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Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Oral Doses of BI 135585 XX in Patients With Type 2 Diabetes

Primary Purpose

Diabetes Mellitus, Type 2

Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
BI 135585
Placebo to BI 135585
Sponsored by
Boehringer Ingelheim
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 2

Eligibility Criteria

20 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  1. Male and postmenopausal or surgically sterilised female patients with an established diagnosis of type 2 diabetes mellitus prior to informed consent
  2. Antidiabetic treatment with diet and exercise alone or with not more than one oral hypoglycaemic drug except glitazones, glucagon-like peptide 1 (GLP-1) analogues or dipeptidyl-peptidase 4 (DPP-4) inhibitors.
  3. Antidiabetic treatment unchanged for 12 weeks prior to informed consent
  4. Glycosylated haemoglobin A1 (HbA1c) ≤ 8.5% at screening
  5. Age ≥ 20 and age ≤ 70 years
  6. BMI ≥ 25 and BMI ≤ 40 kg/m2 (Body Mass Index)
  7. Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation.

Exclusion criteria

  1. Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of not acceptable clinical relevance
  2. Myocardial infarction, stroke or transient ischemic attack within 6 months prior to informed consent
  3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders besides type 2 diabetes, hyperlipidaemia or medically treated hypertension
  4. Gastrointestinal tract surgery that might affect absorption and elimination of drugs
  5. Diseases of the central nerve system (such as epilepsy) or psychiatric disorders or relevant neurological disorders besides polyneuropathy
  6. Chronic or relevant acute infections (e.g. HIV, hepatitis)
  7. History of allergy/hypersensitivity (including allergy to drug or its excipients) that are deemed relevant to subject's safety or the trial by the investigator
  8. Intake of drugs with a long half-life (> 24 hours) within one month prior to administration of the trial drug except for allowed co-medication
  9. Treatment with glitazones, GLP-1 analogues, insulin, DPP-4 inhibitors, systemic or inhaled glucocorticoids, or anti-obesity drugs (e.g. orlistat) within 12 weeks prior to informed consent
  10. Sensitive CYP3A4 substrates (e.g. simvastatin, lovastatin, verapamil, budesonide, buspirone, eplerenone , eletriptan, felodipine, fluticasone, midazolam, saquinavir, sildenafil, vardenafil) or CYP3A4 substrates with narrow therapeutic range (e.g. cyclosporine, ergotamine, pimozide, quinidine, sirolimus, tacrolimus, terfenadine) or drugs that prolong the QT/QTc interval (based on the knowledge at the time of protocol preparation) within 10 days prior to first administration of the trial drug
  11. other exclusion criteria apply.

Sites / Locations

  • 1283.2.1 Boehringer Ingelheim Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

BI 135585

Placebo to BI 135585

Arm Description

once daily doses as oral solution or tablet formulation over 14 days

once daily doses as oral solution or tablet formulation over 14 days

Outcomes

Primary Outcome Measures

Safety and tolerability of BI 135585 will be assessed in a descriptive way using physical examinations (occurence of findings), vital signs, electrocardiograms, laboratory tests, and incidence and severity of adverse events.

