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

Diabetes Mellitus, Type 2 Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02183415
• Other study ID #: 1218.3
• Status: Completed
• Phase: Phase 1
• First received: July 4, 2014
• Last updated: July 4, 2014
• Start date: August 2005

Study information

• Verified date: July 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesNetherlands: Medicines Evaluation Board (MEB)United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. primary completion date: January 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2

Intervention

Drug:
• BI 1356 BS, low dose

• BI 1356 BS, medium dose

• BI 1356 BS, high dose

• Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of tolerability by investigator on a 4-point scale		Day 50	No
Primary	Incidence of adverse events		up to 50 days	No
Primary	Number of patients with abnormal changes in clinical laboratory parameters		Baseline, up to day 50	No
Secondary	Cmax (maximum concentration of the analyte in plasma)		before and up to 43 days after first study drug administration	No
Secondary	tmax (time from dosing to maximum concentration)		before and up to 43 days after first study drug administration	No
Secondary	AUC (area under the concentration-time curve of the analyte in plasma) for several time points		before and up to 43 days after first study drug administration	No
Secondary	Cmax,ss (maximum concentration of the analyte in plasma at steady state over a uniform dosing interval)		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	No
Secondary	Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval)		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	No
Secondary	Cpre,N (predose concentration of the analyte in plasma at steady state immediately before administration of the next dose N)		pre-dose on day 28	No
Secondary	tmax,ss (time from dosing to maximum concentration at steady state)		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	No
Secondary	AUCt,ss (area under the concentration time curve of the analyte in plasma at steady state over a uniform dosing interval)		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	No
Secondary	?z,ss (terminal rate constant in plasma at steady state)		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	No
Secondary	t1/2,ss (terminal half-life of the analyte in plasma at steady state)		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	No
Secondary	MRTpo,ss (mean residence time of the analyte in the body after 12 administrations at steady state)		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	No
Secondary	CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state)		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	No
Secondary	Vz/F,ss (apparent volume of distribution during the terminal phase ?z following an extravascular dose at steady state)		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	No
Secondary	PTF (peak trough fluctuation)		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	No
Secondary	Accumulation ratio (RA) based on Cmax		up to 28 days	No
Secondary	RA,AUC based on AUCt		up to 28 days	No
Secondary	Dipeptidyl-Peptidase IV (DPP-IV) activity for several time points		up to day 43	No
Secondary	Change in fasting plasma glucose (AUEC0-3) after MTT (meal tolerance test )		days -1, 1 and 29	No
Secondary	Plasma glucose levels		up to day 43	No

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