Pharmacokinetics and Safety in Healthy Volunteers

Study Overview
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Brief Summary
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Investigate the pharmacokinetics, safety and tolerability of BI695501 and to establish pharmacokinetic similarity of BI 695501 to adalimumab.

Official Title
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Pharmacokinetics and Safety of BI 695501 in Healthy Subjects: a Randomized, Double-blind, Single Dose, Parallel-arm, Active Comparator Clinical Phase I Study

Conditions
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Healthy

Intervention / Treatment
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* Drug: BI 695501
* Drug: adalimumab-EU source
* Drug: adalimumab-US source


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy males according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (blood pressure [BP] and pulse rate [PR]), 12-lead electrocardiogram (ECG), and clinical laboratory tests; Age-greater than or equal to 18 years and less than or equal to 55 years; Body mass index (BMI) =18.5 to =29.9 kg/m2; and 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 clinically relevant abnormal finding of the medical examination (including blood pressure (BP), pulse rate (PR), and electrocardiogram (ECG) deviating from normal and of clinical relevance; Any evidence of a clinically relevant previous or concomitant disease as judged by the investigator including gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, hormonal disorders, or diseases of the central nervous system (such as epilepsy), psychiatric disorders, or neurological disorders; History of relevant orthostatic hypotension, fainting spells, or blackouts; Chronic or relevant acute infections. A negative result for human immunodeficiency virus (HIV), Hepatitis B (Hep B), and hepatitis C (Hep C) is required for participation; History of relevant allergy/hypersensitivity (including allergy to drug or its excipients); Intake of prescribed or over-the-counter drugs with a long half-life (greater than 24 hours) within at least one month or at least 5 half-lives of the respective drug (whichever is longer) prior to administration or during the trial; Previous exposure of a biologic drug; Use of drugs which might reasonably influence the results of the trial prior to dosing and at any time during the trial; Intake of an investigational drug in another trial within two months prior to intake of study medication in this trial or intake of an investigational drug during the course of this trial; Smoker (greater than 10 cigarettes or greater than 3 cigars or greater than 3 pipes/day); Inability to refrain from smoking during days of confinement at the trial site; History of alcohol abuse (estimated average more than 4 units/day); Unwillingness/inability to refrain from intake of alcoholic beverages from 48 hours prior to the study medication administration and until Day 7 post study medication administration; Unwillingness/inability to limit alcohol intake to a maximum of three units per day until e.o.s.; Current drug abuse; Blood donation (more than 100 mL within four weeks prior to administration of the study medication or during the trial); Vigorous exercise 72 hours prior to dosing. Unwilling to avoid vigorous exercise for 7 days post dosing. Contact sport should be avoided during the entire study; Any out-of-range laboratory values considered clinically significant by the investigator; subjects with creatine kinase (CK) values three times the upper limit of normal (ULN) at Day -1 are excluded from participation; Subjects considered unsuitable for inclusion by the investigator (e.g., inability to understand and comply with the study requirements or presence of any condition which, in the opinion of the investigator, would not allow safe participation in the study); or Inability to comply with dietary regimen of trial site. Subjects with known Human immunodeficiency virus (HIV), Acquired Immunodeficiency Syndrome, other clinically significant immunological disorders, or auto-immune disorders, (e.g., Rheumatoid arthritis (RA), lupus erythematosus, scleroderma, etc.); Subject has received a live or attenuated vaccine within 12 weeks prior to enrolling in the trial; or Positive finding in Interferon-gamma-release assay testing (IGRA-T). In cases where at the screening visit the IGRA result is indeterminate, the subject will have a PPD skin test performed, provided that the screening period timeframe can be maintained. If not, the subject will not be enrolled in this study.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 695501<br>Subject to receive one subcutaneous (s.c.) injection from a prefilled syringe containing BI 695501 | Drug: BI 695501<br>* BI 695501 single s.c. injection<br>|
