The primary objective is to demonstrate that glycemic control, as measured by hemoglobin A1c(HbA1c) at 52 weeks for LY2605541 is noninferior to insulin glargine, when each is combined with preprandial insulin lispro, in patients with type 1 diabetes…
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
A change of HbA1c from baseline to 52 weeks that is not inferior to
glargine when combined with pre-prandial insulin lispro.
Secondary outcome
The secondary objective(s) of the study are:
Gated Secondary Objectives:
To demonstrate that LY2605541 is superior to insulin glargine (each
administered in combination with preprandial insulin lispro) at 52 weeks for:
1. Nocturnal hypoglycemia rate during 52 weeks of treatment
2. HbA1c after 52 weeks of treatment
3. Proportion of patients with HbA1c <7.0% after 52 weeks of treatment using
last-observation-carried-forward (LOCF)
4. Fasting serum glucose (FSG) by laboratory measurement after 52 weeks of
treatment
5. Total hypoglycemia rate during 52 weeks of treatment.
Non-Gated secondary objectives: To compare the efficacy and safety of
LY2605541 versus insulin glargine (each in combination with preprandial insulin
lispro) treatment groups at 26 and 52 weeks (unless otherwise stated) for the
following:
• Total and nocturnal hypoglycemia rates (0-2, 0-12, 0-26, 2-12, 2-26, 12-26,
26-52 weeks)
• Total and nocturnal hypoglycemia incidence (0-2, 0-12, 0-26, 0-52, 2-12,
2-26, 12-26, 26-52 weeks)
• Weight change from baseline
• Self-monitored blood glucose (SMBG) 9-point profiles (fasting, 2-hours
postmorning meal, pre-midday meal, 2-hours post-midday meal, pre-evening meal,
2-hours postevening meal, bedtime [Day 1], and 0300 hour and fasting the
subsequent morning [Day 2])
• Proportion of patients with HbA1c <7.0% at 26 weeks (using LOCF)
• Proportion of patients with HbA1c <=6.5% (using LOCF)
• Proportion of patients with HbA1c <7.0% (using LOCF) and no nocturnal
hypoglycemia.
• HbA1c change from baseline
• HbA1c endpoint at 26 weeks
• Basal, bolus, and total insulin dose (units and units/kg)
• Triglycerides (log transformation prior to analysis), total cholesterol,
low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein
cholesterol (HDL-C)
• Antibodies to LY2605541
• Additional safety endpoints (treatment-emergent adverse events [TEAEs],
serious adverse events [SAEs], vital signs, treatment exposure, other
laboratory measures, etc.)
• FSG by laboratory at 26 weeks
• Fasting blood glucose (FBG) (as measured by SMBG)
• FBG (SMBG) intrasubject patient variability as measured by standard deviation
• 0300 hours blood glucose (BG) to FBG excursion
• Insulin Treatment Satisfaction Questionnaire (ITSQ) at 52 weeks
• Low Blood Sugar Survey (LBSS)
• EuroQoL (EQ)-5D at 52 weeks
• Rapid Assessment of Physical Activity (RAPA)
Background summary
Eli Lilly and Company (Lilly) is developing LY2605541 for the treatment of
diabetes mellitus (type 1 diabetes mellitus [T1DM] and type 2 diabetes mellitus
[T2DM]). LY2605541 is insulin lispro (HUMALOG®, Eli Lilly and Company) with a
covalently bonded 20,000 Dalton (20 kDa)
monomethoxy poly(ethylene glycol) (mPEG). The insulin lispro protein contains 2
chains (A chain and B chain) covalently connected through disulfide bonding. A
single 20 kDa mPEG is covalently linked to the epsilon amine of LysB28 by a
urethane bond. The rationale for the
PEG modification was to delay absorption and reduce clearance of the insulin
molecule, thereby prolonging the duration of action to support a once-daily
dosing regimen in patients with T1DM and T2DM. The time-action profile of
LY2605541 is modulated indirectly through slowed depot
absorption due to increased molecular size and directly as a function of
weakened receptor binding, thus slowing receptor-mediated clearance.
Study objective
The primary objective is to demonstrate that glycemic control, as measured by
hemoglobin A1c
(HbA1c) at 52 weeks for LY2605541 is noninferior to insulin glargine, when each
is combined with preprandial insulin lispro, in patients with type 1 diabetes
mellitus (T1DM). The noninferiority margin is 0.4%.
Study design
• How LY2605541 controls blood sugar as compared to insulin glargine in
patients who are also taking insulin lispro.
• The safety of LY2605541 and any side effects that might be associated with
it.
Intervention
Arm A LY2605541, insuline lispro
arm B insulin glargine, insuline lispro
Study burden and risks
- self injection of insuline
- bloodtests and urine tests
- telemedicine visits
- documentation of blood sugar levels at least 4 times a day
- complete 3 kinds of questionnaires
- 2 9 points of blood sugar profiles
-fasten before visits
-undergo ECGs
Grootslag 1-5
3991 RA Houten
NL
Grootslag 1-5
3991 RA Houten
NL
Listed location countries
Age
Inclusion criteria
[1] Have T1DM based on the World Health Organization (WHO) classification ;[2] Are at least 18 years of age ;[3] Have had diabetes for at least 1 year ;[4] Have an HbA1c value <12% according to the central laboratory at screening ;[5] Body mass index <= 35.0 kg/m2 ;[6] Have been treated for at least 90 days prior to screening with:;• insulin detemir, insulin glargine, or NPH insulin in combination with pre-meal insulin, or ;• self mixed or pre-mixed insulin regimens with any basal and bolus insulin combination administered at least twice daily, or
• continuous subcutaneous insulin infusion therapy.
[7] This inclusion criterion applies to all females only.
• Are not breastfeeding.
• Test negative for pregnancy at the time of screening and time of randomization based on a serum pregnancy test.;• Intend not to become pregnant during the study.;• Have practiced a reliable method of birth control (for example, use of oral contraceptives or levonorgestrel; diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam; intrauterine devices; partner with vasectomy; or abstinence) for at least 6 weeks prior to screening.;• Agree to continue to use a reliable method of birth control during the study, as determined by the investigator (and for 2 weeks following the last dose of study drug).;[8] Have access to a telephone ;[9] Have refrigeration in the home ;[10] Capable of, willing and desirous to do the following: adhere to a multiple daily injection regimen, inject insulin with a vial and syringe and prefilled pen and perform self blood glucose monitoring and record keeping as required by this protocol. Caregiver may do all of the above. ;[11] Have given written informed consent to participate in this study in accordance with local regulations.
Exclusion criteria
[12] Are using twice daily insulin glargine having been inadequately controlled on single daily dosed glargine prior to screening ;[13] Excessive insulin resistance defined as having received a total daily dose of insulin > 1.5 U/kg at the time of randomization.
[14] Receiving any oral or injectable medication (other than insulins or metformin for treatment of polycystic ovarian disease) intended for the treatment of diabetes mellitus other than insulins in the 90 days prior to screening. Note: for subjects on metformin, the following exclusion criteria will apply: have serum creatinine concentration that contraindicates metformin use per the country-specific product labeling.
[15] lipid lowering medication: are using niacin preparations as lipid lowering medication or bile acid sequestrants within 90 days prior to screening or are using lipid lowering medication at a dose that has not been stable for >=90 days prior to screening. If a patient has not been on a stable dose of lipid-lowering medication for >=90 days prior to screening, the site should wait to screen the patient. If the results of the screening laboratory tests require a change to the patient's current lipid-lowering medication or initiation of lipid-lowering medication, it is acceptable to change the lipid-lowering medication for the patient and have the patient return >=90 days later to complete some of the screening procedures again.
[16] Have fasting hypertriglyceridemia (defined as >4.5 mmol/L, >400 mg/dl) at screening, as determined by the central laboratory. ;[17] Have had more than 1 episode of severe hypoglycemia (defined as requiring assistance due to neurologically disabling hypoglycemia) within 6 months prior to screening. ;[18] Have had 2 or more emergency room visits or hospitalizations due to poor glucose control (hyperglycemia or diabetic ketoacidosis [DKA]) within 6 months prior to screening. ;[19] Cardiovascular: have cardiac disease with functional status that is New York Heart Association Class III or IV (per New York Heart Association [NYHA] Cardiac Disease Classification). ;[20] Nieren: een geschiedenis hebben van een niertransplantatie, momenteel een nierdialyse ontvangen of een serum creatinine > 2,5 mg / dL hebben.;[21] Hepatic: have obvious clinical signs or symptoms of liver disease (excluding non-alcoholic fatty liver disease), acute or chronic hepatitis, non-alcoholic steatohepatitis (NASH), or elevated liver enzyme measurements as indicated below: ;• total bilirubin >=2 x the upper limit of normal (ULN) as defined by the central laboratory, or ;• ALT/serum glutamic pyruvic transaminase (SGPT) >2.5 x ULN as defined by the central laboratory, or ;• AST/serum glutamic oxaloacetic transaminase (SGOT) >2.5 x ULN as defined by the central laboratory. ;[22] Malignancy: Have active or untreated malignancy, have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer) for less than 5 years, or are at increased risk for developing cancer or a recurrence of cancer in the opinion of the investigator. ;[23] Allergy: Have known or develop hypersensitivity or allergy to any of the study insulins or their excipients. ;[24] Hematologic: Have had a blood transfusion or severe blood loss within 3 months prior to screening or have known hemoglobinopathy, hemolytic anemia, or sickle cell anemia, or any other traits of hemoglobin abnormalities known to interfere with the HbA1c measurement. ;[25] Glucocorticoid therapy: Receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy (excluding topical, intraocular, intranasal, and inhaled preparations) or have received such therapy within 8 weeks immediately before screening with the exception of replacement therapy for adrenal insufficiency. ;[26] Diagnosed clinically significant diabetic autonomic neuropathy, in the opinion of the investigator.;[27] Have any other condition (including known drug or alcohol abuse or psychiatric disorder including eating disorder) that precludes the patient from following and completing the protocol.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
EudraCT | EUCTR2011-001253-82-NL |
CCMO | NL38481.028.11 |