Trial Outcomes & Findings for Safety and Pharmacokinetics of Multiple Doses of BI 655064 in Healthy Chinese Male Volunteers (NCT NCT02331277)

NCT ID: NCT02331277

Last Updated: 2023-08-21

Results Overview

Percentage of subjects with drug-related adverse events (AEs). Medical judgment was used to determine the relationship between study medication and AEs, considering all relevant factors, including pattern of reaction, temporal relationship, de-challenge or re-challenge, confounding factors such as concomitant medication, concomitant diseases and relevant history.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 12 participants
• Primary outcome timeframe: From the first drug administration until 126 days after last drug administration, up to 148 days.
• Results posted on: 2023-08-21

Participant Flow

This was a randomised, double-blind, placebo-controlled, multiple dose trial.

Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all subjects was adhered to throughout the trial conduct. Rescue medication was allowed for all patients as required.

Participant milestones

Measure	Placebo Subjects received placebo matching to BI 655064 via subcutaneous injection every week, until 4 weeks.	BI 655064 Subjects received BI 655064 240 milligram (mg) via subcutaneous injection every week, until 4 weeks.
Overall Study STARTED	3	9
Overall Study COMPLETED	2	9
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Measure	Placebo Subjects received placebo matching to BI 655064 via subcutaneous injection every week, until 4 weeks.	BI 655064 Subjects received BI 655064 240 milligram (mg) via subcutaneous injection every week, until 4 weeks.
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Safety and Pharmacokinetics of Multiple Doses of BI 655064 in Healthy Chinese Male Volunteers

Baseline characteristics by cohort

Measure	Placebo n=3 Participants Subjects received placebo matching to BI 655064 via subcutaneous injection every week, until 4 weeks.	BI 655064 n=9 Participants Subjects received BI 655064 240 milligram (mg) via subcutaneous injection every week, until 4 weeks.	Total n=12 Participants Total of all reporting groups
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	3 Participants n=5 Participants	9 Participants n=7 Participants	12 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	29.0 Years STANDARD_DEVIATION 4.36 • n=5 Participants	25.1 Years STANDARD_DEVIATION 3.41 • n=7 Participants	26.1 Years STANDARD_DEVIATION 3.87 • 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	3 Participants n=5 Participants	9 Participants n=7 Participants	12 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	3 Participants n=5 Participants	9 Participants n=7 Participants	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the first drug administration until 126 days after last drug administration, up to 148 days.

Population: Treated set (TS): This set included all subjects who were dispensed study medication and were documented to have received at least 1 dose of investigational treatment.

Percentage of subjects with drug-related adverse events (AEs). Medical judgment was used to determine the relationship between study medication and AEs, considering all relevant factors, including pattern of reaction, temporal relationship, de-challenge or re-challenge, confounding factors such as concomitant medication, concomitant diseases and relevant history.

Outcome measures

Measure	Placebo n=3 Participants Subjects received placebo matching to BI 655064 via subcutaneous injection every week, until 4 weeks.	BI 655064 n=9 Participants Subjects received BI 655064 240 milligram (mg) via subcutaneous injection every week, until 4 weeks.
Percentage of Subjects With Drug-related Adverse Events.	66.7 Percentage of subjects	55.6 Percentage of subjects

SECONDARY outcome

Timeframe: Pharmacokinetic samples were collected at -3, 8, 12, 24, 48, 72, 84, 96, 108, 120, 144 and 167.5 hours (h) after first drug administration on day 1.

Population: The pharmacokinetic (PK) set (PKS): This set included all evaluable subjects in TS who provided at least 1 PK parameter. One subject was excluded from the PKS as he developed a positive anti-BI 655064 antibodies response.

Maximum measured concentration of BI 655064 in plasma after the 1st dose (Cmax).

Outcome measures

Measure	Placebo n=8 Participants Subjects received placebo matching to BI 655064 via subcutaneous injection every week, until 4 weeks.	BI 655064 Subjects received BI 655064 240 milligram (mg) via subcutaneous injection every week, until 4 weeks.
Maximum Measured Concentration of BI 655064 in Plasma After the 1st Dose (Cmax)	22.9 microgram (μg) / milliLitre (mL) Geometric Coefficient of Variation 72.3	—

SECONDARY outcome

Timeframe: Pharmacokinetic samples were collected at -3, 8, 12, 24, 48, 72, 84, 96, 108, 120, 144 and 167.5 h after first drug administration on day 1.

