Clinical trial NCT00885118: 4 Weeks Treatment With Empagliflozin (BI 10773) in Japanese Type 2 Diabetic Patients (T2DM)
Official title: A Phase II, Randomised, Double-blind, Placebo-controlled, Multiple Dose Study to Evaluate Pharmacodynamics, Pharmacokinetics, Safety, and Tolerability of Once Daily Oral Administration of BI 10773 (1 mg, 5 mg, 10 mg, and 25 mg) for 28 Days in Japanese Patients With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2009-04-21
Enrollment: 100
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this trial is to evaluate the pharmacodynamics, pharmacokinetics, safety, and tolerability of once daily oral administration of BI 10773 administered for 28 days in Japanese patients with T2DM.


Eligibility criteria: Inclusion criteria:

1. Japanese male or female patients with T2DM treated with diet and exercise alone or with one hypoglycaemic drug other than glitazones.
2. Hemoglobin A1c (HbA1c) at screening (Visit 1)

   * For patients treated with 1 other oral antidiabetic drug: HbA1c between 6.5% and 9.0%.
   * For patients not treated with any antidiabetic drug: HbA1c between 7.0% and 10.0%.
3. Age between 20 and 70 years
4. Body mass index (BMI) between18.0 and 40.0 kg/m2
5. Signed and dated written informed consent before admission to the trial in accordance with the Good Clinical Practice (GCP) and the local legislation.

Exclusion criteria:

1. Antidiabetic treatment with insulin or glitazones within 3 months before obtaining informed consent or with more than 1 oral hypoglycaemic agent at the time of informed consent
2. Fasted blood glucose of \>240 mg/dL (\>13.3 mmol/L) or a randomly determined blood glucose level of \>400 mg/dL (22.2 mmol/L) on 2 consecutive days during wash-out period.
3. Myocardial infarction, stroke, or transient ischaemic attack within 6 months before informed consent.
4. Clinically relevant concomitant diseases other than T2DM, hyperlipidaemia, and medically treated hypertension before the first administration such as

   * Renal insufficiency (calculated estimated glomerular filtration rate \<60)
   * Cardiac insufficiency of New York Heart Association (NYHA) II-IV or other known cardiovascular diseases including hypertension of \>160/95 mmHg,
   * Neurological disorders (such as epilepsy) or psychiatric disorders
   * Acute or clinically relevant chronic infections (e.g., human immunodeficiency virus, hepatitis, repeated urogenital infections)
   * Any gastrointestinal, hepatic, respiratory, endocrine, or immunological disorder
5. Patients under treatment with any concomitant medication except for the following drugs at the time of informed consent.:

   * Statins.
   * Antihypertensives (diuretics not allowed)
   * alpha-Blockers for benign prostate hypertrophy
   * Occasional use of acetylsalicylic acid, ibuprofen, or paracetamol
6. Additional inclusion/exclusion criteria apply

Primary outcomes:
measure: Change From Baseline in Urine Glucose Excretion
timeFrame: baseline and 28 days
measure: Change From Baseline in Fasting Plasma Glucose
timeFrame: baseline and 28 days
measure: Change From Baseline in 8-point Glucose
timeFrame: baseline and 27 days
Secondary outcomes:
measure: Change From Baseline in HbA1c
timeFrame: baseline and 28 days
measure: Change From Baseline in Fructosamine
timeFrame: baseline and 28 days
measure: Change From Baseline in 1,5-anhydroglucitol
timeFrame: baseline and 28 days
measure: Change From Baseline in Fasting Insulin
timeFrame: baseline and 28 days
measure: Change From Baseline in the Area Under the Curve of Plasma Glucose Levels Until 4 Hours After Intake of a Standardised Food (Meal Tolerance Test)
timeFrame: baseline and 28 days
measure: Change From Baseline in the Area Under the Curve of Glucagon Levels Until 4 Hours After Intake of a Standardised Food (Meal Tolerance Test)
timeFrame: baseline and 28 days
measure: Change From Baseline in the Area Under the Curve of Insulin Levels Until 4 Hours After Intake of a Standardised Food (Meal Tolerance Test)
timeFrame: baseline and 28 days
measure: AUCτ,1
timeFrame: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration
measure: AUC0-tz
timeFrame: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration
measure: AUC0-∞
timeFrame: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration
measure: Cmax
timeFrame: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration
measure: t1/2
timeFrame: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration
measure: CL/F
timeFrame: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration
measure: Vz/F
timeFrame: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration
measure: Ae0-24
timeFrame: 0-5, 5-12, 12-24 hour after first drug administration
measure: fe0-24
timeFrame: 0-5, 5-12, 12-24 hour after first drug administration
measure: CLR,0-24
timeFrame: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min, 0-5h, 5-12h, 12-24h after first drug administration
measure: AUCτ,ss
timeFrame: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h after last drug administration
measure: Cmax,ss
timeFrame: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h 48h, 72h after last drug administration
measure: t1/2,ss
timeFrame: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h 48h, 72h after last drug administration
measure: CL/F,ss
timeFrame: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h 48h, 72h after last drug administration
measure: Vz/F,ss
timeFrame: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h 48h, 72h after last drug administration
measure: RA,Cmax
timeFrame: Predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration, and predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h after last drug administration
measure: RA,AUC
timeFrame: Predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration, and predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h after last drug administration
measure: Ae0-24,ss
timeFrame: 0-5, 5-12, 12-24 hour after last drug administration
measure: fe0-24,ss
timeFrame: 0-5, 5-12, 12-24 hour after last drug administration
measure: CLR,ss
timeFrame: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 0-5h, 5-12h, 12-24h after last drug administration
Other outcomes:
Locations:
city: Hachioji, Tokyo
country: Japan
facility: 1245.15.003 Boehringer Ingelheim Investigational Site
city: Koganei, Tokyo
country: Japan
facility: 1245.15.002 Boehringer Ingelheim Investigational Site
city: Nakano-ku, Tokyo
country: Japan
facility: 1245.15.001 Boehringer Ingelheim Investigational Site
city: Suita, Osaka
country: Japan
facility: 1245.15.005 Boehringer Ingelheim Investigational Site
city: Yokohama, Kanagawa
country: Japan
facility: 1245.15.004 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Tuttle KR, Levin A, Nangaku M, Kadowaki T, Agarwal R, Hauske SJ, Elsasser A, Ritter I, Steubl D, Wanner C, Wheeler DC. Safety of Empagliflozin in Patients With Type 2 Diabetes and Chronic Kidney Disease: Pooled Analysis of Placebo-Controlled Clinical Trials. Diabetes Care. 2022 Jun 2;45(6):1445-1452. doi: 10.2337/dc21-2034.
citation: Yasui A, Lee G, Hirase T, Kaneko T, Kaspers S, von Eynatten M, Okamura T. Empagliflozin Induces Transient Diuresis Without Changing Long-Term Overall Fluid Balance in Japanese Patients With Type 2 Diabetes. Diabetes Ther. 2018 Apr;9(2):863-871. doi: 10.1007/s13300-018-0385-5. Epub 2018 Feb 27.
citation: Kanada S, Koiwai K, Taniguchi A, Sarashina A, Seman L, Woerle HJ. Pharmacokinetics, pharmacodynamics, safety and tolerability of 4 weeks' treatment with empagliflozin in Japanese patients with type 2 diabetes mellitus. J Diabetes Investig. 2013 Nov 27;4(6):613-7. doi: 10.1111/jdi.12110. Epub 2013 Jun 25.
citation: Riggs MM, Staab A, Seman L, MacGregor TR, Bergsma TT, Gastonguay MR, Macha S. Population pharmacokinetics of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in patients with type 2 diabetes. J Clin Pharmacol. 2013 Oct;53(10):1028-38. doi: 10.1002/jcph.147. Epub 2013 Aug 13.