Dose Proportionality of Different Dose Strengths of Linagliptin Tablets After Oral Administration to Healthy Male and Female Volunteers

Study Overview
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Brief Summary
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Study to assess the pharmacokinetics and dose proportionality of 1 mg, 2.5 mg and 5 mg tablets of linagliptin

Official Title
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Assessment of Dose Proportionality of Different Dose Strengths of Linagliptin Tablets After Oral Administration to Healthy Male and Female Volunteers in an Open, Randomised, Multiple-dose, Three-period Crossover, Phase I Trial

Conditions
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Healthy

Intervention / Treatment
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* Drug: Linagliptin, low dose
* Drug: Linagliptin, medium dose
* Drug: Linagliptin, high dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female volunteers according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead ECG (electrocardiogram), clinical laboratory tests Age 18 to 55 years (inclusive) BMI (Body Mass Index) 18.5 to 29.9 kg/m2 (inclusive) 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 BP, PR and ECG) deviating from normal and of clinical relevance. Repeated measurement of a systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg Any evidence of a clinically relevant concomitant disease Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Surgery of the gastrointestinal tract (except appendectomy) Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders History of relevant orthostatic hypotension, fainting spells or blackouts Chronic or relevant acute infections History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) Intake of drugs within one month or less than 10 half-lives of the respective drug prior to first study drug administration except if a relevant interaction can be ruled out 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) Alcohol abuse ( average consumption of more than 20 g/day in females and 30 g/day in males) Drug abuse Blood donation (more than 100 mL within four weeks prior to administration or during the trial) Any laboratory value outside the reference range that is of clinical relevance Inability to comply with dietary regimen of trial site For female subjects only: Positive pregnancy test, pregnancy or planning to become pregnant during the study or within 2 months after study completion No adequate contraception during the study and until 1 month after study completion, i.e. not any of the following: implants, injectables, combined oral contraceptives, IUD (intrauterine device), sexual abstinence for at least 1 month prior to enrolment, vasectomised partner (vasectomy performed at least 1 year prior to enrolment), or surgical sterilisation (including hysterectomy). Females, who do not have a vasectomised partner, are not sexually abstinent or surgically sterile will be asked to use an additional barrier method (e.g. condom, diaphragm with spermicide) Lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Linagliptin, low dose<br> | Drug: Linagliptin, low dose<br> <br> |
| Experimental: Linagliptin, medium dose<br> | Drug: Linagliptin, medium dose<br> <br> |
| Active Comparator: Linagliptin, high dose<br> | Drug: Linagliptin, high dose<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ) of linagliptin |  | up to 168 hours after first drug administration at each visit | 
| Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ) of linagliptin |  | up to 168 hours after first drug administration at each visit | 
| Cτ,ss (average measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ) of linagliptin |  | up to 168 hours after first drug administration at each visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ) of CD 1750 |  | up to 168 hours after first drug administration at each visit | 
| Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ) of CD 1750 |  | up to 168 hours after first drug administration at each visit | 
| Number of patients with adverse events |  | up to 53 days | 
| Assessment of tolerability by investigator on a 4-point scale |  | within 10 days after last study drug administration |