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A Study of LY900014 Compared to Insulin Lispro in Participants With Type 2 Diabetes (PRONTO-T2D)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03214380
Recruitment Status : Completed
First Posted : July 11, 2017
Results First Posted : March 27, 2020
Last Update Posted : March 27, 2020
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Description
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Brief Summary:
The purpose of this study is to compare LY900014 to insulin lispro, both in combination with insulin glargine or insulin degludec, in participants with type 2 diabetes (T2D).

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: LY900014 Drug: Insulin Lispro Drug: Insulin Glargine Drug: Insulin Degludec Drug: Metformin Drug: SGLT2 inhibitor Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 933 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Prospective, Randomized, Double-Blind Comparison of LY900014 to Insulin Lispro, Both in Combination With Insulin Glargine or Insulin Degludec in Adults With Type 2 Diabetes PRONTO-T2D
Actual Study Start Date : July 14, 2017
Actual Primary Completion Date : August 14, 2018
Actual Study Completion Date : March 13, 2019

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: LY900014
LY900014 given subcutaneously (SC) with each meal with either 100 U/mL (U-100) basal insulin glargine given SC once or twice daily or U-100 or 200 U/mL (U-200) insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets.
 Drug: LY900014
Administered SC
Other Name: Ultra-Rapid Lispro

Drug: Insulin Glargine
Administered SC

Drug: Insulin Degludec
Administered SC

Drug: Metformin
Administered orally.

Drug: SGLT2 inhibitor
Administered orally.
Active Comparator: Insulin Lispro (Humalog)
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.
 Drug: Insulin Lispro
Administered SC
Other Name: Humalog

Drug: Insulin Glargine
Administered SC

Drug: Insulin Degludec
Administered SC

Drug: Metformin
Administered orally.

Drug: SGLT2 inhibitor
Administered orally.
Experimental: LY900014 Maximum Extended Enrollment (MEE)
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.
 Drug: LY900014
Administered SC
Other Name: Ultra-Rapid Lispro

Drug: Insulin Glargine
Administered SC

Drug: Insulin Degludec
Administered SC

Drug: Metformin
Administered orally.

Drug: SGLT2 inhibitor
Administered orally.
Active Comparator: Insulin Lispro (Humalog) MEE
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.
 Drug: Insulin Lispro
Administered SC
Other Name: Humalog

Drug: Insulin Glargine
Administered SC

Drug: Insulin Degludec
Administered SC

Drug: Metformin
Administered orally.

Drug: SGLT2 inhibitor
Administered orally.


Outcome Measures
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Primary Outcome Measures :
  1. Change From Baseline in Hemoglobin A1c (HbA1c) Efficacy Estimand at Week 26 [ Time Frame: Baseline, Week 26 ]
    Change from baseline in HbA1c was performed using mixed model repeated measures (MMRM) including fixed class effects of treatment, strata (pooled country, type of basal insulin, and number of prandial doses at study entry), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. The efficacy estimand included participant data when baseline and at least one post-baseline measurement were available prior to permanent discontinuation of study drug.


Secondary Outcome Measures :
  1. 1-hour Postprandial Glucose (PPG) Excursion During Mixed-Meal Tolerance Test (MMTT) Efficacy Estimand [ Time Frame: Week 26 ]
    1-hour PPG excursion during MMTT uses the analysis of covariance (ANCOVA) model with strata (pooled country, type of basal insulin, number of prandial doses at study entry, and HbA1c stratum) and treatment as fixed effects and baseline as a covariate. The efficacy estimand included participant data when baseline and at least one post-baseline measurement were available prior to permanent discontinuation of study drug.

  2. 2-hour PPG Excursion During MMTT Efficacy Estimand [ Time Frame: Week 26 ]
    2-hour PPG excursion during MMTT uses the ANCOVA model with strata (pooled country, type of basal insulin, number of prandial doses at study entry, and HbA1c stratum) and treatment as fixed effects and baseline as a covariate. The efficacy estimand included participant data when baseline and at least one post-baseline measurement were available prior to permanent discontinuation of study drug.

  3. Rate of Severe Hypoglycemia [ Time Frame: Baseline through Week 26 ]
    Rate of severe hypoglycemia events per 100 years during a defined period was calculated by total number of severe hypoglycemia episodes within the period divided by the cumulative days on treatment from all participants within a treatment group *36525. Severe hypoglycemia is defined as an event requiring assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. During these episodes, the participant has an altered mental status and cannot assist in his or her own care, or may be semiconscious or unconscious, or experience com with or without seizures, and may require parenteral therapy.

  4. Rate of Documented Symptomatic Hypoglycemia [ Time Frame: Baseline through Week 26 ]
    Documented symptomatic hypoglycemia is an event during which typical symptoms of hypoglycemia are accompanied by blood glucose (BG) of <54 mg/dL [3.0 millimole per liter (mmol/L)]. The rate of documented symptomatic hypoglycemia was estimated by negative binomial model: number of episodes = treatment with log (treatment exposure in days/365.25) as an offset variable.

