Clinical trial NCT02899338: Pharmacokinetics and Safety of BI 695501
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2016-09-14
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 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.
measure: The Maximum Measured Concentration of BI 695501 in Plasma (Cmax) After Administration Via PFS and AI
timeFrame: 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.
measure: 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.
timeFrame: 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 outcomes:
measure: The Percentage of Subjects With Drug-related Treatment-emergent Adverse Events (TEAEs) From Day 1 to Day 70.
timeFrame: From Day 1 to Day 70
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: SGS Life Sciences Services
city: Groningen
country: Netherlands
facility: PRA Health Sciences Onderzoekscentrum Martini
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: