Safety, Pharmacokinetics and Pharmacodynamics of BIRT 1696 BS in Healthy Human Subjects

Study Overview
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Brief Summary
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The objectives are: To assess safety, pharmacokinetics, and pharmacodynamics of BIRT 1696 BS in rising single doses. To assess safety, pharmacokinetics, and pharmacodynamics of single dose of 100 mg BIRT 1696 BS after grapefruit juice. To asses safety and pharmacokinetics of single dose of 400 mg BIRT 1696 BS after a 67 g fat and high caloric breakfast.

Official Title
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Safety, Pharmacokinetics and Pharmacodynamics of Single Rising Oral Doses of BIRT 1696 BS as a Solution (10, 100, 400, 1000, 2000, 3000 mg) in 15 ml PEG 400 to Healthy Human Subjects. A Three Part Study: Part 1 Placebo-controlled, Randomised, Dose Escalating Double Blinded Within Each Dose Level; Part 2 Open Label Grapefruit Juice Effect in 100 mg Dose Level Group; Part 3 Open Label Food Effect in 400 mg Dose Level Group

Conditions
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Healthy

Intervention / Treatment
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* Drug: BIRT 1696 BS
* Drug: Placebo
* Other: Grapefruit juice (GFJ)
* Other: High fat meal (HFM)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female subjects as determined by results of screening Signed written informed consent in accordance with Good Clinical Practice (GCP) and local legislation Age ≥18 and ≤60 years Body Mass Index ≥18.5 and ≤29.9 kg/m2 Exclusion Criteria: Female subjects who are lactating or of child bearing potential as defined by surgically sterile or post menopausal (no periods for at least 12 months and elevated follicle stimulating hormone with low estradiol while on no estrogen supplementation unless surgically sterile). Females should use barrier contraception (e.g. condoms) prior to administration of study medication, during the study and at least one month after release from the study. Women must have had negative blood pregnancy tests Any finding of the medical examination (including blood pressure, pulse rate, and electrocardiogram) deviating from normal and of clinical relevance Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic or hormonal disorders Surgery of gastrointestinal tract (except appendectomy) Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders Relevant history of orthostatic hypotension, fainting spells or blackouts Chronic or relevant acute infections History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator Intake of drugs with a long half-life (> 24 hours) (< 1 month prior to administration or during the trial) Use of any drugs, which might influence the results of the trial, (< 10 days prior to administration or during the trial) Participation in another trial with an investigational drug (< 2 months prior to administration or during trial) Smoker (> 10 cigarettes or >3 cigars or >3 pipes/day) Alcohol abuse (> 60 g/day) Drug abuse Use of methylxanthine-containing drinks or foods (coffee, tea, cola, energy drinks, chocolate, etc.), grapefruit or grapefruit juice, alcohol, green tea, or tobacco < 5 days prior to administration of study drug or during trial Blood donation or loss > 400 mL, < 1 month prior to administration or during the trial Excessive physical activities < 5 days prior to administration of study drug or during trial Clinically relevant laboratory abnormalities Any ECG value outside of the reference range of clinical relevance including, but not limited to QRS interval > 110 ms or QTcB > 450 ms (males) or QTcB > 470 ms (females) Inability to comply with dietary regimen of study centre Inability to comply with the investigator's instructions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIRT 1696 BS<br>single escalating dose phase | Drug: BIRT 1696 BS<br> <br> |
| Experimental: BIRT 1696 BS + GFJ<br>single dose grapefruit effect arm | Drug: BIRT 1696 BS<br> <br> Other: Grapefruit juice (GFJ)<br> <br> |
| Experimental: BIRT 1696 BS + HFM<br>single dose food effect arm | Drug: BIRT 1696 BS<br> <br> Other: High fat meal (HFM)<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events |  | up to 44 days | 
| Number of subjects with clinically significant changes in vital signs |  | up to 44 days | 
| Number of subjects with abnormal changes in laboratory parameters |  | up to 44 days | 
| Number of subjects with abnormal findings in electrocardiogram |  | up to 44 days | 
| Number of subjects with abnormal findings in physical examination |  | up to 44 days | 
| Assessment of tolerability on a verbal rating scale |  | up to 44 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax) |  | up to 48 hours after drug administration | 
| Total area under the plasma drug concentration-time curve from time zero to infinity (AUC0-∞) |  | up to 48 hours after drug administration | 
| Time to the maximum plasma concentration (tmax) |  | up to 48 hours after drug administration | 
| Elimination half-life (t1/2) |  | up to 48 hours after drug administration | 
| Total apparent oral clearance of drug from plasma after oral administration (CL/F) |  | up to 48 hours after drug administration | 
| Apparent volume of distribution based on terminal elimination phase, divided by F (bioavailability factor) (Vz/F) |  | up to 48 hours after drug administration | 
| Mean residence time (MRT) |  | up to 48 hours after drug administration | 
| Urinary excretion |  | up to 24 hours after drug administration | 
| Receptor occupancy as determined by binding of anti-lymphocyte function associated antigen-1 antibody fragment (Fab) |  | up to 168 hours after drug administration | 
| Inhibition of superantigen induced interleukin-2 production ex vivo |  | up to 168 hours after drug administration |