Empa Add on to Insulin in Japanese Patient With Type 1 Diabetes Mellitus

NCT02702011 | Completed Phase 2 Results

• 1 other identifier: 1245.113
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 4

Brief Summary

To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of once daily oral doses of empagliflozin in Japanese patients with type 1 diabetes mellitus as adjunctive therapy to insulin.

Conditions

Diabetes Mellitus, Type 1

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in 24 Hour UGE on Day 7

  Change from baseline in 24 hour urinary glucose excretion on Day 7 calculated as: UGE on Day 7 - UGE on baseline. Baseline is defined as the last observation prior to the first intake of any randomised trial medication.

  Baseline and 7 days

Study Arms (4)

empagliflozin low dose

EXPERIMENTAL

Drug: empagliflozin low dose

empagliflozin medium dose

EXPERIMENTAL

Drug: empagliflozin medium dose

empagliflozin high dose

EXPERIMENTAL

Drug: empagliflozin high dose

placebo

PLACEBO COMPARATOR

Drug: placebo

Interventions

empagliflozin medium dose DRUG

empagliflozin medium dose

empagliflozin low dose DRUG

empagliflozin low dose

empagliflozin high dose DRUG

empagliflozin high dose

placebo DRUG

placebo

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated written informed consent by the date of Visit 1 (screening) in accordance with Good Clinical Practice (GCP) and local legislation
• Japanese male or female patient receiving insulin for treatment of documented diagnosis of type 1 diabetes mellitus (T1DM) for at least 1 year at the time of Visit 1 (screening).
• Fasting C-peptide value of \< 0.6 ng/mL at Visit 2 (placebo run-in) measured by the central laboratory
• Use of, and be willing, based on the investigator's judgment, to continue throughout the duration of the trial Multiple daily injection(MDI) of insulin consisting of at least 1 basal insulin injection and at least 3 daily bolus injections The total daily insulin dose must be\>=0.3 U/kg and \<=1.5 U/kg at Visit 1 (screening)
• HbA1c of 7.5% to 10.0% at Visit 1 (screening) measured by the central laboratory and provided that the patients HbA1c does not increase by \> 0.5% within 3 months before Visit 1 (screening)
• Based on the investigator's judgment, patient must have a good understanding of his/her disease and how to manage it, and be willing and capable of performing the following study assessments (assessed at Visits 1 to 3 and just before randomization)
• patient-led management and adjustment of insulin therapy
• reliable approach to insulin dose adjustment for meals, such as carbohydrate counting
• reliable and regular home-based blood glucose monitoring
• recognize the symptoms of DKA (Diabetic Ketoacidosis), and reliably monitor for ketones
• implementation of an established "sick day" management regimen
• Age \>=20 years and \<=65 years at Visit 1 (screening)
• Body mass index (BMI) \>=18.5 kg/m2 and\<=35.0 kg/m2 at Visit 1 (screening)
• Estimated glomerular filtration rate (eGFR) \>=60 mL/min/1.73m² and \<=150 mL/min/1.73m² as calculated by Japanese equation based on creatinine measured by the central laboratory at Visit 1 (screening)
• Compliance with trial drug administration must be between 80% and 120% during the placebo run-in period, to be judged at Visit 4 and before randomization

You may not qualify if:

• History of T2DM (Type 2 Diabetes Mellitus), maturity onset diabetes of the young (MODY), pancreatic surgery or chronic pancreatitis
• Pancreas, pancreatic islet cells or renal transplant recipient
• T1DM treatment with any other anti-hyperglycaemic drug (e.g., metformin, alpha-glycosidase inhibitors, glucagon-like-peptide 1 (GLP-1) receptor agonists, SGLT-2 (Sodium-Glucose co-transporter-2) inhibitors, pramlintide, inhaled insulin, pre-mixed insulins, etc.) within 3 months except subcutaneous basal and bolus insulin before Visit 1 (screening) or any history of clinically relevant hypersensitivity according to the investigator's judgment
• Occurrence of severe hypoglycemia involving coma and/or seizure that required hospitalization or hypoglycemia-related treatment by an emergency physician or paramedic within 3 months before Visit 1 (screening)
• Occurrence of DKA within 3 months before Visit 1 (screening) and until randomization at Visit 4 (Day 1)
• Irregular sleep/wake cycle (e.g., patients who habitually sleep during the day and work during the night) based on the investigator's judgment
• Acute coronary syndrome (non-STEMI, STEMI, and unstable angina pectoris), stroke or transient ischemic attack within 3 months before Visit 1 (screening)
• Diagnosis of severe gastro paresis based on investigator's judgment
• Diagnosis of brittle diabetes based on the investigator's judgment
• Indication of liver impairment, defined by serum levels of either alanine transaminase (ALT), aspartate transaminase (AST), or alkaline phosphatase above 3 x upper limit of normal (ULN) at Visit 1 (screening) as measured by the central laboratory
• Eating disorders such as bulimia or anorexia nervosa
• Treatment with anti-obesity drugs (e.g., Mazindol), surgery or aggressive diet regimen leading to unstable body weight (based on the investigator's judgment) 3 months before Visit 1 (screening) and until randomization
• Treatment with systemic corticosteroids or planned initiation of such therapy at Visit 1 (screening). Inhaled use of corticosteroids (e.g., for asthma/chronic obstructive pulmonary disease) is acceptable
• Change in dose of thyroid hormones within 6 weeks before Visit 1 (screening) or planned change or initiation of such a therapy at Visit 1 (screening)
• Medical history of cancer or treatment for cancer in the last 5 years before Visit 1 (screening). Resected basal cell carcinoma considered cured is exempted

Sponsors & Collaborators

• Boehringer Ingelheim: lead
• Eli Lilly and Company: collaborator

Study Sites (4)

Souseikai Hakata Clinic

Fukuoka, Fukuoka, 812-0025, Japan

Location

Nishikumamoto Hospital

Kumamoto, Kumamoto, 861-4157, Japan

Location

Shinjuku Research Park Clinic

Tokyo, Shinjyuku-ku, 169-0073, Japan

Location

SOUSEIKAI Sumida Hospital

Tokyo, Sumida-ku, 130-0004, Japan

Location

Related Publications (1)

• Shimada A, Hanafusa T, Yasui A, Lee G, Taneda Y, Sarashina A, Shiki K, George J, Soleymanlou N, Marquard J. Empagliflozin as adjunct to insulin in Japanese participants with type 1 diabetes: Results of a 4-week, double-blind, randomized, placebo-controlled phase 2 trial. Diabetes Obes Metab. 2018 Sep;20(9):2190-2199. doi: 10.1111/dom.13351. Epub 2018 Jun 5.

  PMID: 29766633 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

A limitation of the current study is its short duration and small sample size. Another limitation of this study was that patients in the placebo group had to go through unnecessary dose adjustments of insulin.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2016
• First Posted: March 8, 2016
• Study Start: March 20, 2016
• Primary Completion: September 5, 2016
• Study Completion: October 3, 2016
• Last Updated: April 2, 2018
• Results First Posted: April 2, 2018

Record last verified: 2017-09

Locations

JP (4)