Clinical trial NCT02183415: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BI 1356 BS as Tablet in Patients With Type 2 Diabetes
Official title: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Oral Doses (2.5, 5, and 10 mg q.d. for 28 Days) of BI 1356 BS as Tablet in Patients With Type 2 Diabetes (Randomised, Double-blind, Placebo-controlled Within the Dose Groups)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-07-08
Enrollment: 77
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of BI 1356 BS during 4 week treatment duration


Eligibility criteria: Inclusion Criteria:

* Male and female postmenopausal patients with proven diagnose of type 2 diabetes mellitus treated with diet and exercise only or with one (or two) oral hypoglycaemic agents besides glitazones
* Glycosylated haemoglobin A1 (HbA1c)

  * ≤ 8.5 % at screening for patients treated with diet and exercise and/or one oral hypoglycaemic agent or
  * ≤ 8.0 % at screening for patients treated with two oral hypoglycaemic agents
* Male patients: Age ≥21 and Age ≤70 years
* Female patients: Age ≥60 and Age ≤70 years
* BMI ≥18.5 and BMI ≤35 kg/m2 (Body Mass Index)
* Caucasian ethnicity
* Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation

Exclusion Criteria:

* Any finding of the medical examination (including Blood Pressure, Pulse Rate and Electrocardiogram) deviating from normal and of not acceptable clinical relevance
* Clinically relevant concomitant diseases like renal insufficiency, cardiac insufficiency NYHA (New York Heart Association) II-IV, known cardiovascular diseases including hypertension \> 150/95mmHg, stroke and TIA (transient ischemic attack)
* Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders besides type 2 diabetes, hyperlipidaemia and medically treated hypertension
* Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or relevant neurological disorders besides polyneuropathy
* Chronic or relevant acute infections (e.g. HIV, Hepatitis)
* History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
* Intake of drugs with a long half-life (\> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial except allowed co-medication
* Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
* Participation in another trial with an investigational drug within two months prior to administration or during the trial
* Smoker (\> 10 cigarettes or \> 3 cigars or \> 3 pipes/day)
* Inability to refrain from smoking on trial days
* Alcohol abuse (more than 40 g/day = 5 units/day)
* Drug abuse
* Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
* Excessive physical activities (within one week prior to administration or during the trial)
* Any laboratory value outside the reference range and the clinical relevance is not acceptable (or the value is more than three times higher than the upper limit of the normal range e.g. liver enzymes)
* Change of drug dosing of allowed co-medication (anti-hypertensive agents, acetylic salicylic acid and statins) within the last 3 months
* Fasted blood glucose \> 240 mg/dl (=13.3 mmol/L) on two consecutive days during washout
* Serum creatinine above upper limit of normal at screening

Male Patients:

* Not willing to use adequate contraception (condom use plus another form of contraception e.g. spermicide, oral contraceptive taken by female partner, sterilisation, intrauterine device) during the whole study period from the time of the first intake of study drug until one month after the last intake

Female patients:

* Positive pregnancy test

Primary outcomes:
measure: Assessment of tolerability by investigator on a 4-point scale
timeFrame: Day 50
measure: Incidence of adverse events
timeFrame: up to 50 days
measure: Number of patients with abnormal changes in clinical laboratory parameters
timeFrame: Baseline, up to day 50
Secondary outcomes:
measure: Cmax (maximum concentration of the analyte in plasma)
timeFrame: before and up to 43 days after first study drug administration
measure: tmax (time from dosing to maximum concentration)
timeFrame: before and up to 43 days after first study drug administration
measure: AUC (area under the concentration-time curve of the analyte in plasma) for several time points
timeFrame: before and up to 43 days after first study drug administration
measure: Cmax,ss (maximum concentration of the analyte in plasma at steady state over a uniform dosing interval)
timeFrame: before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration
measure: Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval)
timeFrame: before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration
measure: Cpre,N (predose concentration of the analyte in plasma at steady state immediately before administration of the next dose N)
timeFrame: pre-dose on day 28
measure: tmax,ss (time from dosing to maximum concentration at steady state)
timeFrame: before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration
measure: AUCτ,ss (area under the concentration time curve of the analyte in plasma at steady state over a uniform dosing interval)
timeFrame: before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration
measure: λz,ss (terminal rate constant in plasma at steady state)
timeFrame: before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration
measure: t1/2,ss (terminal half-life of the analyte in plasma at steady state)
timeFrame: before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration
measure: MRTpo,ss (mean residence time of the analyte in the body after 12 administrations at steady state)
timeFrame: before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration
measure: CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state)
timeFrame: before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration
measure: Vz/F,ss (apparent volume of distribution during the terminal phase λz following an extravascular dose at steady state)
timeFrame: before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration
measure: PTF (peak trough fluctuation)
timeFrame: before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration
measure: Accumulation ratio (RA) based on Cmax
timeFrame: up to 28 days
measure: RA,AUC based on AUCτ
timeFrame: up to 28 days
measure: Dipeptidyl-Peptidase IV (DPP-IV) activity for several time points
timeFrame: up to day 43
measure: Change in fasting plasma glucose (AUEC0-3) after MTT (meal tolerance test )
timeFrame: days -1, 1 and 29
measure: Plasma glucose levels
timeFrame: up to day 43
Other outcomes:
Locations:
Study officials:
References: