Trial Outcomes & Findings for Pharmacokinetics and Safety in Healthy Volunteers (NCT NCT02045979)

NCT ID: NCT02045979

Last Updated: 2018-06-20

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 327 participants
• Primary outcome timeframe: 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.
• Results posted on: 2018-06-20

Participant Flow

In this trial 324 healthy subjects were randomized into 3 arms.

All subjects were screened for eligibility to participate in the trial. Subjects attended specialist sites which would then ensure that they (the subject) met all strictly implemented inclusion/exclusion criteria. Subjects were not randomised to trial treatment if any one of the specific entry criteria were violated.

Participant milestones

Measure	BI 695501 Subject to receive a single subcutaneous (s.c.) injection from a prefilled syringe containing 40 milligram (mg)/0.8 millilitre (mL) BI 695501 solution.	US-licensed Humira® Subject to receive a single subcutaneous (s.c.) injection from a prefilled syringe containing 40 mg/0.8 mL US-licensed Humira®	EU-approved Humira® Subject to receive a single subcutaneous (s.c.) injection from a prefilled syringe containing 40 mg/0.8 mL European Union (EU)-approved Humira®.
Overall Study STARTED	108	108	108
Overall Study COMPLETED	106	107	107
Overall Study NOT COMPLETED	2	1	1

Reasons for withdrawal

Measure	BI 695501 Subject to receive a single subcutaneous (s.c.) injection from a prefilled syringe containing 40 milligram (mg)/0.8 millilitre (mL) BI 695501 solution.	US-licensed Humira® Subject to receive a single subcutaneous (s.c.) injection from a prefilled syringe containing 40 mg/0.8 mL US-licensed Humira®	EU-approved Humira® Subject to receive a single subcutaneous (s.c.) injection from a prefilled syringe containing 40 mg/0.8 mL European Union (EU)-approved Humira®.
Overall Study Informed Consent Withdrawn	2	0	1
Overall Study not specified above	0	1	0

Baseline Characteristics

Pharmacokinetics and Safety in Healthy Volunteers

Baseline characteristics by cohort

Measure	BI 695501 n=108 Participants single s.c. injection 40 mg/0.8 mL BI 695501 solution.	US-licensed Humira® n=108 Participants single s.c. injection 40 mg/0.8 mL US-licensed Humira®	EU-approved Humira® n=108 Participants single s.c. injection 40 mg/0.8 mL EU-approved Humira®	Total n=324 Participants Total of all reporting groups
Age, Continuous	30 years STANDARD_DEVIATION 11 • n=5 Participants	31 years STANDARD_DEVIATION 11 • n=7 Participants	30 years STANDARD_DEVIATION 12 • n=5 Participants	31 years STANDARD_DEVIATION 11 • n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	108 Participants n=5 Participants	108 Participants n=7 Participants	108 Participants n=5 Participants	324 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

Population: PK analysis set consisted of all randomized subjects who received the single dose of trial medication (BI 695501, US-licensed - or EU-approved Humira®), had at least one evaluable primary PK endpoint and were without important protocol deviations or violations thought to significantly affect the PK of BI 695501, US-licensed - 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).

Outcome measures

Measure	BI 695501 n=106 Participants single s.c. injection 40 mg/0.8 mL BI 695501 solution.	US-licensed Humira® n=105 Participants single s.c. injection 40 mg/0.8 mL US-licensed Humira®	EU-approved Humira® n=105 Participants single s.c. injection 40 mg/0.8 mL 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®	2630 microgram (µg)*hour (h)/millilitre (mL) Geometric Coefficient of Variation 52.4	2470 microgram (µg)*hour (h)/millilitre (mL) Geometric Coefficient of Variation 51.2	2650 microgram (µg)*hour (h)/millilitre (mL) Geometric Coefficient of Variation 38.5

PRIMARY outcome

Timeframe: 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.

Population: The PK analysis set.

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®.

Outcome measures

Measure	BI 695501 n=106 Participants single s.c. injection 40 mg/0.8 mL BI 695501 solution.	US-licensed Humira® n=107 Participants single s.c. injection 40 mg/0.8 mL US-licensed Humira®	EU-approved Humira® n=106 Participants single s.c. injection 40 mg/0.8 mL 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®	2440 µg*h/mL Geometric Coefficient of Variation 47.8	2300 µg*h/mL Geometric Coefficient of Variation 45.1	2480 µg*h/mL Geometric Coefficient of Variation 33.5

PRIMARY outcome

Timeframe: 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.

Population: The PK analysis set.

Maximum concentration (Cmax) of BI 695501, US-licensed Humira® or EU-approved Humira®.

Outcome measures

Measure	BI 695501 n=107 Participants single s.c. injection 40 mg/0.8 mL BI 695501 solution.	US-licensed Humira® n=108 Participants single s.c. injection 40 mg/0.8 mL US-licensed Humira®	EU-approved Humira® n=107 Participants single s.c. injection 40 mg/0.8 mL EU-approved Humira®
Maximum Concentration (Cmax) of BI 695501, US-licensed Humira® or EU-approved Humira®	3.907 µg/mL Geometric Coefficient of Variation 34.1	3.900 µg/mL Geometric Coefficient of Variation 34.5	4.140 µg/mL Geometric Coefficient of Variation 30.4

SECONDARY outcome

Timeframe: at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168 hours post dosing

Population: The PK analysis set.

