A Study Comparing Insulin Peglispro With Insulin Glargine as Basal Insulin Treatment

Phase 3

Completed

Conditions: Type 2 Diabetes Mellitus

Interventions: Drug: Insulin Peglispro
Drug: Insulin Glargine
Drug: Oral Antihyperglycemic Medications (OAMs)

Registration Number: NCT01894568

Lead Sponsor: Eli Lilly and Company

Brief Summary: The purpose of this study is to compare insulin peglispro (LY2605541) to insulin glargine in Asian insulin naïve participants who have been treated with oral anti hyperglycemia medications. Participants will receive 26 weeks of treatment.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 388

Inclusion Criteria

Have Type 2 Diabetes Mellitus (T2DM) for at least 1 year not treated with insulin
Have been receiving at least two oral antihyperglycemic medications (OAMs) for at least 3 months prior to screening
Have Hemoglobin A1c (HbA1c) of 7.0% to 11.0%, inclusive, according to central laboratory at screening
Body mass index (BMI) ≤35.0 kilogram per square meter (kg/m^2)
Inject insulin with a pre-filled insulin pen and perform Self-Monitored Blood Glucose (SMBG)
Record keeping as required by this protocol
Women of childbearing potential are not breastfeeding, have a negative pregnancy test at screening, do not plan to become pregnant during the study, have practiced reliable birth control during the study and 2 weeks following the last dose of investigational product

Exclusion Criteria

Have used insulin therapy (outside of pregnancy) anytime in the past 2 years, except for short term treatment of acute conditions
Have been treated with rosiglitazone, pramlintide, glucagon-like peptide-1 (GLP-1) receptor agonist within 3 months prior to screening
Are using or have used any of the following lipid-lowering medications: niacin preparations as a lipid-lowering medication and/or bile acid sequestrants within 90 days prior to screening
Local OAM restrictions: have any restrictions for cardiac, renal, and hepatic diseases in the local product regulations
Are taking, or have taken within 3 months before screening, prescription or over-the-counter medications to promote weight loss
Have had any episodes of severe hypoglycemia, diabetic ketoacidosis, or hyperosmolar state/coma within 6 months prior to screening
Have had 1 or more episodes of ketoacidosis or hyperosmolar state/coma in the past 6 months
Have cardiac disease with functional status that is New York Heart Association Class III or IV
Have a history of renal transplantation, or are currently receiving renal dialysis or have serum creatinine ≥2.0 milligram per deciliter (mg/dL) (177 micromole per liter [μmol/L]). Participants taking metformin should not exceed the creatinine level specified in the local label
Have obvious clinical signs or symptoms of liver disease (excluding non-alcoholic fatty liver disease [NAFLD]), acute or any chronic hepatitis, non alcoholic steatohepatitis (NASH), or elevated liver enzyme measurements
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 measurement of HbA1c
Have active or untreated cancer, have been in remission from clinically significant cancer(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
Have known hypersensitivity or allergy to any of LY2605541 and insulin glargine or their excipients
Have pre proliferative and proliferative retinopathy, maculopathy requiring treatment or not clinically stable in the last 6 months, or participants with active changes in subjective eye symptoms as determined by the investigator if an eye exam has not been performed in the last 6 months
Are receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy (excluding topical, intranasal, intraocular, and inhaled preparations) or have received such therapy within the 8 weeks immediately preceding screening
Have fasting triglycerides greater than 400 mg/dL (4.5 mmol/L) at screening as determined by the central laboratory
Have an irregular sleep/wake cycle (for example, participants who sleep during the day and work during the night) in the investigator's opinion

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Insulin Peglispro	Oral Antihyperglycemic Medications (OAMs)	Insulin Peglispro administered subcutaneously (SC) once daily for 26 weeks in combination with Oral Antihyperglycemic Medications (OAMs).
Insulin Glargine	Oral Antihyperglycemic Medications (OAMs)	Insulin Glargine administered SC once daily for 26 weeks in combination with OAMs.
Insulin Peglispro	Insulin Peglispro	Insulin Peglispro administered subcutaneously (SC) once daily for 26 weeks in combination with Oral Antihyperglycemic Medications (OAMs).
Insulin Glargine	Insulin Glargine	Insulin Glargine administered SC once daily for 26 weeks in combination with OAMs.

Primary Outcome Measures

Name	Time	Method
Change From Baseline to Week 26 in Hemoglobin A1c (HbA1c)	Baseline, Week 26	Hemoglobin A1c (HbA1c) is a test that measures a participant's average blood glucose level over the past 2 to 3 months. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis adjusting for treatment, stratification factors (region, sulfonylureas/meglitinide use, baseline Low-Density Lipoprotein \[LDL-C\], visit, treatment-by-visit interaction, and baseline HbA1c as fixed effects and participants as the random effect. P-value is from MMRM with terms for treatment, visit, treatment-by-visit interaction, stratification, and baseline HbA1C.

Secondary Outcome Measures

Name	Time	Method
30-Day Adjusted Rate of Total and Nocturnal Hypoglycemic Events	Baseline to Week 26	Hypoglycemia Events (HE) occurs when blood glucose level ≤ 70 milligram per deciliter (mg/dL) (\<3.9 micromoles per liter \[mmol/L\]). Nocturnal HE includes any total HE that occurred between bedtime and waking. Group mean rates of nocturnal hypoglycemia (per 30 days) are presented and were calculated from negative binomial regression models with treatment, baseline sulfonylurea/meglitinide use, baseline total hypoglycemia event rate, log (exposure/30 days) as the offset in the model. Group Mean is estimated by taking the inverse link function on individual participant covariates first and then averages over all participants.
9-Point Self-Monitored Blood Glucose (SMBG)	Week 0 and Week 26	LS means were calculated using MMRM analysis adjusting for baseline, treatment, stratification factor (region, HbA1c, LDL-C, and SU/meglitinide use), visit and treatment-by-visit interaction. The 9-point SMBG are measured at: Pre-morning meal, 2 hours(hr) post morning meal, pre-midday meal, 2 hr post midday meal, pre-evening meal, 2 hr post pre-evening meal, bedtime, 0300 hr, and pre-morning meal next day, and should be performed on 2 non-consecutive days.
Percentage of Participants With HbA1c ≤6.5%	Week 26	Percentage of participants with HbA1c ≤6.5% at Week 26 were made using a logistic regression model for endpoint used last observation carried forward (LOCF) method including treatment, baseline HbA1c value.
Percentage of Participants With Detectable Anti-Insulin Peglispro Antibodies at Week 26	Week 26	For participants with detectable anti-insulin peglispro antibody level, the percentage of participants with positive cross-react with endogenous insulin was summarized.
Fasting Serum Glucose (FSG)	Weeks 0 and 26	LS means were calculated using MMRM analysis adjusting for baseline, treatment, stratification factor (region, HbA1c, LDL-C, and sulfonylurea \[SU\]/meglitinide use), visit, and treatment-by-visit interaction.
Fasting Blood Glucose (FBG)	Weeks 0 and 26	LS Means were calculated using MMRM analysis adjusting for baseline, treatment, stratification factor (region, HbA1c, LDL-C, and SU/meglitinide use), visit and treatment-by-visit interaction.
Change From Baseline to Week 26 in Body Weight	Baseline, Week 26	LS Means were calculated using MMRM analysis adjusting for baseline, treatment, stratification factor (region, HbA1c, LDL-C, and SU/meglitinide use), visit and treatment-by-visit interaction.
Insulin Dose Per Kilogram (kg) of Body Weight	Week 26	LS means were calculated using MMRM analysis adjusting for baseline, treatment, stratification factor (region, HbA1c, LDL-C, and SU/meglitinide), visit, and treatment-by-visit interaction.
Percentage of Participants Achieving Steady-State of Basal Insulin Dose at 26 Weeks (Time to Steady State for Basal Insulin [Stable Maximum Dose])	Week 26
Concentration of Triglycerides, Total Cholesterol, Low-Density Lipoprotein (LDL-C), and High-Density Lipoprotein Cholesterol (HDL-C) at Week 26	Week 26	LS means were calculated using MMRM analysis adjusting for baseline, treatment, stratification factor (region, HbA1c, LDL-C, and SU/meglitinide use), visit, and treatment-by-visit interaction.
Change From Baseline of European Quality of Life-5 Dimensions - 3 Levels (EuroQoL-5D-3L ) Index Score and Visual Analog Scale (VAS) Health State Score at Week 26	Baseline, Week 26	The EuroQoL-5D-3L questionnaire is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a 3-level scale of 1 to 3 (no problem, some problems, and extreme problems). These combinations of attributes are converted into a weighted health-state Index Score according to the United States population-based algorithm. Scores ranged from -0.11 to 1.0 where a score of 1.0 indicates perfect health. Overall health state score was self-reported using a VAS marked on a scale of 0 to 100 (0 indicates worst imaginable health state and 100 indicates best imaginable health state. LS means were calculated using analysis of covariance (ANCOVA) for actual measures and changes from baseline at endpoint using LOCF method: adjusting for treatment, stratification factors (region, HbA1c and SU/meglitin.
Insulin Treatment Satisfaction Questionnaire (ITSQ) Score	Week 4 and 26	The Insulin Treatment Satisfaction Questionnaire is a validated instrument containing 22 items that assessed treatment satisfaction for participants with diabetes on insulin. The questionnaire measures satisfaction from the following 5 domains: Inconvenience of Regimen, Lifestyle Flexibility, Glycemic Control, Hypoglycemic Control, and Insulin Delivery Device. Data presented are the transformed score on a scale of 0-100, where a higher score indicate better treatment satisfaction. LS means was achieved using a MMRM model for post-baseline measures with stratification factors (country, HbA1c, and SU/meglitinide use) treatment, visit, treatment-by-visit as fixed effects. ITSQ was assessed at Week 4 (baseline) and Week 26.
Change From Baseline to 26 Weeks in Adult Low Blood Sugar Survey (LBSS) Scores	Baseline, Week 26	LBSS is a validated, participant-reported 33-item questionnaire with items rated on a 5-point Likert scale, where 0 = never and 5 - always. The LBSS measures behaviors to avoid hypoglycemia and its negative consequences (15 items) and worries about hypoglycemia and its negative consequences (18 items). Total score is the sum of all items (range 0 to 132). Higher total scores reflect greater fear of hypoglycemia. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country, treatment and metformin use as fixed effects and baseline score as a covariate. LBSS was assessed during screening visit (baseline) and again at Week 26.
Intra-Participant Variability of the Fasting Blood Glucose (FBG)	Week 26	Intra-participant variability of Fasting Blood Glucose (FBG), which was measured by Self Monitored Blood Glucose (SMBG), was assessed by the standard deviation of the FBG measurement at the Week 26 visit. LS means were calculated using a MMRM with baseline fasting blood glucose measurement, stratification factors (country, HbA1c, LDL-C \[\< 100 mg/dL and ≥ 100 mg/dL\], and SU/meglitinide use), treatment, visit, and treatment-by-visit interaction as fixed effects.
Change From Baseline to 12 Weeks in Hemoglobin A1c (HbA1c)	Baseline, Week 12	Hemoglobin A1c (HbA1c) is a test that measures a participant's average blood glucose level over the past 2 to 3 months.LS means were calculated using a MMRM with baseline HbA1C measurement, stratification factors (country, HbA1c, LDL-C \[\< 100 mg/dL and ≥ 100 mg/dL\], and SU/meglitinide use), treatment, visit, and treatment-by-visit interaction as fixed effects.
Percent Hemoglobin A1c at Week 26	Week 26	HbA1c is a test that measures a participant's average blood glucose level over the past 2 to 3 months. LS means were calculated using a MMRM with baseline HbA1C measurement, stratification factors (country, HbA1c, LDL-C \[\< 100 mg/dL and ≥ 100 mg/dL\], and SU/meglitinide use), treatment, visit, and treatment-by-visit interaction as fixed effects.
Percentage of Participants With Total and Nocturnal Hypoglycemic Events (HE)	Baseline to Week 26	Percentage of participants with hypoglycemic events (total or nocturnal) to Week 26 based on BG Threshold 70mg/dL.

Trial Locations

Locations (1): 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.
🇨🇳
Yongkang City, Taiwan
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.
🇨🇳Yongkang City, Taiwan