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A Study of LY900014 in Participants With Type 1 Diabetes (PRONTO-T1D)

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: NCT03214367
Recruitment Status : Completed
First Posted : July 11, 2017
Results First Posted : May 1, 2020
Last Update Posted : May 1, 2020
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Description
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Brief Summary:
The main purpose of this study is to evaluate the efficacy of the study drug LY900014 compared to insulin lispro, both in combination with insulin glargine or insulin degludec, in adults with type 1 diabetes (T1D).

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Mellitus Drug: LY900014 Drug: Insulin Lispro Drug: Insulin Glargine Drug: Insulin Degludec Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1392 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 With an Open-Label Postprandial LY900014 Treatment Group, in Combination With Insulin Glargine or Insulin Degludec, in Adults With Type 1 Diabetes PRONTO-T1D
Actual Study Start Date : July 17, 2017
Actual Primary Completion Date : September 6, 2018
Actual Study Completion Date : August 22, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Arms and Interventions
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Arm Intervention/treatment
Experimental: LY900014
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.
 Drug: LY900014
Administered SC
Other Name: Ultra-Rapid Lispro

Drug: Insulin Glargine
Administered SC

Drug: Insulin Degludec
Administered SC
Active Comparator: Insulin Lispro (Humalog)
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.
 Drug: Insulin Lispro
Administered SC
Other Name: Humalog

Drug: Insulin Glargine
Administered SC

Drug: Insulin Degludec
Administered SC
Experimental: LY900014 Postmeal (Open Label)
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.
 Drug: LY900014
Administered SC
Other Name: Ultra-Rapid Lispro

Drug: Insulin Glargine
Administered SC

Drug: Insulin Degludec
Administered SC
Experimental: LY900014 - Maximum Extended Enrollment (MEE)
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.
 Drug: LY900014
Administered SC
Other Name: Ultra-Rapid Lispro

Drug: Insulin Glargine
Administered SC

Drug: Insulin Degludec
Administered SC
Active Comparator: Insulin Lispro (Humalog)-MEE
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.
 Drug: Insulin Lispro
Administered SC
Other Name: Humalog

Drug: Insulin Glargine
Administered SC

Drug: Insulin Degludec
Administered SC
Experimental: LY900014 Postmeal (Open Label)-MEE
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.
 Drug: LY900014
Administered SC
Other Name: Ultra-Rapid Lispro

Drug: Insulin Glargine
Administered SC

Drug: Insulin Degludec
Administered SC


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 ]

    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 strata (pooled country, type of basal insulin, prandial insulin dosing plan, 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.



Secondary Outcome Measures :
  1. Change From Baseline in 1-hour Postprandial Glucose (PPG) Excursion During Mixed-Meal Tolerance Test (MMTT) Efficacy Estimand at Week 26 [ Time Frame: Baseline, Week 26 ]
    A standardized MMTT was used to characterize postprandial glucose control following administration of the study insulin. Serum glucose measured at 1-hour timepoint after the start of meal minus fasting serum glucose. 1-hour PPG excursion during MMTT uses the ANCOVA model with strata (pooled country, type of basal insulin, prandial insulin dosing plan, 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. Change From Baseline in 2-hour PPG Excursion During MMTT Efficacy Estimand at Week 26 [ Time Frame: Baseline, Week 26 ]
    A standardized MMTT was used to characterize postprandial glucose control following administration of the study insulin. Serum glucose measured at 2-hour timepoint after the start of meal minus fasting serum glucose. 2-hour PPG excursion during MMTT uses the ANCOVA model with strata (pooled country, type of basal insulin, prandial insulin dosing plan, 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 at Week 26 [ Time Frame: Baseline through Week 26 ]
    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 coma with or without seizures, and may require parenteral therapy. 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.

  4. Rate of Documented Symptomatic Hypoglycemia at Week 26 [ 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 ]
    1,5-anhydroglucitol (1,5-AG) is a marker of short-term glycemic control especially postprandial hyperglycemia. 1,5-AG accurately predicts rapid changes in glycemia and is tightly associated with glucose fluctuations and postprandial glucose. LS Mean was calculated 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 ]
    SMBG 10-point profiles were measured at fasting, 1-hour post morning meal, 2-hours post morning meal, pre midday meal, 1-hour post midday meal, 2-hours post midday meal, pre evening meal, 1-hour post evening meal, 2-hours post evening meal, and bedtime. LS Mean 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 ]
    LS Mean 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. LS Mean 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. 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. LS Mean was calculated using the analysis of covariance (ANCOVA) 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. The analysis included data prior to permanent discontinuation of study drug.

  10. Percentage of Participants With HbA1c <7% [ Time Frame: Week 26 ]
    Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.

  11. Change From Baseline in HbA1c at Week 52 [ Time Frame: Baseline, Week 52 ]

    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 MMRM model with variables of baseline, pooled country, type of basal insulin during lead-in, prandial Insulin Dosing Plan, treatment (Type III sum of squares) as fixed factors. The analysis included data prior to permanent discontinuation of study drug.



Eligibility Criteria
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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 T1D for at least 1 year prior to screening and continuously using insulin for at least 1 year.
  • HbA1c of ≥7.0 and ≤9.5%.
  • Use insulin lispro, insulin aspart, or insulin glulisine as prandial insulin.
  • Use insulin glargine, insulin detemir, insulin degludec, or neutral protamine Hagedorn (NPH) insulin as basal insulin.

Exclusion Criteria:

  • Have used other antihyperglycemic medications or therapies (inhaled, oral or injectable) within 90-days of screening.
  • Have had more than 1 severe hypoglycemic episode within 6 months of screening.
  • Have had more than 1 hospitalization related to hyperglycemia or diabetic ketoacidosis within 6 months of screening.
  • Have clinically significant gastrointestinal disease.
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): NCT03214367


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 22, 2017
Statistical Analysis Plan  [PDF] August 14, 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: NCT03214367    
Other Study ID Numbers: 16313
I8B-MC-ITRM ( Other Identifier: Eli Lilly and Company )
2015-005356-99 ( EudraCT Number )
First Posted: July 11, 2017    Key Record Dates
Results First Posted: May 1, 2020
Last Update Posted: May 1, 2020
Last Verified: September 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 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
 Insulin
Insulin, Globin Zinc
Insulin Glargine
Insulin Lispro
Hypoglycemic Agents
Physiological Effects of Drugs