Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Oral Doses of BI 14332 CL as Tablet in Female and Male Patients With Type 2 Diabetes
Primary Purpose
Diabetes Mellitus, Type 2
Status
Terminated
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
BI 14332 CL
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 2
Eligibility Criteria
Inclusion Criteria:
- Male and postmenopausal or hysterectomised female patients with proven diagnosis of type 2 diabetes mellitus treated with diet and exercise only, or with one oral hypoglycaemic agent besides glitazones and who are not taking the maximum approved dose
- Glycosylated haemoglobin A1 (HbA1c) ≥ 6.5% and ≤ 8.5 % at screening for patients treated with diet and exercise and/or one oral hypoglycaemic agent
- Age ≥21 and Age ≤70 years (female hysterectomised and male patients) Age ≥60 and Age ≤70 years (female postmenopausal patients)
- Body Mass Index (BMI) ≥18.5 and BMI ≤35 kg/m2
Exclusion Criteria:
- Any finding of the medical examination (including BP, pulse rate (PR) and ECG) deviating from normal and of not acceptable clinical relevance
- Clinically relevant concomitant diseases like renal insufficiency, cardiac insufficiency New York Heart Association (NYHA) II-IV, myocardial infarction, other known cardiovascular diseases including hypertension > 140/90 mmHg, stroke and 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
- Antidiabetic treatment with more than one oral hypoglycaemic agent or insulin or glitazones and anti-hypertensive treatment with verapamil or diltiazem
- 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)
- Use of drugs which might reasonably influence the results of the trial or that prolong the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days 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
- A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms)
- A history of additional risk factors for Torsade des Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
For female patients:
- Child bearing potential
- Positive pregnancy test
- Lactation period
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
BI 14332 CL
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Number of patients with adverse events
Number of patients with clinically significant findings in vital signs (blood pressure, pulse rate)
Number of patients with clinically significant findings in ECG
Number of patients with clinically significant findings in laboratory tests
Assessment of tolerability by investigator on a 4-point scale
Secondary Outcome Measures
Cmax (maximum concentration of the analyte in plasma)
tmax (time from dosing to maximum concentration)
AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point within the first dosing interval)
AUCτ,1 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 h after administration of the first dose)
Ae0-24 (amount of analyte that is eliminated in urine from the time interval 0 h to 24 h)
fe0-24 (fraction of analyte excreted in urine from time point 0 h to 24 h)
CLR,0-24 (renal clearance of the analyte in plasma from the time point 0 h until the time point 24 h)
Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval)
Cpre,N (predose concentration of the analyte in plasma at steady state immediately before administration of the next dose N)
PTF (peak trough fluctuation)
in percent
RA,Cmax (accumulation ratio based on Cmax)
RA,AUC(accumulation ratio based on AUCτ)
Change in dipeptidyl-peptidase 4 (DPP-IV) activity
Area under the curve of plasma glucose
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02212925
Brief Title
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Oral Doses of BI 14332 CL as Tablet in Female and Male Patients With Type 2 Diabetes
Official Title
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Oral Doses (0.5, 2.5, 10 and 20 mg q.d. for 10 Days) of BI 14332 CL as Tablet in Female and Male Patients With Type 2 Diabetes (Randomised, Double-blind, Placebo-controlled Within the Dose Groups), Followed by a 4-week Treatment Part* (Randomised, Double-blind, Placebo-controlled) of Two Doses (Planned 5 and 20 mg) Selected on the Basis of Tolerability and DPP-4 Inhibition in the Multiple Rising Dose Part
Study Type
Interventional
2. Study Status
Record Verification Date
August 2014
Overall Recruitment Status
Terminated
Study Start Date
November 2006 (undefined)
Primary Completion Date
March 2007 (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
To investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of BI 14332 CL following administration of multiple rising oral doses over 10 days in patients with type 2 diabetes.
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
38 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BI 14332 CL
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
BI 14332 CL
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Number of patients with adverse events
Time Frame
up to 14 days after last drug administration
Title
Number of patients with clinically significant findings in vital signs (blood pressure, pulse rate)
Time Frame
up to 14 days after last drug administration
Title
Number of patients with clinically significant findings in ECG
Time Frame
up to 14 days after last drug administration
Title
Number of patients with clinically significant findings in laboratory tests
Time Frame
up to 14 days after last drug administration
Title
Assessment of tolerability by investigator on a 4-point scale
Time Frame
up to 14 days after last drug administration
Secondary Outcome Measure Information:
Title
Cmax (maximum concentration of the analyte in plasma)
Time Frame
up to 18 days after first drug administration
Title
tmax (time from dosing to maximum concentration)
Time Frame
up to 18 days after first drug administration
Title
AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point within the first dosing interval)
Time Frame
up to 18 days after first drug administration
Title
AUCτ,1 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 h after administration of the first dose)
Time Frame
up to 18 days after first drug administration
Title
Ae0-24 (amount of analyte that is eliminated in urine from the time interval 0 h to 24 h)
Time Frame
up to 11 days after first drug administration
Title
fe0-24 (fraction of analyte excreted in urine from time point 0 h to 24 h)
Time Frame
up to 11 days after first drug administration
Title
CLR,0-24 (renal clearance of the analyte in plasma from the time point 0 h until the time point 24 h)
Time Frame
up to 11 days after first drug administration
Title
Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval)
Time Frame
up to 18 days after first drug administration
Title
Cpre,N (predose concentration of the analyte in plasma at steady state immediately before administration of the next dose N)
Time Frame
up to 18 days after first drug administration
Title
PTF (peak trough fluctuation)
Description
in percent
Time Frame
up to 18 days after first drug administration
Title
RA,Cmax (accumulation ratio based on Cmax)
Time Frame
up to 18 days after first drug administration
Title
RA,AUC(accumulation ratio based on AUCτ)
Time Frame
up to 18 days after first drug administration
Title
Change in dipeptidyl-peptidase 4 (DPP-IV) activity
Time Frame
baseline, up to 18 days after first drug administration
Title
Area under the curve of plasma glucose
Time Frame
baseline, up to 3 hours after intake of standardized meal
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male and postmenopausal or hysterectomised female patients with proven diagnosis of type 2 diabetes mellitus treated with diet and exercise only, or with one oral hypoglycaemic agent besides glitazones and who are not taking the maximum approved dose
Glycosylated haemoglobin A1 (HbA1c) ≥ 6.5% and ≤ 8.5 % at screening for patients treated with diet and exercise and/or one oral hypoglycaemic agent
Age ≥21 and Age ≤70 years (female hysterectomised and male patients) Age ≥60 and Age ≤70 years (female postmenopausal patients)
Body Mass Index (BMI) ≥18.5 and BMI ≤35 kg/m2
Exclusion Criteria:
Any finding of the medical examination (including BP, pulse rate (PR) and ECG) deviating from normal and of not acceptable clinical relevance
Clinically relevant concomitant diseases like renal insufficiency, cardiac insufficiency New York Heart Association (NYHA) II-IV, myocardial infarction, other known cardiovascular diseases including hypertension > 140/90 mmHg, stroke and 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
Antidiabetic treatment with more than one oral hypoglycaemic agent or insulin or glitazones and anti-hypertensive treatment with verapamil or diltiazem
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)
Use of drugs which might reasonably influence the results of the trial or that prolong the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days 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
A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms)
A history of additional risk factors for Torsade des Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
For female patients:
Child bearing potential
Positive pregnancy test
Lactation period
12. IPD Sharing Statement
Links:
URL
http://trials.boehringer-ingelheim.com
Description
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Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Oral Doses of BI 14332 CL as Tablet in Female and Male Patients With Type 2 Diabetes
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