Population: PKS. One subject was excluded from the PKS as he developed a positive anti-BI 655064 antibodies response.

Time from dosing to maximum measured concentration of BI 655064 in plasma after the 1st dose (tmax).

Outcome measures

Measure	Placebo n=8 Participants Subjects received placebo matching to BI 655064 via subcutaneous injection every week, until 4 weeks.	BI 655064 Subjects received BI 655064 240 milligram (mg) via subcutaneous injection every week, until 4 weeks.
Time From Dosing to Maximum Measured Concentration of BI 655064 in Plasma After the 1st Dose (Tmax)	132 hours (h) Interval 72.0 to 168.0	—

SECONDARY outcome

Timeframe: Pharmacokinetic samples were collected at -3, 8, 12, 24, 48, 72, 84, 96, 108, 120, 144 and 167.5 h after first drug administration on day 1.

Population: PKS. One subject was excluded from the PKS as he developed a positive anti-BI 655064 antibodies response.

Area under the concentration-time curve of BI 655064 in plasma after the 1st dose over a uniform dosing interval τ (= 1 week) (AUCτ,1).

Outcome measures

Measure	Placebo n=8 Participants Subjects received placebo matching to BI 655064 via subcutaneous injection every week, until 4 weeks.	BI 655064 Subjects received BI 655064 240 milligram (mg) via subcutaneous injection every week, until 4 weeks.
Area Under the Concentration-time Curve of BI 655064 in Plasma After the 1st Dose Over a Uniform Dosing Interval τ (AUCτ,1)	2610 μg*h/mL Geometric Coefficient of Variation 79	—

SECONDARY outcome

Timeframe: Pharmacokinetic samples were collected at 505, 516, 528, 552, 576, 600, 624, 648, 672, 696, 744, 816, 912, 1008, 1176, 1344, 1512, 1848, 2520 and 3192 h after fourth drug administration on day 22.

Population: PKS. One subject was excluded from the PKS as he developed a positive anti-BI 655064 antibodies response.

Maximum measured concentration of BI 655064 in plasma after the 4th dose (Cmax,4).

Outcome measures

Measure	Placebo n=8 Participants Subjects received placebo matching to BI 655064 via subcutaneous injection every week, until 4 weeks.	BI 655064 Subjects received BI 655064 240 milligram (mg) via subcutaneous injection every week, until 4 weeks.
Maximum Measured Concentration of BI 655064 in Plasma After the 4th Dose (Cmax,4)	74.1 μg/mL Geometric Coefficient of Variation 50.4	—

SECONDARY outcome

Timeframe: Pharmacokinetic samples were collected at 505, 516, 528, 552, 576, 600, 624, 648, 672, 696, 744, 816, 912, 1008, 1176, 1344, 1512, 1848, 2520 and 3192 h after fourth drug administration on day 22.

Population: PKS. One subject was excluded from the PKS as he developed a positive anti-BI 655064 antibodies response.

Time from dosing to maximum measured concentration of BI 655064 in plasma after the 4th dose (tmax,4).

Outcome measures

Measure	Placebo n=8 Participants Subjects received placebo matching to BI 655064 via subcutaneous injection every week, until 4 weeks.	BI 655064 Subjects received BI 655064 240 milligram (mg) via subcutaneous injection every week, until 4 weeks.
Time From Dosing to Maximum Measured Concentration of BI 655064 in Plasma After the 4th Dose (Tmax,4)	84.2 h Interval 12.0 to 144.0	—

SECONDARY outcome

Timeframe: Pharmacokinetic samples were collected at 505, 516, 528, 552, 576, 600, 624, 648, 672, 696, 744, 816, 912, 1008, 1176, 1344, 1512, 1848, 2520 and 3192 h after fourth drug administration on day 22.

Population: PKS. One subject was excluded from the PKS as he developed a positive anti-BI 655064 antibodies response.