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).

Outcome measures

Measure	BI 695501 n=107 Participants single s.c. injection 40 mg/0.8 mL BI 695501 solution.	US-licensed Humira® n=108 Participants single s.c. injection 40 mg/0.8 mL US-licensed Humira®	EU-approved Humira® n=107 Participants single s.c. injection 40 mg/0.8 mL EU-approved Humira®
AUC (0-168) of BI 695501, US-licensed Humira® or EU-approved Humira®	480 µg*h/mL Geometric Coefficient of Variation 41.1	493 µg*h/mL Geometric Coefficient of Variation 40.7	513 µg*h/mL Geometric Coefficient of Variation 39.9

SECONDARY outcome

Timeframe: 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

Population: The PK analysis set.

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).

Outcome measures

Measure	BI 695501 n=107 Participants single s.c. injection 40 mg/0.8 mL BI 695501 solution.	US-licensed Humira® n=108 Participants single s.c. injection 40 mg/0.8 mL US-licensed Humira®	EU-approved Humira® n=107 Participants single s.c. injection 40 mg/0.8 mL EU-approved Humira®
AUC (0-312) of BI 695501, US-licensed Humira® or EU-approved Humira®	957 µg*h/mL Geometric Coefficient of Variation 36.5	967 µg*h/mL Geometric Coefficient of Variation 34.9	1010 µg*h/mL Geometric Coefficient of Variation 31.6

SECONDARY outcome

Timeframe: 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

Population: The PK analysis set.

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).

Outcome measures

Measure	BI 695501 n=107 Participants single s.c. injection 40 mg/0.8 mL BI 695501 solution.	US-licensed Humira® n=108 Participants single s.c. injection 40 mg/0.8 mL US-licensed Humira®	EU-approved Humira® n=107 Participants single s.c. injection 40 mg/0.8 mL EU-approved Humira®
AUC (0-480) of BI 695501, US-licensed Humira® or EU-approved Humira®	1400 µg*h/mL Geometric Coefficient of Variation 35.8	1390 µg*h/mL Geometric Coefficient of Variation 32.2	1440 µg*h/mL Geometric Coefficient of Variation 28.0

SECONDARY outcome

Timeframe: 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

Population: The PK analysis set.

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).

Outcome measures

Measure	BI 695501 n=107 Participants single s.c. injection 40 mg/0.8 mL BI 695501 solution.	US-licensed Humira® n=108 Participants single s.c. injection 40 mg/0.8 mL US-licensed Humira®	EU-approved Humira® n=107 Participants single s.c. injection 40 mg/0.8 mL EU-approved Humira®
AUC (0-648) of BI 695501, US-licensed Humira® or EU-approved Humira®	1730 µg*h/mL Geometric Coefficient of Variation 37.0	1680 µg*h/mL Geometric Coefficient of Variation 33.2	1760 µg*h/mL Geometric Coefficient of Variation 27.2

SECONDARY outcome

Timeframe: 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

Population: The PK analysis set.

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).

Outcome measures

Measure	BI 695501 n=107 Participants single s.c. injection 40 mg/0.8 mL BI 695501 solution.	US-licensed Humira® n=106 Participants single s.c. injection 40 mg/0.8 mL US-licensed Humira®	EU-approved Humira® n=106 Participants single s.c. injection 40 mg/0.8 mL EU-approved Humira®
AUC (0-1032) of BI 695501, US-licensed Humira® or EU-approved Humira®	2190 µg*h/mL Geometric Coefficient of Variation 41.4	2080 µg*h/mL Geometric Coefficient of Variation 38.5	2210 µg*h/mL Geometric Coefficient of Variation 29.1

SECONDARY outcome

Timeframe: 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.

Population: The PK analysis set.

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).

Outcome measures

Measure	BI 695501 n=106 Participants single s.c. injection 40 mg/0.8 mL BI 695501 solution.	US-licensed Humira® n=105 Participants single s.c. injection 40 mg/0.8 mL US-licensed Humira®	EU-approved Humira® n=105 Participants single s.c. injection 40 mg/0.8 mL EU-approved Humira®
AUC 0-∞,Obs of BI 695501, US-licensed Humira® or EU-approved Humira®	2630 µg*h/mL Geometric Coefficient of Variation 52.6	2470 µg*h/mL Geometric Coefficient of Variation 51.3	2640 µg*h/mL Geometric Coefficient of Variation 38.5

SECONDARY outcome

Timeframe: Day 1 through Day 71

Population: The safety analysis set consisted of all subjects who received the single dose of trial medication (BI 695501, US-licensed Humira® or EU-approved Humira®).

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.

