Trial Outcomes & Findings for Pharmacokinetics and Safety of BI 695501 (NCT NCT02899338)

Last Updated: 2018-10-11

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

162 participants

Primary outcome 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.

Results posted on

2018-10-11

Participant Flow

Subjects were randomized in 1:1 ratio to receive BI 695501 (autoinjector) or BI 695501 (prefilled syringe).

Participant milestones

Participant milestones
Measure	BI695501 Prefilled Syringe Patients were administered a single subcutaneous dose of 40 milligram (mg)/0.8 milliliter (mL) BI 695501 (solution for injection) using a prefilled syringe (PFS).	BI695501 Autoinjector Patients were administered a single subcutaneous dose of 40 milligram (mg)/0.8 milliliter (mL) BI 695501 (solution for injection) using an autoinjector (AI).
Overall Study STARTED	81	81
Overall Study COMPLETED	78	79
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	BI695501 Prefilled Syringe Patients were administered a single subcutaneous dose of 40 milligram (mg)/0.8 milliliter (mL) BI 695501 (solution for injection) using a prefilled syringe (PFS).	BI695501 Autoinjector Patients were administered a single subcutaneous dose of 40 milligram (mg)/0.8 milliliter (mL) BI 695501 (solution for injection) using an autoinjector (AI).
Overall Study Adverse Event	1	2
Overall Study Withdrawal by Subject	2	0

Baseline Characteristics

Pharmacokinetics and Safety of BI 695501

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BI695501 Prefilled Syringe n=81 Participants Patients were administered a single subcutaneous dose of 40 milligram (mg)/0.8 milliliter (mL) BI 695501 (solution for injection) using a prefilled syringe (PFS).	BI695501 Autoinjector n=81 Participants Patients were administered a single subcutaneous dose of 40 milligram (mg)/0.8 milliliter (mL) BI 695501 (solution for injection) using an autoinjector (AI).	Total n=162 Participants Total of all reporting groups
Age, Continuous	44.5 Years STANDARD_DEVIATION 14.74 • n=5 Participants	41.5 Years STANDARD_DEVIATION 14.44 • n=7 Participants	43.0 Years STANDARD_DEVIATION 14.62 • n=5 Participants
Sex: Female, Male Female	44 Participants n=5 Participants	43 Participants n=7 Participants	87 Participants n=5 Participants
Sex: Female, Male Male	37 Participants n=5 Participants	38 Participants n=7 Participants	75 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	81 Participants n=5 Participants	81 Participants n=7 Participants	162 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	78 Participants n=5 Participants	77 Participants n=7 Participants	155 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Body weight at baseline	74.84 Kilogram (kg) STANDARD_DEVIATION 15.421 • n=5 Participants	75.25 Kilogram (kg) STANDARD_DEVIATION 14.909 • n=7 Participants	75.04 Kilogram (kg) STANDARD_DEVIATION 15.122 • n=5 Participants

PRIMARY outcome

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.

Population: PKS: The pharmacokinetic set (PKS) consisted of all randomized subjects who received the single dose of trial medication (BI 695501 administered via PFS or AI), had at least 1 evaluable primary PK parameter, and were without important protocol deviations or violations thought to significantly affect the PK of BI 695501.

Outcome measures

Outcome measures
Measure	BI695501 Prefilled Syringe n=76 Participants Patients were administered a single subcutaneous dose of 40 milligram (mg)/0.8 milliliter (mL) BI 695501 (solution for injection) using a prefilled syringe (PFS).	BI695501 Autoinjector n=79 Participants Patients were administered a single subcutaneous dose of 40 milligram (mg)/0.8 milliliter (mL) BI 695501 (solution for injection) using an autoinjector (AI).
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.	2100 microgram hour per milliliter (μg*h/mL) Geometric Coefficient of Variation 43.9	2150 microgram hour per milliliter (μg*h/mL) Geometric Coefficient of Variation 45.2

PRIMARY outcome

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.

Population: PKS

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.

Outcome measures

Outcome measures
Measure	BI695501 Prefilled Syringe n=79 Participants Patients were administered a single subcutaneous dose of 40 milligram (mg)/0.8 milliliter (mL) BI 695501 (solution for injection) using a prefilled syringe (PFS).	BI695501 Autoinjector n=81 Participants Patients were administered a single subcutaneous dose of 40 milligram (mg)/0.8 milliliter (mL) BI 695501 (solution for injection) using an autoinjector (AI).
The Maximum Measured Concentration of BI 695501 in Plasma (Cmax) After Administration Via PFS and AI	3.86 µg/mL Geometric Coefficient of Variation 27.8	3.86 µg/mL Geometric Coefficient of Variation 23.6

PRIMARY outcome

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.

