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A Study to Test How Well Empagliflozin Works in Japanese People With Type 2 Diabetes Who Are Older Than 65 Years

Phase 4
Completed
Conditions
Diabetes Mellitus, Type 2
Interventions
Drug: Placebo
Registration Number
NCT04531462
Lead Sponsor
Boehringer Ingelheim
Brief Summary

This study is to assess the efficacy of empagliflozin 10 mg after 52 weeks compared to placebo in elderly patients with Type 2 diabetes mellitus (T2DM) and to explore if empagliflozin has any impact on patient physical condition compared to placebo in elderly patients with T2DM.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
129
Inclusion Criteria
  • Japanese (defined as patient has parents who are Japanese) patients with diagnosis of Type 2 diabetes mellitus (T2DM) prior to informed consent

  • Glycated hemoglobin (HbA1c) ≥7.0% and ≤10.0% for patients at Visit 1 (screening). If the patient is on treatment with oral antidiabetic drug(s) potentially associated with severe hypoglycaemia (e.g., sulfonylurea or glinides), the following HbA1c value is used as criterion

    • HbA1c ≥7.5% and ≤10.0% for age ≥65 and <75
    • HbA1c ≥8.0% and ≤10.0% for age ≥75
  • Patients on diet and exercise regimen who are drug-naïve (drug-naïve is defined as no antidiabetic drugs for at least 12 weeks prior to informed consent) or on treatment with any oral antidiabetic drug (OAD) other than Glucagon-Like Peptide-1 (GLP-1) agonists and Sodium-glucose cotransporter 2 (SGLT-2) inhibitor. Antidiabetic therapy has to be unchanged for 12 weeks prior to randomisation (any thiazolidinedione therapy has to be unchanged for at least 18 weeks prior to informed consent).

  • Age ≥65 years at informed consent

  • BMI ≥22 kg/m2 at Visit 1 (screening)

  • Male or post-menopausal (a point in time 12 months after a woman's last period) female patients

  • Patient signed and dated written informed consent in accordance with International Conference on Harmonization (ICH)- Good Clinical Practice (GCP) and local legislation prior to admission to the Trial

Exclusion Criteria
  • Uncontrolled hyperglycaemia with a fasting glucose level >200 milligram per deciliter (mg/dL) (>11.1 millimol per Liter (mmol/L)) during run-in period
  • Treatment with insulin within 12 weeks prior to informed consent
  • Impaired cognitive ability as supported by Mini mental state examination (MMSE-J, defined as ≤23) and verified by the investigator at screening
  • Acute coronary syndrome (ST-elevation myocardial infarction [STEMI], non-STEMI, and unstable angina pectoris), stroke or transient ischemic attack within 12 weeks prior to informed consent
  • Indication of liver disease, defined by serum levels of either alanine aminotransferase (ALT = serum glutamic-pyruvic transaminase [SGPT]), aspartate aminotransferase (AST = serum glutamic-oxaloacetic transaminase[SGOT]), or alkaline phosphatase (ALP) above 3 x upper limit of normal (ULN) as determined during screening and run-in period
  • Impaired renal function, defined as Estimated glomerular filtration rate (eGFR) <45 milliliter per minute per 1.73 square meter (mL/min/1.73 m2, severe renal impairment, Modification of Diet in Renal Disease (MDRD) formula) as determined during screening and run-in period
  • Low grip strength defined as <28 kilogram (kg) for male or as <18 kg for female at screening
  • Short length of calf circumference defined as <34 centimeter (cm) for male or 33 cm for female at screening
  • further exclusion criteria apply

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Empagliflozin 10 mgEmpagliflozin-
PlaceboPlacebo-
Primary Outcome Measures
NameTimeMethod
Change in HbA1c From Baseline After 52 Weeks of TreatmentChange in HbA1c from baseline after 52 weeks of treatment was calculated using the MMRM model which is a longitudinal analyses and it incorporates HbA1c values from baseline and after 4 weeks, 12 weeks, 24 weeks, 36 weeks and 52 weeks of treatment.

Change in glycated hemoglobin (HbA1c) (in units of %) from baseline after 52 weeks of treatment was modelled using a restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) which included fixed classification effects for treatment, gender, baseline renal function, visit and visit-by-treatment interaction, and a linear covariate for baseline HbA1c and age. The term "baseline" refers to the last observed measurement prior to the administration of any randomised trial medication.The Least Squares Mean (Standard Error) after 52 weeks of treatment is reported.