Outcome measures

Measure	BI 695501 n=108 Participants single s.c. injection 40 mg/0.8 mL BI 695501 solution.	US-licensed Humira® n=108 Participants single s.c. injection 40 mg/0.8 mL US-licensed Humira®	EU-approved Humira® n=108 Participants single s.c. injection 40 mg/0.8 mL EU-approved Humira®
Number (Proportion) of Subjects With Drug Related Adverse Events	21 participants	29 participants	28 participants

Adverse Events

BI 695501

Serious events: 3 serious events

Other events: 51 other events

Deaths: 0 deaths

US-licensed Humira®

Serious events: 3 serious events

Other events: 52 other events

Deaths: 0 deaths

EU-approved Humira®

Serious events: 2 serious events

Other events: 51 other events

Deaths: 0 deaths

Serious adverse events

Measure	BI 695501 n=108 participants at risk single s.c. injection 40 mg/0.8 mL BI 695501 solution.	US-licensed Humira® n=108 participants at risk single s.c. injection 40 mg/0.8 mL US-licensed Humira®	EU-approved Humira® n=108 participants at risk single s.c. injection 40 mg/0.8 mL EU-approved Humira®
Gastrointestinal disorders Abdominal pain	0.93% 1/108 • Day 1 (first administration of trial medication) until day 71	0.00% 0/108 • Day 1 (first administration of trial medication) until day 71	0.93% 1/108 • Day 1 (first administration of trial medication) until day 71
Infections and infestations Appendicitis	0.00% 0/108 • Day 1 (first administration of trial medication) until day 71	1.9% 2/108 • Day 1 (first administration of trial medication) until day 71	0.00% 0/108 • Day 1 (first administration of trial medication) until day 71
Injury, poisoning and procedural complications Ankle fracture	0.93% 1/108 • Day 1 (first administration of trial medication) until day 71	0.00% 0/108 • Day 1 (first administration of trial medication) until day 71	0.00% 0/108 • Day 1 (first administration of trial medication) until day 71
Injury, poisoning and procedural complications Concussion	0.93% 1/108 • Day 1 (first administration of trial medication) until day 71	0.00% 0/108 • Day 1 (first administration of trial medication) until day 71	0.00% 0/108 • Day 1 (first administration of trial medication) until day 71
Injury, poisoning and procedural complications Hand fracture	0.93% 1/108 • Day 1 (first administration of trial medication) until day 71	0.00% 0/108 • Day 1 (first administration of trial medication) until day 71	0.00% 0/108 • Day 1 (first administration of trial medication) until day 71
Injury, poisoning and procedural complications Laceration	0.00% 0/108 • Day 1 (first administration of trial medication) until day 71	0.93% 1/108 • Day 1 (first administration of trial medication) until day 71	0.00% 0/108 • Day 1 (first administration of trial medication) until day 71
Renal and urinary disorders Nephrolithiasis	0.00% 0/108 • Day 1 (first administration of trial medication) until day 71	0.00% 0/108 • Day 1 (first administration of trial medication) until day 71	0.93% 1/108 • Day 1 (first administration of trial medication) until day 71

Other adverse events

Measure	BI 695501 n=108 participants at risk single s.c. injection 40 mg/0.8 mL BI 695501 solution.	US-licensed Humira® n=108 participants at risk single s.c. injection 40 mg/0.8 mL US-licensed Humira®	EU-approved Humira® n=108 participants at risk single s.c. injection 40 mg/0.8 mL EU-approved Humira®
Gastrointestinal disorders Abdominal pain	1.9% 2/108 • Day 1 (first administration of trial medication) until day 71	6.5% 7/108 • Day 1 (first administration of trial medication) until day 71	0.93% 1/108 • Day 1 (first administration of trial medication) until day 71
Gastrointestinal disorders Diarrhoea	3.7% 4/108 • Day 1 (first administration of trial medication) until day 71	6.5% 7/108 • Day 1 (first administration of trial medication) until day 71	0.00% 0/108 • Day 1 (first administration of trial medication) until day 71
Gastrointestinal disorders Nausea	5.6% 6/108 • Day 1 (first administration of trial medication) until day 71	1.9% 2/108 • Day 1 (first administration of trial medication) until day 71	2.8% 3/108 • Day 1 (first administration of trial medication) until day 71
Infections and infestations Upper respiratory tract infection	17.6% 19/108 • Day 1 (first administration of trial medication) until day 71	15.7% 17/108 • Day 1 (first administration of trial medication) until day 71	20.4% 22/108 • Day 1 (first administration of trial medication) until day 71
Nervous system disorders Headache	23.1% 25/108 • Day 1 (first administration of trial medication) until day 71	23.1% 25/108 • Day 1 (first administration of trial medication) until day 71	25.9% 28/108 • Day 1 (first administration of trial medication) until day 71
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.6% 6/108 • Day 1 (first administration of trial medication) until day 71	1.9% 2/108 • Day 1 (first administration of trial medication) until day 71	3.7% 4/108 • Day 1 (first administration of trial medication) until day 71
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	2.8% 3/108 • Day 1 (first administration of trial medication) until day 71	3.7% 4/108 • Day 1 (first administration of trial medication) until day 71	5.6% 6/108 • Day 1 (first administration of trial medication) until day 71

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

Results disclosure agreements

• Principal investigator is a sponsor employee Other - Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER