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Trial · Interventional

TerminatedPhase 4Results postedRegistry data

A Comparison of Two Treatment Strategies in Older Participants With Type 2 Diabetes Mellitus (T2DM)

Short name IMPERIUM

NCTNCT02072096 (opens ClinicalTrials.gov in a new tab)Other id14842Other idF3Z-MC-IOQLOther id2013-001473-24

Overview

Status
Terminated
Phase
Phase 4
Enrollment
192 participants (actual)
Sponsor
Eli Lilly and Company · Industry
Design
Randomized · Open label (no masking)
Countries
5 countries

United States, Austria, Germany, Puerto Rico, United Kingdom

Start
Feb 2014
Primary completion
Oct 2015
Completion
Oct 2015
First posted
26 Feb 2014 (estimated)
Last update posted
9 Oct 2019
Conditions
Diabetes Mellitus, Type 2

Timeline

1 trial · 1 stopped early · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
201420152016
  1. Ph 4

    IMPERIUM

    NCT02072096

    Feb 2014 to Oct 2015

    Terminated

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

The main purpose of this study is to compare the benefits and risks associated with the use of 2 treatment strategies to lower blood sugar in participants aged 65 and older with T2DM. One strategy is based on the use of oral and injectable medications that only reduce blood sugar (glucose) when it is high. The other strategy is based on non-glucose dependent agents. The trial will last up to 72 weeks for each participant.

Interventions

  • GlimepirideDrug
  • MetforminDrug
  • PioglitazoneDrug
  • AcarboseDrug
  • LinagliptinDrug
  • SitagliptinDrug
  • LiraglutideDrug
  • Insulin GlargineDrug
  • Exenatide once weekly (QW)Drug
  • Exenatide twice daily (BID)Drug

Arms2

  • Experimental

    Strategy A (Glucose-Dependent)

    Participants may receive oral and injectable (glucagon-like peptide-1 receptor agonists \[GLP-1 RA\]) therapies that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label. Treatment may last up to 72 weeks.

  • Active comparator

    Strategy B (Reference)

    Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Insulin glargine is titrated according treatment algorithm. Treatment may last up to 72 weeks.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Percentage of Participants Achieving and Maintaining Individualized Glycated Hemoglobin A1c (HbA1c) Targets Without Clinically Significant Hypoglycemia

    Time frame · Baseline to last participant visit (up to 72 weeks)

    Registry description

    Failed to reach and maintain HbA1c target, without clinically significant hypoglycemia, is defined as having 2 consecutive HbA1c \> upper limit of HbA1c target over 12 weeks starting from Week 24 for participants with HbA1c data beyond Week 24, or Week 24 HbA1c \> upper limit of HbA1c target for participants without HbA1c data beyond Week 24. Clinically significant hypoglycemia is defined as any severe hypoglycemia or repeated hypoglycemia interrupting participants activities or sleep and associated with blood glucose ≤3.9 millimole per liter (mmol/L), or repeated asymptomatic hypoglycemia associated with blood glucose \<3.0 mmol/L. Success is defined as lacking of failure.

Secondary outcomes(5)
  1. Percentage of Participants Requiring Alternative Treatment Due to Glycemic Failure of First Line Injectable Therapy

    Time frame · Baseline to last participant visit (up to 72 weeks)

  2. Number of Participants With Total Hypoglycemia and Other Categories of Hypoglycemia

    Time frame · Baseline to last participant visit (up to 72 weeks)

  3. Change From Baseline of Urinary Albumin to Creatinine Ratio

    Time frame · Baseline, Week 72

    Registry description

    The Urinary Albumin to Creatinine Ratio is used in addition to Estimated Glomerular Filtration Rate (eGFR) to measure the incidence and progression of diabetic kidney disease.

  4. Change From Baseline in Body Mass Index (BMI)

    Time frame · Baseline, Week 72

  5. Change From Baseline of Estimated Glomerular Filtration Rate (eGFR)

    Time frame · Baseline, Week 72

    Registry description

    The eGFR is used in addition to the Urinary Albumin to Creatinine Ratio to measure the incidence and progression of diabetic kidney disease.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeNumber· Baseline to last participant visit (up to 72 weeks)

Percentage of Participants Achieving and Maintaining Individualized Glycated Hemoglobin A1c (HbA1c) Targets Without Clinically Significant Hypoglycemia

GroupValue (percentage of participants)
Strategy A (Glucose-Dependent)64.5
Strategy B (Reference)54.9
Secondary and other outcome results(7)
Secondary outcomeNumber· Baseline to last participant visit (up to 72 weeks)

Percentage of Participants Requiring Alternative Treatment Due to Glycemic Failure of First Line Injectable Therapy

GroupValue (percentage of participants)
Strategy A (Glucose-Dependent)21
Strategy B (Reference)13
Secondary outcomeNumber· Baseline to last participant visit (up to 72 weeks)

Number of Participants With Total Hypoglycemia and Other Categories of Hypoglycemia

GroupValue (Participants)
Strategy A (Glucose-Dependent)10
Strategy B (Reference)50
Secondary outcomeMean· Baseline, Week 72

Change From Baseline of Urinary Albumin to Creatinine Ratio

GroupValue (milligram per millimole (mg/mmol))Spread
Strategy A (Glucose-Dependent)1.8522.99
Strategy B (Reference)1.8516.46
Secondary outcomeMean· Baseline, Week 72

Change From Baseline in Body Mass Index (BMI)

GroupValue (kilogram per square meter (kg/m^2))Spread
Strategy A (Glucose-Dependent)-0.471.56
Strategy B (Reference)0.202.91
Secondary outcomeMean· Baseline, Week 72

Change From Baseline of Estimated Glomerular Filtration Rate (eGFR)

GroupValue (milliliter per minute/1.73 square meter)Spread
Strategy A (Glucose-Dependent)-5.0013.64
Strategy B (Reference)-5.8810.95
Other pre specified outcome· Baseline, Week 72

Change From Baseline in Adult Low Blood Sugar Survey (ALBSS) Score

GroupValue
Strategy A (Glucose-Dependent)not posted
Strategy B (Reference)not posted
Other pre specified outcome· Baseline, Week 72

Change From Baseline in European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Score

GroupValue
Strategy A (Glucose-Dependent)not posted
Strategy B (Reference)not posted

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Strategy A (Glucose-Dependent)Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists \[GLP-1 RA\]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label. Treatment may last up to 72 weeks.–15 / 9882 / 98
Strategy B (Reference)Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Dose titrated by treatment algorithm. Treatment may last up to 72 weeks.–14 / 9374 / 93

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • DerivedHeller SR, Pratley RE, Sinclair A, Festa A, Kiljanski J, Brusko CS, Duan R, Heine RJ. Glycaemic outcomes of an Individualized treatMent aPproach for oldER vulnerable patIents: A randomized, controlled stUdy in type 2 diabetes Mellitus (IMPERIUM). Diabetes Obes Metab. 2018 Jan;20(1):148-156. doi: 10.1111/dom.13051. Epub 2017 Aug 8. PMID 28671753

Eligibility

Who could join, as posted.

Sex
All
Age
from 65 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * Have T2DM based on a history and clinical impression that is consistent with the World Health Organization (WHO) Classification of Diabetes * Have a Clinical Frailty Scale (CFS) score of 4 or above or Total Illness Burden Index (TIBI) score of 5 or above as assessed at screening * Have an A1c \>7.3% and \<10.9% at study entry and are not achieving desired glycemic control as evidenced by A1c measurement at least 0.4% higher than individualized treatment target set at screening. * Have been treated for at least 3 months prior to the study entry with any of the following treatment options: * Diet/exercise only (only if they have known contraindications to metformin treatment) * Any dose of sulfonylurea * Effective or maximally-tolerated doses of metformin, dipeptidyl-peptidase-4 (DPP-4) inhibitor, thiazolidinedione, or acarbose used in monotherapy or in dual combination. The following doses are considered to be effective: * at least 1500 mg of metformin per day * At least 30 mg of pioglitazone per day * At least 4 mg of rosiglitazone per day * At least 75 mg of acarbose per day * Any marketed dose of DPP-4 inhibitor Exclusion Criteria: * Are currently enrolled in a clinical trial involving an investigational product or nonapproved use of a drug or device (other than the investigational product used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study * Have participated, within the last 60 days in a clinical trial involving an investigational product other than the investigational product used in this study. If the previous investigational product has a long half-life, 3 months or 5 half-lives (whichever is longer) should have passed * Have previously completed or withdrawn from this study. This exclusion criterion does not apply to participants who are rescreened prior to randomization * At study entry, have contraindications to sulfonylurea, insulin, or GLP-1 RA * Have a history of pancreatitis, a personal or family history of medullary thyroid carcinoma, or have Multiple Endocrine Neoplasia syndrome type 2 * Have taken any injectable glucose-lowering agent, miglitol, meglitinide, Sodium/Glucose cotransporter-2 inhibitor, or other antihyperglycemia treatment that is not listed in the fourth inclusion criterion for more than 10 days within 3 months prior to the study entry * In the opinion of investigator should have an individualized A1c target set at 8% or higher * Have a body mass index (BMI) greater than 45 kg/m\^2 * Have had more than 1 episode of severe hypoglycemia within 24 weeks prior to the study * Have cardiac disease with functional status that is Class III or IV according to the New York Heart Association Cardiac Disease Classification * Have an estimated glomerular filtration rate (eGFR) \<30 milliliter/minute/1.73 m\^2 (mL/min/1.73 m\^2) or advanced renal disease including history of renal transplantation or currently receiving renal dialysis * Have obvious clinical signs or symptoms or laboratory evidence of liver disease (alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\] \> 2.5 times the upper limit of the reference range) * Receive current therapy for a malignancy, other than basal-cell or squamous-cell skin cancer * Received systemic glucocorticoids within the 3 months prior to entry for more than 14 consecutive days * Have any other condition that precludes the participant from following and completing the study

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