Secondary Outcome Measures
NameTimeMethod
Change of Body Fat Measurement From Baseline to Week 52At baseline and at Week 52

Body fat mass was estimated via bioelectrical impedance analysis (BIA) which is a commonly used method for estimating body composition and it assesses body composition by passing a very small current through the body and assessing differences in impedance caused by the fact that fat and lean tissues have different electrical properties. To measure the body composition the patient barefoot stood on the bench evenly on the toe and heel electrodes and held the grip on each hand.

Change of body fat measurement from baseline to Week 52 was modelled using an Analysis of Covariance (ANCOVA) which included baseline body fat measurement, age, baseline glycated hemoglobin (HbA1c), baseline body mass index (BMI) as linear covariates and sex, treatment as fixed effects.

The term "baseline" refers to the last observed measurement prior to the administration of any randomised trial medication.

Change of Lean Body Mass From Baseline to Week 52At baseline and at Week 52.

Lean body mass (fat-free mass) was estimated via bioelectrical impedance analysis (BIA) which is a commonly used method for estimating body composition, and it assesses body composition by passing a very small current through the body and assessing differences in impedance caused by the fact that fat and lean tissues have different electrical properties. To measure the body composition the patient barefoot stood on the bench evenly on the toe and heel electrodes and held the grip on each hand.

Change of lean body mass from baseline to Week 52 was modelled using an Analysis of Covariance (ANCOVA) which included baseline lean body mass, age, baseline glycated hemoglobin (HbA1c), baseline body mass index (BMI) as linear covariates and sex, treatment as fixed effects.

The term "baseline" refers to the last observed measurement prior to the administration of any randomised trial medication.

Change of Muscle Mass From Baseline to Week 52At baseline and at Week 52

Muscle mass was estimated via bioelectrical impedance analysis (BIA) which is a commonly used method for estimating body composition, and it assesses body composition by passing a very small current through the body and assessing differences in impedance caused by the fact that fat and lean tissues have different electrical properties. To measure the body composition the patient barefoot stood on the bench evenly on the toe and heel electrodes and held the grip on each hand.

Change of muscle mass from baseline to Week 52 was modelled using an Analysis of Covariance (ANCOVA) which included baseline muscle mass, age, baseline glycated hemoglobin (HbA1c), baseline body mass index (BMI) as linear covariates and sex, treatment as fixed effects.

The term "baseline" refers to the last observed measurement prior to the administration of any randomised trial medication.

Change of Total Body Water From Baseline to Week 52At baseline and at Week 52.

Total body water was estimated via bioelectrical impedance analysis (BIA) which is a commonly used method for estimating body composition, and it assesses body composition by passing a very small current through the body and assessing differences in impedance caused by the fact that fat and lean tissues have different electrical properties. To measure the body composition the patient barefoot stood on the bench evenly on the toe and heel electrodes and held the grip on each hand.

Change of total body water from baseline to Week 52 was modelled using an Analysis of Covariance (ANCOVA) which included baseline total body water, age, baseline glycated hemoglobin (HbA1c), baseline body mass index (BMI) as linear covariates and sex, treatment as fixed effects.

The term "baseline" refers to the last observed measurement prior to the administration of any randomised trial medication.

Change of Bone Mineral Content From Baseline to Week 52At baseline and at Week 52.

Bone mineral content (estimated bone mass) was estimated via bioelectrical impedance analysis (BIA) which is a commonly used method for estimating body composition, and it assesses body composition by passing a very small current through the body and assessing differences in impedance caused by the fact that fat and lean tissues have different electrical properties. To measure the body composition the patient barefoot stood on the bench evenly on the toe and heel electrodes and held the grip on each hand.

Change of bone mineral content from baseline to Week 52 was modelled using an Analysis of Covariance (ANCOVA) which included baseline bone mineral content, age, baseline glycated hemoglobin (HbA1c), baseline body mass index (BMI) as linear covariates and sex, treatment as fixed effects.

The term "baseline" refers to the last observed measurement prior to the administration of any randomised trial medication.

Change of Skeletal Muscle Index From Baseline to Week 52At baseline and at Week 52.

Skeletal muscle index is calculated by dividing the limb muscle mass (kg) by the square of the height (m2).

The limb muscle mass was estimated via bioelectrical impedance analysis (BIA) which is a commonly used method for estimating body composition, and it assesses body composition by passing a very small current through the body and assessing differences in impedance caused by the fact that fat and lean tissues have different electrical properties. To measure the body composition the patient barefoot stood on the bench evenly on the toe and heel electrodes and held the grip on each hand.

Change of skeletal muscle index from baseline to Week 52 was modelled using an Analysis of Covariance (ANCOVA) which included baseline skeletal muscle index, age, baseline glycated hemoglobin (HbA1c), baseline body mass index as linear covariates and sex, treatment as fixed effects.

"Baseline" refers to the last observed measurement prior to the administration of any randomised trial medication.

Change of Time in the 5-time Chair Stand Test From Baseline to Week 52At baseline and at Week 52.

For the stand test patients fold their arms across their chest and try to stand up once from a chair. If patients can stand from a chair, they repeat same action five times. It is measured the time required to perform five rise from a chair to an upright position as fast as possible without the use of arms.

Change of time in the 5-time chair stand test from baseline to Week 52 was modelled using an Analysis of Covariance (ANCOVA) which included baseline 5-time chair stand test, age, baseline glycated hemoglobin (HbA1c), baseline body mass index (BMI) as linear covariates and sex, treatment as fixed effects.

The term "baseline" refers to the last observed measurement prior to the administration of any randomised trial medication.

Change of Grip Strength From Baseline to Week 52At baseline and at Week 52.

A Smedley-type dynamometer was used to measure grip strength. The site staff instructed the patient to adjust the grip width so that the second joint of the index finger is approximately 90 degrees (almost right angle). The site staff asked the patient to be careful not to touch the body or clothes with hand while keeping arms down naturally. The site staff made sure that the patient does not wave the grip dynamometer. Grip strength was measured twice alternately left and right.

Change of grip strength from baseline to Week 52 was modelled using an Analysis of Covariance (ANCOVA) which included baseline grip strength, age, baseline glycated hemoglobin (HbA1c), baseline body mass index (BMI) as linear covariates and sex, treatment as fixed effects.

The term "baseline" refers to the last observed measurement prior to the administration of any randomised trial medication.

Trial Locations

Locations (18)

North Alps Medical Center Azumi Hospital

🇯🇵

Nagano, Kitaazumi-gun, Japan

Shinagawa East one Medical Clinic

🇯🇵

Tokyo, Minato-ku, Japan

Chubu Rosai Hospital

🇯🇵

Aichi, Nagoya, Japan

Asama Nanroku Komoro Medical Center

🇯🇵

Nagano, Komoro, Japan

Meitetsu Hospital

🇯🇵

Aichi, Nagoya, Japan

Daido Hospital

🇯🇵

Aichi, Nagoya, Japan

Seino Internal Medicine Clinic

🇯🇵

Fukushima, Koriyama, Japan

Medical Corporation KEISEIKAI Kajiyama Clinic

🇯🇵

Kyoto, Kyoto, Japan

Medical Corporation Hayashi Katagihara Clinic

🇯🇵

Kyoto, Kyoto, Japan

Tokyo Asbo Clinic

🇯🇵

Tokyo, Chuo-ku, Japan

Watanabe Clinic

🇯🇵

Hyogo, Nishinomiya, Japan

Institute Medical Corporation Hitomikai Motomachi Takatsuka Naika Clinic

🇯🇵

Kanagawa, Yokohama, Japan

Gifu University Hospital

🇯🇵

Gifu, Gifu, Japan

Iryouhouijneiwakai Minamiakatsuka Clinic

🇯🇵

Mito, Ibaraki, Japan

Moriya Keiyu Hospital

🇯🇵

Moriya, Ibaraki, Japan

Koshigaya Municipal Hospital

🇯🇵

Saitama, Koshigaya, Japan

Ikebukuro Metropolitan Clinic

🇯🇵

Tokyo, Toshima-ku, Japan

Dojinkinenkai Meiwa Hospital

🇯🇵

Tokyo, Chiyoda-ku, Japan

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