Pharmacokinetics and Safety of BI 695501 Administered Via Prefilled Syringe or Autoinjector

Study Overview
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Brief Summary
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To investigate and compare the pharmacokinetics, safety and tolerability of BI 695501 administered subcutaneously via prefilled syringe or autoinjector

Official Title
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Randomized, Single-dose, Parallel-arm, Open-label Phase I Trial to Investigate and Compare the Pharmacokinetics, Safety and Tolerability of BI 695501 Administered Subcutaneously Via Prefilled Syringe or Autoinjector

Conditions
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Healthy

Intervention / Treatment
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* Drug: BI 695501 prefilled syringe
* Drug: BI 695501 autoinjector


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy male, non-athletic* Caucasian subjects according to the investigator's assessment, based on a complete medical history including a physical examination, vital signs (blood pressure [BP], pulse rate [PR]), 12-lead ECG, and clinical laboratory tests. Age between 18 and 65 years (inclusive) BMI of 18 to 30 kg/m2 (inclusive) BMI 18 to <20, or BMI 20 to <25, or BMI 25 to <=30 Signed and dated written informed consent prior to admission to the trial in accordance with Good Clinical Practice (GCP) and local legislation. Subjects agree to use an acceptable method of contraception during the trial and for 6 month after the dose of trial drug. Non-athletic defined as person performing no more than one hour of exercise per week Exclusion criteria: Any finding in the medical examination (including BP, PR or ECG) that deviates from normal and judged as clinically relevant by the investigator. Any evidence of a concomitant disease judged as clinically relevant by the investigator including gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, hormonal disorders or diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders. History of relevant orthostatic hypotension, fainting spells, or blackouts. Chronic or relevant acute infections. Positive result for HIV, HBV, and hepatitis C (Hep C) at screening. History of relevant allergy or hypersensitivity including allergy to the trial medication, its excipients or device materials (e.g. natural rubber or latex). Intake of drugs with a long half-life (more than 24 hours) within 30 days or less than 5 half-lives of the respective drug prior to administration of trial medication. Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial. Previous exposure to a biologic drug. Intake of an investigational drug in another trial within 2 months prior to intake of trial medication in this trial or intake of an investigational drug during the course of this trial. Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day). Inability to refrain from smoking during days of confinement at the trial site. Alcohol abuse (consumption of more than 4 units/day). Unwillingness/inability to refrain from intake of alcoholic beverages from 48 hours prior to the trial medication administration and until Day 14 post trial medication administration; and/or to limit alcohol intake to a maximum of 3 units per day until e.o.t. Drug abuse or positive drug screening. Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial. Intention to perform excessive physical activities within 1 week prior to administration of trial medication or contact sport during the entire trial and unwilling to avoid vigorous exercise for 14 days post dosing. Inability to comply with dietary regimen of trial site. Any out-of-range laboratory values considered clinically significant by the investigator; subjects with creatine kinase (CK) values 2 times the upper limit of normal (ULN) at Day -1 are excluded from participation. Subject is assessed as unsuitable for inclusion by the investigator, for instance, because he is considered not able to understand and comply with trial requirements, or has a condition that would not allow safe participation in the trial. Subjects with any immunological disorders or auto-immune disorders, (e.g., RA, lupus erythematosus, scleroderma, etc.). Subject has received a live vaccine within 12 weeks prior to enrolling in the trial. History of TB or positive finding in IGRA. Evidence of skin irritation or infection at the planned injection place.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 695501 prefilled syringe<br> | Drug: BI 695501 prefilled syringe<br> <br> |
| Experimental: BI 695501 autoinjector<br> | Drug: BI 695501 autoinjector<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Measured Concentration of BI 695501 in Plasma (Cmax) | Maximum measured concentration of BI 695501 in plasma (Cmax). The rate and extent of absorption of BI 695501 by assessment of maximum plasma concentration following administration via AI or via PFS of a single dose of 40 mg BI 695501. During analysis, it was realized that the PK sample on Day 43 had originally been mistakenly associated with a 1032 h time point, rather than with 1008 h. However, PK parameters are calculated using actual values so this did not impact the analysis results. | PK plasma samples were taken at: 1 hour (h) before drug administration and 1h, 4h, 8h,12h, 24h, 48h, 60h, 72h, 84h, 96h, 108h, 120h, 132h, 144h, 168h, 216h, 336h, 504h, 672h, 840h, 1008h after drug administration. | 
| Area Under the Concentration-time Curve of the BI 695501 in Plasma Over the Time Interval From 0 to 1032 Hours After Dose (AUC0-1032) | Area under the concentration-time curve of the BI 695501 in plasma over the time interval from 0 to 1032 hours after dose (AUC0-1032). The rate and extent of absorption of BI 695501 by assessment of AUC0-1032 following administration via AI or via PFS of a single dose of 40 mg BI 695501. During analysis, it was realized that the PK sample on Day 43 had originally been mistakenly associated with a 1032 h time point, rather than with 1008 h. However, PK parameters are calculated using actual values so this did not impact the analysis results. | PK plasma samples were taken at: 1 hour (h) before drug administration and 1h, 4h, 8h,12h, 24h, 48h, 60h, 72h, 84h, 96h, 108h, 120h, 132h, 144h, 168h, 216h, 336h, 504h, 672h, 840h, 1008h after drug administration. | 
| Area Under the Concentration-time Curve of the BI 695501 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | Area under the concentration-time curve of the BI 695501 in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity) based on observed concentration at time of last measurable concentration. The rate and extent of absorption of BI 695501 by assessment of (AUC0-∞) following administration via AI or via PFS of a single dose of 40 mg BI 695501. During analysis, it was realized that the PK sample on Day 43 had originally been mistakenly associated with a 1032 h time point, rather than with 1008 h. However, PK parameters are calculated using actual values so this did not impact the analysis results. | PK plasma samples were taken at: 1 hour (h) before drug administration and 1h, 4h, 8h,12h, 24h, 48h, 60h, 72h, 84h, 96h, 108h, 120h, 132h, 144h, 168h, 216h, 336h, 504h, 672h, 840h, 1008h after drug administration. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Drug-related Adverse Events (AEs) | Number of subjects with drug-related Adverse Events (AEs). Any event with an onset after the administration of the trial medication up to a period of 70 days was defined as a treatment-emergent AE (TEAE). A treatment-related AE was defined as any TEAE assessed by the investigator as related to the trial medication. | From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period |