Area under the concentration-time curve of BI 655064 in plasma after the 4th dose over a uniform dosing interval τ (= 1 week) (AUCτ,4).

Outcome measures

Measure	Placebo n=8 Participants Subjects received placebo matching to BI 655064 via subcutaneous injection every week, until 4 weeks.	BI 655064 Subjects received BI 655064 240 milligram (mg) via subcutaneous injection every week, until 4 weeks.
Area Under the Concentration-time Curve of BI 655064 in Plasma After the 4th Dose Over a Uniform Dosing Interval τ (AUCτ,4)	10900 μg*h/mL Geometric Coefficient of Variation 49.9	—

SECONDARY outcome

Timeframe: Pharmacokinetic samples were collected at -3, 8, 12, 24, 48, 72, 84, 96, 108, 120, 144 and 167.5 h for Cmax and 505, 516, 528, 552, 576, 600, 624, 648, 672, 696, 744, 816, 912, 1008, 1176, 1344, 1512, 1848, 2520, 3192 and 5880 h for Cmax,4.

Population: PKS. One subject was excluded from the PKS as he developed a positive anti-BI 655064 antibodies response.

Accumulation ratio of BI 655064 in plasma after administration of the 4th dose over the dosing interval τ (= 1 week), expressed as ratio of Cmax after the 4th dose and after the 1st dose (RA,Cmax,4).

Outcome measures

Measure	Placebo n=8 Participants Subjects received placebo matching to BI 655064 via subcutaneous injection every week, until 4 weeks.	BI 655064 Subjects received BI 655064 240 milligram (mg) via subcutaneous injection every week, until 4 weeks.
Accumulation Ratio of BI 655064 in Plasma After Administration of the 4th Dose Over the Dosing Interval τ, Expressed as Ratio of Cmax After the 4th Dose and After the 1st Dose (RA,Cmax,4)	3.24 Ratio of Cmax after the 4th and 1st dose Geometric Coefficient of Variation 24.8	—

SECONDARY outcome

Timeframe: Pharmacokinetic samples were collected at -3, 8, 12, 24, 48, 72, 84, 96, 108, 120, 144 and 167.5 h for AUCτ,1 and 505, 516, 528, 552, 576, 600, 624, 648, 672, 696, 744, 816, 912, 1008, 1176, 1344, 1512, 1848, 2520, 3192 and 5880 h for AUCτ,4.

Population: PKS. One subject was excluded from the PKS as he developed a positive anti-BI 655064 antibodies response.

Accumulation ratio of BI 655064 in plasma after administration of the 4th dose over the dosing interval τ (= 1 week), expressed as ratio of AUC after the 4th dose and after the 1st dose (RA,AUC,4).

Outcome measures

Measure	Placebo n=8 Participants Subjects received placebo matching to BI 655064 via subcutaneous injection every week, until 4 weeks.	BI 655064 Subjects received BI 655064 240 milligram (mg) via subcutaneous injection every week, until 4 weeks.
Accumulation Ratio of BI 655064 in Plasma After Administration of the 4th Dose Over the Dosing Interval τ, Expressed as Ratio of AUC After the 4th Dose and After the 1st Dose (RA,AUC,4)	4.19 Ratio of AUC after the 4th and 1st dose Geometric Coefficient of Variation 32.9	—

