An Individualized treatMent aPproach for oldER patIents: A randomized, controlled stUdy in type 2 diabetes Mellitus - IMPERIUM

• Register: EUCTR
• Last refreshed on: 14 March 2016
• Main ID: EUCTR2013-001473-24-AT
• Date of registration: 20/12/2013
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company
• Public title: An Individualized treatMent aPproach for oldER patIents: A randomized, controlled stUdy in type 2 diabetes Mellitus - IMPERIUM
• Scientific title: An Individualized treatMent aPproach for oldER patIents: A randomized, controlled stUdy in type 2 diabetes Mellitus - IMPERIUM
• Date of first enrolment: 24/01/2014
• Target sample size: 880
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-001473-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: Two antihyperglycemia treatment strategies will be compared Number of treatment arms in the trial: 2

Countries of recruitment

Austria, Germany, United Kingdom, United States

Contacts

• Name: Clinical Trial Registry Office
• Affiliation: Eli Lilly

• Name: Clinical Trial Registry Office
• Affiliation: Eli Lilly

Key inclusion & exclusion criteria

Inclusion criteria:
The study will include patients who are:
• Patients with T2DM based on a history and clinical impression that is consistent with the World Health Organization [WHO] Classification of Diabetes
• Male or female
• Are at least 65 years of age at the time of screening
• Have a CFS of 4 or above AND/OR TIBI score of 5 or above as assessed at Visit 1
• 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 Visit 1.
• Have been treated for at least 3 months prior to the study entry with any of the following treatment options:
o diet/exercise only (only if they have known contraindications to metformin treatment)
o any dose of sulfonylurea
o 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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 970

Exclusion criteria:
Patients will be excluded from the study based on the following criteria:
• Are investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted
• Are Lilly employees or are employees of third-party organizations (TPOs) involved in study who require exclusion of their employees
• 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 patients 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 inclusion criterion [6] (main protocol) 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 BMI greater than 45 kg/m2
• 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 eGFR<30 mL/min/1.73 m2 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 or aspartate aminotransferase > 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 patient from following and completing the protocol.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Diabetes Mellitus, Type 2
MedDRA version: 17.0 Level: LLT Classification code 10063624 Term: Type II diabetes mellitus inadequate control System Organ Class: 100000004861

Intervention(s)

Trade Name: Glucophage 1000mg
Product Name: Metformin
Pharmaceutical Form: Film-coated tablet
Other descriptive name: METFORMIN HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1000-

Trade Name: Actos 15mg
Product Name: Pioglitazone Hydrochloride
Pharmaceutical Form: Tablet
Other descriptive name: PIOGLITAZONE HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-

Trade Name: Glucobay 100mg
Product Name: Acarbose
Pharmaceutical Form:
INN or Proposed INN: ACARBOSE
CAS Number: 56180-94-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: Trajenta
Product Name: Linagliptin
Pharmaceutical Form: Film-coated tablet
CAS Number: 668270-12-0
Other descriptive name: LINAGLIPTIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Trade Name: Januvia 25mg
Product Name: Sitagliptin
Pharmaceutical Form: Film-coated tablet
CAS Number: 654671-77-9
Other descriptive name: SITAGLIPTIN PHOSPHATE MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Trade Name: Byetta 5µg/20µl
Product Name: exenatide twice daily
Pharmaceutical Form: Solution for injection
INN or Proposed INN: EXENATIDE
CAS Number: 141758-74-9
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 5/20µl-

Trade Name: Bydureon
Product Name: exenatide once weekly
Pharmaceutical Form: Powder and solvent for prolonged-release suspension for injection
INN or Proposed INN: EXENATIDE
CAS Number: 141758-74-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-

Trade Name: Victoza
Product Name: Liraglutide
Pharmaceutical Form: Solution for injection
INN or Proposed INN: LIRAGLUTIDE
CAS Number: 204656-20-2
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6-

Trade Name: Amaryl 1 mg Tablet

Primary Outcome(s)

Primary end point(s): The primary outcome measure for this study is a composite of achieving /maintaining individualized A1c targets in the absence of clinically significant hypoglycemia over 72 weeks of therapy. Patients who fail to reach and/or maintain target A1c AND/OR develop clinically significant hypoglycemia will be considered to have failed on the assigned strategy and this event will be captured as a failure event for purposes of survival/success analysis. These patients will not participate further in the Core study. Patients who are able to achieve and maintain the composite primary outcome measure at the completion of the 72 week Core study will be considered to have achieved success on the assigned strategy.

Timepoint(s) of evaluation of this end point: 72 weeks of therapy

Secondary Objective: Safety: Safety parameters that will be assessed include AEs, physical exam findings, body weight, vital signs, and safety laboratory values. Continuous glucose monitoring at baseline and at 24 weeks will be performed in a subset of patients participating in the continuous glucose monitoring addendum.
Health Outcomes: The questionnaires and scoring tools to be used are:
• TIBI –at Visit 1
• CFS – at Visit 1
• ALBSS – at baseline, 48 weeks, 72 weeks, and ET
• EQ 5D 5L – at baseline, 48 weeks, 72 weeks, and ET
• MMSE – at baseline, 48 weeks, 72 weeks, and

Main Objective: The primary objective of this study is to assess the relative success of Strategy A as compared to Strategy B in achieving and sustaining glycemic control in the absence of episodes of clinically significant hypoglycemia. Success of either strategy is defined as achieving and maintaining defined, prerandomization individualized A1c targets without clinically significant hypoglycemia

Secondary Outcome(s)

Secondary end point(s): Safety: Safety parameters that will be assessed include AEs, physical exam findings, body weight, vital signs, and safety laboratory values. Continuous glucose monitoring at baseline and at 24 weeks will be performed in a subset of patients participating in the continuous glucose monitoring addendum.
Health Outcomes: The questionnaires and scoring tools to be used are:
• TIBI –at Visit 1
• CFS – at Visit 1
• ALBSS – at baseline, 48 weeks, 72 weeks, and ET
• EQ 5D 5L – at baseline, 48 weeks, 72 weeks, and ET
• MMSE – at baseline, 48 weeks, 72 weeks, and ET

Timepoint(s) of evaluation of this end point: 48 weeks, 72 weeks

Secondary ID(s)

2013-001473-24-GB

F3Z-MC-IOQL

Source(s) of Monetary Support

Eli Lilly and Company