Trial Outcomes & Findings for Pharmacokinetics and Safety of BI 695501 Administered Via Prefilled Syringe or Autoinjector (NCT NCT02606903)

Last Updated: 2018-12-27

Results Overview

Maximum measured concentration of BI 695501 in plasma (Cmax). The rate and extent of absorption of BI 695501 by assessment of maximum plasma concentration following administration via AI or via PFS of a single dose of 40 mg BI 695501. During analysis, it was realized that the PK sample on Day 43 had originally been mistakenly associated with a 1032 h time point, rather than with 1008 h. However, PK parameters are calculated using actual values so this did not impact the analysis results.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

71 participants

Primary outcome timeframe

PK plasma samples were taken at: 1 hour (h) before drug administration and 1h, 4h, 8h,12h, 24h, 48h, 60h, 72h, 84h, 96h, 108h, 120h, 132h, 144h, 168h, 216h, 336h, 504h, 672h, 840h, 1008h after drug administration.

Results posted on

2018-12-27

Participant Flow

This was randomized, single-dose, parallel-arm, open-label Phase I trial with healthy male subjects.

Participant milestones

Participant milestones
Measure	BI 695501 Autoinjector (AI) Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in auto injector via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Test Product)	BI 695501 Pre-filled Syringe (PFS) Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in pre-filled syringe via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Reference Product)
Overall Study STARTED	35	36
Overall Study COMPLETED	35	36
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetics and Safety of BI 695501 Administered Via Prefilled Syringe or Autoinjector

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BI 695501 Autoinjector (AI) n=35 Participants Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in auto injector via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Test Product)	BI 695501 Pre-filled Syringe (PFS) n=36 Participants Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in pre-filled syringe via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Reference Product)	Total n=71 Participants Total of all reporting groups
Age, Continuous	39.3 Years STANDARD_DEVIATION 13.77 • n=5 Participants	40.1 Years STANDARD_DEVIATION 13.32 • n=7 Participants	39.7 Years STANDARD_DEVIATION 13.45 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	36 Participants n=7 Participants	71 Participants n=5 Participants

PRIMARY outcome

Timeframe: PK plasma samples were taken at: 1 hour (h) before drug administration and 1h, 4h, 8h,12h, 24h, 48h, 60h, 72h, 84h, 96h, 108h, 120h, 132h, 144h, 168h, 216h, 336h, 504h, 672h, 840h, 1008h after drug administration.

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

Outcome measures

Outcome measures
Measure	BI 695501 Autoinjector (AI) n=35 Participants Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in auto injector via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Test Product)	BI 695501 Pre-filled Syringe (PFS) n=36 Participants Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in pre-filled syringe via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Reference Product)
Maximum Measured Concentration of BI 695501 in Plasma (Cmax)	3.79 Micro-gram (µg) per milliliter (mL) Geometric Coefficient of Variation 27.4	3.48 Micro-gram (µg) per milliliter (mL) Geometric Coefficient of Variation 51.0

PRIMARY outcome

Area under the concentration-time curve of the BI 695501 in plasma over the time interval from 0 to 1032 hours after dose (AUC0-1032). The rate and extent of absorption of BI 695501 by assessment of AUC0-1032 following administration via AI or via PFS of a single dose of 40 mg BI 695501. During analysis, it was realized that the PK sample on Day 43 had originally been mistakenly associated with a 1032 h time point, rather than with 1008 h. However, PK parameters are calculated using actual values so this did not impact the analysis results.

Outcome measures

Outcome measures
Measure	BI 695501 Autoinjector (AI) n=35 Participants Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in auto injector via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Test Product)	BI 695501 Pre-filled Syringe (PFS) n=35 Participants Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in pre-filled syringe via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Reference Product)
Area Under the Concentration-time Curve of the BI 695501 in Plasma Over the Time Interval From 0 to 1032 Hours After Dose (AUC0-1032)	1810 μg*h/mL Geometric Coefficient of Variation 47.5	1840 μg*h/mL Geometric Coefficient of Variation 47.1

PRIMARY outcome

Area under the concentration-time curve of the BI 695501 in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity) based on observed concentration at time of last measurable concentration. The rate and extent of absorption of BI 695501 by assessment of (AUC0-∞) following administration via AI or via PFS of a single dose of 40 mg BI 695501. During analysis, it was realized that the PK sample on Day 43 had originally been mistakenly associated with a 1032 h time point, rather than with 1008 h. However, PK parameters are calculated using actual values so this did not impact the analysis results.

Outcome measures

Outcome measures
Measure	BI 695501 Autoinjector (AI) n=35 Participants Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in auto injector via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Test Product)	BI 695501 Pre-filled Syringe (PFS) n=35 Participants Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in pre-filled syringe via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Reference Product)
Area Under the Concentration-time Curve of the BI 695501 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity)	2080 μg*h/mL Geometric Coefficient of Variation 58.2	2110 μg*h/mL Geometric Coefficient of Variation 58.0

SECONDARY outcome

Timeframe: From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period

Population: Safety analysis set (SAF): The SAF consisted of all subjects in the enrolled set who received at least one dose of trial medication and subjects were classified according to treatment received.

Number of subjects with drug-related Adverse Events (AEs). Any event with an onset after the administration of the trial medication up to a period of 70 days 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.

Outcome measures

Outcome measures
Measure	BI 695501 Autoinjector (AI) n=35 Participants Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in auto injector via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Test Product)	BI 695501 Pre-filled Syringe (PFS) n=36 Participants Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in pre-filled syringe via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Reference Product)
Number of Subjects With Drug-related Adverse Events (AEs)	20 Number of Subjects	16 Number of Subjects

Adverse Events

BI 695501 Autoinjector (AI)

Serious events: 0 serious events

Other events: 28 other events

Deaths: 0 deaths

BI 695501 Pre-filled Syringe (PFS)

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

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.
Publication restrictions are in place

Restriction type: OTHER

Measure	BI 695501 Autoinjector (AI) n=35 participants at risk Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in auto injector via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Test Product)	BI 695501 Pre-filled Syringe (PFS) n=36 participants at risk Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in pre-filled syringe via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Reference Product)
General disorders Fatigue	2.9% 1/35 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.	5.6% 2/36 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.
General disorders Influenza like illness	0.00% 0/35 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.	5.6% 2/36 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.
General disorders Injection site erythema	51.4% 18/35 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.	36.1% 13/36 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.
General disorders Injection site induration	11.4% 4/35 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.	2.8% 1/36 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.
General disorders Injection site pain	8.6% 3/35 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.	0.00% 0/36 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.
General disorders Injection site pruritus	2.9% 1/35 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.	5.6% 2/36 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.
General disorders Injection site swelling	20.0% 7/35 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.	8.3% 3/36 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.
Infections and infestations Nasopharyngitis	22.9% 8/35 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.	5.6% 2/36 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.
Injury, poisoning and procedural complications Contusion	8.6% 3/35 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.	0.00% 0/36 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.
Musculoskeletal and connective tissue disorders Neck pain	5.7% 2/35 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.	2.8% 1/36 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.
Musculoskeletal and connective tissue disorders Pain in extremity	5.7% 2/35 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.	0.00% 0/36 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.
Nervous system disorders Headache	11.4% 4/35 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.	16.7% 6/36 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.
Nervous system disorders Paraesthesia	5.7% 2/35 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.	2.8% 1/36 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.7% 2/35 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.	0.00% 0/36 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.
Musculoskeletal and connective tissue disorders Back pain	8.6% 3/35 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.	2.8% 1/36 • From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.