Secondary Outcome Measures

Assessment of Pharmacokinetic parameter Cmax (maximum measured concentration of the analyte in plasma) of BI 135585 following single and multiple dose oral administration
Assessment of Pharmacokinetic parameter tmax (time from dosing to maximum measured concentration) of BI 135585 following single and multiple dose oral administration
Assessment of Pharmacokinetic parameter AUCτ,1 (area under the concentration-time curve of the analyte in plasma over a uniform dosing interval τ after administration of the first dose)
Assessment of Pharmacokinetic parameter λz (terminal rate constant in plasma) of BI 135585 following single and multiple dose oral administration
Assessment of Pharmacokinetic parameter Aet1-t2 (amount of analyte eliminated in urine from the time point t1 to time point t2) of BI 135585 following single and multiple dose oral administration
Assessment of Pharmacokinetic parameter fet1-t2 (fraction of analyte eliminated in urine from time point t1 to time point t2) of BI 135585 following single and multiple dose oral administration
Assessment of Pharmacokinetic parameter CLR,t1-t2 (renal clearance of the analyte from the time point t1 until the time point t2) of BI 135585 following single and multiple dose oral administration
Assessment of Pharmacokinetic parameter Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ) of BI 135585 following single and multiple dose oral administration
Assessment of Pharmacokinetic parameter tmax,ss (time from last dosing to maximum concentration of the analyte in plasma at steady state) of BI 135585 following single and multiple dose oral administration
Assessment of Pharmacokinetic parameter Cpre,ss (predose concentration of the analyte in plasma at steady state immediately before administration of the next dose) of BI 135585 following single and multiple dose oral administration
Assessment of Pharmacokinetic parameter AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ) of BI 135585 following single and multiple dose oral administration
Assessment of Pharmacokinetic parameter λz,ss (terminal rate constant in plasma at steady state) of BI 135585 following single and multiple dose oral administration
Assessment of Pharmacokinetic parameter t1/2,ss (terminal half-life of the analyte in plasma at steady state) of BI 135585 following single and multiple dose oral administration
Assessment of Pharmacokinetic parameter MRTpo,ss (mean residence time of the analyte in the body after multiple oral administrations at steady state) of BI 135585 following single and multiple dose oral administration
Assessment of Pharmacokinetic parameter CL/F,ss (apparent clearance of the analyte in the plasma at steady state following extravascular multiple dose administration) of BI 135585 following single and multiple dose oral administration
Assessment of Pharmacokinetic parameter Vz/F,ss (apparent volume of distribution during the terminal phase λz at steady state following extravascular administration) of BI 135585 following single and multiple dose oral administration
Assessment of Pharmacokinetic parameter PTF (Peak-Trough Fluctuation) of BI 135585 following single and multiple dose oral administration
Assessment of Pharmacokinetic parameter Cavg (average concentration of the analyte in plasma at steady state) of BI 135585 following single and multiple dose oral administration
Assessment of Pharmacokinetic parameter Aet1-t2,ss (amount of analyte that is eliminated in urine at steady state from the time point t1 to time point t2) of BI 135585 following single and multiple dose oral administration
Assessment of Pharmacokinetic parameter fet1-t2,ss (fraction of analyte eliminated in urine at steady state from time point t1 to time point t2) of BI 135585 following single and multiple dose oral administration
Assessment of Pharmacokinetic parameter CLR,t1-t2,ss (renal clearance of the analyte in plasma from the time point t1 until the time point t2 at steady state) of BI 135585 following single and multiple dose oral administration
Assessment of Pharmacokinetic parameter RA,Cmax (Accumulation ratio of the analyte in plasma at steady state after multiple dose oral administration over a uniform dosing interval τ, expresses ratio of Cmax at steady state and after single dose)
Assessment of Pharmacokinetic parameter RA,AUC (Accumulation ratio of the analyte in plasma at steady state after multiple dose oral administration over a uniform dosing interval τ, expresses ratio of AUC at steady state and after single dose)
Assessment of Pharmacokinetic parameter Cpre,N (the predose concentration of the analyte in plasma immediately before administration of the Nth dose after N-1 doses were administered)
Exploratory evaluation of the pharmacodynamics of BI 135585 by determination of 11beta-hydroxysteroid dehydrogenase type 1 activity in adipose tissue (ex vivo)
Exploratory evaluation of the pharmacodynamics of BI 135585 by measuring of cortisol and cortisone and their metabolites in urine

Full Information

First Posted
January 24, 2011
Last Updated
November 18, 2014
Sponsor
Boehringer Ingelheim
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1. Study Identification

Unique Protocol Identification Number
NCT01282970
Brief Title
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Oral Doses of BI 135585 XX in Patients With Type 2 Diabetes
Official Title
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Oral Doses (5 to 100 mg q.d. for 14 Days) of BI 135585 XX in Patients With Type 2 Diabetes Mellitus (Randomized, Double-blind Placebo-controlled Within Dose Groups)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2014
Overall Recruitment Status
Completed
Study Start Date
February 2011 (undefined)
Primary Completion Date
July 2011 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim

4. Oversight

5. Study Description

Brief Summary
The objective of this study is to investigate safety, tolerability, pharmacokinetics and pharmacodynamics of BI 135585 XX following multiple dose administration over 14 days