  5. Change From Baseline in 1,5-Anhydroglucitol (1,5-AG) at Week 26 [ Time Frame: Baseline, Week 26 ]
    Change from baseline in 1,5-AG was analyzed using mixed model repeated measures (MMRM) including fixed class effects of treatment, strata (pooled country, type of basal insulin, HbA1c stratum and number of prandial doses at study entry), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. The analysis included data collected prior to permanent discontinuation of study drug.

  6. Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 26 [ Time Frame: Baseline, Week 26 ]
    Change from baseline in 10-point SMBG values was analyzed using mixed model repeated measures (MMRM) including fixed class effects of treatment, strata (pooled country, type of basal insulin, HbA1c stratum and number of prandial doses at study entry), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. The efficacy estimand included participant data when baseline and at least one post-baseline measurement prior to permanent discontinuation of study drug.

  7. Change From Baseline in Insulin Dose at Week 26 [ Time Frame: Baseline, Week 26 ]
    Change from baseline in insulin dose was analyzed using mixed model repeated measures (MMRM) including fixed class effects of treatment, strata (pooled country, type of basal insulin, HbA1c stratum and number of prandial doses at study entry), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. The analysis included data prior to permanent discontinuation of study drug.

  8. Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) Regimen Inconvenience Domain Score at Week 26 [ Time Frame: Baseline, Week 26 ]

    ITSQ is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes and 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 overall score on a scale of 0-100, where higher scores indicate better treatment satisfaction.

    Change from baseline in ITSQ regimen inconvenience domain score was calculated using the ANCOVA model with strata (pooled country, type of basal insulin, number of prandial doses at study entry, and HbA1c stratum), and treatment as fixed effects and baseline as covariate. The analysis included data prior to permanent discontinuation of study drug.


  9. Change From Baseline in ITSQ Lifestyle Flexibility Domain Score at Week 26 [ Time Frame: Baseline, Week 26 ]

    ITSQ is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes and 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 overall score on a scale of 0-100, where higher scores indicate better treatment satisfaction.

    Change from baseline in ITSQ lifestyle flexibility domain score was calculated using the ANCOVA model with strata (pooled country, type of basal insulin, number of prandial doses at study entry, and HbA1c stratum), and treatment as fixed effects and baseline as covariate. The analysis included data prior to permanent discontinuation of study drug.


  10. Number of Participants With HbA1c <7% [ Time Frame: Week 26 ]
    Number of participants with HbA1c <7% at Week 26.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have been diagnosed (clinically) with T2D, based on the World Health Organization (WHO) classification for at least 1 year prior to screening.

  • Have been treated for at least 90 days prior to screening with:

    • Basal insulin (insulin glargine U-100 [Basaglar/Abasaglar or LANTUS] or U-300, insulin detemir, insulin degludec U-100 or U-200, or neutral protamine Hagedorn [NPH] insulin) in combination with at least 1 prandial injection of bolus insulin (insulin lispro U-100 or U-200, insulin aspart, insulin glulisine, or regular insulin) Or
    • Premixed analog or human insulin regimens with any basal and bolus insulin combination injected at least twice daily

  • Participants may be treated with up to 3 of the following oral antihyperglycemic medications (OAMs) in accordance with local regulations:

    • Metformin
    • Dipeptidyl peptidase-4 (DPP-4) inhibitor
    • Sodium glucose cotransporter 2 (SGLT2) inhibitor
    • Sulfonylurea
    • Meglitinide
    • Alpha-glucoside inhibitor
  • Have an HbA1c value between ≥7.0 and ≤10.0%, according to the central laboratory at the time of screening.
  • Have a body mass index (BMI) of ≤45.0 kilograms per meter squared at screening.

Exclusion Criteria:

  • Have been diagnosed, at any time, with type 1 diabetes (T1D) or Latent Autoimmune Diabetes in Adults.
  • Have hypoglycemia unawareness as judged by the investigator.
  • Have had any episode of severe hypoglycemia within the 6 months prior to screening.
  • Have had 1 or more episodes of diabetic ketoacidosis or hyperglycemic hyperosmolar state within the 6 months prior to screening.
  • Have used thiazolidinediones, Glucagon-Like Peptide 1 (GLP-1) receptor agonist, or pramlintide within 90 days prior to screening.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03214380


Locations
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Sponsors and Collaborators
Eli Lilly and Company
Investigators
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Study Director: 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) Eli Lilly and Company
  Study Documents (Full-Text)

Documents provided by Eli Lilly and Company:
Study Protocol  [PDF] May 19, 2017
Statistical Analysis Plan  [PDF] July 24, 2018

More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT03214380    
Other Study ID Numbers: 16314
I8B-MC-ITRN ( Other Identifier: Eli Lilly and Company )
2015-005357-12 ( EudraCT Number )
First Posted: July 11, 2017    Key Record Dates
Results First Posted: March 27, 2020
Last Update Posted: March 27, 2020
Last Verified: August 15, 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: https://vivli.org/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin
Insulin, Globin Zinc
 Metformin
Insulin Glargine
Insulin Lispro
Sodium-Glucose Transporter 2 Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs
Molecular Mechanisms of Pharmacological Action