Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication LYUMJEV ® is indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus. LYUMJEV ® is a rapid-acting human insulin analog indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus. ( 1 ) FDA label
Also known as LY900014, Insulin lispro, LY900014 (SC), LY900014 (IV), LY900014-U200, LY900014-U100, Lyumjev
Ultra-Rapid Lispro · 26 trials · 9 indications
Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Time as variables.
HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed model repeated measures (MMRM) model with Baseline + Pooled Country + Number of Bolus at Study Entry Stratum + Type of Basal at Lead-in Stratum + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.
Change from baseline in HbA1c was analyzed using mixed model repeated measures (MMRM) and includes fixed class effects of treatment, strata (pooled country, type of basal insulin, and age group), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. An unstructured covariance structure will be used to model the within-participant errors. The Efficacy estimand included data collected prior to permanent discontinuation of study drug through Week 26.
HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with covariates: Baseline + Pooled Country + Personal continuous glucose Monitor (CGM) or Flash glucose monitor (FGM) use during study flag + Treatment + Time + Treatment\*Time (Type III sum of squares). The efficacy estimand included participant data when baseline and at least one post-baseline measurement were available prior to permanent discontinuation of study drug.
Infusion set failure events are defined as premature infusion set changes, due to a pump occlusion alarm OR due to unexplained hyperglycemia with blood glucose (SMBG) \>250 milligrams per deciliter (mg/dL) (13.9 millimoles per liter \[mmol/L\]) that does not decrease within 1 hour following a correction bolus delivered via the pump during the 6 week treatment period. Aggregate rate was calculated for each participant as the total number of events while the participant is on study treatment divided by the days of exposure \[last dose date and time -first dose date and time -duration of pump or treatment interruption\] times 30.
Percentage of Time with Sensor Glucose Values Between 70 and 180 mg/dL (both inclusive) with CGM.
Least Square (LS) mean was determined by mixed-model repeated measures (MMRM) with baseline, period, sequence, strata (Hemoglobin A1c (HbA1c) \[\<=7.0%, \>7.0%\] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization \[\<=75%, \>75%\]), treatment (Type III sum of squares) as fixed factors.
Time to Recovery from Hyperglycemia was defined as tPG140 = time to achieve glucose of 140 Milligrams per deciliter (mg/dL).
Time to Recovery from Hyperglycemia was defined as tPG140 = time to achieve glucose of 140 mg/dL.
Pharmacokinetics (PK): Insulin Lispro AUC time zero to 10 hours.
Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve (AUC(0 -7h)) following Each Treatment Arm for Each Study Part.
PK: Insulin Lispro or Insulin Aspart AUC(0-7h)
PK: Insulin Lispro AUC from time zero to 10 hours
Insulin Lispro AUC From Time Zero to 10 hours post dose (AUC\[0-10h\])
PK: Insulin Lispro AUC for Each Treatment Arm. LY900014 before and after meal and insulin lispro (Humalog) before and after meal were pooled by treatment to evaluate the overall PK of LY900014 and insulin lispro (Humalog) per protocol .
PK: Insulin Lispro AUC for Each Treatment Arm. PK: Insulin Lispro AUC for Each Treatment Arm. LY900014 before and after meal and insulin lispro (Humalog) before and after meal were pooled by treatment to evaluate the overall PK of LY900014 and insulin lispro (Humalog) per protocol .
Pharmacokinetics: Insulin Lispro Area Under the Concentration Curve From Time Zero to 10 Hours Post Dose \[AUC(0-10h)\]
Pharmacokinetics(PK): Insulin Lispro AUC from zero to 10 hours postdose \[AUC(0-10)\] following each treatment arm
Pharmacokinetics(PK): Insulin lispro AUC from time zero to 10 hours post dose \[AUC(0-10h)\].
Pharmacokinetics: Insulin lispro AUC from time zero to 10 hours postdose \[AUC(0-10h)\] for each treatment arm.
PK: Insulin Lispro AUC(0-5h)
PK: Insulin Lispro AUC(0-5h)
PK: Insulin Lispro AUC(0-5h)
PK: Insulin Lispro AUC(0-5h) (Part A)
PK: Insulin Lispro AUC(0-5h) (Part B)
| Arm | Type | Description |
|---|---|---|
| LY900014 | EXPERIMENTAL | LY900014 (100 units/milliliter (U/mL)) is a mealtime insulin administered subcutaneously (SC) 0-2 minutes prior to each meal in combination with insulin glargine (100 U/mL) SC as long-acting insulin. Mealtime (bolus) and long-acting (basal) insulin doses were titrated to achieve glucose targets during the study. |
| Insulin Lispro (Humalog) | ACTIVE_COMPARATOR | Participants received 100 U/mL insulin lispro SC 0-2 minutes before each meal with either basal insulin glargine or insulin degludec given SC once daily. |
| Insulin Lispro | ACTIVE_COMPARATOR | Participants received 100 U/mL insulin lispro (Humalog) given SC 0-2 minutes before each meal with either basal insulin glargine or insulin degludec given SC once daily. |
| LY900014 Postmeal | EXPERIMENTAL | Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal. |
| Ultra-Rapid Lispro | EXPERIMENTAL | Participants received individual dose of 100 units per milliliter (U/mL) ultra rapid lispro by continuous subcutaneous insulin infusion (CSII); where mealtime boluses were delivered 0 to 2 minutes prior to the start of each meal, with basal infusion rates 24 hours/day, and correction boluses as necessary. |
| LY900014 Postmeal (Open Label) | EXPERIMENTAL | LY900014 given SC 20 minutes after the start of each meal with either basal insulin glargine given SC once or twice daily or insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. |
| LY900014 - Maximum Extended Enrollment (MEE) | EXPERIMENTAL | LY900014 given subcutaneously (SC) 0-2 minutes before each meal with either basal insulin glargine given SC once or twice daily or insulin degludec given SC once daily. Preprandial insulin doses were individualized and titrated according to protocol-defined targets. |
| Insulin Lispro (Humalog)-MEE | ACTIVE_COMPARATOR | Insulin lispro given SC 0-2 minutes before each meal with either basal insulin glargine given SC once or twice daily or insulin degludec given SC once daily. Preprandial insulin doses were individualized and titrated according to protocol-defined targets. |
| LY900014 Postmeal (Open Label)-MEE | EXPERIMENTAL | LY900014 given SC 20 minutes after the start of each meal with either basal insulin glargine given SC once or twice daily or insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. |
| LY900014 Maximum Extended Enrollment (MEE) | EXPERIMENTAL | LY900014 given subcutaneously (SC) with each meal with either U-100 basal insulin glargine given SC once or twice daily or U-100 or U-200 insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. |
| Insulin Lispro (Humalog) MEE | ACTIVE_COMPARATOR | Insulin lispro given SC with each meal with either U-100 basal insulin glargine given SC once or twice daily or U-100 or U-200 insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. |
| LY900014 + Insulin Degludec | EXPERIMENTAL | LY900014 (100 units/milliliter (U/mL)) is a prandial insulin administered subcutaneously (SC) 0-2 minutes before meals. Insulin degludec (100 U/mL) is a basal insulin administered once daily SC. Participants received individually adjusted insulin doses during the 35-day titration period. The target glucose values were: fasting glucose 80-110 milligrams per deciliter (mg/dL), overnight glucose excursion (the difference between bedtime and prebreakfast glucose levels) \< or = +/- 30 mg/dL, postprandial glucose peak \<140 mg/dL or \<20% increase from premeal level. Following the titration period, there was an 11-day maintenance period during which the doses were kept unchanged unless for safety reasons. |
| 100 U/mL LY900014 | EXPERIMENTAL | 100 units per milliliter (U/mL) LY900014 administered by continuous subcutaneous insulin infusion (CSII) in one of two study periods. |
| 100 U/mL Insulin Lispro (Humalog) | ACTIVE_COMPARATOR | 100 U/mL Insulin Lispro (Humalog) administered by CSII in one of two study periods. |
| LY900014 U-200 | EXPERIMENTAL | Single subcutaneous (SC) dose of LY900014 U-200 in two of four study periods. |
| LY900014 U-100 | EXPERIMENTAL | Single SC dose of LY900014 U-100 in two of four study periods. |
| LY900014-Part A | EXPERIMENTAL | Participants received single 0.2 U/kg of body weight subcutaneous (SC) bolus injection of 100 U/mL LY900014. |
| Humalog (Insulin Lispro)-Part A | ACTIVE_COMPARATOR | Participants received single 0.2 U/kg of body weight SC bolus injection of 100 U/mL of Humalog. |
| LY900014-Part B | EXPERIMENTAL | Participants received single 0.2 U/kg of body weight SC bolus infusion of 100 U/mL LY900014 delivered using the continuous subcutaneous insulin infusion (CSII) pump. |
| Humalog (Insulin Lispro)-Part B | ACTIVE_COMPARATOR | Participants received single 0.2 U/kg of body weight SC bolus infusion of 100 U/mL Humalog delivered using the CSII pump. |
| Insulin Lispro (Humalog®) | ACTIVE_COMPARATOR | T1DM participants received a single, individualized, SC dose of insulin lispro. |
| Insulin Aspart (NovoRapid®) | ACTIVE_COMPARATOR | T1DM participants received a single, individualized, SC dose of insulin aspart. |
| Insulin Aspart (Fiasp®) | ACTIVE_COMPARATOR | T1DM participants received a single, individualized, SC dose of insulin aspart. |
| Healthy Participants | NO_INTERVENTION | Healthy participants who received no study drug. |
| LY900014-U200 | EXPERIMENTAL | Single subcutaneous (SC) dose of 15 units (U) LY900014 U-200 in two of four study periods |
| LY900014-U100 | EXPERIMENTAL | Single SC dose of 15 U LY900014 U-100 in two of four study periods |
| LY900014 Before Meal | EXPERIMENTAL | Individualized dose of LY900014 administered subcutaneously (SC) immediately before meal in one of four study periods. |
| LY900014 After Meal | EXPERIMENTAL | Individualized dose of LY900014 administered SC 20 minutes after start of meal in one of four study periods. |
| Insulin Lispro (Humalog) Before Meal | ACTIVE_COMPARATOR | Individualized dose of insulin lispro administered SC immediately before meal in one of four study periods. |
| Insulin Lispro (Humalog) After Meal | ACTIVE_COMPARATOR | Individualized dose of insulin lispro administered SC 20 minutes after start of meal in one of four study periods. |
| LY900014 (SC Abdomen) | EXPERIMENTAL | Single dose of 15-U of LY900014 administered subcutaneously (SC) into the abdomen in one period |
| LY900014 (SC Thigh) | EXPERIMENTAL | Single dose of 15-U of LY900014 administered SC into the thigh in one period |
| LY900014 (SC Arm) | EXPERIMENTAL | Single dose of 15-U of LY900014 administered SC into the arm (deltoid) in one period |
| LY900014 (IV) | ACTIVE_COMPARATOR | Single dose of 15-U of LY900014 administered intravenously (IV) in one period |
| Elderly Adults LY900014 | EXPERIMENTAL | Single, subcutaneous (SC) 15-U dose of LY900014 in the elderly adult group. |
| Elderly Adults Insulin Lispro | ACTIVE_COMPARATOR | Single, SC 15-U dose of insulin lispro (Humalog) in in the elderly adult group. |
| Younger Adults LY900014 | EXPERIMENTAL | Single, SC 15-U dose of LY900014 in the younger adult group. |
| Younger Adults Insulin Lispro | ACTIVE_COMPARATOR | Single, SC 15-U dose of insulin lispro (Humalog) in the younger adult group. |
| LY900014 (Part A) | EXPERIMENTAL | Individualized doses of LY900014 administered by injection under the skin once in each of 3 periods |
| Insulin Lispro - Reference (Part A) | ACTIVE_COMPARATOR | Individualized doses of insulin lispro reference formulation administered by injection under the skin once in each of 3 periods |
| LY900014 (Part B) | EXPERIMENTAL | Individualized doses of LY900014 administered by injection under the skin with each meal for 14 days |
| Insulin Lispro - Reference (Part B) | ACTIVE_COMPARATOR | Individualized doses of insulin lispro reference formulation administered by injection under the skin with each meal for 14 days |
| LY900014 - Test (Part A) | EXPERIMENTAL | Individualized doses of LY900014 administered by injection under the skin once in each of 3 periods |
| LY900014 - Test (Part B) | EXPERIMENTAL | Individualized doses of LY900014 administered by injection under the skin immediately before each meal for 14 days |
| Name | Type | Description |
|---|---|---|
| LY900014 | DRUG | Administered SC |
| Insulin Glargine | DRUG | Administered SC |
| Insulin Lispro | DRUG | Administered SC |
| Insulin Degludec | DRUG | Administered SC |
| Ultra-Rapid Lispro | DRUG | Administered SC |
| Metformin | DRUG | Administered orally. |
| SGLT2 inhibitor | DRUG | Administered orally. |
| LY900014 U-200 | DRUG | Administered SC |
| LY900014 U-100 | DRUG | Administered SC |
| Insulin Aspart | DRUG | Administered SC |
| LY900014-U200 | DRUG | Administered SC |
| LY900014-U100 | DRUG | Administered SC |
| LY900014 (SC) | DRUG | Administered SC |
| LY900014 (IV) | DRUG | Administered IV |
| Insulin Lispro (Humalog) | DRUG | Administered SC |
Inclusion Criteria: * Participants diagnosed (clinically) with type 2 diabetes mellitus (T2D) for at least 1 year prior to screening. * Have been treated with basal-bolus multiple daily injection (MDI) therapy for at least 90 days prior to screening including: * Basal insulin glargine U-100, in ...
Ultra-Rapid Lispro is an investigational small molecule being developed for the treatment of Type 1 Diabetes Mellitus. It is designed to be used in adults with this condition, as studied in a Phase 3 clinical trial involving insulin pump therapy.
Ultra-Rapid Lispro is being developed by Eli Lilly and Company, a pharmaceutical company publicly traded under the ticker symbol LLY on the stock exchange.
Ultra-Rapid Lispro is in Phase 3 clinical development. It is an investigational drug, meaning it has not yet been approved by regulatory authorities and is still undergoing clinical trials to evaluate its safety and efficacy.
Ultra-Rapid Lispro has one completed Phase 3 clinical trial with the identifier NCT03830281. This trial compared Ultra-Rapid Lispro to Insulin Lispro (Humalog) in adults with Type 1 Diabetes Mellitus using insulin pump therapy. The trial enrolled 471 participants across multiple countries.
Ultra-Rapid Lispro is not the same as Insulin Lispro (Humalog). In the clinical trial NCT03830281, Ultra-Rapid Lispro was compared directly against Insulin Lispro as an active control, indicating they are distinct drug products being evaluated for similar use in Type 1 Diabetes Mellitus.