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Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BI 1356 BS as Tablet in Patients With Type 2 Diabetes

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ClinicalTrials.gov Identifier: NCT02183415
Recruitment Status : Completed
First Posted : July 8, 2014
Last Update Posted : July 8, 2014
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

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

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Drug: BI 1356 BS, low dose Drug: BI 1356 BS, medium dose Drug: BI 1356 BS, high dose Drug: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 77 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
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 Start Date : August 2005
Actual Primary Completion Date : January 2006

Resource links provided by the National Library of Medicine

Drug Information available for: Linagliptin

Arm Intervention/treatment
Experimental: BI 1356 BS, low dose Drug: BI 1356 BS, low dose
Experimental: BI 1356 BS, medium dose Drug: BI 1356 BS, medium dose
Experimental: BI 1356 BS, high dose Drug: BI 1356 BS, high dose
Placebo Comparator: Placebo Drug: Placebo



Primary Outcome Measures :
  1. Assessment of tolerability by investigator on a 4-point scale [ Time Frame: Day 50 ]
  2. Incidence of adverse events [ Time Frame: up to 50 days ]
  3. Number of patients with abnormal changes in clinical laboratory parameters [ Time Frame: Baseline, up to day 50 ]

Secondary Outcome Measures :
  1. Cmax (maximum concentration of the analyte in plasma) [ Time Frame: before and up to 43 days after first study drug administration ]
  2. tmax (time from dosing to maximum concentration) [ Time Frame: before and up to 43 days after first study drug administration ]
  3. AUC (area under the concentration-time curve of the analyte in plasma) for several time points [ Time Frame: before and up to 43 days after first study drug administration ]
  4. Cmax,ss (maximum concentration of the analyte in plasma at steady state over a uniform dosing interval) [ Time Frame: 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 ]
  5. Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval) [ Time Frame: 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 ]
  6. Cpre,N (predose concentration of the analyte in plasma at steady state immediately before administration of the next dose N) [ Time Frame: pre-dose on day 28 ]
  7. tmax,ss (time from dosing to maximum concentration at steady state) [ Time Frame: 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 ]
  8. AUCτ,ss (area under the concentration time curve of the analyte in plasma at steady state over a uniform dosing interval) [ Time Frame: 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 ]
  9. λz,ss (terminal rate constant in plasma at steady state) [ Time Frame: 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 ]
  10. t1/2,ss (terminal half-life of the analyte in plasma at steady state) [ Time Frame: 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 ]
  11. MRTpo,ss (mean residence time of the analyte in the body after 12 administrations at steady state) [ Time Frame: 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 ]
  12. CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state) [ Time Frame: 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 ]
  13. Vz/F,ss (apparent volume of distribution during the terminal phase λz following an extravascular dose at steady state) [ Time Frame: 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 ]
  14. PTF (peak trough fluctuation) [ Time Frame: 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 ]
  15. Accumulation ratio (RA) based on Cmax [ Time Frame: up to 28 days ]
  16. RA,AUC based on AUCτ [ Time Frame: up to 28 days ]
  17. Dipeptidyl-Peptidase IV (DPP-IV) activity for several time points [ Time Frame: up to day 43 ]
  18. Change in fasting plasma glucose (AUEC0-3) after MTT (meal tolerance test ) [ Time Frame: days -1, 1 and 29 ]
  19. Plasma glucose levels [ Time Frame: up to day 43 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02183415     History of Changes
Other Study ID Numbers: 1218.3
First Posted: July 8, 2014    Key Record Dates
Last Update Posted: July 8, 2014
Last Verified: July 2014
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Linagliptin
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action