| Active Comparator: adalimumab-EU source<br>Subject to receive one subcutaneous (s.c.) injection from a prefilled syringe containing adalimumab-EU source | Drug: adalimumab-EU source<br>* adalimumab-EU source single s.c. injection<br>|
| Active Comparator: adalimumab-US source<br>Subject to receive one subcutaneous (s.c.) injection from a prefilled syringe containing adalimumab-US source | Drug: adalimumab-US source<br>* adalimumab-US source single s.c. injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration Time Curve (AUC) From Time Zero to Infinity (AUC 0-∞) of BI 695501, US-licensed Humira® or EU-approved Humira® | Area under the concentration time curve (AUC) from time zero to infinity (AUC 0-∞) of BI 695501, US-licensed Humira® or EU-approved Humira®. Abbreviation used: Pharmacokinetics (PK). | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 1032, 1320 h post dosing and on day 71 post dosing. | 
| Area Under the Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC0-tz) of BI 695501, US-licensed Humira® or EU-approved Humira® | Area under the concentration time curve from time zero to last measurable concentration (AUC0-tz) of BI 695501, US-licensed Humira® or EU-approved Humira®. | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 1032, 1320 h post dosing and on day 71 post dosing. | 
| Maximum Concentration (Cmax) of BI 695501, US-licensed Humira® or EU-approved Humira® | Maximum concentration (Cmax) of BI 695501, US-licensed Humira® or EU-approved Humira®. | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 1032, 1320 h post dosing and on day 71 post dosing. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC (0-168) of BI 695501, US-licensed Humira® or EU-approved Humira® | Area under the concentration time curve (AUC) from time zero to 168 hours post dose (AUC 0-168) of BI 695501, US-licensed Humira® or EU-approved Humira®. PK is the abbreviation for Pharmacokinetic(s). | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168 hours post dosing | 
| AUC (0-312) of BI 695501, US-licensed Humira® or EU-approved Humira® | Area under the concentration time curve (AUC) from time zero to 312 hours post dose (AUC 0-312) of BI 695501, US-licensed Humira® or EU-approved Humira®. PK is the abbreviation for Pharmacokinetic(s). | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312 hours post dosing | 
| AUC (0-480) of BI 695501, US-licensed Humira® or EU-approved Humira® | Area under the concentration time curve (AUC) from time zero to 480 hours post dose (AUC 0-480) of BI 695501, US-licensed Humira® or EU-approved Humira®. PK is the abbreviation for Pharmacokinetic(s). | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480 hours post dosing | 
| AUC (0-648) of BI 695501, US-licensed Humira® or EU-approved Humira® | Area under the concentration time curve (AUC) from time zero to 648 hours post dose (AUC 0-648) of BI 695501, US-licensed Humira® or EU-approved Humira®. PK is the abbreviation for Pharmacokinetic(s). | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648 hours post dosing | 
| AUC (0-1032) of BI 695501, US-licensed Humira® or EU-approved Humira® | Area under the concentration time curve (AUC) from time zero to 1032 hours post dose (AUC 0-1032) of BI 695501, US-licensed Humira® or EU-approved Humira® PK is the abbreviation for Pharmacokinetic(s). | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 1032 hours post dosing | 
| AUC 0-∞,Obs of BI 695501, US-licensed Humira® or EU-approved Humira® | Area under the concentration time curve (AUC) from time zero to infinity (AUC 0-∞) based on the last observed concentration at time of last measureable concentration (tz) of BI 695501, US-licensed Humira® or EU-approved Humira®. PK is the abbreviation of Pharmacokinetic(s). | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 1032, 1320 h post dosing and on day 71 post dosing. | 
| Number (Proportion) of Subjects With Drug Related Adverse Events | All events with an onset after the first administration of the trial medication up to a period of 70 days after the last administration of the trial medication (i.e., end of the REP) was assigned to the treatment phase for evaluation and 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. All safety data were displayed and analyzed using descriptive statistical methods. No formal inferential analyses were planned for safety comparisons. Tabulations of frequencies and proportions, as appropriate were used for the evaluation of categorical (qualitative) data, and tabulations of descriptive statistics were used to analyze continuous (quantitative) data. | Day 1 through Day 71 |