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

BI 655064

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo n=3 participants at risk Subjects received placebo matching to BI 655064 via subcutaneous injection every week, until 4 weeks.	BI 655064 n=9 participants at risk Subjects received BI 655064 240 milligram (mg) via subcutaneous injection every week, until 4 weeks.
Ear and labyrinth disorders Vertigo positional	0.00% 0/3 • From the first drug administration until 126 days after last drug administration, up to 148 days.	11.1% 1/9 • From the first drug administration until 126 days after last drug administration, up to 148 days.
Eye disorders Conjunctival hyperaemia	33.3% 1/3 • From the first drug administration until 126 days after last drug administration, up to 148 days.	0.00% 0/9 • From the first drug administration until 126 days after last drug administration, up to 148 days.
Gastrointestinal disorders Abdominal discomfort	33.3% 1/3 • From the first drug administration until 126 days after last drug administration, up to 148 days.	0.00% 0/9 • From the first drug administration until 126 days after last drug administration, up to 148 days.
Gastrointestinal disorders Breath odour	33.3% 1/3 • From the first drug administration until 126 days after last drug administration, up to 148 days.	0.00% 0/9 • From the first drug administration until 126 days after last drug administration, up to 148 days.
Gastrointestinal disorders Diarrhoea	33.3% 1/3 • From the first drug administration until 126 days after last drug administration, up to 148 days.	0.00% 0/9 • From the first drug administration until 126 days after last drug administration, up to 148 days.
Gastrointestinal disorders Gingival bleeding	33.3% 1/3 • From the first drug administration until 126 days after last drug administration, up to 148 days.	0.00% 0/9 • From the first drug administration until 126 days after last drug administration, up to 148 days.
Gastrointestinal disorders Mouth ulceration	33.3% 1/3 • From the first drug administration until 126 days after last drug administration, up to 148 days.	0.00% 0/9 • From the first drug administration until 126 days after last drug administration, up to 148 days.
General disorders Chest discomfort	33.3% 1/3 • From the first drug administration until 126 days after last drug administration, up to 148 days.	0.00% 0/9 • From the first drug administration until 126 days after last drug administration, up to 148 days.
General disorders Chest pain	33.3% 1/3 • From the first drug administration until 126 days after last drug administration, up to 148 days.	22.2% 2/9 • From the first drug administration until 126 days after last drug administration, up to 148 days.
General disorders Fatigue	0.00% 0/3 • From the first drug administration until 126 days after last drug administration, up to 148 days.	11.1% 1/9 • From the first drug administration until 126 days after last drug administration, up to 148 days.
General disorders Injection site bruising	0.00% 0/3 • From the first drug administration until 126 days after last drug administration, up to 148 days.	11.1% 1/9 • From the first drug administration until 126 days after last drug administration, up to 148 days.
Infections and infestations Upper respiratory tract infection	33.3% 1/3 • From the first drug administration until 126 days after last drug administration, up to 148 days.	22.2% 2/9 • From the first drug administration until 126 days after last drug administration, up to 148 days.
Musculoskeletal and connective tissue disorders Arthralgia	33.3% 1/3 • From the first drug administration until 126 days after last drug administration, up to 148 days.	11.1% 1/9 • From the first drug administration until 126 days after last drug administration, up to 148 days.
Musculoskeletal and connective tissue disorders Pain in extremity	33.3% 1/3 • From the first drug administration until 126 days after last drug administration, up to 148 days.	11.1% 1/9 • From the first drug administration until 126 days after last drug administration, up to 148 days.
Musculoskeletal and connective tissue disorders Muscle twitching	0.00% 0/3 • From the first drug administration until 126 days after last drug administration, up to 148 days.	11.1% 1/9 • From the first drug administration until 126 days after last drug administration, up to 148 days.
Nervous system disorders Headache	33.3% 1/3 • From the first drug administration until 126 days after last drug administration, up to 148 days.	22.2% 2/9 • From the first drug administration until 126 days after last drug administration, up to 148 days.
Nervous system disorders Hypoaesthesia	33.3% 1/3 • From the first drug administration until 126 days after last drug administration, up to 148 days.	0.00% 0/9 • From the first drug administration until 126 days after last drug administration, up to 148 days.
Psychiatric disorders Affect lability	33.3% 1/3 • From the first drug administration until 126 days after last drug administration, up to 148 days.	0.00% 0/9 • From the first drug administration until 126 days after last drug administration, up to 148 days.
Respiratory, thoracic and mediastinal disorders Nasal pruritus	0.00% 0/3 • From the first drug administration until 126 days after last drug administration, up to 148 days.	11.1% 1/9 • From the first drug administration until 126 days after last drug administration, up to 148 days.
Skin and subcutaneous tissue disorders Acne	66.7% 2/3 • From the first drug administration until 126 days after last drug administration, up to 148 days.	44.4% 4/9 • From the first drug administration until 126 days after last drug administration, up to 148 days.

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 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