Population: PKS

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.

Outcome measures

Outcome measures
Measure	BI695501 Prefilled Syringe n=76 Participants Patients were administered a single subcutaneous dose of 40 milligram (mg)/0.8 milliliter (mL) BI 695501 (solution for injection) using a prefilled syringe (PFS).	BI695501 Autoinjector n=79 Participants Patients were administered a single subcutaneous dose of 40 milligram (mg)/0.8 milliliter (mL) BI 695501 (solution for injection) using an autoinjector (AI).
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.	2250 μg*h/mL Geometric Coefficient of Variation 50.3	2330 μg*h/mL Geometric Coefficient of Variation 50.4

SECONDARY outcome

Timeframe: From Day 1 to Day 70

Population: All treated subjects (i.e. all subjects who received 1 dose of trial medication) were included in the safety analysis set (SAF).

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.

Outcome measures

Outcome measures
Measure	BI695501 Prefilled Syringe n=81 Participants Patients were administered a single subcutaneous dose of 40 milligram (mg)/0.8 milliliter (mL) BI 695501 (solution for injection) using a prefilled syringe (PFS).	BI695501 Autoinjector n=81 Participants Patients were administered a single subcutaneous dose of 40 milligram (mg)/0.8 milliliter (mL) BI 695501 (solution for injection) using an autoinjector (AI).
The Percentage of Subjects With Drug-related Treatment-emergent Adverse Events (TEAEs) From Day 1 to Day 70.	37.0 Percentage of participants	38.3 Percentage of participants

Adverse Events

BI695501 Autoinjector

Serious events: 2 serious events

Other events: 47 other events

Deaths: 0 deaths

BI695501 Prefilled Syringe

Serious events: 1 serious events

Other events: 41 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	BI695501 Autoinjector n=81 participants at risk Patients were administered a single subcutaneous dose of 40 milligram (mg)/0.8 milliliter (mL) BI 695501 (solution for injection) using an autoinjector (AI).	BI695501 Prefilled Syringe n=81 participants at risk Patients were administered a single subcutaneous dose of 40 milligram (mg)/0.8 milliliter (mL) BI 695501 (solution for injection) using a prefilled syringe (PFS).
Injury, poisoning and procedural complications Ligament rupture	1.2% 1/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.	0.00% 0/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.	1.2% 1/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.
Nervous system disorders Seizure	1.2% 1/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.	0.00% 0/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.

Other adverse events

Other adverse events
Measure	BI695501 Autoinjector n=81 participants at risk Patients were administered a single subcutaneous dose of 40 milligram (mg)/0.8 milliliter (mL) BI 695501 (solution for injection) using an autoinjector (AI).	BI695501 Prefilled Syringe n=81 participants at risk Patients were administered a single subcutaneous dose of 40 milligram (mg)/0.8 milliliter (mL) BI 695501 (solution for injection) using a prefilled syringe (PFS).
Gastrointestinal disorders Abdominal discomfort	9.9% 8/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.	11.1% 9/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.
Gastrointestinal disorders Diarrhoea	3.7% 3/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.	6.2% 5/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.
Gastrointestinal disorders Nausea	9.9% 8/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.	4.9% 4/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.
General disorders Influenza like illness	6.2% 5/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.	6.2% 5/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.
General disorders Injection site erythema	17.3% 14/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.	8.6% 7/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.
General disorders Injection site haematoma	7.4% 6/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.	0.00% 0/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.
General disorders Injection site induration	4.9% 4/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.	6.2% 5/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.
General disorders Injection site pain	6.2% 5/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.	4.9% 4/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.
General disorders Injection site swelling	7.4% 6/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.	6.2% 5/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.
Infections and infestations Nasopharyngitis	13.6% 11/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.	11.1% 9/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.
Musculoskeletal and connective tissue disorders Back pain	6.2% 5/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.	9.9% 8/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.
Nervous system disorders Headache	19.8% 16/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.	13.6% 11/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.5% 2/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.	11.1% 9/81 • From single dose administration till 10 weeks; up to 70 days All events with an onset after the single dose of trial medication up to a period of 10 weeks (70 days) were assigned to the treatment phase for evaluation and were considered to be TEAEs. The SAF population was used which consisted of all subjects that received a single dose of trial medication.

Additional Information

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Boehringer Ingelheim

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Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
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