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
72 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BI 135585
Arm Type
Experimental
Arm Description
once daily doses as oral solution or tablet formulation over 14 days
Arm Title
Placebo to BI 135585
Arm Type
Placebo Comparator
Arm Description
once daily doses as oral solution or tablet formulation over 14 days
Intervention Type
Drug
Intervention Name(s)
BI 135585
Intervention Description
oral doses given to approximately 5-6 parallel groups of 12 subjects (9 on active and 3 on placebo) over 14 days
Intervention Type
Drug
Intervention Name(s)
Placebo to BI 135585
Intervention Description
oral doses given to approximately 5-6 parallel groups of 12 subjects (9 on active and 3 on placebo) over 14 days
Primary Outcome Measure Information:
Title
Safety and tolerability of BI 135585 will be assessed in a descriptive way using physical examinations (occurence of findings), vital signs, electrocardiograms, laboratory tests, and incidence and severity of adverse events.
Time Frame
up to 16 days post treatment
Secondary Outcome Measure Information:
Title
Assessment of Pharmacokinetic parameter Cmax (maximum measured concentration of the analyte in plasma) of BI 135585 following single and multiple dose oral administration
Time Frame
up to 10 days post treatment
Title
Assessment of Pharmacokinetic parameter tmax (time from dosing to maximum measured concentration) of BI 135585 following single and multiple dose oral administration
Time Frame
up to 10 days post treatment
Title
Assessment of Pharmacokinetic parameter AUCτ,1 (area under the concentration-time curve of the analyte in plasma over a uniform dosing interval τ after administration of the first dose)
Time Frame
up to 10 days post treatment
Title
Assessment of Pharmacokinetic parameter λz (terminal rate constant in plasma) of BI 135585 following single and multiple dose oral administration
Time Frame
up to 10 days post treatment
Title
Assessment of Pharmacokinetic parameter Aet1-t2 (amount of analyte eliminated in urine from the time point t1 to time point t2) of BI 135585 following single and multiple dose oral administration
Time Frame
up to 10 days post treatment
Title
Assessment of Pharmacokinetic parameter fet1-t2 (fraction of analyte eliminated in urine from time point t1 to time point t2) of BI 135585 following single and multiple dose oral administration
Time Frame
up to 10 days post treatment
Title
Assessment of Pharmacokinetic parameter CLR,t1-t2 (renal clearance of the analyte from the time point t1 until the time point t2) of BI 135585 following single and multiple dose oral administration
Time Frame
up to 10 days post treatment
Title
Assessment of Pharmacokinetic parameter Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ) of BI 135585 following single and multiple dose oral administration
Time Frame
up to 10 days post treatment
Title
Assessment of Pharmacokinetic parameter tmax,ss (time from last dosing to maximum concentration of the analyte in plasma at steady state) of BI 135585 following single and multiple dose oral administration
Time Frame
up to 10 days post treatment
Title
Assessment of Pharmacokinetic parameter Cpre,ss (predose concentration of the analyte in plasma at steady state immediately before administration of the next dose) of BI 135585 following single and multiple dose oral administration
Time Frame
up to 10 days post treatment
Title
Assessment of Pharmacokinetic parameter AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ) of BI 135585 following single and multiple dose oral administration
Time Frame
up to 10 days post treatment
Title
Assessment of Pharmacokinetic parameter λz,ss (terminal rate constant in plasma at steady state) of BI 135585 following single and multiple dose oral administration
Time Frame
up to 10 days post treatment
Title
Assessment of Pharmacokinetic parameter t1/2,ss (terminal half-life of the analyte in plasma at steady state) of BI 135585 following single and multiple dose oral administration
Time Frame
up to 10 days post treatment
Title
Assessment of Pharmacokinetic parameter MRTpo,ss (mean residence time of the analyte in the body after multiple oral administrations at steady state) of BI 135585 following single and multiple dose oral administration
Time Frame
up to 10 days post treatment
Title
Assessment of Pharmacokinetic parameter CL/F,ss (apparent clearance of the analyte in the plasma at steady state following extravascular multiple dose administration) of BI 135585 following single and multiple dose oral administration
Time Frame
up to 10 days post treatment
Title
Assessment of Pharmacokinetic parameter Vz/F,ss (apparent volume of distribution during the terminal phase λz at steady state following extravascular administration) of BI 135585 following single and multiple dose oral administration
Time Frame
up to 10 days post treatment
Title
Assessment of Pharmacokinetic parameter PTF (Peak-Trough Fluctuation) of BI 135585 following single and multiple dose oral administration
Time Frame
up to 10 days post treatment
Title
Assessment of Pharmacokinetic parameter Cavg (average concentration of the analyte in plasma at steady state) of BI 135585 following single and multiple dose oral administration
Time Frame
up to 10 days post treatment
Title
Assessment of Pharmacokinetic parameter Aet1-t2,ss (amount of analyte that is eliminated in urine at steady state from the time point t1 to time point t2) of BI 135585 following single and multiple dose oral administration
Time Frame
up to 10 days post treatment
Title
Assessment of Pharmacokinetic parameter fet1-t2,ss (fraction of analyte eliminated in urine at steady state from time point t1 to time point t2) of BI 135585 following single and multiple dose oral administration
Time Frame
up to 10 days post treatment
Title
Assessment of Pharmacokinetic parameter CLR,t1-t2,ss (renal clearance of the analyte in plasma from the time point t1 until the time point t2 at steady state) of BI 135585 following single and multiple dose oral administration
Time Frame
up to 10 days post treatment
Title
Assessment of Pharmacokinetic parameter RA,Cmax (Accumulation ratio of the analyte in plasma at steady state after multiple dose oral administration over a uniform dosing interval τ, expresses ratio of Cmax at steady state and after single dose)
Time Frame
up to 10 days post treatment
Title
Assessment of Pharmacokinetic parameter RA,AUC (Accumulation ratio of the analyte in plasma at steady state after multiple dose oral administration over a uniform dosing interval τ, expresses ratio of AUC at steady state and after single dose)
Time Frame
up to 10 days post treatment
Title
Assessment of Pharmacokinetic parameter Cpre,N (the predose concentration of the analyte in plasma immediately before administration of the Nth dose after N-1 doses were administered)
Time Frame
up to 10 days post treatment
Title
Exploratory evaluation of the pharmacodynamics of BI 135585 by determination of 11beta-hydroxysteroid dehydrogenase type 1 activity in adipose tissue (ex vivo)
Time Frame
up to 24 hours post treatment
Title
Exploratory evaluation of the pharmacodynamics of BI 135585 by measuring of cortisol and cortisone and their metabolites in urine
Time Frame
up to 24 hours post treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Male and postmenopausal or surgically sterilised female patients with an established diagnosis of type 2 diabetes mellitus prior to informed consent Antidiabetic treatment with diet and exercise alone or with not more than one oral hypoglycaemic drug except glitazones, glucagon-like peptide 1 (GLP-1) analogues or dipeptidyl-peptidase 4 (DPP-4) inhibitors. Antidiabetic treatment unchanged for 12 weeks prior to informed consent Glycosylated haemoglobin A1 (HbA1c) ≤ 8.5% at screening Age ≥ 20 and age ≤ 70 years BMI ≥ 25 and BMI ≤ 40 kg/m2 (Body Mass Index) Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation. Exclusion criteria Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of not acceptable clinical relevance Myocardial infarction, stroke or transient ischemic attack within 6 months prior to informed consent Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders besides type 2 diabetes, hyperlipidaemia or medically treated hypertension Gastrointestinal tract surgery that might affect absorption and elimination of drugs Diseases of the central nerve system (such as epilepsy) or psychiatric disorders or relevant neurological disorders besides polyneuropathy Chronic or relevant acute infections (e.g. HIV, hepatitis) History of allergy/hypersensitivity (including allergy to drug or its excipients) that are deemed relevant to subject's safety or the trial by the investigator Intake of drugs with a long half-life (> 24 hours) within one month prior to administration of the trial drug except for allowed co-medication Treatment with glitazones, GLP-1 analogues, insulin, DPP-4 inhibitors, systemic or inhaled glucocorticoids, or anti-obesity drugs (e.g. orlistat) within 12 weeks prior to informed consent Sensitive CYP3A4 substrates (e.g. simvastatin, lovastatin, verapamil, budesonide, buspirone, eplerenone , eletriptan, felodipine, fluticasone, midazolam, saquinavir, sildenafil, vardenafil) or CYP3A4 substrates with narrow therapeutic range (e.g. cyclosporine, ergotamine, pimozide, quinidine, sirolimus, tacrolimus, terfenadine) or drugs that prolong the QT/QTc interval (based on the knowledge at the time of protocol preparation) within 10 days prior to first administration of the trial drug other exclusion criteria apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim
Organizational Affiliation
Boehringer Ingelheim
Official's Role
Study Chair
Facility Information:
Facility Name
1283.2.1 Boehringer Ingelheim Investigational Site
City
Neuss
Country
Germany

12. IPD Sharing Statement

Learn more about this trial

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Oral Doses of BI 135585 XX in Patients With Type 2 Diabetes

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