Pharmacokinetics and Safety of BI 695501

Study Overview
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Brief Summary
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To characterize and compare the pharmacokinetics and to assess the safety of BI 695501 after single injection using either auto injector or prefilled syringe.

Official Title
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Randomized, Single-dose, Parallel-arm, Open-label Phase I Trial to 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: BI695501 Prefilled syringe
* Drug: BI695501Autoinjector


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age between 18 and 65 years (inclusive) BMI of >17.5 to <35.0 kg/m2 Healthy male or female 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. Subjects who meet any of the following criteria: Surgically sterilized (confirmed 6 month prior to enrollment) Have surgically sterilized sexual partner (confirmed 6 month prior to enrollment) Postmenopausal, defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous levels of follicle-stimulating hormone (FSH) above 40 U/L and estradiol below 30 ng/L is confirmatory) Subjects agree to use an adequate contraception, starting from the begin of the trial and until 6 months after the dose of the trial drug: e.g. any of the following methods plus condom: implants, injectables, combined oral or vaginal contraceptives, intrauterine device Signed and dated written informed consent in accordance with Good Clinical Practice (GCP) and local legislation prior to admission to the trial Exclusion criteria: Previous exposure to adalimumab or proposed adalimumab biosimilar drugs. Any finding in the medical examination (including blood pressure (BP), pulse rate (PR) or electrocardiogram (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, hepatitis B virus (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). Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial. Intake of an investigational drug in another trial within 2 months or 5 half-lives (whichever longer) prior to planned administration of the trial medication in this trial or intake of an investigational drug during the course of this trial. Alcohol abuse (consumption of more than 28 units/week). 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 500 mL within 30 days prior to administration of trial medication or intended donation during the trial. Intention to perform excessive physical activities within 4days 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 to be 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., Rheumatoid arthritis (RA), lupus erythematosus, scleroderma, etc.). Subject has received a live vaccine within 12 weeks prior to enrolling in the trial. History of tuberculosis (TB) or positive finding in Interferon-gamma release assay (IGRA). Evidence of skin irritation or infection at the planned injection place. Currently enrolled in another investigational device or drug study Any condition that, in the investigator´s opinion, makes them an unreliable study subject or unlikely to complete the trial Women who are pregnant, nursing, or who plan to become pregnant while in the trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI695501 Autoinjector<br> | Drug: BI695501Autoinjector<br> <br> |
| Active Comparator: BI695501 Prefilled syringe<br> | Drug: BI695501 Prefilled syringe<br> <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 of BI 695501 in Plasma Over the Time Interval From 0 to 1368 Hours (AUC0-1368) After Administration Via PFS and AI. | The AUC0-1368 of 40 mg BI 695501 administered via PFS and AI was measured. Plasma concentrations were measured using a validated enzyme-linked immunosorbent assay (ELISA). Only concentration values within the validated concentration range of 0.025 to 2.0 micrograms per millilitre (µg/mL) and actual sampling times were used. | From 0 to 1368 hours post-dose. Samples were collected pre-dose and 1, 4, 8, 12, 24, 48, 60, 72, 84, 96, 108, 120, 132, 144, 168, 216, 336, 504, 672, 840, 1032, and 1368 hours post-dose. | 
| The Maximum Measured Concentration of BI 695501 in Plasma (Cmax) After Administration Via PFS and AI | The Cmax of 40 mg BI 695501 administered via PFS and AI. Plasma concentrations were measured using a validated ELISA. Only concentration values within the validated concentration range of 0.025 to 2.0 µg/mL and actual sampling times were used. | From 0 to 1368 hours post-dose. Samples were collected pre-dose and 1, 4, 8, 12, 24, 48, 60, 72, 84, 96, 108, 120, 132, 144, 168, 216, 336, 504, 672, 840, 1032, and 1368 hours post-dose. | 
| Area Under the Concentration-time Curve of BI 695501 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) After Administration Via PFS and AI. | The AUC0-∞ of 40 mg BI 695501 administered via PFS and AI. Plasma concentrations were measured using a validated ELISA. Only concentration values within the validated concentration range of 0.025 to 2.0 µg/mL and actual sampling times were used. | Samples were collected pre-dose and 1, 4, 8, 12, 24, 48, 60, 72, 84, 96, 108, 120, 132, 144, 168, 216, 336, 504, 672, 840, 1032, and 1368 hours post-dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Subjects With Drug-related Treatment-emergent Adverse Events (TEAEs) From Day 1 to Day 70. | A treatment-related TEAE was defined as any TEAE assessed by the Investigator as related to the trial medication. A TEAE was defined as an adverse event (AE) that started or worsened in severity on or after the single dose of trial medication up to 10 weeks (70 days) post-dose. | From Day 1 to Day 70 |