have a body mass index greater than 40 kilograms per meter squared (kg/m2).
- Have had more than one episode of severe hypoglycemia within 6 months prior to entry into the study.
- Have congestive heart failure.
- Have an irregular sleep/wake cycle (for example, patients who sleep during the day and work during the night).
Trial locations and contacts
9 sites in 5 countries.
9 sites in 5 countries
South Africa3 sites
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Kempton Park, 1619
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Kenilworth, 7708
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Kuilsriver, 7580
Poland2 sites
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Bialystok, 15-276
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Rzeszów, 35-0723
Turkey (Türkiye)2 sites
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Istanbul, 34662
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Konya, 42075
Croatia1 site
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Zagreb, HR-10000
Romania1 site
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Bucharest, 020475
About this study
Official title: A Comparison of Insulin Lispro MM Intensive Mixture Therapy With Progressive Dose-Titration of Insulin Lispro LM or Biphasic Insulin Aspart 30/70
Investigation into patients with type 2 diabetes mellitus not achieving adequate glycemic control while treated with combination of premixed insulin analogue formulations twice daily and metformin will be randomly assigned to follow one of two insulin treatment strategies used in combination with metformin administration. The aim of the trial is to try to achieve optimal metabolic control and explore full therapeutic potential of the strategies, patients in both arms will follow progressive insulin dose titration algorithms for 16 weeks.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- Insulin Biphasic Aspart 30/70, insulin lispro LM, insulin lispro MM
- Keywords
- diabetes, type 2
- 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.
Insulin Biphasic Aspart 30/70Drug
Participant adjusted dose, twice daily, injected subcutaneously for 16 weeks
insulin lispro LMDrug
Also called Low Mix, Humalog
Participant adjusted dose, injected subcutaneously for 16 weeks - possibility of using instead of insulin lispro MM before evening meal if there is a risk of hypoglycemia after the dinner or high fasting glucose levels.
insulin lispro MMDrug
Also called Mid Mix, Humalog
Participant adjusted dose, three times per day, injected subcutaneously for 16 weeks
insulin lispro LMDrug
Also called Low Mix, Humalog
Participant adjusted dose, twice daily, injected subcutaneously for 16 weeks
| Study group | Role | What they receive |
|---|---|---|
| insulin lispro LM + insulin lispro MM | Experimental | Three times per day subcutaneous injection of insulin lispro mid mixture (MM) with the possibility to change the evening injection of MM to insulin lispro low mixture (LM) if fasting blood glucose target is not achieved. Receives: Drug: insulin lispro LM; Drug: insulin lispro MM |
| Insulin Biphasic Aspart 30/70 or Insulin Lispro LM | Active comparator | Twice daily subcutaneous injection of either insulin biphasic aspart 30/70 or insulin lispro low mixture (LM) (continuation of analogue formulation used before study enrollment). Receives: Drug: Insulin Biphasic Aspart 30/70; Drug: insulin lispro LM |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hemoglobin A1c (HbA1c) at 16 Week Endpoint
Measured: 16 weeks
Secondary outcomes (9)
Percentage of Patients Achieving Hemoglobin A1c (HbA1c) <7% and HbA1c ≤6.5% at 16 Week Endpoint
Measured: 16 weeks
Change From Baseline in Hemoglobin A1c (HbA1c) at 16 Week Endpoint
Measured: Baseline, 16 Weeks
2-hour Postprandial Plasma Glucose Concentrations After the Midday Meal From Self-monitored 7-point Plasma Glucose at 16 Week Endpoint
Participants self-monitored their blood glucose concentrations at 7 time points: three premeal and three 2-hour postprandial meal measurements for the morning (breakfast), midday (lunch), and evening (dinner) meals, as well as a 3:00 AM measurement. Results presented here are for the blood glucose concentrations 2-hours after the midday meal at Week 16.
Measured: 16 weeks
Mean 2-hour Postprandial Blood Glucose Excursions After Midday Meal at 16 Week Endpoint
Participants self-monitored their blood glucose concentrations at 7 time points: three premeal and three 2-hour postprandial meal measurements for the morning (breakfast), midday (lunch), and evening (dinner) meals, as well as a 3:00 AM measurement. Results presented here are for the difference (excursion) between midday premeal and 2-hour postprandial midday meal blood glucose concentrations at Week 16.
Measured: 16 weeks
Mean Daily Blood Glucose Values at 16 Week Endpoint
Measured: 16 weeks
Number of Patients With Self-reported Hypoglycemic Episodes
Hypoglycemia: any time a patient feels, or another person observes, that patient is experiencing a sign/symptom that he or she would associate with hypoglycemia or a plasma-equivalent glucose measurement ≤70 mg/dL. Nocturnal hypoglycemia: hypoglycemia occurring after bedtime and prior to morning meal and morning dose of insulin or metformin. Severe hypoglycemia: hypoglycemia where patient requires assistance from another person and which is associated with either a blood glucose level less than 50 mg/dL or prompt recovery after oral carbohydrate, intravenous glucose or glucagon administration.
Measured: Baseline through 16 weeks
30-Day Adjusted Rate of Hypoglycemic Events
Hypoglycemia: any time a patient feels, or another person observes, that patient is experiencing a sign/symptom that he or she would associate with hypoglycemia or a plasma-equivalent glucose measurement ≤70 mg/dL. Nocturnal hypoglycemia: hypoglycemia occurring after bedtime and prior to morning meal and morning dose of insulin or metformin. Severe hypoglycemia: hypoglycemia where patient requires assistance from another person and which is associated with either a blood glucose level less than 50 mg/dL or prompt recovery after oral carbohydrate, intravenous glucose or glucagon administration.
Measured: Baseline through 16 weeks
Change From Baseline in Weight at 16 Week Endpoint
Measured: Baseline, 16 weeks
Total Daily Insulin Dose at 4 Weeks and 12 Weeks
Measured: 4 weeks and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2006 (estimated)
- Study startOct 2006
- Primary completionMar 2009
- Study completionMar 2009
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.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe 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
- 302 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern Time (UTC/GMT - 5 hours, EST), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00393705
- Sponsor's protocol ID
- 10916
- Other IDs
- F3Z-VI-S019
- Acronym
- S019
- Status last verified
- Jul 2010
- First submitted
- 26 Oct 2006
- Last updated
- 20 Jul 2010
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Comparison of Insulin Lispro MM Intensive Mixture Therapy With Progressive Dose-Titration of Insulin Lispro LM or Biphasic Insulin Aspart 30/70
- ClinicalTrials.gov ID
- NCT00393705
- Acronym / sponsor ID
- S019 / 10916
- Conditions
- Diabetes Mellitus, Type 2
- Keywords
- diabetes, type 2
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 302 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- Oct 2006
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 30 Oct 2006 (estimated)
- Results
- Posted 27 Apr 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Investigation into patients with type 2 diabetes mellitus not achieving adequate glycemic control while treated with combination of premixed insulin analogue formulations twice daily and metformin will be randomly assigned to follow one of two insulin treatment strategies used in combination with metformin administration. The aim of the trial is to try to achieve optimal metabolic control and explore full therapeutic potential of the strategies, patients in both arms will follow progressive insulin dose titration algorithms for 16 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| insulin lispro LM + insulin lispro MM | Experimental | Drug: insulin lispro LM, Drug: insulin lispro MMThree times per day subcutaneous injection of insulin lispro mid mixture (MM) with the possibility to change the evening injection of MM to insulin lispro low mixture (LM) if fasting blood glucose target is not achieved. |
| Insulin Biphasic Aspart 30/70 or Insulin Lispro LM | Active comparator | Drug: Insulin Biphasic Aspart 30/70, Drug: insulin lispro LMTwice daily subcutaneous injection of either insulin biphasic aspart 30/70 or insulin lispro low mixture (LM) (continuation of analogue formulation used before study enrollment). |
Who may qualify
- Ages
- 30 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Have type 2 diabetes (World Health Organization [WHO] classification).
- Are at least 30 years of age and less than 75 years of age.
- Have been receiving hypoglycemic treatment with premixed insulin analogue (either with insulin lispro LM or biphasic insulin aspart 30/70) administered twice daily in combination with at least 1500 milligrams (mg) of metformin per day for at least 60 days immediately prior to the study.
- Have a hemoglobin A1c 1.2 to 1.8 times the upper limit of the normal reference range at the local laboratory at Visit 1 or
- Have at least 6 of 9 of the postprandial blood glucose values recorded in the period between Visit 1 and Visit 2 exceeding 180 milligrams per 100 milliliters (mg/dl) (10.0 millimole per liter [mmol/l]).
Key exclusion criteria (5 listed)
- Are taking any other oral anti-diabetic medication (OAM) not mentioned in inclusion criterion.
- Have a body mass index greater than 40 kilograms per meter squared (kg/m2).
- Have had more than one episode of severe hypoglycemia within 6 months prior to entry into the study.
- Have congestive heart failure.
- Have an irregular sleep/wake cycle (for example, patients who sleep during the day and work during the night).
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 Biphasic Aspart 30/70Participant adjusted dose, twice daily, injected subcutaneously for 16 weeks | Drug | Insulin Biphasic Aspart 30/70 or Insulin Lispro LM |
| insulin lispro LMAlso: Low Mix, HumalogParticipant adjusted dose, injected subcutaneously for 16 weeks - possibility of using instead of insulin lispro MM before evening meal if there is a risk of hypoglycemia after the dinner or high fasting glucose levels. | Drug | insulin lispro LM + insulin lispro MM |
| insulin lispro MMAlso: Mid Mix, HumalogParticipant adjusted dose, three times per day, injected subcutaneously for 16 weeks | Drug | insulin lispro LM + insulin lispro MM |
| insulin lispro LMAlso: Low Mix, HumalogParticipant adjusted dose, twice daily, injected subcutaneously for 16 weeks | Drug | Insulin Biphasic Aspart 30/70 or Insulin Lispro LM |
Primary outcome
Hemoglobin A1c (HbA1c) at 16 Week Endpoint
Time frame: 16 weeks
9 secondary outcomes
Percentage of Patients Achieving Hemoglobin A1c (HbA1c) <7% and HbA1c ≤6.5% at 16 Week Endpoint
Time frame: 16 weeks
Change From Baseline in Hemoglobin A1c (HbA1c) at 16 Week Endpoint
Time frame: Baseline, 16 Weeks
2-hour Postprandial Plasma Glucose Concentrations After the Midday Meal From Self-monitored 7-point Plasma Glucose at 16 Week Endpoint
Time frame: 16 weeks
Mean 2-hour Postprandial Blood Glucose Excursions After Midday Meal at 16 Week Endpoint
Time frame: 16 weeks
Mean Daily Blood Glucose Values at 16 Week Endpoint
Time frame: 16 weeks
Number of Patients With Self-reported Hypoglycemic Episodes
Time frame: Baseline through 16 weeks
30-Day Adjusted Rate of Hypoglycemic Events
Time frame: Baseline through 16 weeks
Change From Baseline in Weight at 16 Week Endpoint
Time frame: Baseline, 16 weeks
Total Daily Insulin Dose at 4 Weeks and 12 Weeks
Time frame: 4 weeks and 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2010.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Lilly Clinical Trial RegistryLink 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.
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern Time (UTC/GMT - 5 hours, EST) study director
Eli Lilly and Company
9 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Insulin Biphasic Aspart 30/70, insulin lispro LM and insulin lispro MM in people with Diabetes Mellitus, Type 2, run by Eli Lilly and Company at 9 sites in 5 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 6 inclusion and 5 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 20 Jul 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in South Africa, Poland, Turkey (Türkiye), Croatia, Romania. 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 27 Apr 2010). 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?
Hemoglobin A1c (HbA1c) at 16 Week Endpoint (time frame: 16 weeks). 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 20 Jul 2010.